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Desires, Relations, Intimacy & Exploitation: An Introductory Mind Genomics Cartography

Abstract

We present two methods-oriented studies on sexuality, one dealing with the discussion of sexuality in the context of a relationship, the second with the societal protection of sex workers. Both studies used consumer respondents to evaluate systematically varied combinations of messages about the topic, the combinations created by experimental design, following the method of Mind Genomics. Study 1 on discussions of sexual intimacy presents Mind Genomics to understand the way people process information, their criteria for decision-making, and the nature of possibly easy-to-understand mind-sets, i.e., different criteria of importance assigned to the same pieces of information. Study 2 on the protection and recourse given to legal workers shows how to assess the interaction between person and situation as drivers of judgments and drivers of engagement. Both studies point to the emerging science of Mind Genomics as an easy, rapid, and cost-effective ways to create archival databases, to introduce new ways of thinking, and to democratize research world-wide, respectively.

Introduction

During the past three decades the focus of researchers has steadily increased on issues involving intimacy, specifically sexual intimacy between consenting partners (love, romance), as well as sexual intimacy as a business (sex workers.) Sexuality in its many manifestations has always attracted research because of its centrality in daily life, but as society has evolved, issues of sexuality have become intertwined with emotions, with public health (e.g., sexually transmitted disease), and finally with issues of the law (e.g., prostitution and the issues revolving around sex workers.)

The topics of love, sexuality, sexual exploitations, and societal reactions each have spawned enormous literatures. Table 1 shows the number of ‘hits’ for Google® and for Google Scholar®, for each of these topics, at the time of this writing, December 2019,

Table 1. Number of citations dealing with sex and its ramifications.

Topic

Citations–Google®

Citations–Google Scholar®

Love

18 billion

3.34 million

Sexuality

80 million

2.47 million

Sexual exploitation

72 million

1.03 million

Societal response to sexual exploitation

59 million

0.20 million

No set of studies can hope to be comprehensive, given the long history of the study of sexuality, the many manifestations in daily life, and the many cultures as well as stages of individual development that must be considered. Rather, we introduce here a new approach to the study of sexuality, the science of Mind Genomics, designed to take small snapshots of a topic, focus in depth on a specific, limited topic, and work with small, affordable samples of respondents.

The worldview of Mind Genomics involves a small, limited topic, investigating the patterns of decision making within that topic. Rather than emerging out of the history of the hypothetico-deductive method, isolating a variable and studying that variable in an experiment, Mind Genomics proceeds in the reverse direction. One might think of the Mind Genomics researcher as a cartographer faced with a new land. The cartographer measures the relevant variables of a topographical area, deduces the nature of the structure below, and maps the land. The cartographer creates maps, not theories. In the case of Mind Genomics, the ‘land’ is the world of sexuality. The cartography of this paper deals with the reactions to issues of sexual intimacy (one set of experiments), and reactions to issues of sex workers (another set of experiments.)

Exploring two topics of sex using Mind Genomics to generate insights and hypotheses

The topic of sexual behavior spans a wide range of topics, from the physical to the emotional to the legal, and to the societal. It is impossible to cover even a very small fraction of the topics with a set of experiments or surveys. The strategy of this paper is to demonstrate how the emerging science of Mind Genomics can generate an affordable, powerful database at the start of a research initiative, using simple ideas, simple thinking, consumer research, and powerful analyses, meaningful even with samples that are traditionally considered ‘small’.

The emerging science of Mind Genomics (Moskowitz & Gofman, 2007) [1], traces its intellectual heritage to the systematized thinking using experimental design to structure the test stimuli, as well as to sociology and consumer research for transforming the ideas into questions to be answered, and finally to the Socratic method to create the system as an inductive knowledge-development technique, easily applied in practice

Experimental design

Experimental design allows a researcher to understand the effects of a variable, either tested along in ‘splendid isolation’ or tested as part of a mixture (Box, Hunter & Hunter, 1978) [2]. Mind Genomics deals with the ordinary situation, wherein a person is presented with a combination of ideas, as the typical situation of daily life. The person responds to the combination, making a decision. But just what specific component of the combination or set of components ‘drive’ that decision? Experimental design sets up efficient combinations of independent variables, messages or elements in the language of Mind Genomics. It is the response to these systematically created mixtures, which, through regression reveals, quite directly the contribution of each Message or Element to the response. The response, in turn, is what the respondent answers.

Sociology and consumer research

These social science disciplines rely upon the responses of people to questions about behavior, or upon the measurement of the behavior of people in situations, i.e., upon attitude versus upon behavior, respectively. Where possible a meaningful behavioral measure may be better than an attitude, although the term ‘meaningful’ is important as a qualifier.

Over almost a century there has been a subtle current of belief that implicit measures are better than explicit ones, e.g., that EEG (brain waves) or GSR (activation) or pupil behavior (dilation, pupil motion) somehow are better than simple attitudinal ratings because the former are more objective, more biological (Boring, 1929) [3].

The foregoing use of ‘meaningful’ is not what is meant here. Rather, the term ‘meaningful’ is used in the sense that the measure to be meaningful must be a direct correlate of the mind of the person, whether person in society or an ordinary citizen faced with a choice. Mind Genomics uses the responses to combinations of messages, i.e., combinations of elements as the meaningful measure, since a great deal of behavior in everyday life is responses to mixtures. Mind Genomics goes the additional step by creating combinations of these messages, presenting them to respondents, measuring the reactions, and then estimating the contribution of each message.

The Socratic Method

The approach is grounded empiricism, not in the hypothetico-deductive method. There is no hypothesis to be tested. Rather, there is a topic to be studied. The topic of interest is presented to the researcher, who must create four questions which ‘tell a story’ about the topic. The questions are not necessarily final, but rather represent the way the topic is thought about, either those who are grounded in the topic, or even novices with no idea at all, so-called ‘newbies’. The four questions each motivate four answers, or a total of 16 answers, as shown in the next sections. The researcher then combines these answers into small vignettes, obtains responses to the vignettes, and shows how the different answers shed light on the topic.

The best way to show the Mind Genomics method is through a case history, dealing with a topic relevant to an individual, or even beyond the individual to a group, and to society. This paper focuses on two aspects of sexual behavior, the first dealing with discussions of sexual intimacy and disease protection between consenting partners, the second dealing with protection of the ‘sex’ worker. These are but two of the perhaps hundreds of topics in the rainbow of topics in sexuality. We show how a one-day experiment can produce data for each topic, making it feasible to explore hundreds of topics about sexuality in the time frame of a year, with affordable, rapid, insightful and archival data.

Study 1 – Discussinag disease prevention between two consenting & emotionally-involved partners

A great deal has been written about sexual relations between consenting partners, from issues to measurements (e.g., Fisher et. al., 2013; Montesi, et. al., 2013; Stephenson, et. al., 2010). [4, 5, 6] The topics range from the emotions felt by the participants to the behavior of adolescents versus older individuals, and on to the issues caused by the ravages of sexually transmitted disease (Harvey et al., 2016; Katz et al., 2000; Peplau et. al., 2007; Widman et. al., 2006). [7, 8, 9, 10] Our focus in this experiment is the couple’s discussion of issues around the prevention of sexually transmitted diseases using methods under their control. The study was motivated by author Ortiz’s plan to sponsor a campaign to reduce sexually transmitted disease.

Method

The Mind Genomics study begins with the creation of the four questions and the four answers to each question. These appear in Table 2 and were created by author Ortiz as part of a campaign against sexually transmitted diseases. The important thing to realize from Table 2 is that the study does not exhaust the topic. Indeed, Mind Genomics studies are not designed as single, exhaustive treatments of a subject, treatments which generate a large volume of disparate information. Rather, Table 2 shows a preliminary attempt to understand four aspects of the topic. The reality is that there may be 40 or 400 aspects of the topic. When one attempts to cover a topic thoroughly, the entire endeavor may collapse because, in common folk wisdom ‘the perfect is often the enemy of the good.’ The Mind Genomics strategy is to create a set of such small studies, accrete the results, and identify emergent patterns ‘from the bottom up.’ Mind Genomics represents the inductive way to learn, i.e., by discovering patterns, rather than by confirming or disconfirming ingoing hypotheses.

Table 2. Sexual Intimacy: Four questions and four answers to each question.

 

Question A: How do you communicate to your partner that you want to exchange STD results before sexual activity?

A1

Discussing STD precautions planning in a phone conversation

A2

Discussing STD precautions planning through texting

A3

Discussing STD precautions planning in an email

A4

Discussing STD precautions planning during lunch

 

Question B: How do you ensure your own safety before, during, and after sex?

B1

Using condoms during sex

B2

Getting tested regularly

B3

Both partners using birth controls

B4

Knowing partner’s prior sexual history

 

Question C: When is the best time to have a conversation with your partner about safe sex?

C1

Talking about safe sex when you first start dating

C2

Talking about safe sex before engaging in sexual activity

C3

Talking about safe sex during the first conversation about intimacy

C4

Talking about safe sex on the first date

 

Question D: What kind of answers do you think a partner can give your request for safe sex?

D1

Partner says: “Let’s get tested”

D2

Partner says: “There’s no need for safe sex”

D3

Partner says: “Let’s use protection”

D4

Partner says: “Safe sex is the best move”

The researcher combines these elements (the answers A1-D4) into small, easy to read combinations, so-called vignettes. The actual experimental design is created as ‘kernel,’ in which the 16 elements are statistically independent of each other, allowing for subsequent analysis by OLS (ordinary least-squares) regression. The kernel, or basic experimental design is permuted so that the design structure remains the same, but the individual combinations changes in a permutation pattern (Gofman & Moskowitz, 2010.) [11] Table 3 shows the experimental design for one respondent (independent variables in the subsequent analysis), and then the ratings, binary transformation (Bin) and Consideration or response Time (CT) (the dependent variables in the subsequent analysis.)

Table 3. Example of the data from one respondent, prepared for statistical analysis.

 

The 16 answers or elements in binary form.
1=present in the vignette, 0=absent from the vignette

Ratings & transformation
 Top3 = Comfortable

Vig

A1

A2

A3

A4

B1

B2

B3

B4

C1

C2

C3

C4

D1

D2

D3

D4

Rating

Top3

CT

1

0

1

0

0

0

1

0

0

1

0

0

0

0

0

0

1

9

100

9.0

2

0

1

0

0

0

0

1

0

0

1

0

0

1

0

0

0

9

100

6.9

3

1

0

0

0

0

0

0

1

0

0

0

0

1

0

0

0

5

1

9.0

4

0

0

0

0

0

0

1

0

0

1

0

0

0

1

0

0

3

1

9.0

5

0

0

0

0

0

1

0

0

0

0

0

1

0

0

0

0

3

1

0.7

6

0

0

0

1

0

0

1

0

0

0

0

0

0

0

0

1

5

0

0.4

7

0

0

1

0

0

0

0

1

0

0

0

0

0

0

0

0

8

100

0.3

8

1

0

0

0

0

0

0

0

0

1

0

0

0

0

0

1

4

1

0.7

The structure of the vignettes follows these conventions:

The experimental design, metaphorically a booklet of recipes of the same ingredients to create different dishes. The experimental design specifies the composition of vignettes comprising two elements, three elements, and four elements, respectively.

Each respondent is required to evaluate 24 vignettes, all different from each other. Across the 24 vignettes, each element appears five times and is absent 19 times. A vignette comprises at most one element or answer from any question (Table 3.) This strategy of testing both complete vignettes (one answer from each question) and incomplete vignettes (no answer from either one or two questions) ensures that the analysis of the data by OLS (ordinary least-squares) regression generates coefficients having absolute value, where ratios of coefficients are meaningful.

Each respondent evaluates 24 unique, different vignettes. The underlying experimental design ensures that the 24 vignettes for each respondent differ from the 24 vignettes for any other respondent. The benefit to this permutation scheme is that the Mind Genomics experiment covers a great deal of the so-called ‘design space’. The benefit to the researcher is one need not know ‘what works’ ahead of the study. In contrast, in other research methods using experimental design of messages (so-called conjoint analysis; Green & Srinivasan, 1990), [12] the researcher selects one set of combinations, and tests that set with many people in order to suppress the variation by averaging. Whether averaging out the variation in the typical approach or averaging out the variation by looking at a great deal of the design space ultimately proves to be better is still a matter of dispute.

Table 3 show the 24 vignettes as rows. The 16 elements are shown as A1-D4, corresponding to the four questions and the four answers in each question featured in Table 1.

The column labelled Rat is the 9-point rating assigned to the vignette by the respondent. Table 3 shows the respondent ratings of all 24 vignettes.

The column labelled Top3 is the ‘binary’ transformation of the 9-point ratings, with ratings of 1–6 transformed to 0, and a very small random number added to the transformed number For ratings 7–9 the rating is transformed to 100, and again a very small random number is added to the transformed number.

The addition of the random number is done so that the regression analysis will not ‘crash’ when the analysis creates individual-level models to generate mind-set segments. When a respondent rates all 24 vignettes between either 1–6 or between 7–9, respectively, then transformed ratings will all become either 0 or 100, respectively for the Top 3 measure, and the regression model using the Top3 measure as the dependent variable will ‘crash.’ Adding a small random number prevents that crash, ensuring that the statistical analysis proceeds without incident.

Finally, the column labelled CT is Consideration Time, or Response Time, defined as the number of seconds elapsing between the presentation of the vignette on the screen and the rating assigned by the respondent. The vignettes are short, so that any Consideration Time longer than 9 seconds is assumed to reflect the respondent’s multi-tasking and is brought to the value 9.0. The use of the term Consideration Time makes the number more meaningful to the reader, because the magnitude of the CT can be associated with the time it takes the respondent to consider the element.

The analysis of Mind Genomics data proceeds in a straightforward manner, enabled by the experimental design for the creation of the different vignettes. The experimental design created for a single individual ensures that the 16 elements or answers for that individual appear independently of each other among the 24 vignettes. Putting together a set of such experimental designs, each different from the others simply by a permutation scheme, maintain the statistical independence of the 16 elements.

An easy-to-interpret analysis (OLS Regression) relates the presence/absence of the 16 elements to the binary rating. OLS regression uses the 16 elements as independent variables, and the binary transformation, Top3, as the dependent variable. The regression incorporates the relevant cases, namely the 24 rows from each respondent who belongs to the subgroup. Thus, when it comes to the model or equation for ‘males,’ only the data from the male respondents are used. Each male respondent contributes 24 cases or observations.

The regression model estimates the parameters of this simple equation: Top3 = k0 + k1(A1) + k2(A2) … + k16(D4). Top3 is defined as ‘comfortable talking about the topic.

The parameters for the total panel and key subgroups appear in Table 4. The table shows total panel, gender, age groups, relationship status, and the response from all respondents, but broken out into the results from Vignettes 1–12 (Half1) and then from Vignettes 13–24 (Half2). This final comparison shows us whether the respondents ‘change their criteria’ as the study proceeds

Table 4. Parameters (additive constant, coefficients) for equations relating the presence/absence of the 16 elements for binary transformed rating ‘comfortable talking about the topic (prevention of sexually transmitted disease.)’. The table is sorted by the coefficients for the total panel.

 

Top 3 = Comfortable talking about the topic

Tot

Male

Fem

A25 Older

A24 Younger

Q3 Single

Q3 Relationship

Half1

Half2

 

Additive constant (k0)

61

55

65

73

43

60

62

62

61

D3

Partner says: “Let’s use protection”

6

5

8

6

6

6

6

5

6

A1

Discussing STD precautions planning in a phone conversation

4

2

6

3

6

6

1

5

3

D4

Partner says: “Safe sex is the best move”

4

3

4

5

3

7

0

9

-4

B2

Getting tested regularly

4

8

0

3

4

-1

9

5

3

A2

Discussing STD precautions planning through texting

3

-3

8

-1

6

1

4

-10

15

B3

Both partners using birth controls

3

8

-3

-3

10

-5

11

13

-11

C2

Talking about safe sex before engaging in sexual activity

3

4

3

-2

10

6

1

0

6

B4

Knowing partner’s prior sexual history

3

9

-2

3

3

-2

9

5

3

B1

Using condoms during sex

2

4

1

-1

6

-4

8

7

-4

C3

Talking about safe sex during the first conversation about intimacy

2

8

-4

-2

7

3

0

-2

5

C1

Talking about safe sex when you first start dating

-2

1

-3

-4

3

-3

0

-3

0

D1

Partner says: “Let’s get tested”

-2

-6

2

-2

-2

-4

0

-1

-6

A4

Discussing STD precautions planning during lunch

-2

-8

3

-1

-4

-3

-2

-6

2

A3

Discussing STD precautions planning in an email

-3

-2

-3

-5

0

-3

-3

-8

3

C4

Talking about safe sex on the first date

-8

-5

-10

-8

-7

-8

-8

-9

-6

D2

Partner says: “There’s no need for safe sex”

-28

-22

-33

-27

-29

-30

-26

-25

-33

The additive constant is a measure of basic comfort talking about the topic, but with no elements in the vignette. The basic comfort for the total panel is 61, meaning that in the absence of any elements, 61% of the responses will be 7–9. That is, about 3 in 5 times the response will be ‘comfortable.’ The only group showing less comfort is the younger respondents (additive constant = 43), whereas their complementary age group, the older respondents, age 25 and older, is more comfortable (additive constant = 73).

There are some elements which ‘stand out’ from the others, topics about which the respondents feel very comfortable discussing. The elements below list the strong performing elements. Although there are strong performing elements, as shown by the coefficient, an underlying theme or story does not appear.

Total – None

Males

Knowing partner’s prior sexual history
Getting tested regularly
Both partners using birth controls
Talking about safe sex during the first conversation about intimacy

Females

Partner says: “Let’s use protection”
Discussing STD precautions planning through texting

Age 25 or older – None

Age 24 or younger

Talking about safe sex before engaging in sexual activity
Both partners using birth controls

Single – None

In a relationship

Both partners using birth controls
Getting tested regularly
Knowing partner’s prior sexual history
Using condoms during sex

First half of the individual’s vignettes (vignette 01- vignette 12)

Both partners using birth controls
Partner says: “Safe sex is the best move”

Second half (vignette 13 – vignettes 24)

Discussing STD precautions planning through texting

An increasing focus of Mind Genomics is upon Consideration Time (CT). In experimental psychology the term Consideration Time may be replaced by either Reaction Time or Response Time. CT is defined as the number of seconds (to the nearest tenth of second) between the presentation of the test stimulus, the vignette, and the rating assigned by the respondent. The term Consideration Time’ is used to underscore that the response is not only the time to perceive and react, but to read and consider.

The computation of response time is straightforward. The Mind Genomics algorithm relates the response time to the presence/absence of the elements, using the same form of equation as done for the Top3 value (comfort, in Table 3). The only difference is that the equation for consideration time has no additive constant. That is, the ingoing assumption is that without any elements in the vignette, the consideration time should be 0.

Table 5 shows the six elements with long consideration times in at least one group of responses or in either the first half or the second half of the Mind Genomics experiment, respectively. In turn, Table 6 shows the Consideration Times for the full set of elements across the different subgroups.

Table 5. The six elements showing long (estimated) consideration times of 1.5 seconds or longer.

 

Elements showing long consideration times (1.5 seconds +)

Groups

C3

Talking about safe sex during the first conversation about intimacy

4

C2

Talking about safe sex before engaging in sexual activity

3

B3

Both partners using birth controls

2

A4

Discussing STD precautions planning during lunch

1

D4

Partner says: “Safe sex is the best move”

1

B4

Knowing partner’s prior sexual history

1

To give a perspective, the typical consideration time of a full vignette for less serious topics may be 1–2 seconds. People make up their mind quickly for topics considered to be of minor import, perhaps System 1 in the language of Nobel Laureate Daniel Kahneman in his book Thinking Fast, Thinking Slow (Kahneman, 2011) [13] In contrast, topics of sexual discussion may involve System 2, the slower, more deliberate thinking which is the hallmark of a serious topic.

Table 6. The full set of consideration times for the total panel and key subgroups.

 

Consideration Time

Total

Male

female

Age 25+

Age 24 Younger

Single

Relationship

First Half

Second Half

B3

Both partners using birth controls

1.4

1.4

1.4

1.5

1.4

1.6

1.2

1.5

1.0

C2

Talking about safe sex before engaging in sexual activity

1.4

0.8

1.9

1.3

1.5

1.0

1.7

1.6

1.2

C3

Talking about safe sex before engaging in sexual activity

1.4

1.4

1.5

1.3

1.7

1.6

1.3

1.6

1.4

A4

Discussing STD precautions planning during lunch

1.3

1.2

1.3

0.9

1.8

1.1

1.4

1.3

1.1

B1

Using condoms during sex

1.3

1.2

1.3

1.3

1.2

1.3

1.2

1.4

1.0

A2

Discussing STD precautions planning through texting

1.2

1.1

1.2

1.1

1.3

1.2

1.1

1.3

1.1

B4

Knowing partner’s prior sexual history

1.2

1.0

1.3

1.0

1.4

1.4

0.9

1.6

0.7

C1

Talking about safe sex when you first start dating

1.1

0.8

1.4

0.9

1.4

1.2

1.1

1.4

0.9

D4

Partner says: “Safe sex is the best move”

1.1

1.0

1.2

0.9

1.3

1.2

1.1

1.5

0.8

A1

Discussing STD precautions planning in a phone conversation

1.0

0.9

1.0

0.9

1.1

1.1

0.8

0.6

1.3

A3

Discussing STD precautions planning in an email

1.0

1.0

1.1

1.0

1.0

1.0

1.0

1.1

1.0

C4

Talking about safe sex on the first date

1.0

0.8

1.1

1.0

0.9

1.1

0.9

1.0

1.1

B2

Getting tested regularly

0.9

0.9

0.9

1.0

0.8

1.0

0.8

1.1

0.6

D3

Partner says: “Let’s use protection”

0.9

0.6

1.2

0.9

0.7

1.0

0.8

1.4

0.3

D2

Partner says: “There’s no need for safe sex”

0.8

0.8

0.8

0.7

1.0

0.7

1.0

1.0

0.6

D1

Partner says: “Let’s get tested”

0.7

0.8

0.7

0.6

0.9

0.8

0.7

1.4

0.2

Three emergent mind-sets

One of the ongoing tenets of Mind Genomics is that within any topic where human judgment plays a role, there are usually at least two different groups of people, having different criteria about the same topic. That is, for those topics involving judgment, people disagree. The disagreement may be minor, or major, depending upon the people, the topic, and the information presented.

Researchers have uncovered these differences as a matter of course when studying the criteria for human judgment. The differences themselves exist, but Mind Genomics goes one step further beyond noting the differences. Mind Genomics attempts to uncover, classify and then understand the nature of these differences, creating a set of mind-sets embodying the different criteria for judgment. Mind Genomics can go one step further, creating a tool, the PVI (personal viewpoint identifier), to predict the way new people will respond to the information, i.e., an assignment tool. The analogy is to color science and colorimetry. Mind Genomics creates the ‘color science’ for a topic, and then crafts the tool to identify these mind-sets in the population at large. In the interest of length, the PVI for these data are not presented in this paper.

Mind Genomics follows these steps to identify the emergent mind-sets, with all the information needed present in the data from the basics study:

  1. Create the data matrix, with the rows corresponding to the respondents, and the columns corresponding to the elements. For the data presented here, the data matrix comprises 16 columns, one for each element. (The additive constant is not used). The data matrix comprises 50 rows, one row for each respondent.
  2. Define the distance between rows (respondents) by a single number. The choice of the number can range from the simple Euclidean distance to a distance between patterns, defined as (1-Pearson correlation between two rows). Mind Genomics uses the latter (1 – Pearson Correlation, or 1-R).
  3. The distance metric (1-R) ranges from a low of 0 when two rows are perfectly correlated, to a high of 2 when two rows are perfectly but inversely correlated.
  4. The program, k-means clustering (Dubes & Jain, 1980), [14] creates complementary and exhaustive groups, called clusters or segments.
  5. Mind Genomics creates two clusters and assigns each respondent to one of the two clusters.
  6. Mind Genomics then creates three clusters, and assigns every respondent to one of the three clusters
  7. The data from respondents in each cluster are analyzed separately, first for the model for comfort (Top3) and then for the model for Consideration Time.
  8. The strongest performing elements for each set of clusters are used to determine whether there is a coherent story (interpretability), and whether the number of clusters is as few as necessary (parsimony). It is important to have as few clusters (mind-sets) as possible, provided that the clusters are interpretable, i.e., make sense.

Table 7 suggests three mind-sets, based upon the clustering using the coefficients for comfortable. Recall that the ingoing coefficients come from the data wherein the response (1–9 scale) was converted to 0 (ratings 1–6) or 100 (ratings 7–9.).

Table 7. Coefficients for ‘Comfortable with talking about the topic of preventing sexually transmitted disease,’ as well as Consideration Time, for three emergent mind-sets.

 

 

Top 3 = Comfortable talking about the topic

 

Consideration
Time

 

 

MS1

MS2

MS3

 

MS1

MS2

MS3

 

Additive constant (k0)

59

69

52

 

 NA

 NA

NA 

 

Mind-Set 1 – Actual conversation

 

 

 

 

 

 

 

D3

Partner says: “Let’s use protection”

17

2

-2

 

0.9

0.9

0.8

D4

Partner says: “Safe sex is the best move”

10

3

-9

 

1.3

1.0

1.1

B2

Getting tested regularly

9

0

-5

 

0.9

1.0

0.7

D1

Partner says: “Let’s get tested”

9

-6

-14

 

1.0

0.5

0.8

 

Mind-Set 2 – Discuss safe sex as prelude to intimacy

 

 

 

 

 

 

 

A1

Discussing STD precautions planning in a phone conversation

1

7

-4

 

0.5

1.9

-0.3

C2

Talking about safe sex before engaging in sexual activity

-1

7

-2

 

1.2

1.6

0.9

C3

Talking about safe sex during the first conversation about intimacy

-2

5

0

 

1.5

1.6

1.0

 

Mind-Set 3 – Safe sex the responsibility of both partners

 

 

 

 

 

 

 

B3

Both partners using birth controls

4

0

5

 

1.3

1.8

0.7

 

Not- comfortable for any segment

 

 

 

 

 

 

 

C1

Talking about safe sex when you first start dating

-6

-1

4

 

1.3

1.0

0.9

B4

Knowing partner’s prior sexual history

6

0

1

 

1.5

1.3

0.5

A2

Discussing STD precautions planning through texting

1

4

0

 

0.9

1.7

0.3

B1

Using condoms during sex

4

2

-1

 

1.4

1.4

0.6

A4

Discussing STD precautions planning during lunch

-11

1

-1

 

0.8

2.0

0.2

A3

Discussing STD precautions planning in an email

-1

-7

-4

 

0.3

2.0

0.0

C4

Talking about safe sex on the first date

-13

-6

-5

 

0.9

1.2

0.6

D2

Partner says: “There’s no need for safe sex”

-13

-50

-7

 

0.8

1.1

0.5

The three mind-sets can be really divided into one group which feels comfortable with actual conversation as shown by quotation marks (Mind-Set 1), and the remaining two groups, which are less responsive to the elements. We might be satisfied with two mind-sets, not three, one responsive to conversation (Mind-Set 1), and others. On the other hand, the differences between Mind-Set 2 (Discuss safe sex as a prelude to intimacy) and Mind-Set 3 (Safe sex as the responsibility of both partners) points to some key differences between these two groups. That difference between Mind-Sets 2 and 3 is underscored by the differences between the mind-sets in terms of Consideration Time. Mind-Set 2 (discuss safe sex) spends a lot longer than Mind-Set 3 (focuses on responsibility) when reading and rating the vignettes.

Study 2 – Recourse & Protection for the sex worker

The recent literature is replete with discussions of sex trafficking, and other offenses (Van der Meulen, et. al., 2018; Kempadoo & Doezema, 2018) [15, 16] Those stories talk about the system which creates and benefits from the sex worker, and not generally about the sex worker in terms of emotions and personal development (Bekteshi et. al., 2012; McClain & Garrity, 2011.) [17, 18].

This second study was inspired by the interests of marketing students in a graduate course in Bogota, Colombia. The students under the instruction of a8uthor Herrera, investigated the nature and magnitude of the interaction between the WHO (who is the sex worker), the DANGER (what is the danger facing a sex worker in Colombia), as they drive the response of ‘protection of’ and ‘legal recourse available to’ the sex worker. Over the past decades there has been a recognition that prostitution and allied activities constitute a profession with the workers deserving he benefits and protection due to any person who works in a job. The study approach was the same, in terms of creating the four questions, developing four answers to each question (Table 8), and then presenting the vignettes to the respondents. The 24 students themselves offered to be respondents, and so we present this second study as a methodological advancement within the emerging science of Mind Genomics.

Table 8. Sex worker – Four questions and four answers to each question.

 

Question A: Who is the person who is the sex worker?

A1

Worker: A young woman who is just starting out in life

A2

Worker: An older woman who has gone bankrupt

A3

Worker: A young, very handsome, male student who needs money

A4

Worker: A young, very beautiful, female student who needs money

 

Question B: What is a danger which confront a sex worker?

B1

Danger: Getting beaten up and robbed

B2

Danger: Not getting paid

B3

Danger: Shunned as undesirable person

B4

Danger: Shame and disgraceful feelings inside

 

Question C: How do we institute ongoing physical safety for the sex worker?

C1

Protection: Have officers assigned to red light districts

C2

Protection: Register them and give them safety electronic alarms

C3

Protection: Have the local newspaper write positive articles about sex workers

C4

Protection:  Have a special legal office to deal with those hurt sex workers

 

Question D: What legal recourse can we create for the sex worker?

D1

Legal Recourse: Special attorneys for sex workers

D2

Legal Recourse: Steep fines for those who cheat sex workers

D3

Recourse: Special “shaming” notices for those who hurt sex workers

D4

Legal Recourse: Union for sex workers, to increases rights

Creating scenarios to uncover interactions among answers

The first study presented in the previous sections treated all 16 answers as independent variables, which in fact they are. In this second study, we created the study specifically to comprise a WHO (the sex worker), the danger that the person would face (DANGER), and then two different types of protection (ongoing physical safety, legal recourse, respectively.) Thus, the first two answers are really ‘set-ups’ to frame the information, that information given by protection and recourse. The objective was to identify how different ‘set-ups,’ i.e., combinations of WHO and DANGER, drive the response to protections and to recourse, respectively. The analysis below explicates the approach to study interactions, using two sets of vignettes. The first set comprises a single sex worker exposed to four different dangers. The second set comprises four sex workers, each facing the same danger.

Set 1 – sex worker constant, danger varies

Select one person to study. It does not matter which one, since we are interested in the method. For the sake of simplicity, we study one specific sex worker; an older woman who has gone bankrupt. We create five different strata, varying by the danger to which the individual (older woman) can be exposed. Each stratum thus can be defined as having one type of worker (the older woman), and one type of danger. Each individual danger and ‘no danger’ jointly define the stratum. For each stratum we run a simple model using the eight elements as predictors, the four elements describing physical protection, and the four elements describing legal recourse. Our model has no additive constant, because the rating is ‘agree/disagree.’ The additive constant makes no intuitive sense. We create this model for the rating question, again converted to binary (Top2, for agree), and then for consideration time. Table 9 presents the coefficients for agree (coefficients of 60 or higher shown in shaded cells, bold type.) Table10 presents the coefficients for consideration time (5 seconds and higher shown in shaded cell, bold type.) Both tables also show the average coefficient across all eight elements.

Table 9. Interactions between Sex Worker, Danger as stratifying variables, and legal recourse and protection as variables to be considered when disagreeing or agreeing.

 

 Person constant, danger varies

Worker: An older woman who has gone bankrupt

 

Agree (Top2 on the 5-point rating scale)

Danger: Absent from vignette

Danger: Not getting paid

Danger: Shunned as undesirable person

Danger: Getting beaten up and robbed

Danger: Shame and disgraceful feelings inside

 

Average Agree Coefficient
across C1-D4

31

25

22

22

21

D1

Legal Recourse: Special attorneys for sex workers

64

35

66

20

101

C3

Protection: Have the local newspaper write positive articles about sex workers

61

40

45

14

-14

C1

Protection: Have officers assigned to red light districts

46

9

12

47

-114

C2

Protection: Register them and give them safety electronic alarms

40

51

12

26

8

C4

Protection:  Have a special legal office to deal with those hurt sex workers

21

4

-20

12

-59

D3

Recourse: Special “shaming” notices for those who hurt sex workers

16

41

37

25

114

D2

Legal Recourse: Steep fines for those who cheat sex workers

1

44

49

60

80

D4

Legal Recourse: Union for sex workers, to increases rights

0

-27

-23

-30

49

The coefficients are high because two of the variables are not considered in the model. Thus, the binary transformed rating, ‘agree’ (4–5), must be allocated across eight elements, not 16 elements, even though the vignettes still comprised 2–4 elements.

What is remarkable about the table is the dramatic interaction among the ingoing facts of the case, specifically WHO the sex worker is, and the DANGER the sex worker faces, and the specific protections and recourses selected.

  1. On average across the eight elements (four protection, four recourse), the level of agreement is similar close across all four Dangers for the single person (older woman)
  2. Yet, the specific interactions are dramatic. For example, when the Danger is shame and disgraceful feelings inside’ the sex worker, the strongest Recourse is: Special “shaming” notices for those who hurt sex workers. In contrast, when the Danger is getting beaten up and robbed, the strongest performing else is the legal Recourse: Steep fines for those who cheat sex workers.

When we move to Consideration Time (Table 10), we see that with an older woman who has gone bankrupt, we emerge with dramatically different Consideration Times. The longest Consideration Time comes from the combination of the older woman with ‘not getting paid’ and with ‘shunned as undesirable person’, both an average of 4.6 seconds.

Table 10. Interactions between Sex Worker, Danger as stratifying variables, and legal recourse and protection as variables driving ‘Consideration Time’ when rating disagree vs agree.

 

Person constant, danger varies

Worker: An older woman who has gone bankrupt

 

Consideration Time

Danger: Absent from vignette

Danger: Not getting paid

Danger: Shunned as undesirable person

Danger: Getting beaten up and robbed

Danger: Shame and disgraceful feelings inside

 

Average Consideration Time across C1-D4

3.5

4.6

4.6

3.6

2.0

C4

Protection:  Have a special legal office to deal with those hurt sex workers

7.1

3.6

4.9

2.3

0.5

C1

Protection: Have officers assigned to red light districts

5.8

6.0

7.4

-3.7

-6.4

C2

Protection: Register them and give them safety electronic alarms

5.5

5.4

4.2

-1.2

-2.1

C3

Protection: Have the local newspaper write positive articles about sex workers

4.6

7.3

3.9

1.1

-1.6

D1

Legal Recourse: Special attorneys for sex workers

3.8

3.5

3.3

6.1

0.6

D3

Recourse: Special “shaming” notices for those who hurt sex workers

0.8

2.3

6

7.8

7.7

D2

Legal Recourse: Steep fines for those who cheat sex workers

0.5

4.2

4.1

7.9

9.1

D4

Legal Recourse: Union for sex workers, to increases rights

0.2

4.5

3.2

8.2

8.1

There is also a noticeable interaction between the person (older woman who has gone bankrupt), the nature of the danger from the outside (not getting paid / shunned as undesirable), versus from the inside (‘’shame and disgraceful feelings.”). The outside actions / dangers generate longer Consideration Times.

The Consideration Times do not generate as clear a pattern as do the Agreement coefficients. So-called ‘objective measures’ in research may be attractive because of a belief that they are ‘tapping something real,’ but the interpretation of what they are tapping may be harder, and undoubtedly problematic.

Set 2 – danger constant, person varies

Select one danger to study. It does not matter which danger is held constant for purposes of explicating the approach. For simplicity, we focus on an emotional danger from the person’s self-image, ‘shame disgraceful feeling inside.’ As before, we create five different strata anew, varying by the sex worker. Thus, each of five strata has one danger (shame disgraceful feeling inside) and one of four sex workers, as well as the case of ‘no sex worker’.

For each of the five strata we run a simple model using the eight elements as predictors, as we did before, the four for physical protection, and the four for legal protection, respectively Our model has no additive constant. Table 11 presents the coefficients for agree (coefficients of 60 or higher shown in shaded cells, bold type.) Table 12 presents the coefficients for consideration time (5 seconds and higher shown in shaded cell, bold type.) Both tables also show the average coefficient across all eight elements.

  1. On average, for a given danger, the average coefficients vary, from a high achieved by vignettes featuring the young woman who is just starting out (average coefficient = 35), to a low achieved by vignettes featuring an older woman who has gone bankrupt (average = 21).
  2. When the danger is ‘shame and disgraceful feelings inside’), most of the strong performing elements are plausible, i.e., legal recourse, rather than protection. The shame and disgraceful feelings do not present danger.

Table 11. Interactions between Danger and Worker as stratifying variables, and legal recourse and protection as variables to be considered when disagreeing or agreeing.

 

Danger constant, person varies

Danger: Shame and disgraceful feelings inside

 

Agree: Needs social intervention below

Worker: Absent from vignette

Worker: A young woman who is just starting out in life

Worker: A young, very beautiful, female student who needs money

Worker: A young, very handsome, male student who needs…

Worker: An older woman who has gone bankrupt

 

Average coefficient C1-D4

40

35

31

30

21

D4

Legal Recourse: Union for sex workers, to increases rights

67

67

120

-28

49

D2

Legal Recourse: Steep fines for those who cheat sex workers

60

11

-8

70

80

D1

Legal Recourse: Special attorneys for sex workers

49

50

54

19

101

D3

Recourse: Special “shaming” notices for those who hurt sex workers

44

-21

33

41

114

C1

Protection: Have officers assigned to red light districts

36

49

37

33

-114

C3

Protection: Have the local newspaper write positive articles about sex workers

34

33

22

28

-14

C2

Protection: Register them and give them safety electronic alarms

34

47

-19

48

8

C4

Protection:  Have a special legal office to deal with those hurt sex workers

-3

42

9

29

-59

Finally, Table 12 shows the how Consideration Time for each of the protection and recourse elements vary with the single fixed danger (shame and disgrace inside), the four different types of sex workers, and the Consideration Time. All Consideration Times are high (4.2- 4.8) except for the older woman who has gone bankrupt (2.0). For the younger sex workers, the focus is protection. For the older sex worker, the focus is legal recourse.

Table 12. Interactions between Danger and Worker as stratifying variables, and legal recourse and protection as variables affecting Consideration Time when assigning a rating of disagree agree for legal recourse and protection.

 

Danger constant, person varies

Danger: Shame and disgraceful feelings inside

 

Consideration Time

Worker: Absent from vignette

Worker: A young woman who is just starting out in life

Worker: A young, very beautiful, female student who needs money

Worker: A young, very handsome, male student who needs

Worker: An older woman who has gone bankrupt

 

Average Consideration Time C1-D4

3.9

4.6

4.8

4.2

2.0

C1

Protection: Have officers assigned to red light districts

9.4

7.0

8.8

2.3

-6.4

C4

Protection:  Have a special legal office to deal with those hurt sex workers

9.2

6.7

9.1

2.9

0.5

C3

Protection: Have the local newspaper write positive articles about sex workers

7.9

5.0

5.7

4.5

-1.6

C2

Protection: Register them and give them safety electronic alarms

6.7

3.0

4.3

3.5

-2.1

D4

Legal Recourse: Union for sex workers, to increases rights

0.6

7.4

4.7

4.3

8.1

D3

Recourse: Special “shaming” notices for those who hurt sex workers

-0.4

0.1

5.3

5.6

7.7

D2

Legal Recourse: Steep fines for those who cheat sex workers

-1.0

1.9

-0.1

6.6

9.1

D1

Legal Recourse: Special attorneys for sex workers

-1.2

5.3

0.9

3.7

0.6

Discussion – Mind Genomics as a tool to map and to understand relationships

As suggested by the introduction, the field of sexuality, and especially the sexual behavior of intimate couples and the issues involved with sex workers have created in their wake an enormous literature. This paper does not address that literature, and especially does not attempt to answer questions raised by previous studies. Such an effort requires an encyclopedia of papers, not a single short research note. Rather, the objective here is to introduce a way to understand a topic from the inside-out, from the mind of the person, from a combination of psychological ‘thinking’ and consumer research methods.

The tradition of today’s science can be summarized by the term ‘hypothetico-deductive.’ The term means that we create a hypothesis about the nature of behavior, and then perform the requisite experiments either to falsify the hypothesis, or to not-falsify it. Not falsifying a hypothesis does not mean that the hypothesis is correct, but rather that for the time-being the hypothesis may be accepted. The focus of today’s research thus becomes increasingly narrow. The rigors of scientific research demand an almost superhuman concentration to focus the research on the specific problem. Little is left to the exploration of new ideas.

When it comes to the study of human behavior, the many aspects, the nuances, and the impossible-to-remove interactions among the variables make the hypothetico-deductive system interesting, but not particularly productive. One has pieces of information, some convincing than others. Yet, one is missing a narrative, not necessary spun from narratives and stories, but rather emerging from easy-to-do studies. The sheer difficulty of doing inexpensive, comprehensive, focused experiments with people force the researcher either to rely on questionnaires (self-reports), or to weave a story from interviews, or a limited number of experiments.

The approach presented here, Mind-Genomics, demonstrates the opportunity to create a new archival literature on people, personal relations, focusing either on specifics, on limited topics, or on a set of topics which bring into focus a bigger picture. What we see in these two studies is the relative ease of doing computer-aided experiment with messaging in order to identify how the person thinks about a topic. The experiments are short, iterative, yet generate information emerging from the structure of the experiment. The test stimuli are cognitively rich. The richness means that beyond the emergent patterns (what other studies discover) lies the responses to individually, meaningful, relevant, and possible important stimuli. The responses to the individual stimuli teach, rather than having value simply because they are part of an emergent pattern.

Acknowledgement

Attila Gere wishes to acknowledge and thank the Premium Postdoctoral Research Program of the Hungarian Academy of Sciences.

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Conferences Vs Candidates: Selling Intangibles to Ages, Genders & Mind-Sets

Abstract

Two studies were run to understand the driving factors for intangibles, the first study dealing with attendance at an academic/business conference, the second dealing with the likelihood of voting for a candidate promoting specific values. In each study, groups of US respondents, varying in age and gender, each evaluated unique sets of 24 vignettes, comprising 16 different messages with the vignettes created by experimental design, following the Mind Genomics paradigm.Noticeable and occasionally significant age and gender differences emerged in the set of elements driving positive responses, but the group differences did not tell a coherent story. Only when the respondents were divided into mind-sets, based upon the pattern of their responses did a coherent story emerge, both for the first experiment on conferences, and the second experiment on candidates. Focusing analysis on age and gender may hinder the search for more profound difference among people, one based upon mind-set. With mind-sets, inter-individual variation in thinking about a topic becomes to become more interpretable and meaningful.

Introduction

Convincing others to do something may occupy a great deal of time. Whether the convincing is to have a child eat or behave, convincing children to study, convincing another to become romantically involved, purchase, and so forth, the normal life of a person in society is grounded in the act of persuading.  A great deal of a nation’s literature, a great deal of psychology and sociology, not to mention economics, deals with the various aspects of attempts to convince.

Convincing individuals varies by the nature of the topic. Thousands of years ago the Greeks, masters of rhetoric, realized that it was both the substance of the argument and the form of the argument which were important.  Yet, to make the topic simple, we may summarize the process by first observing the problem, second by proposing solutions, third explaining how the solutions will work, and fourth, appealing to the individual interests of the audience.  Beyond that, the rest is method and content, respectively, for those wanting to do the convincing, and by the need states and susceptibilities of those who are to be convinced. The literature of decision making is vast and cannot be dealt in a simple ‘methods paper.’ Rather, the objective of this paper to present a new, alternative approach, Mind Genomics, which emerges from experimental psychology and disciplined behavioral science [1]. Mind Genomics at its heart comprises experiments which identify ‘causation’ when messages are used to convince a decision maker.

This paper introduces a relatively new approach to study the art of ‘convincing.’ Mind Genomicshas been used in the form of conjoint measurement to understand what messages one to use in order to convince. Mind Genomics focuses in the application of conjoint measurement to the decisions, and the decision rules, of the everyday experience [2, 3]. The paper use Mind Genomics to compare two types of ‘convincing,’ one to ‘sell a professional conference,’ the other to sell a ‘candidate’ for an election. Historically, conjoint measurement has been used to identify the relative importance of factors in a considered decision, such as insurance selection, or health benefits. The respondent is provided with pairs of stimuli, whose composition is known for each alternative in the pair. The respondent must select one of the two stimuli. The pattern of selections can be processed by an accepted computation scheme to generate the ‘utilities’ or ‘impact’ of each element of the set of elements.  The methods can be tedious, but have found use in large-scale, expensive, but critical decisions, such as the choice of medical and so forth [4].

Mind Genomics – foundations and processes

The scientific method teaches that variables should be separated and studied in ‘splendid isolation.’  For most variables the isolation works, but not necessarily in messages. Typically, messages come to people in combinations, with the different messages complementing each other, suppressing each other, or even synergizing with each other so that the whole, the combination, often is far more impactful than would be by the sum of individual impacts.   In normal life, we do not encounter single messages, except perhaps for those signaling ‘emergency’ or ‘danger.’  When we are exposed to single messages in a research context or in public opinion polling, we focus unduly on the topic, and give biased answers by trying to ‘guess’ the correct answer, or answer in the way that the researcher expects.

The Mind Genomics approach differs dramatically from the conventional one-at-a-time approach espoused by traditional research. The researcher presents the respondent with different combinations of messages, instructing the respondent to ‘vote’ for the combination.  The approach seems a bit odd, based upon the traditional method of ‘one at a time.’   When compared to conventional approaches, we can say that that the Mind Genomics approach is more Socratic, holistic, yet systematic, and oriented towards creating combinatorial models for persuasion and communication:

Holistic: The test stimuli are combinations of messages, not single messages alone. The holistic approach simulates what we see in real, daily life. For the most part, we deal with mixtures of stimuli coming at us all the time. When we talk, walk, drive, read, eat, and so forth, we do not pay attention to one variable, except perhaps for a very short time to examine it more closely. We live in the moment, the moment comprising a kaleidoscope of changing combinations.

Socratic: The Socratic method comprises a question and answer dialogue. Carried out effectively, the dialogue reveals the underlying structure of the topic. Socratic dialogue is not the pure science to which we are accustomed (nomothetic), for it is intensely individual rather than general (idiographic).  Yet, for topics studying the act of judgment itself, the Socratic method can generate the necessary test material by which the researcher uncovers some individual ‘rules’ of decision.  

Systematic: The abovementioned answers to questions are ‘elements,’ namely simple, easy to comprehend statements, almost factoids. These elements or answers to questions are combined by the discipline of experimental design into small, easy to read combinations. [2]. Mind Genomics is based upon the belief that when making a decision the respondent ‘grazes’ for information, rather than ingests, chews, and digests, respectively. The Mind Genomics research process recognizes grazing, and is designed to be fast and minimally intellectual, metaphorically similar to grazing at a superficial level. No effort is made to combine the different elements into a flowing paragraph.

Models:  Mind Genomics develops mathematical models showing how each element or answer ‘drives’ the response. The response may be a rating (would not attend to would attend, would vote for candidate to would vote for candidate), the selection of an emotion or feeling from a set of several alternatives (happy, sad, curious, excited, etc.), the selection of a price, the selection of an end use, etc.  The models show the linkage between the different elements and the rating.

Steps in the Process – Creation of raw materials through a Socratic process: The researcher selects a topic. The researcher then asks four questions which ‘tell a story.’ Asking the four questions can be hard, and forces creative and critical thinking. Most people are not educated to ask questions in a systematic way, in contrast to a reporter or writer who does so by habit when creating a coherent story. Once the four questions are asked, it become very easy to provide four simple answers to each question. The concern is often raised as to whether the questions are truly the ‘correct questions’ to ask, and in turn, whether the four answers to each question suffice, as well as whether or not they are the proper answer. It takes a while to disabuse the novice of the reality that there are no correct questions nor answers, but rather report ‘blocks’ at this stage, because they either cannot think of questions, and freeze up, or they take the instruction literally, and cannot ‘tell a story.’  With practice, however, they realize that the narrative can tell a story, but not the polished story to which they have been accustomed.

Steps in the Process –Creating the vignettes using experimental design to specify combinations: Mind Genomics traces back to the evaluation of combinations of messages, with the combinations prescribed by experimental design, or metaphorically by a set of recipes which combine the individual messages into known combinations. For the Mind Genomics studies run here, with the four questions and four answers per question, each respondent evaluated a unique set of 24 vignettes or combinations. Each vignette comprised 2, 3 or 4 answers, at most one answer from each question. The answers are coded 0 when absent from a vignette, and 1 when presented in a vignette. The experimental design ensures that each respondent evaluates the 16 answers in different combinations, and that the answers or elements are statistically independent of each other.  The statistical independence will allow the researcher to create individual-level equations, one for each respondent, relating the presence/absence of the 16 elements either to the binary transformed rating (0/100) or to the consideration time (CT).

Table 1 shows the schematic for eight vignettes from Respondent #1. The respondent evaluated the eight vignettes in sequence. The combination is defined by the experimental design. A ‘0’ represents the fact that the element was absent from the vignette. A ‘1’ represents the fact that the element was present in the vignette. The respondent rating on a 9-point scale was recorded, along with CT, consideration time, the number of seconds elapsing between the presentation of the vignette on the screen and the rating. The CT is recorded to the nearest tenth of a second.

Table 1. Eight vignettes from the conference study.

Order

A1

A2

A3

A4

B1

B2

B3

B4

C1

C2

C3

C4

D1

D2

D3

D4

Rating

CT

1

0

0

1

0

0

0

0

0

0

0

1

0

1

0

0

0

4

9.0

2

1

0

0

0

0

0

0

1

1

0

0

0

0

0

0

0

4

4.5

3

1

0

0

0

0

0

1

0

0

0

0

0

1

0

0

0

4

3.0

4

0

0

0

1

0

0

0

1

1

0

0

0

0

0

0

0

4

2.0

5

0

1

0

0

0

0

0

0

0

0

0

1

0

1

0

0

5

3.2

6

0

1

0

0

0

0

1

0

0

1

0

0

0

0

0

1

6

2.9

7

0

0

1

0

0

1

0

0

0

1

0

0

0

0

1

0

5

6.1

8

0

0

0

1

0

0

1

0

0

0

0

1

0

0

1

0

5

4.6

Study 1 – ‘Selling a conference’

Study 1 focused on how one ‘sells’ or at least advertises a conference about the evolving area of data analytics, when the audience comprises random people.

Conferences are important as a key venue for academics. It is important to market conferences, to communicate what the conference provides for the attendee [5]. Beyond the conference as an academic product to be marketed, the conference is a topic of interested in itself, The conference is a contained environment where relevant interpersonal behaviors are strongly demonstrated. Researchers have investigated conferences from the outside, from the benefits of the respondent [6].  One of the key benefits is making connections [7].

Conferences themselves are a venue for sociological and psychological research. The conference is a specific venue, offering the chance to observe a variety of different behaviors. For example, one research avenue is to study behavior at conferences in terms of the behaviors of males versus females. An anthropological approach might look at the conference as a venue wherein certain attitudes are manifest in behaviors, in the so-called ‘lived experience’ [8]. There are a variety of dimensions to conferences, dimensions which can serve as the foundation of research to understand the mind and motivations of those who attend the conference. These dimensions range from the conference as a venue of information to be disseminated and learned, involving different groups, such as academics versus practitioners, respectively [9, 10], as well as networking vs knowledge [11–13].  Then there is the ever-present dimension of the conference as a venue to introduce students, and to let the students interact with senior professionals [14, 15].

Table 2 presents the four questions and the 16 answers.   The actual questions were recorded, along with the answers, and then slightly edited to ensure proper English.  Note that the answers are simple, with three dots (…) replacing some connectives, to make reading easier.It is important to note that the elements or messages, i.e., the answers to the questions, are simple. They are descriptive, and generally feature a single idea. They will be combined in a simple way, as a set of phrases, centered, on the screen, one atop the other, with no effort to connect them. Although it seems quite ‘stark’ and unreal to have a paragraph or concept comprise a block of phrases with no connectives, the reality is that this structure makes the task easy for the respondent, who really ‘grazes’ for information, rather than reading the entire concept in depth.  When the same task is implemented with paragraphs created in better English style, as grammatically correct paragraphs, the task becomes onerous and boring. Mind Genomics studies are generally executed on the Internet, often with respondents recruited by a panel provider specializing in the process of panel creation and deployment for research studies. For this study, the researchers entered the questions, answers, and rating scale in a program designed to run these studies. The program, BimiLeap (short for Big Mind Learning Application), mixes the answers according to an experimental design, presenting 24 combinations of elements to each respondent who participates. The entire process takes 3–5 minutes for a respondent.

Table 2. Conference, list of elements.

 

Question A: What is the conference topic?

A1

teach how machines help you market and sell much better

A2

teach you how big data about people help you sell more

A3

marketing secrets to sell to customers

A4

learn how find a really good customer

 

Question B: What is special about the conference?

B1

features workshop …learn practice and grow

B2

have drinks and meals and snacks with real experts

B3

workshop to learn technology made easy and fun

B4

Meet interesting people who can really teach you

 

Question C: Who should attend the conference?

C1

made for new hired young folk

C2

for students to really make them grow

C3

business employers go to meet young potential hires

C4

students go to meet and select mentors

 

Question D: What is interesting about the conference beyond the topic?

D1

when you leave you free technology good & gift basket

D2

two days of fun BEFORE AND AFTER in a great location

D3

organized around an archaeological site you can explore

D4

near A SEASIDE TOWN IN SEASON

The respondents were 50 Americans, 18 years or older. The respondents were provided by a panel company specializing in providing anonymous respondents for these types of studies (Luc.id, Inc.)   The actual elements were created at a conference of professors and students. Each respondent evaluate a unique set of 24 vignettes, created by experimental design. The experimental design ensures that all 16 elements are statistically independent of each other, permitting the use of OLS, ordinary least-squares linear regression, to relate the presence or absence of the element to the rating.  An algorithm permuted or modified the specific combinations, maintaining the underlying experimental design, but ensuring that the specific combinations different from one respondent to another [16]. The research benefit of permutation is to generate a more representative and thus a more valid model because the researchtests more of the potential mixtures of elements. That is, rather than reducing variability by testing the same limited set of combinationsmany times, and suppressing variability by averaging it out, Mind Genomics deals with variability by covering a wider array of potential test combination. Mind Genomics is statistically powerful, and conservative by design, measuring many stimuli rather than imputing from a less noisy, far less representative sample of possible vignettes.

Ratings, transformations, and averages: The original ratings were assigned on a anchored 9-point scale (1=Do not choose … 9=Choose.) The practice of Mind Genomics is to divide the rating scale into two parts. We did this division two times. The first time was ‘Choose to attend’ (1–6 transformed to 0 to denote not choose to attend; 7–9 transformed to 100 to denote choose to attend).  The second time was ‘Reject’, (1–3 transformed to 100 to denote reject; 4–9 transformed to 0 to denote not reject.) The program further recorded the ‘consideration time’ (CT), operationally defined as the number of seconds between the appearance of the vignette on the screen and the respondent’s rating of the vignette on the 9-point scale.

Table 2 shows the mean ratings for the three dependent variables by key subgroups. These subgroups are total, gender, age, and the two mind-sets or clusters of respondents, with respondents in the same cluster showing similar patterns of response coefficients (see below).  It is clear from Table 2 that the subgroups differ from each other in their ratings.

Table 2A. Means of the dependent variables (Accept, Reject, Consideration Time) for key subgroups.

 

Conference – Means of Dependent Variables

Conference

Attend
(7–9 = 100)

Reject
(1–3 = 100)

CT
Consideration Time

Total

49

16

3.5

Male

57

13

3.0

Female

34

22

4.2

Young Age 21–39

43

8

2.9

Old Age 40+

51

20

3.8

Mind-Set 2A Attends for fun

48

16

4.0

Mind-Set 2B Attends for professional reasons

50

16

2.7

Males are much more likely to say ‘I will attend’ than are females (57 versus 34, meaning that 57% of the responses of males to the vignettes are 7–9, whereas only 34% of the responses of females are 7–9).

Older respondents are more likely to say I will attend than do younger respondents (51 vs 43)

Dividing the respondents into groups based upon the pattern of how elements drive ‘attend’ (i.e., mind-sets) suggest no difference in frequency of responding ‘attend,’ but as we will see, strong differences in the elements which drive them to say ‘attend.’

The differences in ‘reject’ can be interpreted in the same way.

When we measure the consideration time, we see that women take longer to respond, that older take longer to respond, and that Mind-Set 2A takes longer to respond

Thus far, all that the data has revealed is the average rating and the response time. Those measures provide some idea of the differences between groups. Furthermore, Mind Genomics provides far deeper information for the simple reason that the elements themselves are cognitively rich, having deep meaning.  It is not simply the stimulus, but the fact that the stimulus can be understand in and of itself.

Modeling to show causality: The next step, this time for deeper understanding, creates a simple model or equation, relating the presence/absence of the 16 elements to the binary ratings. The regression modeling, OLS regression (ordinary least-squares) works with the full data set of respondents in the subgroup. The output is a simple linear expression relating the presence/absence of the 16 elements to the rating, after the binary transformation.  The regression model lacks an additive constant, for the simple reason that in the absence of elements the respondent is not likely to either accept or reject the conference.  This is called ‘regression through the origin.’

We express the equation as: Binary transformed rating = k1(A1) + k2(A2) …k16(D4)

Deep learning – total panel, age and gender:  It is from the coefficients and their commonality that we learn the most about what drives ‘accept’ the conference, i.e., expect to attend.  Table 3 shows the strong performing elements presented in shaded cells, and bold font.  Strong performing is based upon the fact that in previous studies these coefficients are both statistically significant (from inferential statistics), and meaningful in terms of ‘real-word’ situations. When we look at the commonality of strong performing elements across elements and subgroups, we see different sets of strong-forming elements.  If we had to hazard a guess about which elements are consistently strong performers, we would say that the answers to Question D (What is interesting about the conference beyond the topic?).  That finding may be correct at the superficial level, but it leaves out the world of people who attend conferences to become stronger in their profession.

Table 3. Coefficients of the models relating the presence/absence of the elements to the ‘attend’ rating, after recoding

 

Conference – Attend
(ratings 1–6 recoded as 0; ratings of 7–9 recoded as 100)

Total

Young (21–39)

Old (40+)

Male

Fem

A1

teach how machines help you market and sell much better

13

13

13

15

4

A2

teach you how big data about people help you sell more

3

3

5

5

-4

A3

marketing secrets to sell to customers

10

3

13

4

18

A4

learn how find a really good customer

15

13

17

10

20

B1

features workshop..learn practice and grow

16

12

17

18

12

B2

have drinks and meals and snacks with real experts

17

11

20

20

12

B3

workshop to learn technology made easy and fun

14

8

17

16

10

B4

Meet interesting people who can really teach you

11

-1

17

10

12

C1

made for new hired young folk

5

11

2

15

-9

C2

for students to really make them grow

14

22

11

22

4

C3

business employers go to meet young potential hires

7

5

9

14

0

C4

students go to meet and select mentors

7

18

1

13

-3

D1

when you leave you free technology good & gift basket

26

19

30

24

28

D2

two days of fun BEFORE AND AFTER in a great location

28

31

26

32

23

D3

organized around an archaeological site you can explore

19

6

24

25

10

D4

near A SEASIDE TOWN IN SEASON

24

29

21

28

22

Beyond the discovery of ever-present individual differences, variation in the criteria of judgment, is the postulation by Mind Genomics that for every topic of experience, no matter how ‘micro’, there are a limited number of different groups, mind-sets, metaphorically alleles or variations of genes. These mind genomes do not need to covary with the typical groupings to which we have become accustomed, e.g., age, gender, and nor even behavior and attitude, such as attending conferences.

The comparison of Mind Genomes to the science of biological genomics is, to stress the point, metaphorical. In the biological science of Genomics, the belief is that there are actual alleles that can be manipulated and reinserted into cells to change their behavior. There is the belief that these alleles have actual physical reality. In the world of Mind Genomics, the mental alleles are hypothetical constructs, patterns of decision criteria which emerge from the statistical method of clustering, a procedure in the mathematics of numerical analysis. That is, there is no belief in the physical reality of the mind genome, the mental allele, but just a convenient, and sensible group of ideas which float together.

These mind genomes or mind-sets emerge from the pattern of coefficients for the different elements, with the pattern uncovered by experimentation (our respondent study with the 50 respondents), the creation of individual-level models (made possible by the experimental design), and then the clustering individuals by the pattern of their coefficients (application of clustering, a method in numerical analysis.)

When we follow the procedure of experimentation, modeling, clustering, afterwards extracting meaningful sets of ideas or clusters, we end up with three different groups.Clustering simply places the objects (here respondents) into a set of complementary, non-overlapping groups, using mathematical criteria. The objective to minimize the number of clusters (parsimony), as well as ensure that each cluster or mind-set makes sense (interpretability).  Table 4 shows the performance of all 16 elements by total, and by each of the two emergent mind-sets, i.e., emergent clusters of respondents based on the pattern of coefficients. It is clear from Table 4 that separating the mind-sets allows the strong performing elements to do far better than they do when the data from all 50 the respondents are combined to create the one group, total panel. Mind-set segmentation through clusteringremoves much of the suppression of element performance attributable to the opposing patterns of responses of different mind-sets to the same element.  The countervailing forces emerge, and can be separated from each other, placed by the researcher into the different mind-sets (clusters), with the result being radically different patterns of coefficients released by the suppressing, mutually cancelling effect by the opposite mind-set.

Table 4. Performance of elements driving Choosing a Conference. Data based on the total panel and the two mind-sets.

 

Dependent Variable: Attend the conference

Tot

MS 2A

MS2B

 

Mind-Set 1 – Attends for fun

 

 

 

D2

two days of fun BEFORE AND AFTER in a great location

28

35

16

D4

near A SEASIDE TOWN IN SEASON

24

32

12

D1

when you leave you free technology good & gift basket

26

26

25

D3

organized around an archaeological site you can explore

19

23

13

C2

for students to really make them grow

14

16

10

 

Mind-Set 2B– Attends for professional reasons

 

 

 

B2

have drinks and meals and snacks with real experts

17

10

27

B3

workshop to learn technology made easy and fun

14

8

23

B1

features workshop..learn practice and grow

16

12

21

B4

Meet interesting people who can really teach you

11

5

21

A4

learn how find a really good customer

15

14

19

A3

marketing secrets to sell to customers

10

8

17

 

Not strong in either mind-set

 

 

 

A1

teach how machines help you market and sell much better

13

14

12

C3

business employers go to meet young potential hires

7

7

7

A2

teach you how big data about people help you sell more

3

3

6

C1

made for new hired young folk

5

4

4

C4

students go to meet and select mentors

7

9

1

Engagement – Measurement of consideration time (CT) for conference elements: In order to identify the existence of mental processing of stimulus input, such as our elements, experimental psychologists introduced the notion of reaction time, later called response time, and now in this stage of Mind Genomics called ‘consideration time.’ The underlying notion is that longer consideration times signal that more complicated mental processing is occurring.The original measures of reaction time were done when the respondent was instructed to observe a test stimulus (see, feel, hear, taste, smell), and then report when the respondent could detect the stimulus (i.e. the stimulus was present), or report when the respondent could recognize the nature of the stimulus. The right-most column of Table 2 above presents the average consideration times (CT) for the 24 vignettes rated by each respondent in the relevant subgroups. Table 2 suggests that, on average, the time to read and rate a vignette is approximately 3.5 seconds.  The younger respondents read and rate the vignettes far more quickly than do the older respondents (2.9 seconds vs 3.8 seconds). Males read and rate the vignettes far more quickly than do females (3.0 seconds vs 4.2 seconds). Finally, Mind-Set 2B (Conferences for professional development) reads and rates the vignettes far more quickly than does Mind-Set 2A (Conferences for fun), specifically 2.7 seconds versus 4.0

Knowing the consideration time tells us something about the general speed of reading and decision- making but does not tell us anything about the consideration time given to the individual elements. That consideration time is a measure of engagement of the respondent with the message. The engagement may be short or long for a variety of reasons, such as length and complexity of the message, basic ‘stickiness’ of the message to keep the respondent focused, and so forth. The respondent cannot tell the researcher which particular element in a vignette ‘engages’ attention, but through experimental design and modeling, along with a measure of response time to the entire vignette, the researcher can estimate the number of seconds that is most likely taken up by the specific element, such as a particularly provocative phrase. Systematic design reveals just what just what phrases are ‘sticky’, when they are ‘sticky,’ and with whom.

The strategy is the same as used to develop the models relating the presence/absence of the 16 elements to the rating. The analysis uses OLS (ordinary least-squares) regression to relate the presence/absence of the elements to the consideration time, measured to the nearest 10thof a second.  The equation is the same, except for the dependent variable: Consideration Time (Time interval from presentation to rating) = k1(A1) + k2(A2) …k16(D4)

Table 5 suggests a different story for the commonality among the longest consideration times for the group:

Total panel –serious aspects such as workshops and mentors

Younger –mentors and growth

Older respondents – learning new technology easily and with fun

Males – workshops and mentors

Females – learn new technology, learn at the start of the career

Mind-Set 2A (Conferences are for fun) – learning new skills, then many of the professional growth elements

Mind-Set 2 B (Conferences are for professional development) – no elements show unusually long engagement. Equal attention is paid to all elements

Table 5. Consideration time for all elements by total panel and key subgroups (conference).Element coefficients of 1.2 seconds or higher are shown in shaded cells.

 

Consideration Time for each element
Conference

Tot

Young (21–39)

Old (40+)

Male

Fem

MS 2A- Fun

MS2B – Prof. Development

B3

workshop to learn technology made easy and fun

1.5

1.0

1.8

1.0

2.4

1.7

1.1

B1

features workshop …learn practice and grow

1.3

1.1

1.3

1.3

1.3

1.5

0.8

C2

for students to really make them grow

1.2

1.4

1.2

0.8

1.6

1.4

1.0

C4

students go to meet and select mentors

1.2

1.4

1.1

1.2

1.1

1.5

0.6

D2

two days of fun BEFORE AND AFTER in a great location

1.2

1.1

1.3

1.1

1.4

1.5

0.7

B2

have drinks and meals and snacks with real experts

1.2

0.9

1.2

1.1

1.3

1.3

1.1

C3

business employers go to meet young potential hires

1.1

1.1

1.2

0.9

1.4

1.3

0.9

C1

made for new hired young folk

1.0

0.7

1.2

0.6

1.6

1.3

0.6

D3

organized around an archaeological site you can explore

0.9

0.8

1.0

0.6

1.2

1.0

0.7

A3

marketing secrets to sell to customers

0.8

0.2

1.1

0.8

0.9

0.7

1.1

D1

when you leave you free technology good & gift basket

0.8

0.7

0.9

0.7

1.1

0.8

0.8

D4

near A SEASIDE TOWN IN SEASON

0.8

0.7

0.9

0.5

1.2

1.0

0.6

B4

Meet interesting people who can really teach you

0.8

0.5

0.9

0.7

0.9

0.9

0.7

A1

teach how machines help you market and sell much better

0.8

0.6

0.8

1.0

0.6

0.9

0.6

A2

teach you how big data about people help you sell more

0.7

0.6

0.8

0.8

0.9

0.8

0.7

A4

learn how find a really good customer

0.7

0.5

0.7

0.8

0.7

0.8

0.4

Study 2 – ‘Selling a political candidate’

If the topic of conferences is of interest to academics and to those sponsoring conferences, in contrast, the topic of political candidates and their messaging is of interest to virtually everyone, or almost everyone, especially in elections where two or more sides, radically opposite, vie for power.   Furthermore, election and the messaging of the candidates must address the many different dimensions on which a candidate can appeal to her or his audience, and the many different facets, the granularity of each dimension, that must somehow be considered

More than 80 years ago, the mind of the voter was already of interest [17], but of course one could go back centuries to Machiavelli, to Aristotle, and to Plato for even older points of view. These philosophers talked a great deal about citizens and their leaders. Many of their points, including appeal to emotion, hold today.  One need only read Machiavelli’s ‘Prince,’ Aristotle’s ‘Politics’ or Plato’s ‘Dialogue’ to see the politics of today presented by the eminent thinkers of the past. Today’s world works with tools taken from marketing, attempting to persuade people to vote in the same way one might persuade people to buy toothpaste [18].  There is a great deal of effort put in by consultants, polling organizations, and so forth to identify messages which at once most strongly resonate with the electorate, as well as being appropriate, realistic, and believable. Despite the best efforts of marketers to provide honest data, perhaps somewhat copy-edited (‘massaged’), today’s political messaging is believed a lot less than was the case years and decades before [19].

Marketing theory has also entered political messaging and polling. The notion of inward vs outward orientation in the mind of a consumer has been applied to an Australian election, revealing the application of this construct to election messaging [20].This inward versus outward orientation more clearly focuses on what affects the voter, and moves beyond the more tradition of description of one’s behavior, such as mudslinging, defined both as allegations about the candidate’s family, but also references to an opponent’s voting record, broken campaign promises, rumors on health and financial dealings, and the use of harsh language.

More recent approaches to studying political communication focus on how to legitimize one’s point of view, and not just to convince the voter based upon one or two key points. Legitimizing one’s point of view is akin to building one’s brand, again recognizing the mind of marketing, as it enters the political arena [21] discussed the political communication as exemplified by George Bush and by Barack Obama, when they had already won the election, and were trying to convince the electorate about their efforts of the war on terror, in 2007 and 2009. In Reye’s words, ‘strategies of legitimization can be used individually or in combination with others and justify social practices through: (1) emotions (particularly fear), (2) a hypothetical future, (3) rationality, (4) voices of expertise and (5) altruism.’By 2010, the marketing concepthad entered the world of communication. The five strategies, or motivations for message, just above, would be quite familiar to today’s marketer. The final aspect making a study of political messaging interesting is the increasing importance of social media on the political process. Research published almost a decade ago suggest that in the early years of social media the interplay of social media and political viewpoint was not particularly strong [22]. Kim’s words of a decade ago can be contrasted with the emergence of political messaging in the form both of real news and of fake news.  It is worthwhile quoting Kim’s now-passe language, quite important in 2011, and probably based upon research conducted the year or two before. It would hard to substantiate Kim’s words today, as of this writing.

The increasing popularity of social network sites (SNSs) has raised questions about the role of social network media in the democratic process. This study explores how use of SNSs influences individuals’ exposure to political difference. The findings show a positive and significant relationship between SNSs and exposure to challenging viewpoints, supporting the idea that SNSs contribute to individuals’ exposure to cross-cutting political points of view. Partisanship was not found to interact with SNS use, suggesting that SNSs contribute to expanding exposure to dissimilar political views across individuals’ partisanship. Online political messaging also has a direct effect on exposure to dissimilar viewpoints, and it mediates the association between SNSs and exposure to cross-cutting political views.  (Bold added for emphasis)

Specifics of the candidate study: The principles underlying the Mind Genomics studies remain the same, no matter what the topic.  The second study, done around the same time concerned a political candidate, of an unnamed political party. The respondents were US adults, recruited by the same company as the respondents in Study 1 on ‘selling a conference.’

The key differences in the two studies were the topic, the elements (Table 6), and the use of a 5-point scale, rather than a 9-point scale for the scale. For the rating of ‘win’, the 5-point scale was transformed to the binary values of 0 (ratings 1–3), and 100 (ratings 4–5). For the rating of ‘lose,’ the 50point scale was transformed the binary value of 100 (ratings 1–2), and 0 (ratings 3–5). All modeling was done using the binary scale, not the original scale.

Table 6. Candidate – List of elements

 

Question A: What is the situation of the country?

A1

The country has economic problems

A2

The people are skeptical about politics in general

A3

The country is experiencing political instability

A4

The people suffer from unemployment

 

Question B: Describe the candidate’s personality.

B1

He/she is rightfully egocentric

B2

He/she concerned about people well-being

B3

He/she has a vision to develop the country

B4

He/she is going to be the people’s voice in government

 

Question C: How does the candidate draws people to himself/herself?

C1

He/she is always on tv

C2

He/she has been active all the time not only during the campaign

C3

He/she listens to people personally

C4

He/she talks about own achievement

 

Question D: How does the candidate call to action?

D1

He/she is a role model

D2

He/she tell others to do his/her job

D3

He/she corrupts people for vote

D4

He/she doesn’t care about acting at all

Table 7 give a sense of the response patterns for the different vignettes, across the different groups. What is most interesting is that when the topic is political, something serious and relevant to the respondents, the consideration time is a second longer than the consideration time for the conference (3.5 seconds for the conference, 4.4 seconds for the candidate.) The experimental design is the same, the elements are approximately of the same size, but the respondents spend more time reading.  This pattern, longer consideration times for important topics, has continued to emerge again and again in experiments by author Moskowitz (unpublished data)

Table 7. Means of the dependent variables (Accept, Reject, Consideration Time) for key subgroups

 

Candidate – Means of Dependent Variables

 Candidate

Vote For
(4–5
à100)

Vote Against (1–2à 100)

Consideration Time

Total

37

35

4.4

Young (21–39)

34

34

3.9

Old (40+)

38

35

4.8

Male

31

36

4.2

Female

41

34

4.7

MS2C – Protect

26

36

4.5

MS 2D – Develop

44

34

4.4

Table 8 shows the results for Total, Age and Gender, respectively.

Table 8. Performance of elements driving Choosing a Conference. Data based on the total panel, age and gender, respectively.

 

 

Tot

Young (21–39)

Old (40+)

Male

Female

A1

The country has economic problems

8

13

6

20

-1

A2

The people are skeptical about politics in general

13

20

10

17

10

A3

The country is experiencing political instability

15

21

11

21

11

A4

The people suffer from unemployment

15

15

16

22

10

B1

He/she is rightfully egocentric

12

9

14

12

12

B2

He/she concerns about people’s well-being

20

17

23

17

23

B3

He/she has a vision to develop the country

19

24

17

20

18

B4

He/she is going to be the people’s voice in government

20

18

22

20

21

C1

He/she is always on tv

4

2

4

0

7

C2

He/she has been active all the time not only during the campaign

14

17

11

9

19

C3

He/she listens to people personally

20

18

21

12

27

C4

He/she talks about own achievement

0

-8

4

-3

3

D1

He/she is a role model

21

17

24

12

28

D2

He/she tell others to do his/her job

-4

-14

2

-9

-1

D3

He/she corrupts people for vote

-6

-7

-5

-13

-2

D4

He/she doesn’t care about acting at all

1

-3

2

-13

10

The key drivers for winning are the personal characteristics of the candidate, especially the care about the people and being a role model.

He/she concerned about people well-being

He/she has a vision to develop the country

He/she is going to be the people’s voice in government

He/she concerns about people well-being

He/she has a vision to develop the country

He/she is going to be the people’s voice in government

Some key differences emerge, mostly in terms of degree

Men are concerned about the situation in the country

Women are concerned about the candidate ‘being involved’

Younger respondents do not like a boastful, dominating person who tells others what to do. In contrast, older respondents don’t care.  This is a subtle but an importance difference between different age cohorts, representing an emerging sensitivity to ‘authenticity’

Applying the clustering approach to the 50 coefficients generates two clearly different, and interpretable mind-sets, shown in Table 9. Mind-Set 1 responds to the candidate as a leader in the unstable times. Mind-Set 2 responds to the candidate as a nation builder.

Table 9. Performance of elements driving voting for a candidate. Data based on the total panel and the two mind-sets.

 

 

Tot

MS2C

MS2D

 

Mind-Set 2C – Candidate as a leader

 

 

 

A2

The people are skeptical about politics in general

13

21

6

A3

The country is experiencing political instability

15

19

11

D1

He/she is a role model

21

19

24

 

Mind-Set 2D – Candidate as nation builder

 

 

 

B3

He/she has a vision to develop the country

19

-2

35

B2

He/she concerns about people’s well-being

20

5

31

B4

He/she is going to be the people’s voice in government

20

7

29

B1

He/she is rightfully egocentric

12

-2

23

C3

He/she listens to people personally

20

15

22

 

Elements not strongly motivating to either mind-set

 

 

 

A4

The people suffer from unemployment

15

15

14

C2

He/she has been active all the time not only during the campaign

14

13

14

D4

He/she doesn’t care about acting at all

1

-1

5

A1

The country has economic problems

8

15

3

C1

He/she is always on tv

4

7

0

D2

He/she tell others to do his/her job

-4

-7

0

D3

He/she corrupts people for vote

-6

-5

-6

C4

He/she talks about own achievement

0

7

-7

We finish the detailed analyses of the by looking at the consideration time attributable to each element. Recall from the previous analysis of conferences that the form of the model for consideration time comprised a simple linear model, without an additive constant.  The experimental design for this study of a candidate is precisely the same as the experimental design for the study of a conference, namely 24 vignettes comprising 2–4 elements per vignette. When we deconstruct the contribution of each element to consideration time (Table 10) we find that virtually all but three of the consideration times are 1.0 second or longer, several twice as long at 2.0 and 2.1 seconds. Thus, the topic itself, is a major driver of consideration time, a subject to be explored more fully.  There is no clear pattern of covariation between the response time and who the respondent is, except that the younger respondents show somewhat shorter consideration times, very much shorter for descriptions of the candidate’s personal behavior (e.g., C1 and C4.)

Table 10. Consideration time for all elements by total panel and key subgroups (conference)

 

Consideration time for each element: Election of a candidate

Tot

Age 20–39

Age 40 Plus

Male

Female

MS1 Political leader

MS2 Builder

D4

He/she doesn’t care about acting at all

2.0

2.0

2.0

2.0

2.0

1.5

2.4

C2

He/she has been active all the time not only during the campaign

2.0

1.8

2.0

2.2

1.8

2.0

1.9

B4

He/she is going to be the people’s voice in government

1.9

1.5

2.1

1.9

1.9

1.8

2.0

A4

The people suffer from unemployment

1.9

1.8

1.9

1.7

2.0

2.2

1.7

B1

He/she is rightfully egocentric

1.8

1.8

1.9

2.0

1.6

1.9

1.7

C3

He/she listens to people personally

1.7

1.0

2.1

1.9

1.6

1.9

1.6

B3

He/she has a vision to develop the country

1.7

1.2

2.1

1.9

1.6

1.9

1.6

A2

The people are skeptical about politics in general

1.7

1.3

1.8

1.5

1.8

1.9

1.5

A1

The country has economic problems

1.7

1.7

1.7

1.6

1.8

1.8

1.6

D3

He/she corrupts people for vote

1.6

1.6

1.6

1.3

1.8

1.4

1.8

C4

He/she talks about own achievement

1.6

0.9

1.9

1.7

1.5

1.9

1.4

C1

He/she is always on tv

1.6

0.7

2.0

1.8

1.4

1.8

1.5

B2

He/she concerns about people’s well-being

1.6

1.3

1.8

1.7

1.5

1.7

1.4

A3

The country is experiencing political instability

1.6

1.4

1.7

1.3

1.8

1.6

1.5

D1

He/she is a role model

1.5

1.6

1.4

1.3

1.6

1.4

1.6

D2

He/she tell others to do his/her job

1.4

1.3

1.5

0.9

1.8

1.2

1.5

Who belongs to these mind-sets, and how to discover them

The mind-sets for both the conference and the candidate make sense. Yet, a standard cross tabulation of membership in the mind-set versus the standard classifications of gender and age suggest that the mind-sets do not divide simply across easy-to-measure subgroups based upon who a person IS. Table 11 shows the cross tabulation of mind-set membership versus age and gender. There is no clear relation. Indeed from author Moskowitz’s experience, except for the most obvious of cases (e.g., age versus concern with problem of dying), the relation between the way a person thinks and who the person IS appears to be tenuous at best.  Furthermore, even asking a person about general thoughts regarding a topic does not suffice to place a person into a mind-set

Table 11. Two-way table showing the relation between membership in a mind-seg (column) and both age and gender, respectively.

Conference

Total

MS2A:  Fun Seeker

MS2B: Prof.  Development

Total

39

25

14

Male

22

15

7

Female

17

10

7

Age 23–39

11

9

2

Age 40+

28

16

12

Candidate

Total

MS2C: Political Leader

MS2D: Nation Builder

Total

54

23

31

Male

25

13

12

Female

29

10

19

Age 23–39

19

7

12

Age 40+

35

16

19

A new way be developed to probe membership in a group defined by the specifics or granular aspects of the way a person thinks about a topic. Conferences and candidates are large subjects. The mind-sets which emerge are limited to the topic revolving around questions and answers investigated in the Mind Genomics study. It may well be that the easiest way to discover the membership of a person in a mind-set segment is to accept the fact that the mind-set segment is granular at best. That ‘best’ may be to assign a new person to the granular-based mind-set uncovered in the Mind Genomics experiment. Authors Gere and Moskowitz have created an algorithm based on the separation of the mind-sets across the 16 elements. Using a Monte-Carlo simulation, they identified a set of six elements, the pattern of binary answers to which, suggest membership in one mind-set or the other.   Figure 1 shows the PVI, the personal viewpoint identifier, emerging from this exercise.

Mind Genomics-035 PSYJ_F1

Figure 1. The PVI (personal viewpoint identifier), comprising six questions for each topic. The pattern of answers assigns a respondent to one of the two mind-sets.

Discussion

The typical study of a topic involves a few stimuli, rarely varied systematically, but evaluated by many people, respondents in the world of public opinion polling and consumer research, subjects or observers in the world of psychology.  The objective of these studies is typically to confirm a hypothesis. The use of large numbers of respondents has become sacrosanct in many areas of science, for the simple reason that with these large number of respondents the sampling distribution of ratings is more precise, with smaller standard errors. Mind Genomics as presented here provides the researcher with a different strategy. Rather than being developed within the constraints and world-view of the traditional world of the ‘hypothetico-deductive,’ Mind Genomics approaches the topic by exploring a wide, albeit feasible, range of alternative aspects, evaluated by the respondent in formats, vignettes, simulating a more typical way that nature presents information to people, namely in the form of  mixtures.  The systematic variation of the composition of these mixtures by experimental design allow the researcher to pick out the operative variables to which the respondent attends.

As we review the process of the two studies, we come upon the following key factors which differentiate Mind Genomics studies from other studies of the same topic:

Mind Genomics studies focus on the mind of the respondent, weaving a story, but without having the respondent elaborate and tell the story. Qualitative research focuses on the mind of the respondent as well but requires that the respondent participate in a dialog. The experienced researcher, like an experienced therapist, may pull out underlying motives, thoughts, defenses, and biases, but the researcher should be experienced must shunt aside presuppositions. In contrast, Mind Genomics, attempting the same outcome, works with responses to cognitively rich expressions, the elements, not chosen by the respondent, but by the researcher. Mind Genomics studies can be executed more rapidly, more generally, and more cost-effectively.  What Mind Genomics lacks, however, is the skilled interpretation, when such skill exists. Mind Genomics studies can be likened to the MRI of the Mind.  Each individual Mind Genomics study creates 24 vignettes for each respondent, with the vignettes differing from respondent to respondent. Thus, in one Mind Genomics study with 30 respondents, we deal with 720 different snapshots of the same problem. One need not know the ‘correct’ or best combinations to test. Mind Genomics studies create, metaphorically, a realistic ‘picture’ of the topic from which one can discover new things or reaffirm hypotheses and conjectures which seem simplistic after the fact, but hard to confirm ahead of time.

We have illustrated two different studies and show slightly different dynamics of each. The speed and ease of a Mind Genomics study makes it possible to execute one or two studies a day and create a rich library of knowledge about any topic involving the decision of a respondent when faced with various pieces of information. A science of such decision rules, appropriate indeed and archives, may constitute a new direction for sciences of the mind, and of society.

Acknowledgement 

Attila Gere wishes to acknowledge and thank the Premium Postdoctoral Research Program of the Hungarian Academy of Sciences.

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Tinnitus in Adolescents – Intrinsic and Extrinsic factors

Abstract

Objective: To identify factors influencing the onset and the development of tinnitus among adolescents.

Patients and methods: 1260 high school students in Gothenburg participated in a health screening program during their first and third year of high school (age 16 and 19). Measurements included screening audiometry (thresholds were measured if the students failed the 20 dB HL) and patient reported outcomes, covering; noise exposure, use of cell phones, psychological well-being and students’ experiences of spontaneous tinnitus (ST), noise induced tinnitus (NIT) and temporary thresholds shift (TTS). Half of the group participated in occupational education programs (n=662), which was considered by the school health authorities as a noisy environment, and the other half in quiet, mostly theoretical programs (n=598).

Results: Over the three years in school, the students did not develop more hearing loss, tinnitus or TTS, than their initial level. Hearing loss did not correlate to ST, NIT or TTS. Frequent use of cell phones was highly correlated to NIT and TTS. The most important noise exposure factors were playing an instrument or attending concerts. An interesting observation was the influence of anxiety in all reported symptoms, i.e. ST, NIT and TTS.

Conclusion: This study points to the multifaceted nature of tinnitus, where noise exposure and anxiety are two strong influencing factors. However, hearing loss as measured by screening audiometry, did not correlate to the presence of tinnitus. The students listening habits, such as playing instruments and listening to music, live or recorded, correlated significantly to ST, NIT and TTS in this population. In our study, the single most influential factor for any form of subjective hearing symptoms is anxiety, which has also previously been reported for adults.

Key words

Adolescent, Anxiety, Child, Hearing loss, Noise, Stress, Tinnitus

Key messages

Live music is more highly linked to the emergence of tinnitus than listening to portable music players. When adolescents seek help for tinnitus of any kind, look for signs of untreated anxiety disorder.

Introduction

Noise can lead to hearing loss but also to stress reactions and stress related diseases [1–4]. Tinnitus is often one of the results of noise, where both hearing loss and stress reactions contribute to the symptom. Children’s auditory systems differ from adults in anatomy of the outer ear, sound transfer function [5] and central processing [6]. As concluded in an earlier review [7], longitudinal studies that focus on factors contributing to hearing loss in children are few/sparse. So far there is no direct evidence linking high frequency hearing loss and noise in children, as there is for adults, yet clear correlations with hereditary factors exist. Noise exposure in children’s leisure time is not regulated per se as it is in the work place, and schools in Sweden are not entitled to the same monitoring as the adult work places are Young people and children seeking medical help for tinnitus, report more often that tinnitus started after noise exposure, be it school hours or leisure [7]. Although there are reports on high noise levels in the elementary schools or pre-schools [8–10], it is the adult that complains of noise-induced tinnitus and the child or toddler is given less consideration. When asked, children report experience of tinnitus in between 30% and 53% [11–14]. Experience of temporary threshold shift (TTS) in the young population has not been the focus of many studies, yet those that do examine TTS [15, 16], report frequencies of 35% recurrence in teenagers. This recurrence seems to increase with experience of noise induced tinnitus (NIT), hearing loss, tobacco use and heredity of hearing loss [1]. Prolonged noise exposure has been shown to damage hearing [17], lower cognitive performance [18, 19] and evoke tinnitus [2, 20–22]. Noise induced tinnitus can signal minor cochlear lesions as well as a dysfunction of the efferent system [23, 24] and can also be linked to a vulnerable psychological type [25]. Similar to spontaneous tinnitus (ST), a connection to psychiatric disorders has been established [26–28] and a serotonergic vulnerability suggested [29]. The presence of serotonin in the auditory system has been well documented [30] and there are discussions on the functional link between tinnitus and depression [26, 27, 30, 31]. Despite this, we still do not know whether children and adolescents are more sensitive to noise and/or more prone to developing any kind of tinnitus, even though there are observations suggesting that the young auditory pathway does not function in the same way as the adult [6]. The ability to understand speech in a noisy environment develops over time and young children suffer the consequences of ambient noise the most [32]. The assumption that music is less hazardous than occupational noise is generally based on studies which have investigated the hearing in professional musicians and one experimental study on 10 volunteers [33–35]. However, the listening patterns and the voluntary exposure to live or recorded music may differ in adults versus the younger population [36, 37] and, as for occupational noise, in the young population it consists mainly of the school environment. It is difficult to compare epidemiological studies on tinnitus in children, as well as in adults, as the definitions of the symptom vary. Prevalence studies of tinnitus in children and adolescents also differ (with regards to hearing status of the study population) depending on whether it is an unselected or selected population. There are numerous studies on young adults, starting from 18 years of age, but not that many select a strictly paediatric population. A brief summary of tinnitus prevalence in children, recorded in studies dating back from 1972, is listed in Table 1. A more comprehensive review has been done by Rosing et al [38], but still battling with the same issues of lack of definitions of the studied symptoms and heterogeneous study populations.

Table 1. Prevalence of tinnitus in children reported in 1972–2016

Authors (year of publication)

n

Age range

Prevalence of tinnitus (any kind)  % within group

 

 

 

Normal hearing

Any HI

Hearing tests not performed

Nodar (1972)

2000

10–18

13

 

 

Graham (1979)

92

12–18

 

66

 

Graham (1981)

66

12–18

 

29

 

Mills and Cherry (1984)

110

4–17

44

30

 

Nodar (1984)

56

?

 

55

 

Mills et al (1986)

93

?

29

 

 

Viani (1989)

102

6–17

 

23

 

Martin and Snashall (1994)

67

2–16

50

50

 

Aust (2002)

1420

5–17

 

 

7

Holgers (2003)

964

7

13

9

 

Holgers and Pettersson (2005)

671

13–16

 

 

53

Holgers and Juul (2006)

274

9–16

 

 

46

Aksoy et al (2007)

1020

6–16

15

 

 

Savastano (2007)

1100

6–16

26

8

 

Coelho et al (2007)

506

5–12

38

45

 

Raj-Koziak et al (2011)

60212

7

32

43

 

Figueiredo et al (2011)

100

15–30

18

 

 

Juul et al (2011)

756

7

41

58

 

Giles et al (2012)

145

19–26

 

 

15

Bartnik et al (2012)

59

7–17

44

56

 

Mahboubi et al (2013)

3520

12–19

7.5

10

 

Park et al (2014)                

3047

12–19

18

18

 

Humphriss et al (2016)

7092

11

28

 

 

Table 1. Prevalence or occurrence of tinnitus in children, with the original numbers extracted and re-calculated as to allow the easiest inter-study comparison.

There are distinctions between objective and subjective tinnitus, distinctions based on aetiology, impact or triggers. In this study, the definition of tinnitus in terms of subjective tinnitus will be that of an aberrant perception of sound unrelated to an acoustic source of stimulation, internal or external. Spontaneous tinnitus will be defined as subjective tinnitus without any prior acoustic stimulation and noise induced tinnitus as tinnitus appearing in close time connection to prior noise exposure, subjectively defined.

Subjects and methods

Starting in the year 2004, 1260 high school students in Gothenburg were given the opportunity to participate in a health screening program during their first and their third/last year of high school (age 16 and 19). Written consent from both the students and their parents were obtained. Of these 1260 students, 155 declined to participate. The young students were enrolled in equal parts from noisy, occupational education programs (n=662) and not noisy, mostly theoretical programs (n=598). Hearing thresholds were obtained from 1105 students in the first year (611 in noisy programs and 494 in quiet programs) and 816 students were followed up in the third year (493 and 325, respectively). The exclusion criterion for follow-up in the third grade was discontinuation of their studies, since it proved to be difficult to follow the drop-out students.

Screening audiometry: The screening program was performed by a school nurse, trained in performing screening audiometry. The tests were performed in the school nurses offices, so as to mirror the standard school entry screening conditions. Standard pure tone audiometry in both ears, with ear phones over 0.5, 1, 2, 3, 4, 6 and 8 kHz was conducted out at 20 dB HL. Thresholds were measured if the student did not pass the screening level, i.e., they did not obtain the 20 dB HL on at least one frequency.

Questionnaire: The nurse collected anthropometric data and administered an extensive questionnaire battery regarding the students’ own perception of health and well-being (including 1. HADS – Hospital Anxiety and Depression Scale [39], 2. noise exposure during school and leisure time and 3. hearing problems such as spontaneous tinnitus, noise induced tinnitus or temporary threshold shift). The students also responded to questions regarding their listening habits, in terms of playing instruments, attending concerts, listening to music on stereos or portables devices, playing computer games, going to the cinema, target shooting, use of mobile phones (with or without hands-free earphones) and use of hearing protection devices. Excerpt from the questionnaire is presented at the end. The same questions covering the experience of ST, NIT and TTS have also been used in previous studies from our research group [1, 11] on a total of 1635 children and adolescents. The questions are not yet formally validated but have been constructed based on previously revised questionnaires. These in turn, have been assessed by the audiologist performing all school entry hearing screenings to be easily understood even by young children.

Statistics: The dependent variables were the three: Spontaneous Tinnitus (ST), Noise Induced Tinnitus (NIT) and Temporary Threshold Shift (TTS). The hearing data were analysed frequency by frequency in correlation analyses, as well as dichotomised in multiple stepwise logistic regression analyses to groups of Hearing loss “Yes”/”No” (meaning screening audiometry level 20 dB failed or passed). The independent variables were: Gender, Noisy Program, Hearing Loss, Anxiety, Depression and for the listening habits – Instruments, Concerts, All live music (created by pooling Instruments and Concerts), Computer, Disco, Mobile phone, Mobile phone with headphones and Recorded music. For statistical purposes, all questionnaire answers were dichotomised, where response options “Never” and “Once/Rarely” were treated as “No” and “Often/Sometimes” and “Very often” were treated as “Yes”. When analysing the HAD-scale, scores above the cut-off level of 7 were considered as positive for depression-related symptoms and above 9 for anxiety, in accordance with the recommendations for application in adolescents [40]. For each subject, the difference between the results of each variable in the first year (Year 1) and the third year (Year 3) was calculated. The created ∆-variables were used where applicable. All noise variables were tested for correlations using Spearman’s rho or univariate logistic regression. The analyses were conducted identically for all three dependent variables (ST, NT, TTS). The independent variables with significant outcome were put in a multiple stepwise logistic regression analysis. The probabilities attained in the final models were then applied in ROC-curves for calculation of model strength with Area under the Curve (AUC). Variables were tested for, and fulfilled the criteria for normal distribution. Grading of correlation strength was as follows: 0 < |r| < .3 weak correlation, 3 < |r| < .7 moderate correlation, |r| > 0.7 strong correlation. Data were analysed using SPSS 19.0 for Windows. This study was approved by the Ethical Committee in Gothenburg (125–04) and performed according to the Helsinki declaration.

Results

Descriptives:

More boys than girls joined occupational education programs and more boys with pre-existing hearing loss entered these programs rather than the quieter theoretical programs, see Table 2. The students did not differ in experience of NIT, ST or TTS in respect of the chosen program, but overall, girls were more likely to report any of these three symptoms.

Table 2. Noisy program vs. hearing and gender at the start of the program

Gender

Hearing loss either side

 

No

Yes

Total

 

Boy

Noisy program

No

N

202

39

241

 

% within hearing loss

37,1%

26,2%

34,8%

 

Yes

N

342

110

452

p=0,015

% within hearing loss

62,9%

73,8%

65,2%

 

Total

N

544

149

693

 

Girl

Noisy program

No

N

207

45

252

 

% within hearing loss

60,7%

64,3%

61,3%

 

Yes

N

134

25

159

p=0,593

% within hearing loss

39,3%

35,7%

38,7%

 

Total

N

341

70

411

 

Total

Noisy program

No

N

409

84

493

 

% within hearing loss

46,2%

38,4%

44,7%

 

Yes

N

476

135

611

p=0,040

% within hearing loss

53,8%

61,6%

55,3%

 

Total

N

885

219

1104

 

Table 2. Distribution of gender in the noisy and quiet programs. Correlations between noisy or quiet program and hearing loss either side (pass = No, fail = Yes); Chi2-test. Percentage numbers represent the proportion of students with normal hearing (first column) or hearing loss (second column) within the respective program.

In the third year, many students had dropped out from school, mostly within the theoretical programs, thus reducing the observed number from 1105 to 816. The follow-up screening audiometry did differ slightly in some students in isolated frequencies and created therefore odd effects of statistically significant difference at 500 Hz in the left ear alone, due to seven students in the quiet group reporting 5 dB better thresholds and 8 students in the noisy group reporting 5 dB worse thresholds. The same effect was present in the right ear at 3000 Hz with sixteen students in the noisy group reporting a 5 dB worse threshold. In the clinical setting we do not consider such minute changes in isolated frequencies as significant, why this mathematical result is considered to be representative of a mass effect of multiple comparisons. When calculating with the dichotomised variable Hearing loss, there were no significant differences between the sufferers

Correlations and regression analyses:

All the noise variables and HADS reports were tested for correlations using univariate logistic regression. The variables with significant outcome were used in multiple stepwise logistic regression analyses. The probabilities attained in final model were then applied in ROC-curves for calculation of model strength with Area under the Curve (AUC). The odds ratios for the variables in the final models are presented, with their confidence intervals, in Figures 1 and 2. Figure 1 presents the models for ST, NIT and TTS in Year 1 and Figure 2 for the ST, NIT and TTS in Year 3. For cinema, target shooting and use of noise protection, there were no significant correlations (data not shown) (Insert Fig 1, 2).

OHT-2020-101_Jolanta Juul_f1

Figure 1. Logistic regression of the dependent variables ST, NIT and TTS for Year 1. The results from the three multivariate stepwise logistic regression analyses of the independent variables Gender, Hearing Loss, Noisy Program, Anxiety, Depression and listening habits (listed in Subjects and Methods).

OHT-2020-101_Jolanta Juul_f2

Figure 2. Logistic regression of the dependent variables ST, NIT and TTS for Year 3. The results from the three multivariate stepwise logistic regression analyses of the independent variables Gender, Hearing Loss, Noisy Program, Anxiety, Depression and listening habits (listed in Subjects and Methods).

Playing instruments and attending concerts were pooled in to one variable, called ‘All Live Music’, as to separate from ‘Recorded Music’, which here signifies portable music players, iPod, mp3 or stereo. As seen in clinical practice, the three hearing symptoms (ST, NIT and TTS) often coincide. In our results, ST shared weak to moderate correlations with NIT and TTS, whereas NIT and TTS shared correlations of moderate strength, all with p-values of <0,001, see Table 3.

Table 3. Correlations ST, NIT and TTS

Year 1 Spearman’s rho

ST

NIT

TTS

ST

Correlation Coefficient

1,000

0,287

0,167

Sig. (2-tailed)

 

<,001

<,001

N

1104

1102

1099

NIT

Correlation Coefficient

0,287

1,000

0,372

Sig. (2-tailed)

<,001

 

<,001

N

1102

1108

1103

TTS

Correlation Coefficient

0,167

0,372

1,000

Sig. (2-tailed)

<,001

<,001

 

N

1099

1103

1104

Year 3 Spearman’s rho

ST

NIT

TTS

ST

Correlation Coefficient

1,000

0,404

0,287

Sig. (2-tailed)

 

<,001

<,001

N

807

807

807

NIT

Correlation Coefficient

0,404

1,000

0,399

Sig. (2-tailed)

<,001

 

<,001

N

807

815

815

TTS

Correlation Coefficient

0,287

0,399

1,000

Sig. (2-tailed)

<,001

<,001

 

N

807

815

816

Table 3. Correlations between Spontaneous Tinnitus, Noise Induced Tinnitus and Temporary Threshold Shift; Spearman’s rho.

The relevant results and models for each symptom group follow below.

Spontaneous Tinnitus:

In Year 1, 33 % of the children (N=368 children, 37% of the girls and 31% of the boys) reported recurrent ST. Two years later the numbers had risen to 37% (39% of the girls, 36% of the boys). A pre-existing hearing loss at the first audiometry in Year 1 did not correlate to ST but heredity of hearing loss did correlate. History of prior ear infections or transmyringeal drainage (TMD) correlated with ST only, see Table 4.

Table 4. ST vs. Ear infections

 

 

 

Ear infections

 

 

Total

 

 

 

 

Never

1-2 times

Many times

TMD in childhood

 

ST

No

N

378

228

62

55

723

 

 

 

Expected

353,2

233,7

74,8

61,4

 

 

 

Yes

N

151

122

50

37

360

 

 

 

Expected

175,8

116,3

37,2

30,6

 

p=0,001

Table 4. Spontaneous Tinnitus vs. ear infections and transmyringeal drainage, N observed and expected, Chi2-test.

Children affected with ST scored significantly higher on both the anxiety and depression parts of the HADS. Through multiple stepwise logistic regression analysis we obtained an overall model for the development of ST. The final variables for Year 1 and Year 3 are presented in Figures 1 and 2. For both years the model for ST contained All Live Music and Anxiety. In Year 1 the linear constant was ST: =-1.055 +0.238xAll Live Music +1.026xAnxiety with AUC = 0.614 and for Year 3 it was ST: =-0.972 + 0.391xAll Live Music +0.772xAnxiety with AUC = 0.625. Fitted probabilities with confidence intervals from these models are shown in Figure 3, diamonds showing Year 1 and circles Year 3.

OHT-2020-101_Jolanta Juul_f3

Figure 3. Fitted probabilities of suffering from spontaneous tinnitus if anxiety or noise exposure from live music is present. Diamonds represent Year 1 and filled circles Year 3. The lines signify confidence intervals of 95%.

Noise Induced Tinnitus:

During the first phase of data collection, 55% of the students (N=610, 64% of the girls and 50% of the boys) reported recurrent NIT. Two years later 54% (58% of the girls, 52% of the boys) still experienced the symptom. Pre-existing hearing loss at entry did not correlate to NIT, but heredity did. Children affected with NIT scored significantly higher on the anxiety part of the HADS, but the results did not reach significance in regard of self-reported depressive traits. The multiple stepwise logistic regression analysis results are presented in Figures 1 and 2. In Year 1 the multiple stepwise regression model for NIT showed the strongest correlates to be: Gender, All Live Music and Anxiety, in comparison to Year 3, where the variables differed slightly: i.e., All Live Music, Disco, Hands-free and Anxiety instead. The linear constants were as follows: for Year 1 NIT: =-0.319 + 0.544xGender +0.418xAll Live Music + 0.610xAnxiety (AUC = 0.631) and for Year 3 NIT: =-0.507 + 0.542xAll Live Music +0.414xDisco+0.457xHands-free+ 0.514xAnxiety (AUC = 0.632). This is the only model where gender is statistically significant and also only in Year 1. In the first year, an unusually large portion of the girls (64 % vs. 49%) reported having experience of NIT, while the other symptoms remained in parity with the boys. In the third year, that difference was no longer discernible.

Temporary Threshold Shift:

In the first grade, 39% (N=425, 43% of the girls and 36% of the boys) confirmed recurrent TTS. Two years later the number had increased to 54% (equal gender distribution). Pre-existing hearing loss at school entry did not correlate to TTS, but heredity for hearing loss did. Children reporting TTS scored significantly higher on both the anxiety and depression parts of the HADS. Frequent use of cell phones was highly correlated to NIT and TTS, but the use of earphones did not seem to have any protective influence. The logistic regression presented in Figures 1 and 2 showed the strongest variables to be: All Live Music, Mobile, Recorded Music and Anxiety in Year 1 and All Live Music, Computer and Anxiety in Year 3. The linear constants present as: TTS for Year 1: =-1.396 + 0.517xAll Live Music + 0.374xMobile + 0.317xRecorded Music + 0.688xAnxiety (with AUC = 0.638), TTS for Year 3: =-0.663 + 0.479xAll Live Music -0.357xComputer + 0.523xAnxiety (with AUC = 0.637). For Year 1, mobiles were of significant importance in the development of TTS. The same pattern was present also for Year 3, however, the multiple regression analysis for this variable did not show statistical significance with p= 0.071, yet certainly a trend. The main outcomes of this study were the models of strongest correlates. These models point to several noise exposure factors were live music seems to represent a hazardous environment and possibly unprotected listening habits. These models have a rather weak strength when calculated for with AUC, but what is markedly apparent is the influence of anxiety in all reported symptoms.

Discussion

First and foremost we must answer the question whether the working environment of our students is appropriate, at least from the perspective of noise exposure. The students did not develop more hearing loss, tinnitus or TTS over the three years in school, reassuring as protective measures go. An Argentinian study noticed nevertheless a slight increase in hearing thresholds using a similar observation paradigm as we (15 year olds retested two years later) in youths reporting exposure to loud music[41]. A shortcoming of this type of investigation is the screening audiometry. We do not map the full extent of the subjects hearing but stop at the 20 dB level. Also, in a clinical setting we do not acknowledge small changes in isolated frequencies but in cohort studies we look for trends, were even small changes might prove important. Pre-existing hearing loss at the start of the investigation did not correlate to ST, NIT or TTS in either Year 1 or Year 3. This might be a result of precautionary behaviour and noise avoidance in individuals with subjectively known impaired hearing. Heredity of hearing loss did correlate to all three symptoms, which is more difficult to explain. We can speculate that perhaps the individuals with heredity of hearing loss have not yet developed evidently lowered thresholds but may signal their higher vulnerability with the presence of tinnitus. More girls reported (any of the) hearing symptoms and surprisingly more NIT in the first year and not the third. This finding is interesting and difficult to interpret, since there are two conflicting possible arguments. There are discussions suggesting estradiol serves a protective function in the female auditory system[42] however, this effect could be counterbalanced by a higher prevalence of anxiety in girls[43]. A recent meta-analysis of tinnitus in a pooled population of over 28,000 adolescents confirmed this gender difference [44]. As this study focuses on environmental and psychological impacts, the overall models for each symptom do not include any of the other two hearing symptoms. Although this was calculated for, we feel the presentation is simpler and easier to follow logically without what can be strongly considered as confounding factors. Adding NIT and TTS to the final ST regression model, adding ST and TTS to NIT and ST/NIT to the TTS model did in fact increase the overall strength of the models but only just slightly and at the cost of losing some of the other variables, without any obvious logical pattern to it. As shown in Table 2, the experience of NIT or TTS does correlate weakly to ST, but it is between the variables NIT and TTS we see the strongest correlation, likely signifying that both are more noise related by nature than is ST. We believe that perhaps all three symptoms are interconnected and represent different facets of auditory sensitivity. When calculating for factors influencing the onset of any kind of the discussed hearing symptoms, we should focus on what can be prevented or alleviated (such as noise exposure or anxiety) rather than what describes an already present and probably unavoidable sensitivity (such as concurrent TTS or NIT). The observed difference, with a higher prevalence of already present hearing loss in the occupational education group, could represent different prior noise exposure habits or perhaps are these two socioeconomically different groups with different health service seeking pattern? The noise in school did not seem to influence the youngsters negatively, but the following 16 hours of leisure time were of significance, for instance when looking for just one powerful noise impact factor, playing instruments and attending concerts appear (one or the other) in all of the analyses. These are activities where protecting one’s hearing is controversial and not always possible or wanted [45]. We also noticed a pattern were the variables annotating playing instruments or attending concerts were the two strongest of environmental factors, yet they tended to alternate in strength and sometimes cancel each other. As these two factors arguably could represent more or less the same environment and listening habits, they were pooled into one variable and analysed together. The fact that playing computer games seemed to protect from TTS in Year 3, having a negative B-value, could perhaps represent that year’s population of gamers as being less interested in attending live music scenes and instead choosing the home and the computer as leisure activities? Or perhaps it could be an effect of noise protection from sound conditioning [46]? Mobile phones were noted as a factor in TTS but this is more difficult to explain since the technology had evolved rapidly between the years Year 1 and Year 3 and mobile phones were being merged with portable music players. In Year 1, only 6.4% students used earphones vs. 12.4% in Year 3, while the number reporting use of mobile phones remained unaltered at 70%. Unfortunately, we do not know what the students referred to when answering the question of how much they used their mobile phone with or without hands-free earphones, i.e. if it was for phone calls and therefore being exposed to possibly harmful electromagnetic radiation or if it was for listening to music and thus being exposed to possible high speaker output levels [47]. Both expositions are potential factors in the development of tinnitus [36, 48, 49]. More interestingly, all three hearing symptoms were highly correlated to anxiety and such a correlation, between tinnitus and mood disorders, has been previously established in adults. Generally, anxiety is much more common than depression in youngsters [7], a finding which was also again demonstrated by the frequency numbers in this study. While in the adult population tinnitus appears more strongly correlated to depression than anxiety [27], the reverse seems to be the case for adolescents. The influences for this are yet to be established, if it is due to the psychological development of the young mind or perhaps a slightly different balance in the neurotransmitter systems [50]. Irrespective of cause, the importance of identifying symptoms of anxiety and depression in a youngster complaining of tinnitus is apparent. This study further highlights the importance of educating the young population in terms of noise protection at live venues, both as a visitor and a performer, and once a youth does seek help for tinnitus of any kind, then signs of an untreated anxiety disorder need to be investigated.

Questionnaire regarding hearing symptom and listening habits:

  1. After you have listened to loud music or noise, have you ever noticed a worsening of your hearing shortly after the cessation of the music or noise? (TTS)

       No, never 

       Yes, once 

       Sometimes

       Often

  2. After you have listened to loud music or noise, have you ever noticed a ringing, buzzing, hissing or beeping noise in your ears shortly after the cessation of the music or noise? (NIT)

       No, never

       Yes, once

       Sometimes

       Often

  3. Have you ever noticed a ringing, buzzing, hissing or beeping sound in your ears even if you have not been exposed to loud noise? (ST)

       No, never

       Yes, once

       Sometimes

       Often

If you have answered NO to the questions 2 and 3, you can skip the questions 5 through 7.

  1. How often do you have a ringing, buzzing, hissing or beeping sound in your ears?

       Rarely

       Often

       All the time

  2. Is the sound bothersome for you?

       No

       Sometimes

       Often

       Always

  3. How did the sound start?

       Suddenly

       Gradually

  4. How long have you had this sound?

    ..…..weeks …….months

  5. How often do you:

     

    Never

    Sometimes

    Often

    Very often

    Use noise protection in noisy environments?

       

       

       

       

    listen to recorded music in mp3, ipod or equal?

       

       

       

       

    Talk on your mobile phone?

       

       

       

       

    Use handsfree ear phones with your mobile phone?

       

       

       

       

  6. How often do you: 

    Go to concerts?

    Never

    Rarely

    6–12/yr

    Twice/month

    Several/month

    Go to disco?

       

       

       

       

       

    Go to cinema?  

       

       

       

       

       

    Play instruments?     

       

       

       

       

       

    Use PlayStation/computer/equal with head phones

       

       

       

       

       

    Shoot for target practice/use exploding materials?

       

       

       

       

       

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Efficacy of L-Ornithine L-Aspartate for the prevention and Treatment of Hepatic Encephalopathy in Cirrhosis: An Update of the Evidence Base

Abstract

The advent of well-established procedures for the determination of clinical trial quality based on risk of bias assessments has resulted insubstantial improvements in the quality of systematic reviews and meta-analyses relating to the assessment of Randomized Controlled Trials (RCTs) on the efficacy of treatments for a range of clinical conditions. In the current review, manual and electronic searches of databases using appropriate keywords were used to assess the evidence base for the use of L-ornithine L-aspartate (LOLA) for the prevention and treatment of Hepatic Encephalopathy (HE), a common neuropsychiatric complication of liver cirrhosis. Making use of current risk of bias techniques, seven systematic reviews with accompanying meta-analyses were identified in which the results of RCTs on the efficacy of LOLA for the treatment of HE were analyzed. A clear consensus of opinion was observed in support of the efficacy of LOLA for lowering of blood ammonia and for the concomitant improvement of mental status in patients with overt HE (OHE) and in five of the six meta-analyses in patients with minimal HE (MHE). Evidence in support of a beneficial effect of LOLA for the prevention of OHE in patients with cirrhosis was reported in a novel systematic review and meta-analysis involving the analysis of six RCTs in patients with cirrhosis and a range of clinical presentations where successful OHE prevention/prophylaxis was accompanied in all cases by significant reductions of blood ammonia. Both, intravenous and oral formulations of LOLA were found to be effective. Reduction in the progression of MHE to OHE was independently confirmed in a subsequent meta-analysis. Two systematic reviews with network meta-analyses compared the efficacy of LOLA to other available agents. Only treatment with LOLA or branched-chain amino acids (BCAAs) resulted in significant improvements in mental status and LOLA was judged to be the most effective agent with respect to clinical improvement and concomitant reduction of blood ammonia. In the case of MHE, rifaximin, lactulose and LOLA were equivalent in clinical efficacy and were each superior to probiotics. LOLA was superior to lactulose or probiotics for the prevention of episodes of OHE in patients with MHE compared to placebo/no treatment; rifaximin was ineffective in this regard.

Keywords

L-ornithine L-aspartate, LOLA, hepatic encephalopathy, clinical trials, RCTs, hyperammonemia, meta-analysis, systematic review, prevention, treatment, cirrhosis, sarcopenia, prophylaxis

Introduction

A variety of agents with the capacity to lower circulating ammonia represent the mainstay for the prevention and treatment of Hepatic Encephalopathy (HE) in patients with cirrhosis. Such agents include non-absorbable disaccharides, antibiotics, ammonia-sequestering compounds and metabolic intermediates related to the operation of the urea cycle. L-ornithine L-aspartate (LOLA) is a 1:1 stable salt of the naturally-occurring amino acids L-ornithine and L-aspartic acid. LOLA has well-established pharmacokinetic and pharmacodynamic properties and is available in either intravenous or oral formulations [1]. Increases in the use of LOLA for HE prevention and treatment of HE in patients with cirrhosis has resulted in a significant increase in the number of reports of the findings of RCTs on the efficacy of LOLA in this patient population and a number of reviews and meta-analyses on the subject have recently been published. For the current study, manual and electronic searches of databases using appropriate keywords were used to review and update the evidence base for the efficacy of LOLA for the prevention and treatment of HE in patients with cirrhosis. Particular attention was paid to assessment of the results of published RCTs, critical reviews, systematic reviews and meta-analyses in which the results of these trials were assessed. In addition, comparisons of the efficacy of LOLA compared to other currently-available agents listed above has been addressed by assessment of the results of the results of two network meta-analyses. Since its discovery as an effective ammonia-lowering agent some 50 years ago [2], LOLA has been shown to act by virtue of the fact that one of its constituents, L-ornithine is a urea cycle substrate and both amino acids are substrates for transaminase reactions in multiple tissues including liver, brain and skeletal muscle leading to the production of glutamate, the obligate substrate for Glutamine Synthetase (GS). These two metabolic pathways, namelythe synthesis of urea (liver) and of glutamine (liver, brain, skeletal muscle) represent the major pathways for the elimination of excess ammonia under normal physiological conditions. In both acute and chronic liver failure, the metabolic capacity of the liver is severely compromised and urea and glutamine synthesis may fall to below 20% of normal values. This results in a spectacular increase in capacity of skeletal muscle to replace liver as the major ammonia-removal organ, a mechanism that results from increased expression of the gene coding for GS in muscle [3] resulting in increases in enzyme activities and increased glutamine synthesis. [4] In this way, it has been demonstrated that LOLA is effective for the treatment of muscle wasting (sarcopenia) in cirrhosis [5], a condition which, like HE is caused, at least in part, by the toxic actions of ammonia [6]. However, improvements in metabolic ammonia-removal mechanisms are not the only ones where by LOLA treatment has beneficial effects on HE in cirrhosis. It has been demonstrated that LOLA has significant hepato-protective actions [7] mediated by the synthesis of the anti-oxidant glutathione (GSH) as well as the production of nitric oxide leading to improvements in hepatic microcirculation. [7, 8]

Efficacy of LOLA for the treatment of hyper ammonemia and HE in cirrhosis

Beneficial effects of intravenous or oral formulations of LOLA have been reported in over 25 published Randomized Controlled Trials (RCTs). In most cases efficacy was defined in terms of LOLA’s ammonia-lowering actions together with improvements in HE grade (for OHE) or psychometric test scores (for MHE). The last three years have seen the completion of several new trials and meta-analyses devoted to the assessment of the efficacy of LOLA for the treatment of HE in cirrhosis some of which have challenged or confirmed the results of earlier work. Consequently, the present review is an up-to-date summary of the results of systematic reviews (with meta-analyses where available) of RCTs published through December 2019 on the efficacy of LOLA for the prevention and treatment of HE in patients with cirrhosis.

1.1  Efficacy of LOLA for the treatment of HE in cirrhosis: early critical reviews of RCTs

Results of clinical trials conducted in the 1980’s and 1990’s suggested that LOLA had the potential to lower blood ammonia and decrease the severity of HE. In order to assess this possibility two critical analyses were undertaken. In the first analysis, a search of indexed medical journals in which the results of RCTs were described in patients with cirrhosis and HE treated with LOLA. Four RCTs published during the period 1993–2000 for a total of 217 patients met inclusion criteria two of which made use of a parallel group design that included patients with MHE and two trials using a crossover design and patients with low-grade (I or II) OHE. [9] LOLA treatment led to lowering of blood ammonia [9] in patients with HE when compared to placebo using either intravenous (iv) or oral formulation of LOLA. This lowering of blood ammonia was accompanied by improvements in psychometric test scores but was not uniformly accompanied by improvements in mental status measured using the PSE Index procedure [9] (Table 1).

Table 1. Critical reviews of RCTs for LOLA treatment of HE in cirrhosis

Study ID

Year

No of trials

No of patients

Type of HE

Ammonia-lowering

Outcome parameters

Reference

Perez Hernandez JL

2011

5

623

MHE, OHE

Yes

Improvement of mental status, Ammonia, Hospitalization time

Ann Hepatol 2011; 10 (Suppl 2): S66-S69

Summary
Database searches of controlled trials identified six meeting the inclusion criteria for a total of 623 patients. LOLA infusions let to improvement in neuropsychiatric status, decreased serum ammonia with minimal adverse events.

Soarez PC

2009

4

217

MHE, OHE

Yes

Ammonia; Improvement in psychometric test

Arq Gastroenterol 2009 Jul-Sep; 46(3): 241–7.

Summary
Database searches of controlled clinical trials (English language) yielded four RCT’s with a total of 217 patients for inclusion in the analysis. LOLA (iv or oral) treatment resulted in reduced hyperammonemia compared to placebo and improved psychometric test scores. Small trial/patient numbers and low methodological quality limited beneficial effect in patients with OHE.

In a second critical analysis published two years later, searches were made of RCTs that were again published in indexed journals as well as in Medline, Cochrane and PubMed databases in which the efficacy of ivLOLA was assessed in patients with cirrhosis and HE. Six trials met inclusion criteria for a total of 623 patients 422 of which had cirrhosis while the remainder had acute liver failure [10].Trial quality was assessed using the Jadad Composite scale. [11] Venous ammonia concentrations decreased in the LOLA treatment group compared to placebo and these decreases were accompanied by significant improvements in the stage of HE assessed by West Haven criteria (Table 1).

1.2  Efficacy of LOLA for the treatment of HE in cirrhosis: systematic reviews of RCTs with meta-analyses

Results of seven systematic reviews each accompanied by meta-analysis of the results of RCTs on the efficacy of LOLA for the efficacy of treatment of MHE/OHE in patients with cirrhosis have been completed and published in the last 20 years starting with an in house analysis of five trials from Merz Pharmaceuticals (Germany) [12] Subsequent analyses by investigators from China. [13–15] Europe [16, 17] Canada [18] and India [19] followed involving up to 36 trials and 2377 patients with cirrhosis and HE. Summaries of the numbers of RCTs, patients, year, type of HE, outcome parameters, publication reference and short synopsis of the major findings are provided in Table 2.

Table 2. Systematic reviews with meta-analysis of RCTs for LOLA treatment of HE in cirrhosis

Study ID

Year

No of trials

No of patients

Type of HE

Ammonia-lowering

Outcome parameters

Reference

Butterworth RF

2018

10

884

MHE, OHE

Yes

Benefit for OHE; MHE iv/oral, NH3-lowering

J Clin Exp Hepatol. 2018; 8(3):301–313.

Summary
Electronic and manual searches were made of databases to identify RCTs for inclusion. Ten RCTs were included for a total of 884 patients with cirrhosis and HE Random effects model used to express pooled risk ratio (RR) or Mean difference (MD).  Both intravenous and oral formulations of LOLA found to be effective for lowering of blood ammonia [MD: -17.5 µmol/l (-27.73, -7.26)] p<0.0008 and improvement of mental state for patients with MHE [RR: 2.15, 95% CI: 1.48–3.14) p<0.0001)] or OHE [RR: 1.19, 95% CI: 1.01–1.39, p<0.03]. Oral LOLA was particularly effective for treatment of MHE.

Goh ET

2018

22

1375

MHE, OHE

Yes

Benefit for OHE/MHE, NH3-lowering

Cochrane Database Syst Rev. 2018;5:CD012410

Summary
Electronic and manual searches of databases, conference proceedings and correspondence with investigators and pharmaceutical companies yielded 22 RCTs involving 1375 patients with cirrhosis and HE or risk of development of HE for which outcome data was available. LOLA had a beneficial effect on HE compared to placebo/no intervention for all trials [RR: 0.70, 95% CI: 0.59–0.88] but evidence was judged to be very low quality leading investigators to conclude that outcomes were uncertain. However, subsequent sub-group analyses of completed RCTs and/or RCTs with findings published as full papers demonstrated significant improvements in mental state: 12 completed trials, 994 patients : RR:0.63, 95% CI: 0.48–0.83, p<0.001], 12 published trials, 1032 patients: RR:0.65,95% CI: 0.50–0.85, p<0.0017]. Both iv and oral formulations appeared to be effective in this analysis.

Bai M

2013

8

646

MHE, OHE

Yes

Benefit for OHE; MHE, NH3-lowering

J Gastroenterol Hepatol. 2013; 28 (5):783–92.

Summary
Searches of databases revealed 8 RCTs that assessed the efficacy of LOLA for treatment of HE in 646 patients with cirrhosis. LOLA was significantly more effective than placebo/no intervention for improvement in all types of HE [RR: 1.49, 95% CI: 1.10–2.01, p<0.01] as well as for patients with OHE or MHE when analysed separately. These improvements were accompanied by significant reductions in fasting blood ammonia [MD: -18.26, 95% CI: -26.96—9.56, p<0.01].

Hu Wei

2012

6

432

MHE, OHE

Yes

Serum ammonia, NCT-A, Clinical remission rate

Chin J Evidence-based Med 2012; (12)7: 799–803

Summary
Database searches of RCT’s of LOLA (iv or oral) for treatment of HE in cirrhosis yielded six placebo-controlled trials and 432 patients. LOLA significantly reduced serum ammonia (p<0.0001), improved NCT-A scores (p<0.0001) and clinical remission rates (p<0.01).

Jiang Q

2009

3

212

Chronic OHE (1,2)

Yes

Benefit for OHE not MHE

J Gastroenterol Hepatol. 2009 Jan;24 (1):9–14

Summary
Searches of electronic databases yielded 3 RCTs of 212 patients of sufficiently high quality (assessed by Jadad score) for inclusion in the analysis. LOLA significantly improved HE scores [RR: 1.89, 95% CI: 1.32–2.71, p<0.0005]. Subgroup analysis revealed significant efficacy of LOLA compared to placebo (2 trials) or lactulose (1 trial) in patients with grades I or II HE but not in patients with MHE.

Delcker M

2000

5

246

MHE, OHE

Yes

Ammonia, improvement of mental state, psychometric test scores

Hepatology 2000; 32(4):604

Summary
This review with meta-analysis was the first conducted by the manufacturers of LOLA and consisted of assessment of the efficacy of iv LOLA in 5 RCTs versus placebo. Two of the trials were subsequently published. Treatment with LOLA for 7 days resulted in significant improvements of NCT-A scores and mental state as a function of the lowering of blood ammonia.

Results were, in general, remarkably consistent with all seven meta-analyses showing evidence of improvements of mental state in patients with MHE or OHE [12–19] that was accompanied by lowering of blood ammonia in all cases. When assessed separately, either intravenous or oral formulations of LOLA were found to be effective for the treatment of HE [15–18] However, occasional inconsistencies were noted and this was attributed to differences in experimental design, inclusion/exclusion criteria or methodology used for the determination of mental state. For example, in one earlier study the patient population included cirrhotics as well as patients with Acute Liver Failure (ALF) [14]; the pathophysiology and treatment goals for the two conditions are quite distinct. In a second study, LOLA treatment was found to be ineffective for improvement of psychometric test scores in patients with MHE [13] but was found to be effective in all subsequent analyses in which this was addressed [15,18]. One possible explanation likely relates to the differences in the nature of the psychometric test procedures used in these analyses (e.g. use of the outdated PSE Index scoring system in one analysis[13]versus multiple well-established psychometric testing procedures such as NCT-A, B and PHES in the others). It is important to note that there are also areas of investigation relating to the efficacy of LOLA for the treatment of HE in cirrhosis that have been largely omitted from these earlier analyses. For example, few of these analyses investigated the possible beneficial effects of LOLA on ammonia lowering or mental state improvement in patients with higher grades (III and IV) of HE [12,14].In addition, there are no published systematic reviews and/or meta-analyses relating to the efficacy of LOLA for the prevention and treatment of HE in cirrhosis in which the new system of classification of HE (i.e. Covert, Overt grades II,III,IV) was employed. The advent of well-established procedures for the determination of trial quality based on risk of bias assessments has led to significant improvements in the quality of subsequent systematic reviews with meta-analyses. Such procedures include use of the Jadad Composite Scoring system [11] and, more recently, by the Cochrane Handbook for Systematic Reviews and Interventions[20]. Combinations of the two systems have also been employed[18,21].These systems used for assessment of risk of bias of each RCT take into account sequence generation during randomization, allocated sequence concealment, blinding of participants and personnel and completeness of outcome data[11,20]. In the first systematic review with meta-analysis undertaken under the above guidelines, Bai and co-workers searched manual and/or electronic databases to reveal eight RCTs with 646 patients with cirrhosis and OHE or MHE in which the efficacy of LOLA (iv or oral formulations) was compared to placebo/no intervention [15]. Study endpoints were improvement in HE and lowering of blood ammonia. LOLA was significantly more effective than placebo/no intervention for improvement of all types of HE with RR: 1.49, 95% CI:1.10–2.01, p<0.01 by Random Effects model. Significant benefit was also recorded for improvement of OHE with RR: 1.33, 95% CI: 1.04–1.69, p<0.02 by Random Effects model as well as for MHE with RR: 2.25, 95%CI: 1.33–2.82, p<0.01 by Fixed Effects model. Reduction of fasting blood ammonia significantly favored LOLA over placebo/no intervention with p<0.01. In a subsequent systematic review with meta-analysis, 10 RCTs with 884 patients with cirrhosis and HE satisfied inclusion criteria. [18]  Study quality and risk of bias were assessed using the Jadad Composite scale combined with the Cochrane Scoring Tool and the Random Effects Model was employed to express pooled Risk Ratio (RR) or Mean Difference (MD) with associated 95% Confidence Intervals (CI). Comparison with placebo/no intervention control data, LOLA was found to be significantly more effective for improvement of mental scores in all types of HE [RR: 1.36, 95% CI: 1.10–1.69, p<0.005] as well as in patients with OHE [RR: 1.19, 95% CI: 1.01–1.39, p<0.03] or MHE [RR: 2.15, 95% CI: 1.48–3.14, p< 0.0001]. LOLA treatment resulted in significant lowering of blood ammonia in these patient groups [MD: -17.5umol/L, 95% CI: -27.73 to -7.26, p<0.008]. The oral formulation of LOLA was found to be particularly effective for the treatment of patients with MHE. A similar systematic review with meta-analysis identified 15 RCTs and 1023 patients with cirrhosis and HE in which treatment with LOLA resulted in significant benefit for subgroups of patients with acute episodes of HE or with chronic HE but not in patients with MHE in an initial analysis of the data [16]. One year later, a large number of additional trials were added to this particular investigation giving a total of 36 RCTs with 2377 patients. Regrettably, data for the majority of these additional trials was found to be seriously lacking due to early trial abandonment as well as incomplete information required for assessment of risk of bias and trial outcomes leading the investigators to rate them as very low quality and to express uncertainty in the reliability of the findings [17]. Fortunately, there was a sufficient number of completed and/or published trials in this study to permit subgroup analysis in relation to the efficacy of LOLA for the treatment of HE. The relevant data was:

For completed trials [12 trials, 994 patients, RR: 0.63, 95% CI: 0.48–0.83, p<0.001]

For published trials [12 trials, 1026 patients, RR: 0.65, 95% CI: 0.50–0.85, p<0.00017]

These findings confirm those of three previous systematic reviews with meta-analysis dedicated to the assessment of the efficacy of LOLA for the treatment of OHE or MHE [15–19]

1.3  Efficacy of ammonia scavengers other than LOLA for the treatment of HE in cirrhosis: results of a meta-analysis

Searches of on-line databases and clinical trials registries yielded 11 RCTs that met inclusion criteria. [22] Meta-analysis using Risk Ratios (RR) or Mean Differences (MD) with 95% CI was performed with bias assessment. By design, the agents selected for this analysis did not include LOLA even though, as demonstrated and discussed in section 2.2 (above), it is the best-established agent currently employed clinically for the treatment of HE that specifically targets ammonia. Selection of most of these agents was undoubtedly inspired by their successful use for ammonia-lowering in cases of acute or chronic hyperammonemia associated with congenital deficiencies of urea cycle enzymes. Such agents included sodium benzoate (three trials), glycerol phenylbutyrate (one trial) and ornithine phenylacetate (two trials) in addition to AST-120 (two trials) and polyethylene glycol (three trials) for a total of 499 patients receiving test substance versus 444 receiving placebo or lactulose. Eight of the eleven trials were assessed as very low quality having high risks of bias. [22] Not surprisingly, significant reductions of blood ammonia were observed in placebo-controlled trials of sodium benzoate, glycerol phenylbutyrate and ornithine phenylacetate but with no observable effects of the latter substance on HE grade. Sodium benzoate, polyethylene glycoland AST-120 treatments failed to show significant improvements in HE grade compared to lactulose. These results led the authors to conclude that, although there was potential for reduction of blood ammonia by these agents, their effects on clinical outcome remain uncertain. This appeared to be primarily due to the low quality of the trials selected for the analysis. [22]

1.4  Efficacy of LOLA for OHE prevention and prophylaxis: systematic review with meta-analysis

There is a paucity of available published reports of systematic reviews with meta-analysis of RCTs dedicated to the evaluation of the efficacy of LOLA for the prevention of HE in patients with cirrhosis. Sporadic reports are limited in number to sub-groups of patients but results so far have been inconsistent [16,19] largely due to small trial numbers and low patient enrollment in addition to very low quality of the data leading investigators to conclude that the evidence for prevention of either OHE or MHE was uncertain. [17] Consequently a new systematic review with meta-analysis was undertaken to review the evidence base in support of a beneficial effect of LOLA for the prevention/prophylaxis of OHE in patients with cirrhosis. Electronic and manual searches identified 6 RCTs that met inclusion criteria for a total of 384 patients. [21] Five of the six trials were considered to be high quality with low risk of bias by Jadad-Cochrane criteria. LOLA treatment led to a significant reduction in the rate of progression of MHE to OHE compared to placebo/no intervention (three trials) with RR: 0.23, 95% CI: 0.07–0.73, p<0.01. LOLA treatment was also effective for secondary OHE prophylaxis, for primary OHE prophylaxis following gastrointestinal bleeding (one trial) and for post-TIPSS prophylaxis (one trial). Successful OHE prevention/prophylaxis was accompanied by significant reductions of blood ammonia and either iv or oral formulations of LOLA appeared to be effective for the slowing of progression of MHE to OHE. The effectiveness of LOLA versus placebo for reduction of the progression of MHE to OHE in patients with cirrhosis was independently confirmed in a subsequent meta-analysis. [19]

Table 3. Systematic reviews with meta-analysis of RCTs for OHE prevention/prophylaxis by LOLA

Butterworth RF

2019

6

384

MHE, OHE

No

OHE prevention; progression from MHE to OHE

Metab Brain Dis 2019. https://doi.org/10.1007/s11011-019-00463-8

Summary
Electronic and manual searches together with pre-established inclusion/exclusion criteria revealed 6 RCTs for a total of 384 patients with cirrhosis at risk for development of OHE. Treatment with iv or oral LOLA led to significant reductions in the risk of progression to OHE in patients with MHE [3 trials with RR: 0.23, 95% CI:0.07–0.73) p,0.01. LOLA was also effective for secondary OHE prophylaxis [1 trial with RR: 0.389, 95% CI: 0.174–0.870, p<0.002] and for OHE prophylaxis following acute variceal bleeding [ 1 trial with RR: 0.42, 95% CI: 0.16–0.98, p<0.03] and for OHE prophylaxis post-TIPSS [1 trial with OR:0.20, 95% CI: 0.06–0.88, p<0.03]. OHE prevention/prophylaxis was accompanied by significant reductions of blood ammonia. Both iv and oral formulations of LOLA were effective.

JPPR 19 - 123_Butterworth RF_F1

Figure 1a. Forest Plot for the efficacy of LOLA versus placebo/no intervention for the prevention of progression of MHE to OHE (Abid et al. 2011; Mittal et al. 2011; Alvares-da-Silva et al. 2014), secondary OHE prophylaxis (Varakanahalli et al. 2018), primary OHE prophylaxis(Higuera-de-la-Tijera et al. 2018) or post-TIPSS OHE prophylaxis (Bai et al. 2014)

JPPR 19 - 123_Butterworth RF_F2

Figure 1b. Forest plot for the efficacy of LOLA versus placebo/no intervention for the prevention of progression from MHE to OHE in patients with cirrhosis

Efficacy of LOLA compared to other currently-available agents for the treatment of HE in cirrhosis: network meta-analyses

RCTs directly comparing the efficacy of LOLA with other available agents such as non-absorbable disaccharides, antibiotics and probiotics have consistently shown that LOLA is equivalent and, in some cases, superior to these alternatives. For example, in an RCT published in 2006, patients randomized to lactulose or LOLA manifested comparable decreases of blood ammonia but only patients in the LOLA arm of the trial showed improvements in psychometric test scores, mental state grade, asterixis grade or EEG. [23] These observations were followed by two systematic reviews with network meta-analyses in which the efficacy of LOLA for the treatment of HE in patients with cirrhosis was compared to other available agents. The first analysis addressed the treatment of OHE [23], the second one focused on the treatment of MHE and on the progression from MHE to OHE [19].

Table 4. Network meta-analyses of RCTs comparing efficacy of LOLA versus other available agents for treatment of HE in cirrhosis

Study ID

Year

No of trials

No of patients

Type of HE

Ammonia-lowering

Outcome parameters

Reference

Dhiman RK

2019

25

1563

MHE, OHE

Yes

Comparable efficacy of LOLA for reversal of MHE; Prevention of OHE

Clin Gastroenterol Hepatol. 2019 Aug 30. pii: S1542–565(19) 30969–3. doi: 10.1016/j.cgh.2019.08.047

Summary
A systematic search of databases for RCTs evaluating treatments for MHE and prevention of deterioration to OHE resulted in a Network meta-analysis with surface under cumulated ranking (SUCRA) for rifaximin, lactulose, probiotics, probiotics + lactulose or LOLA compared to placebo/no treatment. Twenty five trials identified with 1563 patients with cirrhosis and MHE. LOLA was effective for reversal of MHE [ OR: 4.45, 95% PrI: 2.67–7.42, SUCRA: 47.2%, moderate quality] compared to placebo/no treatment and LOLA and lactulose were most effective for preventing episodes of OHE. Comparative analysis revealed no superiority between other agents and LOLA.

Zhu GQ

2015

20

1.007

OHE

No

LOLA=BCAA>LAC>NEO

Aliment Pharmacol Ther 2015; 41: 624–635

Summary
Literature searches including databases revealed 20 eligible RCTs for inclusion in this Network meta-analysis comparing efficacy of LOLA to that of BCAAs, non-absorbable disaccharides and neomycin compared to observation. The analysis combined direct and indirect evidence to estimate Odds Ratio (OR) and mean difference (MD) between treatments. Compared to observation, only LOLA [OR: 3.71, p<0.001] and BCAAs [OR: 3.37, p<0.001] improved clinical efficacy significantly. There was a trend suggesting that LOLA was the most effective intervention with respect to clinical improvement [OR” 1.10]. LOLA treatment resulted in a significant reduction in blood ammonia [MD:-20.18, 95% CI: -40.12—0.27].

1.5  Network meta-analysis: treatment of OHE by LOLA vs other agents

Electronic and manual searches of key databases yielded 20 RCTs that satisfied inclusion criteria for 1007 patients with cirrhosis and OHE who were treated with non-absorbable disaccharides, neomycin, rifaximin, LOLA or BCAAs versus observation only. Network meta-analysis combined direct and indirect evidence to obtain Odds Ratios (ORs) or Mean Differences (MDs) between treatments based on clinical outcomes. [23] Compared to observation only, treatment with LOLA [OR: 3.71, p< 0.001] or BCAAs [OR: 3.37, p<0.001] resulted in significant improvements in clinical efficacy. It was also concluded that LOLA had the potential to be the most effective intervention with respect to clinical improvement [OR: 1.10], rifaximin [OR: 1.31], non-absorbable disaccharides [OR: 2.75] or neomycin [OR: 2.22]. Moreover, LOLA treatment resulted in a significant reduction in blood ammonia [MD: -20.18, 95% CI: -40.12 to -0.27]compared to observation alone.

1.6  Network meta-analysis: treatment of MHE by LOLA vs other agents

Search of databases for RCTs evaluating available treatments for MHE in patients with cirrhosis yielded 25 trials for 1563 patients that satisfied inclusion criteria. There were two primary outcomes, namely reversal of MHE and prevention of progression from MHE to OHE using meta-analysis followed by Network meta-analysis. SUCRA was employed to pool direct and indirect estimates and to rank the various treatments.

Rifaximin, lactulose and LOLA were equivalent in efficacy and were each superior to probiotics with or without lactulose shown below:

  • Rifaximin [OR:7.53, 95% PrI: 4.45–12.73, SUCRA: 89.2%; moderate quality]
  • Lactulose [OR: 5.39, 95% PrI: 3.60–8.07, SUCRA: 67.2%; moderate quality]
  • LOLA [OR: 4.45, 95% PrI: 2.67–7.42, SUCRA: 47.2%; moderate quality]
  • Probiotics+ lactulose [OR: 4.66, 95% PrI: 1.90–11.39, SUCRA: 52.4%; low quality]
  • Probiotics [OR: 3.89, 95%PrI: 2.52–6.02, SUCRA: 34.1%; low quality]

LOLA was superior to lactulose or probiotics for the prevention of episodes of OHE in patients with MHE compared to placebo/no treatment as shown below:

  • LOLA [OR: 0.19, 95% PrI: 0.04–0.91, SUCRA: 75.1%; moderate quality]
  • Lactulose [OR: 0.22, 95% PrI: 0.09–0.52, SUCRA: 73.9%; moderate quality]
  • Probiotics [OR: 0.27, 95% PrI: 0.11–0.62, SUCRA: 59.6%; low quality.

Rifaximin, on the other hand, was ineffective for OHE prevention [19].

Conclusion

The advent of well-established procedures for the determination of trial quality based on risk of bias assessments such as the Jadad Composite Scoring system followed, more recently, by the Cochrane Handbook for Systematic Reviews and Interventions has resulted in significant improvements in the quality of systematic reviews and meta-analyses of clinical trials. Making use of such procedures, seven systematic reviews with accompanying meta-analysis were published in the last 20 years all of which focused on the analysis of the results of RCTs on the efficacy of LOLA for the efficacy of treatment of MHE and/or OHE in patients with cirrhosis. An initial in-house meta-analysis by Merz Pharmaceuticals (Germany) published in 2000 was followed by systematic reviews and meta-analyses conducted by international investigators from China, Europe, Canada and India. Analysis of the findings from these seven meta-analyses reveals a clear consensus of opinion in support of the efficacy of LOLA for lowering of blood ammonia and for the concomitant improvement of mental status in patients with cirrhosis and OHE in all cases. For MHE, results from five of the six meta-analyses in which it was assessed also yielded significant positive results. A recent meta-analysis assessing the efficacy of other agents with the demonstrated capacity to lower blood ammonia in a range of clinical settings confirmed the lowering of blood ammonia by most agents. However, effects on HE severity were inconsistent leading the investigators to question the quality of the studies. By design, LOLA had not been included in the list of agents assessed in this analysis. The evidence in support of a beneficial effect of LOLA for the prevention of OHE in patients with cirrhosis was reviewed in a novel systematic review and meta-analysis involving six RCTs for a total of 384 patients in a range of clinical presentations. LOLA treatment led to a significant reduction in progression of MHE to OHE compared to placebo/no intervention (three trials) and LOLA treatment was also effective for secondary OHE prophylaxis (one trial), primary OHE prophylaxis following variceal bleeding (one trial) and for post-TIPSS prophylaxis (one trial). Successful OHE prevention/prophylaxis was accompanied in all cases by significant reductions of blood ammonia and either iv or oral formulations of LOLA appeared to be effective for the slowing of progression of MHE to OHE. The effectiveness of LOLA versus placebo for reduction of the progression of MHE to OHE in patients with cirrhosis [20] was independently confirmed in a subsequent meta-analysis. The efficacy of LOLA was compared to other currently-available agents for the treatment of HE in cirrhosis using the technique of network meta-analyses. Two systematic reviews with network meta-analyses have been published in which the efficacy of LOLA for the treatment of HE in patients with cirrhosis was compared to other available agents. The first analysis addressed the treatment of OHE; the second one focused on the treatment of MHE as well as the progression from MHE to OHE.

For treatment of OHE, only treatment with LOLA or BCAAs resulted in significant improvements in clinical efficacy. It was also concluded that LOLA had the potential to be the most effective intervention with respect to clinical improvement and LOLA treatment resulted in concomitant reductions of blood ammonia. For the treatment of MHE, rifaximin, lactulose and LOLA were found to be equivalent in efficacy and were each superior to probiotics with or without lactulose. LOLA was superior to lactulose or probiotics for the prevention of episodes of OHE in patients with MHE compared to placebo/no treatment. Rifaximin, on the other hand, was found to be ineffective for OHE prevention.

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Incidence and risk factors associated with cervical cancer in sub-Saharan Africa: A systematic review

Abstract

Cervical cancer is the second most common leading cause of cancer death among women worldwide. Annually, ≥ 300,000 women die of cervical cancer and the majority of these deaths occur in developing regions of the world including sub-Sahara Africa. Human papillomavirus (HPV) is necessary but not a sufficient cause of cervical cancer. This review paper evaluated risk factors associated with cervical cancer in sub-Saharan Africa, using recent epidemiological studies. The main risk factors associated with cervical cancer in the sub-Saharan African women were; infection with high-risk HPV subtypes, HIV infection, socio-economic factors, age at first sexual intercourse, multiple sexual partners, and long-term use of oral contraceptives. Multi-parity, early pregnancies, and cigarette smoking are some of the risk factors associated with an increased risk of cervical cancer in sub-Saharan Africa. In addition, candidate gene studies have identified a number of single nucleotide polymorphisms mainly within the immune response genes to be associated with cervical cancer risk. Recently, dysbiosis of the cervical microbiome has been associated with cervical cancer risk in sub-Saharan African women.

Keywords

Cervical cancer, Incidence, Sub-Saharan Africa, HPV, Risk Factors

Introduction

Cervical cancer is the second most common leading cause of cancer death among women worldwide [1]. More than 300,000 cervical cancer deaths are reported annually and the majority of these deaths are from developing regions of the world. Squamous cell carcinoma (SCC) and adenocarcinoma (ADC) are the main histological types of cervical cancer [2,3]. SCC begins in epithelial cells of the ectocervix while ADC develops in the glandular cells that line the endocervix [4]. Approximately 80% and 20% of all cervical cancers are SCC and ADC, respectively [5]. ADC is more aggressive and frequently have distant metastases. Patients with ADC tend to have lower five-year survival rates and require an alternative approach to treatment than those with SCC [6]. This review paper evaluates the incidence and risk factors associated with cervical cancer in sub-Saharan Africa, using recent evidence from epidemiological studies.

Incidence of cervical cancer

The incidence of cervical cancer has been decreasing steadily for the past three decades in industrialized regions of the world [7]. However, in developing regions of the world especially in sub-Saharan Africa, the incidence of cervical cancer is increasing at an alarming rate [8]. The age-standardized incidence rate (ASIR) of cervical cancer in sub-Saharan Africa was estimated to be 34.9/100, 000 women [1]. Moreover, ASIR of cervical cancer varies greatly within sub-Saharan Africa, with ASIRs of 43.4/100, 000 women reported in southern Africa, 40.1/100, 000 women in eastern Africa, 29.6/100, 000 women in western Africa, and 26.8/100, 000 women in middle Africa [1], (Figure 1). According to the global cancer statistics of 2018, Eswatini has the highest incidence of cervical cancer followed by Malawi. The ASIRs of cervical cancer in Eswatini and Malawi are 75.3/100, 000 and 72.9/100, 000 women, respectively. Moreover, it is estimated that in the absence of any intervention, nearly 16.5 million cervical cancer cases will occur in sub-Saharan Africa in the next five decades [9].

Risk factors for cervical cancer

1. Human papillomavirus (HPV) infection

HPV is necessary but not sufficient cause of cervical cancer [10]. Approximately 90% of cervical cancers are attributed to HPV infection [11]. HPV, a small, non-enveloped, double-stranded circular DNA viruses belong to the Papovaviridae family [12]. There are ≥150 HPV subtypes that have been identified and characterized so far. These subtypes are categorized into high and low-risk according to their ability to cause malignant tumours. The high-risk HPV subtypes include 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 69, 73, and 82 [13]. Within this category, HPV subtypes 16 and 18 are the most oncogenic and contribute ≥ 70% of all cervical cancer cases [14].

Over 90% of HPV is cleared by the immune system within two years after infection [15]. However, a small proportion of infections especially those with high-risk HPV subtypes can persist and progress to cervical cancer. HPV encodes eight early viral regulatory protein (E1 to E8) and two late structural proteins (L1 and L2), which are crucial for cervical carcinogenesis [16–18]. The E1 and E2 are required for viral DNA replication. The E2 suppresses E6 and E7 viral oncoprotein, E4 and E5 help viral assembly, whereas L1 and L2 are involved in capsid formation [19]. HPV usually integrate its DNA into the human genome for replication. However, the integration of HPV into the human DNA disrupts the E2 functionality, thus resulting in a higher expression of E6 and E7 oncoprotein [20]. These oncoproteins invade the host immune system, deregulate the cell cycle control and apoptosis, thus allowing viral persistence. Dysregulation of the cell cycle and apoptosis lead to cellular transformation and immortalization, which is an important step in cervical tumorigenesis [19]. Specifically, E6 bind to tumour suppressor gene (TP53) and prevents apoptosis, whilst E7 oncoprotein promotes cellular proliferation and differentiation [21].

AWHC 2020-301_Abram Bunya Kamiza_F1

Figure 1. Age-standardized incidence rate of cervical cancer in sub-Saharan Africa. Adapted from Global cancer statistics 2018, International Agency for Research on Cancer, World Health Organization.

A retrospective study from 38 countries in North America, Latin America, Caribbean, Europe, Africa, Asia, and Oceania revealed that ≥ 85% of cervical cancer tissues were HPV positive [11]. In addition, 70% of cervical cancer cases were reported to be caused by HPV subtype 16 and 18 [22]. Studies have suggested that in addition to high-risk HPV subtypes been associated with cervical cancer, certain low-risk HPV subtypes such as subtype 6 and 11 also play a crucial role in cervical carcinogenesis [23–25]. However, these low-risk HPV subtypes are commonly associated with benign genital warts. Epidemiological studies have confirmed the direct role of several HPV subtypes in the development of cervical cancer [26,27]. Persistent infection with high-risk HPV subtypes has also been implicated in other cancers including that of the anus, penis, vulva, vagina, and oropharynx [10,28]. These findings suggest that HPV is not only associated with cervical cancer but also other cancers.

2. Human immunodeficiency virus (HIV) infection

HIV exacerbates the risk of cervical cancer. Population-based studies have reported that HIV-positive women are more likely to develop cervical cancer than HIV-negative women [29,30]. In Senegal, HIV-positive women were 2.55, (95% CI 1.69–3.86) times more likely to progress from HPV infection to cervical cancer than HIV-negative women [31]. A case-control in Eswatini reported that HIV positive women were 5.24 times increased risk of cervical cancer than HIV negative women [32]. The increased risk of cervical cancer among HIV-positive women is particularly important in sub-Saharan Africa, where HIV infection is endemic. In Rwanda, Singh et al. reported a higher prevalence of high-risk HPV subtypes in HIV-positive women than in HIV-negative women [33]. In Zambia, HIV-positive individuals were two-timed more likely to be co-infected with high-risk HPV subtypes than HIV-negative individuals [34]. In Zimbabwe and South Africa, HIV-positive women were more likely to have abnormal cervical cytology than HIV-negative women [35,36]. A number of studies have indicated that HIV infection suppresses the immune system’s ability to clear the HPV infection [37–39], leading to persistent infection, which subsequently leads to cervical abnormalities and cancer. Moreover, HIV infection significantly decreases cervical cancer survival among HIV-positive women in Botswana [40].

3. Socio-economic status

Low socioeconomic status (SES) has been associated with an increased risk of cervical cancer in studies from both developing and developed countries [41–43]. A case-control study in the United States reported a 1.8-fold increased risk of cervical cancer among women who reside in poor counties in Ohio compared to those who reside in affluent counties [42]. El-moselhy et al. reported that women with low education level, unskilled, and reside in rural areas in Egypt were more likely to develop cervical cancer than those with high SES [43]. In Tanzania, women with no formal education were 4.30, (95% CI 3.50–5.31) increased the risk of cervical cancer compared to women with high education level [44]. Moreover, women with low SES were 2.3-fold more likely to die from cervical cancer compared to those with high SES [42]. Differences in SES as defined by education, occupation, and annual income play a major role in disparities in the incidence and mortality of cervical cancer. Women with low SES tend to engage in risky sexual behaviour like prostitution [45], which increases the risk of contracting sexually transmitted diseases (STDs) like HPV and HIV, which are important risk factors of cervical cancer. Moreover, women with low SES tend to lack health-seeking behavior [46], hence they are less likely to participate in cancer screening programmes.

4. Age at first sexual intercourse

Early age at first sexual intercourse is associated with risky sexual behaviour like having unprotected sex and multiple sexual partners, which are important risk factors of HPV and HIV [47]. A number of studies have reported an increased risk of cervical cancer with an early age at first sexual intercourse [48–50]. In Nigeria, women with an early onset of sexual intercourse ≤17 years were 3.7-fold increased risk of cervical cancer compared to those aged ≥ 18 years old [49]. A case-control study in Ethiopia indicated that women who experience sexual intercourse earlier than 15 years were 6.7-times more likely to develop cervical cancer than women who experience sexual intercourse between the ages of 21–25 years [50]. Compared with women with age at first sexual intercourse of ≥18 years, the odds ratio of developing cervical cancer was 1.90 and 2.60 among women with age at first sexual intercourse between the ages of 16–17 and <15 years old, respectively [51]. Previous studies have suggested that immature cervix is susceptible to high-risk HPV subtypes, which lead to persistent HPV infection and subsequently increased the risk of cervical cancer among young women [52].

5. Multiple sexual partners

Sexual activities are the main risk factors of HPV infection especially among those with multiple sexual partners [32,50]. Kassa et al. reported a 5.86-fold increased risk of cervical cancer among women with multiple sexual partners in Ethiopia [50]. In Eswatini, Jolly et al. reported an odds ratio 3.00, (95% CI 1.02–8.85) of developing cervical cancer among women with multiple sexual partners after adjusting for age at first sexual intercourse [32]. Moreover, a meta-analysis study suggested that having multiple sexual partners, with or without HPV infection, is an important risk factor of cervical cancer among sexually active women [53].

6. Multi-parity and early pregnancy

Multi-parity has been associated with an increased risk of cervical cancer [46,54]. Women who engage in early sexual intercourse may become pregnant at a young age and are more likely to be parous later in life [55]. Early pregnancies have been associated with an increased risk of cervical cancer [49]. The increased risk of cervical cancer among women with early pregnancies may be due to cervical trauma experienced during early childbearing or by high parity births [55]. A pooled analysis of eight case-control studies indicated that women who were parous at a young age were more likely to develop cervical cancer later in life [56]. Louie et al. suggested that the increased risk of cervical cancer among highly parous women may be attributed to sexual and reproductive events occurring at a young age [55].

7. Oral contraceptive use

Long-term use of oral contraceptives has been associated with cervical cancer risk [50,57]. In Ethiopia and Kenya, women with long-term use of oral contraceptives were associated with an increased risk of cervical cancer compared to women who do not use oral contraceptives [50,57]. A meta-analysis study of 28 case-control studies concluded that long-term use of oral contraceptive is an important risk factor of cervical cancer [58]. Moreover, an animal model study indicated that mouse treated with longer duration of estrogen developed cervical cancer than mouse treated with short duration of estrogen [59]. Interestingly, the incidence of cervical cancer has been found to decline over time as women stopped using oral contraceptives [60,61]. These findings suggest that long-term use of oral contraceptives is an important risk factor of cervical cancer especially among women of reproductive age.

8. Cigarette smoking

While cigarette smoking is commonly associated with lung cancer, it also plays a crucial role in carcinogenesis of many other cancers, including cervical cancer [62]. The International Agency for Research on Cancer classified tobacco as a group one carcinogen. A pooled analysis study revealed an increased risk of cervical cancer in current smokers as compared to non-smokers after adjusting for HPV infection and other environmental factors [63]. Min et al. showed that the risk of cervical cancer increased not only in women who smoke but also in women who are exposed to second-hand smoke [64]. The biological mechanism that underlies the increased risk of cervical cancer among women who smoke is not completely understood. However, studies have suggested that smoking inhibits the clearance of HPV infection by the immune system [65,66]. Surprisingly, the association between cigarette smoking and cervical cancer is stronger in SCC than in ADC [67]. The increased risk of SCC among women who smoke is not fully understood as it has rarely been investigated. However, quitting cigarette smoking has been reported to be associated with a decreased risk of cervical cancer [68]. Roura et al. reported a 2-fold decreased risk of developing cervical cancer among women who quit cigarette smoking.

9. Host genetic factors

Approximately 1% of women with chronic HPV infection progress to cervical cancer [69]. Magnuson et al. estimated that 27% of all cervical cancers are attributed to host genetic factors [70]. Studies have identified a number of single nucleotide polymorphisms (SNPs) mainly within the immune response genes to be associated with cervical cancer [71–74]. In Tunisia, a case-control study identified three SNPs (rs1800871, rs1800872, and rs3024490) within IL10 to be associated with an increased risk of cervical cancer [71]. In South Africa, CCR2-V64L G>A was associated with an increased risk of cervical cancer [72]. Zida et al. and Ben et al. identified TNF-α-308G>A and HLA-DRB1*15 and DQB1*06 to be associated with cervical carcinogenesis among HPV-negative women in Tunisia [73,74]. Apart from the immune response genes been heavily associated with cervical cancer, TP53 has also been implicated in cervical tumorigenesis. A candidate gene study in the black South African population indicated that TP53 rs1042522 SNP is associated with cervical cancer in HPV-negative women [75]. This finding reveals the direct role of host genetic factors in the aetiology of cervical cancer. However, the association between host genetic factors and cervical cancer has rarely been investigated in sub-Saharan Africa. Hence, more genetic studies with larger sample sizes and probably using genome-wide approaches are needed in sub-Saharan Africa to fully understand the aetiology of cervical cancer.

10. Cervical microbiome

Dysbiosis of the cervical microbiome has been associated with cervical cancer risk [76–78]. In Tanzania, Klein et al. reported that Staphylococcus, Pseudomonadales and Mycoplasmatales species were associated with high-grade squamous intraepithelial lesions in HIV-positive women [76]. Curty et al. found Gardnerella, Aerococcus, Schlegelella, Moryella, and Bifidobacterium to be associated with cervical lesions [77]. Moreover, a case-control study by Oh et al.
reported that Atopobium vaginae, Gardnerella vaginalis, and Lactobacillus iners were associated with an increased risk of cervical cancer [78]. Vagina and ectocervix are normally colonized by Lactobacillus species, which inhibit the growth of other bacterial species [79]. Inhibition of these bacteria species is crucial in maintaining the cervical epithelial barrier to HPV entry. However, reduction in the number of Lactobacillus species, result in colonization of cervical epithelium by other bacteria species [80]. These bacterial species produce enzymes and metabolites that compromise the cervical epithelium barrier [81], thus facilitating HPV entry into basal keratinocytes. In Kenya, bacterial vaginosis, trichomonas vaginosis, and Candida species were associated with high-risk HPV infection [82], which is an important risk factor of cervical cancer. Moreover, fungal and some of the bacterial species have been reported to enable HPV persistent, thus leading to cervical cancer [83].

Prevention and screening

1. HPV vaccination

HPV vaccination is becoming the primary prevention of cervical cancer and other HPV-associated cancers. Currently, the Food and Drug Administration approved three HPV vaccines including Gardasil 9, Gardasil, and Cervarix [84]. Gardasil 9 is a nanovalent vaccine produced by Merck [85]. This vaccine target nine HPV subtypes, seven of which are high-risk (16, 18, 31, 33, 45, 52 and 58) and two of which are low-risk (6 and 11). This vaccine target HPV subtypes that cause ≥ 90% of HPV-associated cancers worldwide [86]. Gardasil (Merck and Kenilworth) is a quadrivalent vaccine, thus targeting two high-risk subtypes (16 and 18) and two low-risk subtypes (6 and 11), and covering ≥ 80% of HPV-associated cancers [87]. Cervarix is a bivalent HPV vaccine produced by GlaxoSmithKline, targeting two high-risk HPV subtypes 16 and 18, which contribute 70% of cervical cancer worldwide [87].

However, these vaccines cannot prevent pre-existing infections and are administered to pre-adolescent girls between the ages of 9–15 years [84]. Uptake of these vaccines is low in developing countries, especially in sub-Saharan Africa [88]. However, most countries are now implementing HPV vaccination in school-going children. It is estimated that ≥ 6.7 million cervical cancer cases could be prevented if HPV vaccination coverage is scaled up to 80–100% globally by the year 2020 [9]. However, it will take several decades in sub-Saharan Africa to see the impact of HPV vaccination.

2. Pap smear test

Pap smear is a screening test used to check cervical lesions. It is usually performed in women of reproductive age and who are sexually active [89]. Pap smear can detect early cervical dysplasia in its earliest form. Once cervical abnormalities are detected, the best way is to treat the precancerous lesions before they can fully develop into cancer. Countries that have successfully implemented cervical cancer screening have also significantly reduced both the incidence and mortality of cervical cancer, especially SCC [90,91]. The HPV DNA test has also been recommended to be included in cervical cancer screening package among women of reproductive age [89]. Cervical cytology together with HPV DNA test has higher sensitivity than screening with Pap smear alone [92]. A recent study suggested that rapid scale-up of HPV vaccination and screening from 2020 onwards will rapidly decrease the incidence and mortality of cervical cancer in the next five decades [9]. However, cervical cancer screening coverage is still low in sub-Saharan Africa [93], and there is a need for rapid scale-up to avert the high incidence and mortality of cervical cancer.

3. Visual inspection with acetic acid (VIA)

VIA is an alternative cervical cancer screening method viable in sub-Saharan Africa, as it is cheap, easy to use, does not require a physician or pathologist to perform, and tend to have shorter turn-around time than Pap smear [94]. In VIA, about 5% acetic acid (vinegar) is applied to the cervix and then visualized with a lamp. The precancerous lesions on the cervix normally turn white when combined with acetic acid whilst normal cervix do not change colour [95]. A number of studies in sub-Saharan Africa have indicated that VIA has a higher sensitivity than Pap smear [96–99]. Specifically, VIA has a high sensitivity for SCC which contribute ≥ 80% of cervical cancers in sub-Saharan Africa [97]. However, previous studies have indicated that VIA tends to have lower specificity than Pap smear [96–98]. Nonetheless, VIA is comparable to Pap smear and the World Health Organization recommended VIA as a primary cervical cancer screening method in developing countries, where pathology laboratories are limited. The low cervical cancer screening rate in sub-Saharan Africa may be attributed to inadequate funding, lack of awareness campaign, lack of health-seeking behaviour, low SES, and long-distance to access healthcare facility [100]. Cervical cancer can also be prevented by having safe sex, monogamous relationship and adopting a healthy lifestyle like quitting cigarette smoking, alcohol consumption and engaging in regular physical activity.

Summary and conclusion

The incidence of cervical cancer is highest in sub-Saharan Africa. Epidemiological studies have indicated that infection with high-risk HPV subtypes is crucial in the carcinogenesis of cervical cancer. Apart from HPV infection, HIV, SES, age at first sexual intercourse, multiple sexual partners, oral contraceptive use, multi-parity, early pregnancies, cigarette smoking, host genetic factors, and dysbiosis of the cervical microbiome are also important risk factors associated with cervical cancer in sub-Saharan Africa. However, cervical cancer can be prevented by HPV vaccination and early detection through screening. Gardasil and Cervarix are two HPV vaccines that are currently used to prevent cervical cancer and other HPV-associated cancers in sub-Saharan Africa. Scaling up HPV vaccination and decentralization of cervical cancer screening programmes from tertiary-level to primary-level care is crucial in preventing the incidence and mortality of cervical cancer in sub-Saharan Africa. Moreover, future cervical cancer prevention programmes should include other risk factors associated with the disease.

Funding: None.

Conflicts of Interest: None

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A New Tool for Assessing Bladder Outlet Obstruction

Abstract

Objective: Assessing the role of transrectal Doppler ultrasound in estimating degree of bladder outlet obstruction, in patients with benign prostatic hyperplasia.

Methods: Fifty two patients aged from 55 to 70with the clinical diagnosis of BPH were recruited. Patients with cancer prostate, neurogenic bladder, previous lower urinary tract intervention, were excluded. Urologic evaluation included, thorough history, IPSS, neurologic examination, digital rectal examination, urine analysis, PSA, uroflowmetry, transrectal doppler ultrasonography. The correlations were analysed between the resistive index of prostatic capsular artery, and maximum flow rate (Qmax).

Results: A significant increase in RI correlated to decrease in Qmax (r= -0.398, p<0.016) was found. Also there was significant increase in RI correlated to increase in IPSS (r=0.535, p<0.001). AS regard Qmax, there was significant decrease in Qmax correlated to increase in IPSS (r=-0.654, p<0.001).

Descriptive Statistics

 

Range

Mean

±

SD

Age(year)

55

70

63.863

±

4.643

IPSS

1

35

19.882

±

9.361

Q Max(ml/sec)

2.6

17.9

9.097

±

4.591

PSA(ng/ml)

0.9

33

10.903

±

8.776

Total gland volume(gm)

20

295

82.922

±

45.808

Adenoma(gm)

9

202

51.524

±

35.149

Residual urine(ml)

0

450

77.030

±

96.311

RI

0.29

0.95

0.728

±

0.110

Conclusion: Transrectal Doppler can be used as a tool to measure degree of bladder outlet obstruction, through measuring resistive index of prostatic capsular artery.

Introduction

Arterial resistivity index (also called as Resistive index, abbreviated as RI), developed by LeandrePourcelot, in 1982.Which is a measure of pulsatile blood flow that reflects the resistance to blood flow caused by microvascular bed distal to the site of measurement [1]. Owing to advent of Doppler imaging, RI measurement in patients with LUTS has become a promising parameter for the diagnosis of BPH. It was found that a hyperplastic prostate tissue pushed the capsule out as it grew thus increasing the intraprostatic pressure as well as RI. The increase of the intraprostatic pressure is equally distributed throughout the whole prostate, so the increase of RI was found in both peripheral and transition zones [1]. Also as regard PDUS, the technique has been found to enhance prostate cancer detection. Spectral waveform measurements by power Doppler TRUS may be promising for the differentiation of PCa in patients with benign diseases as an adjunct to systematic sampling in the presence of ultrasonographically detectable lesions accompanied by positive rectal examination findings and suspicious PSA levels [2].

Resistive index of prostatic capsular artery for evaluating obstruction

It was used for the first time by Kojima and his colleagues in the differentiation of the normal prostate in BPH patients. [1]

How BPH increases RI of prostatic capsular artery?

How prostatic RI increases in BPH patients, is still  not completely understood, may be the hypertrophied prostate squeezes the capsule outwards, which results in an increase in intraprostatic pressure and prostatic RI. [3]

Supporting Evidence

This is supported by the decrease in RI value after a prostatectomy. [1]

Doxazosin treatment significantly decreased prostatic RI in BPH patients. [4]

It was shown that the RI increases significantly correlated to the increase in prostatic volume, and that there was a significant difference in RI between patients with normal prostate and those with BPH. [1]

Which branch of prostatic artery to measure RI and which zone?

An increase of the RI of capsular arteries correlated with prostatic parameters in patients with BPH, however, no correlation between the RI of urethral arteries and prostatic parameters was found. The findings suggested that the RI of capsular arteries may become the index for measuring lower urinary obstruction in the future. [5]

How is RI measured?

The indices depend on ratios involving the peak systolic velocity (PSV), the end diastolic velocity (EDV) and mean velocity (MV) through one cycle. RI is one of the primary indices used clinically and is calculated through the following equation. [1]

RI = PSV – EDV

Power Doppler versus color Doppler:

Weakness points:

It is hypothesized that an enlargement of the median lobe may not impact RI value as it does not impose increased resistance to capsular arteries. The association of intravesical prostatic protrusion (IPP) could add for a more precise diagnosis in this scenario [1].

Patients and Methods:

This study was conducted on 52 patients presenting with LUTS due to BPH, to the outpatient clinic at Kasr Al-Aini University Hospital, Mansoura Urology and Nephrology Centre, and The National Institute of Urology and Nephrology.

Patients

Inclusion criteria: Patients aged from 55 to 70 years presenting with LUTS due to BPH.

Exclusion criteria: Patients who had one or more of the following were excluded from the study: Patients with prostate cancer (In cases of abnormal PSA, or abnormal DRE, TRUS biopsy was done to exclude cancer). Patients with history of lower urinary tract interventions. Patients with neurogenic bladder (based on history, clinical examination and post voiding residual volumes).

Methods: All patients were subjected to:

Thorough history taking

Full history was taken from all cases as regards:

  1. Personal history: This included age, occupation, special habits of medical importance and sexual history.
    1. Past history:
    2. Surgical history: previous lower urinary tract interventions.
    3. Medical history: Diabetes Mellitus, Hypertension, and neurogenic disorders.
    4. Family history: Cancer prostate
  2. Presenting complaint: All patients had a self-administered, validated Arabic version of IPSS questionnaire.
  3. Full clinical examination
    1. Each patient was thoroughly examined:
    2. General examination: It was done in all patients with including neurologic examination.
    3. Genitourinary examination: Digital rectal examination was done to every patient to assess prostate size, surface, and consistency, and also assessing anal tone, or as a part of bulbo-cavernosus reflex test.
  4. Labs
  5. Urine analysis and culture.
  6. PSA (free and total).
  7. Uroflowmetry: It was done to assess the urine flow and measure the Qmax. Cases in which detrouserhypocontractility was suspected (due to neurogenic insult, diabetes or very old age >70), were omitted. Transrectal Ultrasonography and Doppler: To measure size of prostate, adenoma, residual volume. Doppler was used to measure resistive index of prostatic capsular artery. The machine used is BK medical flex 400.
  8. Statistical Analysis:  Data were collected, verified, revised then edited on personal computer. Categorical variables were expressed as absolute and relative frequencies while continuous variables were presented as mean values ± standard deviation (SD). Comparisons were made between continuous and ordinal variable using student t test, comparisons were made between 2 continuous variables using Pearson’s correlation. Sensitivity and Specificity was calculated using chi-square test. Statistical analysis was performed using SPSS (statistical package version sixteen). Difference was considered statistically significant at a P value < 0.05 and highly significant at P value < 0.01.

Results

Number of Patients enrolled in this study was 52 patients .Range of age was 55–70 with mean age 63.8 ± 4.6. Eight parameters were studied and the values of these studies were summarized in table (3).

Table 1. Summary of result

Descriptive Statistics

 

Range

Mean

±

SD

Age(year)

55

70

63.863

±

4.643

IPSS

1

35

19.882

±

9.361

Q Max(ml/sec)

2.6

17.9

9.097

±

4.591

PSA(ng/ml)

0.9

33

10.903

±

8.776

Total gland volume(gm)

20

295

82.922

±

45.808

Adenoma(gm)

9

202

51.524

±

35.149

Residual urine(ml)

0

450

77.030

±

96.311

RI

0.29

0.95

0.728

±

0.110

The mean patient’s age was 63.86 years, the mean IPSS was 19.88, the mean Qmax was 9.09 ml/sec, the mean PSA was 10.9ng/ml, the mean total gland volume was 82.92 gm, the mean adenoma volume was 51.52 gm, the mean residual urine volume was 77.03 ml, the mean resistive index was 0.73.

Mean resistive index for obstructed group was 0.76, while for the non obstructed group was 0.69.

Normal RI of prostatic capsular artery is 0.55–0.71 [6].

Table 2. Correlation between Qmax and other factors in question for being indicator of degree of obstruction.

Correlations

 

Q Max

r

P-value

Age

-0.017

0.923

IPSS

-0.654

<0.001*

PSA

0.013

0.955

P. Size

-0.111

0.519

Adenoma

-0.028

0.886

Residual V

-0.201

0.269

The only statistical significance was found in correlation between Qmax and IPSS (r = –0.654, p < 0.001).

No statistical significance was found in correlation between Qmax and age (r = –0.017, p = 0.923), no statistical significance was found in correlation between Qmax and PSA (r = 0.013, p = 0.955),  no statistical significance was found in correlation between Qmax and prostate size (r = –0.111, p = 0.519), no statistical significance was found in correlation between Qmax and adenoma volume (r = –0.028 , p = 0.866), no statistical significance was found in correlation between Qmax and residual volume of urine (r = –0.201, p = 0.269).

Table 3. Correlation between RI, Qmax and other factors in question for being indicator of degree of obstruction.

Correlations

 

RI

r

P-value

Q Max

-0.398

0.016*

Age

0.008

0.954

IPSS

0.535

<0.001*

PSA

-0.166

0.347

P. Size

0.023

0.875

Adenoma

0.071

0.656

Residual V

0.243

0.173

Statistical significance was found in correlation between RI and Qmax (r = –0.398, p = 0.016), and between RI and IPSS (r = –0.398, p = 0.016).

Table 4. Range of resistive index of capsular prostatic artery for each group of IPSS.

Group

Number of patients

Minimum resistive index

Maximumresistive index

Mild

4

0.29

0.67

Moderate

21

0.55

0.89

Severe

27

0.61

0.95

The patients were divided according to IPSS as follows: mild symptoms (0–7), moderate symptoms (8–19), and severe symptoms (20–35) groups. In the mild symptoms group RI ranged from 0.29 to 0.67, in the moderate symptoms group RI ranged from 0.55 to 0.89, in the severe symptoms group RI ranged from 0.61 to 0.95.

Table 5. Calculating sensitivity, specificity, PPV, and NPV of RI of prostatic capsular artery.

 

Diseased (obstructed, Qmax<10ml/sec)

Non diseased
(not obstructed, Qmax ≥10ml/sec)

Total

+ve
(RI >0.71)

20

6

26

-ve
(RI ≤0.71)

8

18

26

 

28

24

 

Twenty six patients had resistive index more than 0.71, 20 of them were truly obstructed i.e., Qmax less than 10ml/sec, and 6 of them were not obstructed, i.e., Qmax more than  10ml/sec. On the otherside there were also 26 patients whose resistive index was less than or equal 0.71, 18 of them were not obstructed Qmax more than 10ml/sec, but there was 8 obstructed Qmax less than 10ml/sec.

Sensitivity = 71%

PPV = 77%

Specificity = 75%

NPV = 69%

At RI 0.75,

Sensitivity = 57%

PPV = 88%

Specificity = 89%

NPV = 60%

At RI 0.8,

Sensitivity = 38%

PPV = 100%

Specificity = 100%

NPV = 54%

At RI 0.85,

Sensitivity = 27%

PPV = 100%

Specificity = 100%

NPV = 50%

Table 6. Sensitivity, specificity, PPV and NPV of RI of prostatic capsular artery at different resistive indices.

RI

Sensitivity

Specificity

PPV

NPV

0.75

57

89

88

60

0.8

38

100

100

54

0.85

27

100

100

50

IJNUS 2019-102_Shady Emara_F1

Figure 1.Scatter chart showing an inversely proportional relationship between Qmax and IPSS.

IJNUS 2019-102_Shady Emara_F2

Figure 2. Scatter chart showing an inversely proportional relationship between RI and Qmax.

IJNUS 2019-102_Shady Emara_F3

Figure 3. Scatter chart showing a directly proportional relationship between RI and IPSS.

#Sensitivity and specificity of RI:

Positivity of the test was assumed to be RI >0.71 (the upper limit of RI of normal prostatic capsular artery from Kojima study).

The diseased group was assumed to be those with Qmax< 10 ml/sec. (according to cut off established by Nitti et al 90% of men with a Qmax of less than 10 mL/sec are obstructed).

Discussion

Thanks to doppler imaging invention RI measurement in patients with LUTS has become a promising parameter for the diagnosis of BPH. It was found that a hyperplastic prostate tissue pushed the capsule out as it grew thus increasing the intraprostatic pressure as well as RI. The increase of the intraprostatic pressure is equally distributed throughout the whole prostate, so the increase of RI was found in both peripheral and transition zones [1]. In a Turkish study, the authors have intervened with Afluzosin XL 10 mg given to 34 patients with LUTSs for a month. They have found significant relationship between RI, Qmax, IPSS, and PSA. The mean RI value was 0.72+0.06 before medication and decreased significantly to 0.66+0.04 after the treatment (p<0.05). There was no relationship between RI and age (r=0.23, p>0.05). This study also depended on uroflowmetry rather than urodynamics [7].

In a study by Kojima M and colleges, they investigated the relationship between the resistive index (RI) of the prostate as measured by transrectal power Doppler with age, transrectal ultrasound planimetry and parameters of pressure-flow study.  A total of 140 elderly patients with lower urinary tract symptoms and no previous treatment for lower urinary tract symptoms, prostate cancer, bladder dysfunction or urethral stricture were investigated. A mean RI of 0.72±0.06 (range 0.59–0.88) was measured in patients with BPH versus a mean value of 0.64±0.04 (range 0.55–0.71) in those with a normal prostate (P<0.0001). The strongest correlation was found between RI and pdet (r = 0.401, P<0.005), followed by pdetQmax (r = 0.360,P<0.01) and the Abrams-Griffiths number (r = 0.330, P<0.05). This study depended on urodynamics to obtain the Pdet, thus bladder outlet obstruction index BOOI could be calculated and correlated with the RI. On the otherside, the authors didn’t mention IPSS as one of parameters for judging degree of bladder outlet obstruction [6]. The reason for the increase in RI in BPH has not been established, but it may be because the growing hypertrophic prostate pushes the capsule outward and thereby increases intraprostatic pressure and RIs [8].

In our study, 28 patients out of 52 (54%) were diagnosed obstructed i.e., Qmax less than 10 ml/sec, 21 (40%) patients were equivocal i.e., Qmax 10–15 ml/sec, and 3 patients (6%) were not obstructed i.e., Qmax more than 15 ml/sec. We have correlated between the resistive index, Qmax, IPSS, PSA, age, prostate volume, and adenoma volume. There was a significant increase in RI correlated to decrease in Qmax (r = –0.398, p < 0.016). Also there was significant increase in RI correlated to increase in IPSS (r = 0.535, p < 0.001). AS regard Qmax, there was significant decrease in Qmax correlated to increase in IPSS (r = –0.654, p < 0.001).

Conversely, no relation was found between degree of obstruction and other parameters; age, PSA, prostate volume, adenoma volume, residual volume.

At a cutoff of 0.71 the resistive index distinguished patients with and without bladder outlet obstruction with 71% sensitivity and 75% specificity, reflecting BOO severity in patients with BPH. At cut off of 0.8, RI is highly specific 100%, so it can strongly confirm the diagnosis of obstruction. Our results are consistent with those of Zhang X et al 2012, at nearly equal resistive index (0.71 in our study and 0.69 in Zhang study), the resistive index had sensitivity 71% compared to 78% in Zhang study. While specificity was 75% in our study, it was 86% in Zhang study.

The value of measuring the prostatic resistive index vs. pressure-flow studies in the diagnosis of bladder outlet obstruction caused by benign prostatic hyperplasia: TRUS is less invasive, cheaper and less time-consuming than pressure flow study, and measures prostatic size, which is useful in planning management [9]. Spectral waveform measurements by power Doppler transrectal ultrasonography may be useful in differentiating prostate cancer from benign hypertrophy [2]. One point of criticism was that we used uroflowmtery instead of urodynamics for assessing bladder outlet obstruction. However we obviated cases that may have detrouserhypocontractlity by excluding patients older than 70 years, excluding patients with suspected neurogenic element, and patients with very large residual volumes suggesting chronic retention.

Comparing results of our study with those of other studies:

Mean age:

Table 7. Comparing patient age in different studies

Study

Mean age (years)

Our study

63.9

Osama et al 2012

66.8

Hitoshi et al 2009

71.1

Zhang X et al 2012

67.5

Mean prostatic volume:

Table 8. Comparing prostate volume in different studies.

Study

Mean prostatic volume (grams)

Our study

82.9

Osama et al 2012

75.1

Hitoshi et al 2009

71.6

Zhang X et al 2012

53.5

Limitations of the study

When comparing values of RIs between IPSS groups (mild, moderate, severe), there was overlap between groups, i.e., some patients with mild symptoms had higher RI than some patients with moderate symptoms, and some patients with moderate symptoms had higher RI than some patients with severe symptoms, we attribute this overlap to the following:

Cases with only enlarged median lobe. It is hypothesized that an enlargement of the median lobe may not impact RI value as it does not impose increased resistance to capsular arteries. The association of intravesical prostatic protrusion (IPP) could add for a more precise diagnosis in this scenario [1]. There is some sort of selection bias. This group of age (55–70) mostly, will have cardiovascular risk factors placing further burdens on their prostatic blood flow. Prostate RI values are highly linked to overall metabolic syndrome and smoking in addition to BPH [10]. So, we recommend a study upon younger population in conjunction with cardiologists for assessing cardiovascular risk factors, thus excluding all factors than can influence RI other than pathology of BPH. IPSS questionnaire is sometimes a difficult task for the patient, and they tend to just complete it carelessly, this is due to many factors: poor vision in old age (which is the case of most patients with BPH), low level of education, or lack of interest.

Conclusion

RI can be used as a modality for assessing BPH patients and anticipating success of surgery. RI is a good indicator for degree of bladder outlet obstruction due to BPH, rather than other parameters as prostate volume, adenoma volume, residual volume, and PSA. Further research in this field will even allow the use of this modality to investigate other pathologies affecting the prostate and can be used also to evaluate the outcome of management.

Recommendation

We recommend a study upon younger population in conjunction with cardiologists for assessing cardiovascular risk factors like atherosclerosis, hyperlipdemia, and smoking. Thus excluding all factors than can influence RI other than pathology of BPH. Further studies in larger cohorts are required to validate the reliability of prostate capsular artery RI.

References

  1. Abdelwahab O, El-Barky E, Khalil MM, Kamar A (2012) Evaluation of the resistive index of prostatic blood flow in benign prostatic hyperplasia. International braz j urol 38: 255–257. [Crossref]
  2. Ahmet Tuncay Turgut, Esin Ölçücüoğlu, Pinar Koşar, Pinar Özdemir Geyik, Uğur Koşar, et al. (2007) et al. Power Doppler Ultrasonography of the Feeding Arteries of the Prostate Gland. Journal of Ultrasound in Medicine 26: 875–883.
  3. Yencilek E, Koyuncu H, Arslan D, Bastug Y (2014) The measurement of the prostatic Resistive Index is a reliable ultrasonographic tool to stratify symptoms of patients with benign prostatic hyperplasia. Medical Ultrasonography 16: 208–213. [Crossref]
  4. Ozden C, Gunay I, Deren T, Bulut S, Koparal S, et al. (2009) Effect of Doxazosin on prostatic resistive index in patients with benign prostate hyperplasia. Fırat Tıp Dergisi 14: 171–174.
  5. Tsuru N, Kurita Y, Masuda H, Suzuki K, Fujita K (2002) Role of Doppler ultrasound and resistive index in benign prostatic hypertrophy. International Journal of Urology 9: 427–430. [Crossref]
  6. Kojima M, Ochiai A, Naya Y, Okihara K, Ukimura O, et al. (2000) Doppler Resistive Index in Benign Prostatic Hyperplasia: Correlation with Ultrasonic Appearance of the Prostate and Infravesical Obstruction. European Urology 37: 436–442. [Crossref]
  7. Ayhan Karaköse, Turgut Alp, Numan Doğu Güner, Bekir Aras, Sabahattin Aydın (2010) The role of Doppler ultrasonography and resistive index in the diagnosis and treatment of benign prostate hyperplasia. TürkÜrolojiDergisi / Turkish Journal of Urology 36: 292–297.
  8. Kwon SY, Ryu JW1, Choi DH, Lee KS (2016) Clinical Significance of the Resistive Index of Prostatic Blood Flow According to Prostate Size in Benign Prostatic Hyperplasia. International Neurourology Journal 20: 75–80. [Crossref]
  9. Aldaqadossi HA, Elgamal SA, Saad M (2012) The value of measuring the prostatic resistive index vs. pressure-flow studies in the diagnosis of bladder outlet obstruction caused by benign prostatic hyperplasia. Arab Journal of Urology 10: 186–191. [Crossref]
  10. Baykam MM, Aktas BK, Bulut S, Ozden C, Deren T, et al. (2015) Association between prostatic resistive index and cardiovascular risk factors in patients with benign prostatic hyperplasia. The Kaohsiung Journal of Medical Sciences 31: 194–198. [Crossref]

The Introduction of Researches of Myofascial Release and Case Reports

Abstract

Myofascial release (MFR) is a technique for resolving fascial restriction; i.e., the fascia trapped with moderate pressure is continuously expanded to expand collagen fibers as well as fascial elastin fibers. In recent years fascia has increasingly been studied, as the roles and importance of fascia have become apparent. In many case reports pain and postural alignment have been designated as the outcome, and changes before and after MFR have been observed. Controlled studies have included a variety of researches for the presence or absence of the effects of MFR on patients with certain diseases, comparison of MFR with other techniques, and basic studies on the effects of MFR in healthy persons. It has been believed, however, that systematic reviews are of various quality levels because of the obscure content of intervention and insufficient exclusion of bias in spite of the favorable effects and the moderate quality of MFR techniques. The future task confronting us is thought to accumulate controlled studies, which will allow acquiring definite blinding and distinctly explaining fascial changes by detailed intervention methods.

Introduction

Myofascial release (MFR) is a technique for relieving fascial restriction; i.e., the fascia trapped with moderate pressure is expanded continuously, by which collagen fibers, as well as fascial elastin fibers, are expanded. Since MFR yields no any pain to the person treated by MFR without use of any specific tool, it can be used for every disease over all age groups; i.e., it is available for acute/chronic pain, restricted range of motion (ROM), conditioning in children and the aged, sports injury, and so on [1]. Some investigators have reported the origin of MFR. MFR is a fruit of soft tissue mobilization according to an American physical therapist, John F. Barnes [2], one of the Structural Integration (Rolfing®) techniques developed by an American biochemist, Ida P. Rolf [3], and a product of the technique developed by Thomas W. Myers [4], the author of “Anatomy Train”, who directly received training from Ida P. Rolf.

In recent years the roles and importance of fascia have become apparent, and at the same time fascia is being increasingly studied. Despite that MFR exerts the effects non-invasively on fascia via the superficial skin and fat layer, many MFR researches have designated changes in physical function, including changes in alignment and ROM, as the outcome. For this reason, the questions of whether fascia can be actually found or not and of how fascia changes remained. In recent years, however, imaging-out of fascia by an ultrasound imaging diagnostic device and observation of changes in the properties of fascia have become possible. This article introduces some previous researches for MFR with the author’s case reports. Self-MFR and foam roller MFR are excluded from the present study.

Previous Researches

Case reports

Barnes has reported treatment of a 35-year-old female patient who has suffered from thoracic outlet syndrome for 2 years. The 30-minute treatment including expansion of her upper limbs and MFR of the iliac muscle was conducted twice to three times a day for 2 weeks. Her pain was reduced, swing of her upper limbs during walking was normalized, kyphosis was improved, her body trunk and pelvis were restored to a median position, and the right-to-left load became even [5]. Le Bauer et al. have reported treatment of an 18-year-old female patient, who has suffered from bimodal scoliosis for 6 years. The 60-minute treatment including MFR involving her body trunk and expansion of her both lower limbs was conducted twice a day for 2 weeks. Postural alignment, X-ray images, pain, the condition with scale 22 based on the Scoliosis Research Society, and ROM of thoracolumbar rotation were markedly improved [6].

Martin has reported treatment of a female patient with diffuse systemic sclerosis. The treatment included 11 sessions of MFR involving the head and neck and 9 sessions of MFR involving her body trunk, and it took 60 minutes for each session. The treatment was conducted for 5 months, and symptoms of Raynaud’s phenomenon, thoracic mobility, and orificial distance were improved [7]. Walton has reported treatment of a 35-year-old female patient with primary Raynaud’s phenomenon. The 45-minute treatment including MFR of the region ranging from the neck to the dorsal surface of the chest and expansion of her upper limbs was conducted for 3 weeks. The duration and frequency of the appearance of Raynaud’s phenomenon and the severity of pain were decreased [8]. Many case reports have designated pain and postural alignment as the outcome and observed changes before and after MFR.

Controlled studies

Barnes et al. have divided 10 orthopedic outpatients into an MFR group of 6 patients who were treated with MFR [of the quadriceps muscle of thigh (QMT), iliopsoas muscle, and the contralateral iliopsoas muscle] for 10 minutes and a control group of 4 patients who were subjected only to lie on a bed for 10 minutes, and compared both groups concerning lateral tilt angle of the pelvis [the mean difference in the distance between the right and left anterior superior iliac spine (ASIS) and the central point at patient’s feet]. The difference in the distance was significantly reduced in MFR group, increasingly showing the symmetric form of the pelvis [9]. Takeda et al. have conducted MFR of the greater pectoral muscle and smaller pectoral muscle in 25 patients with retentive hemiplegia, and compared the angle of abduction of the shoulder on the affected side, speed and the degree of easiness of patients’ daily living lives, and 10-meter walking speed before and after MFR. They have reported the significant improvement in the abduction angle and the speed of the patients’ daily living lives [10]. Marszaiek has conducted MFR of the head, neck, upper limbs, and the upper body trunk in 40 patients who have undergone total laryngectomy. The esophageal pressure was significantly decreased after MFR, having led to easy training of esophageal phonation [11]. Some other reports have shown that MFR of the head and neck in patients with the forward head posture has induced the significant improvement in the craniospinal angle, neck disability index, and cervical ROM [12, 13] and that MFR of the body trunk involving the low back in low back pain patients has induced significant improvement in pain and the influence of low back pain on daily living activities [14–16].

Kain et al. have compared each ROM of flexion, extension, and abduction of the shoulder between an MFR group of 18 healthy subjects who underwent precordial MFR for 3 minutes and a hot pack group of 13 healthy subjects who underwent hot pack for 20 minutes. Both groups showed significantly increased ROM, compared to that before the implementation, except that only the flexion angle was significantly higher in the MFR group than in the hot pack group [17]. Henley et al. have compared heart rate on a tilt (50°) table, normalized ECG, and respiration rate between an MFR group of 17 healthy subjects who underwent MFR of the neck for 2 minutes and a pseudo-MFR group of 17 healthy subjects with their neck only touched by rater’s hands. Tachycardiac rate and normalized ECG were significantly increased in both groups, compared to those at rest, whereas the tachycardiac rate and the normalized ECG were lower in the MFR group than in the pseudo-MFR group [18].

Kuruma et al. have compared ROM of knee joint flexion, muscle stiffness, and reaction time among a QMT-MFR group of 10 healthy subjects who underwent MFR of the QMT for 8 minutes, a hamstrings (H)-MFR group of 10 healthy subjects who underwent MFR of H for 8 minutes, and a stretching group of 10 healthy subjects who underwent stretching of QMT. All groups significantly showed improvement in ROM, while reaction time was significantly reduced in the QMT-MFR and H-MFR groups [19]. Ichikawa et al. have compared muscle stiffness and the fascial transmission distance on ultrasonic images among an MFR group of 12 healthy subjects who underwent MFR of the lateral great muscle for 4 minutes, 10-min-hot-pack group of 12 healthy subjects who underwent hot pack for 10 minutes, and 20-min-hot-pack group of12 healthy subjects who underwent hot pack for 20 minutes. There were significant changes in muscle stiffness and the fascial transmission distance only in the MFR group [20].

We have compared angles of active and passive extension and elevation of lower limbs and muscle strength (extension/flexion of the knee joint) before intervention and for 6 days after intervention among an H-MFR group of 10 healthy subjects who underwent MFR of hamstrings (H), a QMT (re-education)-MFR group of 10 healthy subjects who underwent muscle re-education exercises of QMT (40 times at muscle strength of 40% of 1 repetition maximum) following MFR of H, and an H (re-education)-MFR group of 10 healthy subjects who underwent muscle re-education exercises of H following MFR of H. Improvements in the extension and elevation angles for the lower limbs and the muscle strength of knee flexion were much more in the H (re-education)-MFR group than in two other groups. There were also significant differences between those 6 days after and before the implementation. In the H-MFR group there were significant differences in the angle of extension and elevation of lower limbs and muscle strength of knee flexion between those for 4 days after and before MFR [21]. To investigate the fascial properties after MFR, we clarified intra-rater reliabilities [ICC (1, 1)] 4 days after measurements of superficial and deep fascial transmission distances on ultrasound images of lateral head of the gastrocnemius muscle by using an ultrasound imaging diagnostic device and measurement of muscle stiffness according to real-time tissue elastographic function (superficial layer: 0.89; deep layer: 0.98; muscle stiffness: 0.90) [22]. We compared ROM of ankle dorsal flexion, muscle strength of ankle plantar flexion, fascial transmission distance, and muscle stiffness before and after intervention and for 4 days after intervention between an MFR group of 17 healthy subjects who underwent MFR of the lateral head of gastrocnemius muscle for 3 minutes and a stretching group of 17 healthy subjects who underwent static stretching for 3 minutes. In both groups, ROM and fascial transmission distance were increased and muscle stiffness was decreased immediately after the intervention, compared to those before intervention. Immediately after the intervention muscle strength was increased in the MFR group and decreased in the stretching group, while ROM, muscle strength, and fascial transmission distance were increased and muscle stiffness was decreased 4 days after the intervention than those before the intervention only in the MFR group [23]. Thus, there have been a variety of controlled studies including comparative studies on the presence/absence of the effects of MFR on patients with certain diseases and between MFR and other techniques, as well as basic researches of the effects of MFR on healthy persons.

Systematic reviews

Yang et al. [24] have inspected 1329 references in the literature concerning chest physiotherapy for pneumonia in adults in 2010, which included 6 references of randomized controlled trials (434 subjects). As a result, it was revealed that osteopathic therapy including MFR allowed admission period and the duration required for intravascular and systemic antibiotic treatment having been decreased, although any symptom of pneumonia or X-ray finding was not improved [22]. Yuan et al. have investigated minutely 532 references in the literature concerning treatment for fibromyalgia in 2015, and 2 references about randomized trials of MFR (145 subjects) were included in meta-analysis. As a result, it was revealed that MFR had moderate evidence of its effects particularly on pain, anxiety, and depression [25]. McKenney et al. have examined closely 88 references in the literature to investigate the quality and reliability of MFR in 2013, and 10 references of randomized trials were included. Ajimsha et al. have also investigated 3 systematic reviews in 2019. The thus-described researchers’ studies have provided evidence of the favorable effects of MFR and the moderately technical quality, but according to them, it has various degrees of quality for the reason that the intervention contents are obscure and that bias is insufficiently removed. They have brought their researches to a conclusion by saying that individual systematic review will become a beginning toward future investigation of higher quality [26, 27].

Case reports

The author encountered 2 patients who acquired characteristic improvement as a result of MFR. These cases are introduced below. The first case was a male patient in his 50s, a physician, whose chief complaint was low back pain. When he tried to stand up after morning medical examination, he could not stand up because of low back pain. As for sites of low back pain, he had both lumbar regions, but the pain was particularly severe in the right region. He had no idea of any event by which low back pain was manifested in his recent daily activities. According to inquiries about his past history, he had right second metatarsal capital fracture 6 months ago. He has been unable to bear any load on the affected site and shown claudication because of pain for a while. At present, he had no pain in the right second metatarsal bone. He felt low back pain in getting-up and standing positions and during walking. Since he had pain when load was given to the affected site, evaluation was started with his feet on the assumption that the right second metatarsal capital fracture was responsible for low back pain. Subsequently, high-density regions were recognized in the right long extensor muscle of great toe, right anterior tibial muscle, lateral head of the right gastrocnemius muscle, right biceps muscle of thigh, right iliac muscle, bilateral lumbar iliocostal muscle, and bilateral lumbar quadrate muscles. Except for the lumbar quadrate muscles, it was considered that claudication to avoid using the second metatarsal bone resulted in the condition in which fascial dysfunction has spread along the anterior and posterior motion arrangement (referred to the concept of fascia and fascial approach) (Figure 1). Faced with this situation, we considered the feet as the cause of the condition, and we conducted MFR on each of the right long extensor muscle of great toe, right anterior tibial muscle, and lateral head of the right gastrocnemius muscle for 3 minutes. After MFR, low back pain was reduced from score 8 to score 3 based on the Numerical Rating Scale. When MFR was conducted on each of the bilateral lumbar iliocostal muscles for 2 minutes, low back pain disappeared and he felt no physical disorder at his low back. His subsequent course also appeared favorable.

IJOT 19 SI - 104_Yasuki Katsumata_F1

Figure 1. Fascia showing the ascending spread of high-density areas.

The second case was a male patient in his 80s, and diagnosed as having had left middle cerebral arteriosclerosis. Owing to (rt-PA) thrombolysis, paralysis was improved from complete paralysis to moderate right hemiplegia. It was improved even to mild paralysis by 3-week rehabilitation, and he acquired retentive self-supporting in a standing position and walking without support with light assistance. However, improvement of function of swallowing was worse than that of physical function. It was assumed from postural evaluation that anterior cephalic presentation and unbalance between the right and left postural alignments (effortive on the non-affected side) inhibited movements of the masticatory muscle and muscles of tongue. On this assumption, MFR of the suboccipital muscles, left sternocleidomastoid muscle, suprahyoid muscles, posterior region of neck, and upper fibers of left trapezius muscle, and expansion of the left upper limb were conducted for 40 minutes a day for 3 days. As a result, the anterior cephalic presentation was improved (Figure 2), the right and left postural alignments showed symmetric balance (Figure 3), and the swallowing function was also improved (Table 1).

IJOT 19 SI - 104_Yasuki Katsumata_F2

Figure 2. Postural alignment on the sagittal plane (rightward motion) before and after the treatment.

IJOT 19 SI - 104_Yasuki Katsumata_F3

Figure 3. Postural alignment on the frontal plane (ante-motion) before and after the treatment.

Table 1. Evaluation of the swallowing function before and after the treatment.

 

Before intervention

After intervention

Swallowing

Swallowed after several times

Swallowed after once or twice

The amount ingested

1/3 spoonful

a spoonful

Pharyngeal residue

(+)

(±)

Cough

(+) immediately after meals

(+) after some mouthfuls

Tongue protrusion

(-)

(+)

Conclusion

Establishment of evidence of the effects of MFR seems to be delayed, while approach to fascia is increasingly spreading along with the increasing recognized importance of fascia. The future task confronting us is thought to accumulate controlled studies, which will allow distinctly explaining fascial changes under the condition of definite blinding by detailed intervention methods.

References

  1. Takei H (2001) Myofascial Release. Rigakuryoho Kagaku. Apr: 103–107 (Japanese).
  2. Barnes JF (1990) How It Bagan Myofascial Release the search for excellence. Washington, USA: National Library of Medicine Pg No: 1–2.
  3. Yasushi F (2005) An Outline of Rolfing. Japanese Journal of Complementary and Alternative Medicine. Feb: 37–43(Japanese).
  4. Earls J, Myers TW (2010) An Introduction to Fascial Release Technique Fascial Release for Structural Balance Chichester, UKB: Lotus Publishing Pg No: 4–16.
  5. Barnes JF (1996) Myofascial release in treatment of thoracic outlet syndrome. J Bodyw Mov Ther  Jan: 53–57.
  6. LeBauer A, Brtalik R, Stowe K (2008) The effect of myofascial release (MFR) on an adult with idiopathic scoliosis. J Bodyw Mov Ther 12: 356–363. [crossref] 
  7. Martin MM (2008) Effects of the myofascial release in diffuse systemic sclerosis. J Bodyw Mov Ther Apr: 1–9.
  8. Walton A (2008) Efficacy of myofascial release techniques in the treatment of primary Raynaud’s phenomenon. J Bodyw Mov Ther Pg No: 274–280.
  9. Barnes MF, Gronlund RT, Little MF, Personius WJ (1997) J Bodyw Mov Ther. Oct: 289–296.
  10. Takeda S, Takahashi K, Kawasaki T, Kaneko T, et al. (2005) Ijikinouso cchuukatamahi kanja Mahisoku kyoubukingunn henokinnmakuriri- sunoouyou [abstract] Rigakuryouhougaku  32(Suppl 2): ID-868 (Japanese).
  11. Marszaiek S (2009) Estimation of influence of myofascial release techniques on esophageal pressure in patients after total laryngectomy. Eur Arch Otorhinolaryngol May: 1305–1308.
  12. Kim J, Kim S, Shim J, Kim H (2018) Effects of McKenzie exercise, Kinesio taping, and myofascial release on the forward head posture. J Phys Ther Sci Pg No: 1103–1107.
  13. Aggarwal A, Shete AV, Palekar TJ (2018) Efficacy of Suboccipital and Sternocleidomastoid Release Technique in Forward Head Posture Patients With Neck Pain: A Randomized Control Trial. Int J Physiother Pg No: 149–155.
  14. Tozzi P1, Bongiorno D, Vitturini C (2011) Fascial release effects on patients with non-specific cervical or lumbar pain. J Bodyw Mov Ther 15: 405–416. [crossref] 
  15. Ajimsha MS, Daniel B, Chithra S (2014) Effectiveness of myofascial release in the management of chronic low back pain in nursing professionals. J Bodyw Mov Ther 273–281.
  16. Arguisuelas MD, Lison JF, Domenech-Fernandez J, Martinez-Hurtado I (2019) Effects of myofascial release in erector spinae myoelectric activity and lumbar spine kinematics in non-specific chronic low back pain: Randomized controlled trial. Clin Biomech (Bristol, Avon) 27–33.
  17. Kain J, Martorello L, Swanson E, Sego S (2010) Comparison of an indirect tri-planar myofascial release (MFR) technique and a hot pack for increasing range of motion. J Bodyw Mov Ther 63–67.
  18. Henley CE, Ivins D, Mills M, Wen FK, et al. (2008) Osteopathic manipulative treatment and its relationship to autonomic nervous system activity as demonstrated by heart rate variability a repeated measures study. Osteopath Med Prim Care 2–7.
  19. Kuruma H, Takei H, Nitta O, Furukawa Y, et al. (2006) Kinmakuriri-su to sutorecchingu womochiita rigakuryouho ukouka no hikakukentou [abstract] Rigakuryouhougaku 2006; 34 (Suppl 2) ID-259 (Japanese).
  20.  Ichikawa K, Takei H, Usa H, Mitomo S, et al. (2015) Comparative analysis of ultrasound changes in the vastus lateralis muscle following myofascial release and thermotherapy: a pilot study. J Bodyw Mov Ther 327–336.
  21. Katsumata Y, Takei H, Hori T, Hayashi H (2016) Influences of muscle re-education exercises for myofascial extensibility and muscle strength after myofascial release. Rigakuryoho Kagaku 99–106.
  22. Katsumata Y, Takei H, Hayashi H, Ichikawa K (2017) Intra- and Inter-rater Reliabilities of measurements of fascial displacement and muscle stiffness by using ultrasound images. Rigakuryoho Kagaku 215–220 (Japanese).
  23. Katsumata Y, Takei H, Sasaki Y, Watanabe K (2019) Ultrasonographic changes in fascial properties over time after myofascial release. Integr J Orthop Traumato 1–6.
  24. Yang M, Yuping Y, Yin X, Wang BY, et al. (2010) Chest physiotherapy for pneumonia in adults. Cochrane Database Syst Rev CD006338.
  25. Yuan SL, Matsutani LA, Marques AP (2015) Effectiveness of different styles of massage therapy in fibromyalgia: a systematic review and meta-analysis. Man Ther 257–264.
  26. McKenney K, Elder AS, Elder C, Hutchins A (2013) Myofascial release as a treatment for orthopaedic conditions: a systematic review. J Athl Train 522–527.
  27. Ajimsha MS, Shenoy PD (2019) Improving the quality of myofascial release research – A critical appraisal of systematic reviews. J Bodyw Mov Ther 561–567.

Fascial Manipulation® for Trigger Finger (Snapping Finger)

Summary

A 41-year-old female patient, who developed trigger finger after she repeated cervical sprain several times, underwent myofascial evaluation and treatment, which were based on Fascial Manipulation®, in addition to evaluation by physical therapy, and favorable results were obtained. She showed symptoms of trigger finger, which suddenly occurred, for 5 months. Palliative treatment was the only method for the symptoms, and they did not reach improvement. The site and tissue, which are responsible for the condition, were specified first on evaluation by physical therapy. Subsequently addition of exercise test and palpation test for fascia in view of a past history and timeline may appropriately approach to problems with high-density sites and force transmission of the fascia related to pain.

Introduction

Many cases of trigger finger have been believed to be idiopathic, and the symptoms occur spontaneously. Some reports have indicated the relevance to occupational or repetitive activities [1]. For the pathogeneses, much attention was paid to specification of sites of myofascial dysfunction in view of a past history and living activity level and routes of force transmission, as well as conventional tests and evaluation. This article describes favorable results of the myofascial evaluation and treatment, which were based on Fascial Manipulation® (FM®) and conducted in addition to evaluation by physical therapy, in a patient who developed trigger finger after she repeated cervical sprain several times.

Roles of fasciae

Fascia has been explained at the International Conference of Scientific Research of Fascia, as follows: “Fascia, a soft tissue constituent of the connective tissue system all over the human body, forms a 3-D matrix in the whole body to support structures “[2]. Fascia spread over all organs, muscles, bones, and nerve fibers to cover them. The definition of fascia includes aponeurosis, ligament, tendon, retinaculum, articular capsule, capsules of organs and vessels, epineurium, meninges, periosteum, and intra- and intermuscular fibers of all fasciae. All of them indicate that fasciae have important roles in muscular biomechanics, coordination of muscular peripheral movements, and maintenance of proprioceptor and postures.

Some muscle fibers of epimysium enter the deep fascia; i.e., 37% of muscle origins and insertions enter the deep fascia and intermuscular septum (myofascial expansion) without insertion and the inserted tendon [3]. When fascial dysfunction occurs, muscle spindle and nociceptor are stimulated, spreading along the fascial arrangement via the deep fascia. For instance, aponeurotic fasciae cover the whole muscles of the upper limb, and collagen fiber bundles are arranged in different directions in the aponeurotic fasciae. The thoracic muscles receive tension at a proximal site by insertion of various fasciae, enabling to slide between them and inferior muscles. The brachial fasciae are connected at a proximal site to axillary fascia, greater pectoral fascia, deltoid fascia, and dorsolateral fascia, while they are connected to antebrachial fascia at a distal site. The mediolateral intermuscular septum is originated from the brachial fascia, by which the upper arm is divided into the front and the rear parts as segments. At the elbow the brachial fascia is reinforced by the anterior and rear retinacula, and the anterior retinaculum is composed of the brachial biceps aponeurosis. The brachial biceps aponeurotic expansion branches off two directions. In one direction a fiber bundle extends like a bow obliquely and medially below and binds at the antebrachial fascia. Inside the elbow many muscle fibers of the round pronator muscle and radial carpal flexor are inserted into the antebrachial fascia from the inside. In the other direction collagen fiber bundles are running in parallel to a median line of the forearm in a longitudinal direction. This fibrous expansion reaches the antebrachial fascia between the radial carpal flexor and the humeroradial muscle. Therefore, when the brachial biceps (muscle) tendon is extended at a proximal site, two force lines appear in a medial direction corresponding to the coved fibers and in a direction longitudinally running along the central part of the forearm.

On movements of the upper limbs in various directions, fascial expansion activates fascial proprioceptor with a specific moving pattern and extends a specific site of the brachial fascia, connecting different sites to transmit force. Owing to the relationship between the muscle and fascia coordinative movement to the periphery is realized by performance of movement in a correct direction and correct recognition [2, 4].

Fascia has a role in enhancement of muscle sliding. There is hyaluronic acid in loose connective tissue between deep fascial layers and between epimysium and endomysium, which acts as a lubricant [5]. When hyaluronic acid aggregation is induced by trauma, overuse, etc., fascial layer sliding is restricted. Contraction of the epimysium causes tendon extension due to high density of epimysium, and the extension stimulates the articular receptor to lead to its excitement and pain around the joint. When the body has pain, it responds to the pain with secondary compensation by a posture to avoid the pain. The change in base tension due to the compensation will be controlled by up-and-down tension on the competitive or ipsilateral side, leading to increased complication of the symptoms [6].

FM®

The subjects of FM® treatment include the point [referred to by Centre of Coordination (CC)] on the epimysium, to which one-way muscle strength converges, and the point [referred to by Centre of Fusion (CF)], to which force of adjacent two deep fascia (aponeurotic fascia) units converges. The body is divided into 14 segments, and a functional unit related to movement in each direction is called as fascial unit. All the segments include 6 CC points. There are 6 directions of movement: Sagittal plane (antemotion: AN and retromotion: RE); frontal plane (lateromotion: LA and mediomotion: ME); and horizontal plane (extrarotation: ER and intrarotation: IR). Each fascial unit is designated from the movement direction and segment. For example, the fascial unit of anterior movement of CU (elbow) is designated as AN-CU. There are 4 directions of movement of CF: Anterio-lateral (Ante-Latero: AN-LA); anterior-medial (Ante-Medio: AN-ME); retrolateral (Retro-Latero: RE-LA); and retromedial (Retro-Medio: RE-ME) [6,7]. CC forms the one-way continuous arrangement (called as fascial arrangement) associated with movement direction along the sagittal, frontal, and horizontal planes [8]. For example, the facial arrangement of anterior movement of the upper limbs is composed of 5 fascial units, i.e., AN-SC (scapula), AN-HU (upper arm), AN-CU, AN-CA (carpus), and AN-DI (finger), and anterior movement of the upper limbs is induced by the arrangement. CF has a fascial diagonal line, which appears on a diagonal line of fascial arrangement, and a fascial spiral, which integrates articular elements with retinaculum to influence wide-range pain. It comes to be important for treatment which arrangement has a problem [6, 7].

Pathogeneses of Trigger Finger (Snapping Finger)

Trigger finger is tenosynovitis of the flexor tendon due to imbalance between the tendon sheath and the flexor tendon passing the sheath. Transmission disorder occurs in the tendon sheath to lead to pain, swelling, and heat sensation of fingers. It has been reported that thickening of the tendon sheath, ligamentous intrathecal narrowing, edematous enlargement of the tendon itself, and so on are responsible for these conditions [9]. The augmentation of the symptoms early in the morning and amelioration of the symptoms by day are frequently observed. When they advance, a snapping phenomenon develops, and it may ultimately result in secondary contracture of the Proximal Inter Phalangeal (PIP) joint. The symptoms also frequently appear in a plurality of fingers. It has been believed that the phenomenon is one of the most common causes of hand pain in adults. It has also been reported that the prevalence is ca. 2% of the general population, and tends to be high in women in their fifties or sixties. The prevalence in women in the later stages of pregnancy is also high, and the condition is also characterized by its frequent occurrence due to overuse of hand and as sports injury. It frequently occurs in patients with diabetes, rheumatoid arthritis, or those under the conditions such as amyloidosis, in which systemic accumulation of proteins occurs. As for the treatment, some investigators have reported evidence of moderate efficacy of conservative intervention including the short-term use of Non-Steroidal Anti-Inflammatory drug (NSAID) [10]. The orthotic treatment has also been widespread [11]. In case of conservative therapy, surgical treatment may also be selected when any improvement is not achieved by conservative therapy.

Treatment case

1. General information

A patient is a 41-year-old woman, housewife.

The chief complaints included flexion contracture of and resting pain in the left thumb MP joint and thumb movement pain, and she grasped with difficulty because of pain.

Approximately 5 months ago she suddenly had left thumb pain and restricted Range of Motion (ROM) at the time of rising from her bed. In the early stage the pain was gradually reduced by day, but in the next morning she repeated pain and restricted ROM. The pain gradually augmented even by day. She visited a hospital, and received intrathecal steroid injection with a diagnosis of trigger finger. Even so, the symptoms were not improved. Subsequently she had an attempt to receive acupuncture as well, but the pain augmented. Her left thenar swelling also appeared, and she could do daily living activities (ADL), including clothespin pinching, taking out coins, grasping dish and mobile phone, etc., with difficulty. Thus, she came to interfere with the whole range of housework.

Diagnosis: Trigger finger (snapping finger)

Past history:

20 years of age: Cervical sprain-due to numbness in the region ranging from neck to left hand (traffic accident)

25 years of age: Surgery for right inguinal hernia

30 years of age: Cervical sprain-due to numbness in the region ranging from neck to left hand (traffic accident). Treated by cervical collar fixation

36 years of age: Cervical sprain-due to numbness in the region ranging from neck to both hands (traffic accident)

38 years of age: Right 5th metatarsal fracture

39 years of age: Cervical sprain (a violent fall)

In her late thirties she repeated pain around the scapula once or twice a year.

41 years of age: Lt Thumb trigger finger (snapping finger)

2. Evaluation by physical therapy

Pain: Resting pain (+), movement pain (+), numbness (-)

Active movement: ROM restriction in all directions of left thumb CM joint, in association with pain with score 8 based on the Numerical Rating Scale (NRS).

Passive movement: ROM restriction in all directions of left thumb CM joint, in association with NRS 8 pain.

Neurological test: Various neurological tests (-)

End feel: Empty

Joint play test: Hypermobility of C4th/5th and 5th/6th; low mobility of TH1st/2nd.

Muscle tightness: Brachioradial muscle, long palmar muscle, round pronator muscle, biceps muscle of arm, scalenus, and smaller pectoral muscle.

Observation of posture: Round back and forward head.

Observation of motion: Difficult movements of grasping and pinching.

3. Hypothesis

This patient developed numbness in her both upper limbs after she sustained cervical sprain several times. Since she had a past history of cervical collar fixation, her cervical vertebrae were examined. Various neurological tests are negative at present. She repeated cervical sprain, and had the imbalanced trunk because of coexistence of hypermobility of the cervical vertebrae with low mobility of the thoracic vertebrae. The patient may have been forced to have compensation for various postures under the situation with her unstable neck. It was further considered that the poor alignment accelerated excessive tension of her neck and chest to have led to tension stress to her left thumb through fascial arrangement and expansion from the trunk to the upper limbs. On the hypothesis that the stress spread from the cervicothoracic vertebrae downward, fascia was evaluated.

4. Palpation test [High density level (*~***)]: Comparative palpation test was conducted in TH (thorax), SC, and CA. LT LA-CA***, Bi LA-TH***, Lt LA-SC**, Rt LA-CL (neck)**, Lt ME-CA**, and Lt ME-CU**.

Palpation test revealed high density at the above-described sites, indicating remarkable areas of high density on the frontal plane arrangement.

5. Treatment

First treatment: Lt LA-CA (Figure 1), Lt LA-CU, Lt LA-DI (Figure 2), Lt ME-DI (Figure 3), and Lt ME-CA (Figure 4) (++).

IJOT 19 SI - 103_Atushi Yoshida_F1

Figure 1. Lt LA-CA.

IJOT 19 SI - 103_Atushi Yoshida_F2

Figure 2. Lt LA-DI.

IJOT 19 SI - 103_Atushi Yoshida_F3

Figure 3. Lt ME-DI.

IJOT 19 SI - 103_Atushi Yoshida_F4

Figure 4. Lt ME-CA.

Second treatment: Lt LA-CA, Lt LA-SC (Figure 5), Rt LA-CL, Lt ME-CU, and Bi LA-TH (Figure 6) (+++).

IJOT 19 SI - 103_Atushi Yoshida_F5

Figure 5. Lt LA-SC.  

IJOT 19 SI - 103_Atushi Yoshida_F6

Figure 6. Lt LA-TH.

6. Treatment results

Although pain on grasping movement was reduced and ROM was improved after the first treatment, she complained of tension on her neck and upper back. One week later she received the second treatment, and pain on pinching movement, restricted ROM, and a sensation of tension on her upper back disappeared.

Discussion

The patient repeated cervical sprain, and had numbness in the region ranging from her neck to fingers. However, the region was not consistent with the dermatome of the C4th/5thor 5th/6th, which showed cervical hypermobility, and the site of numbness varied day by day. The patient’s condition repeated remission and exacerbation. Her life in such a situation is presumed to have caused various compensatory postures and activities. One of these causes is fascial compensation. Excessive tension of her trunk, which is originated from cervical instability, is considered to have received stress through fascial expansion to the hand along the arrangement of fascial connection. For this reason arrangement of fascial balance between the proximal and distal positions may have led to reduction in symptoms by intervention along the arrangement.

Conclusion

This article described the importance of evaluation and treatment with FM® from a musculofascial viewpoint for a patient who developed trigger finger after she repeated cervical sprain several times.

It has been believed that the occurrence of trigger finger is idiopathic. The symptoms appear spontaneously and have correlation with occupational or repetitive activities. The condition shows compensatory movements due to fascial dysfunction very frequently. Not only palliative treatment of the present symptoms but also specification of the causative sites and tissue by physical therapeutic evaluation may make an appropriate approach possible to resolve problems with the high-density site of pain and force transmission by addition of movement test and precise palpation test for fascia in view of a past history and the timeline. It is further important for trigger finger patient to do exercise for correction of compensatory movements after improvement in fascial sliding and the high-density site and to advance the movement to functional movement and to ADL movement.

References

  1. ……………………………
  2. Atsushi Yoshida (2019) The interaction between muscle and fascia (myofascial chain).  Spine & Spinal Cord. 32: 301–306.
  3. …………….
  4. Stecco C (2018) Atlas of Functional Anatomy of Fascial System.  Hitoshi Takei (Tr.). Ishiyaku Publishers, Inc. : 234–291.
  5. Hitoshi Takei (2014) Expansion of Systemic and Therapeutic Technique.  H. Takei, et al. (Ed.). KYODO ISHO SHUPPAN CO., LTD., Tokyo.
  6. Atsushi Yoshida (2015) Practical approach to muscle and fascia (Special Issue: Manipulative physical therapy for sports injury). The Journal of Clinical Sports Medicine. 32: 1000–1004.
  7. Stecco L et al (2011) Fascial Manipulation—Theory Edition. H. Takei (Tr.) Ishiyaku Publishers, Inc., Tokyo.
  8. Schleip et al (2015) Membrane and Fascia. Up-to-date knowledges and therapeutical approach. H. Takei (Tr.), Ishiyaku Publishers, Inc., Tokyo, 343–349.
  9. Misako Nishimori: Pathological characteristics of tenosynovitis of the flexor tendon (trigger finger) on ultrasonic images of the joint.  Japanese Journal of Medical Ultrasound Technology. 38: 2013.
  10. ……………….
  11. ………………..

Treatment for low back pain using Fascial Manipulation

Introduction

Fascial Manipulation® (FM®), a modality of manipulative physical therapy originated with an Italian physical therapist, Luigi Stecco, is classified roughly into two types, i.e., FM® for musculoskeletal dysfunction and FM® for internal dysfunction.  In the FM® for musculoskeletal dysfunction, a route to fascial compensation is revealed from results of inquiries, exercise test, and palpation test, and then points of Center of Coordination (CC) and Center of Fusion (CF), which are associated with the compensation, are treated.  In general, FM® is therapeutically designed to recover the feature of sliding of the deep fascia and to improve patient’s pain, Range of Motion (ROM), and muscle strength [1,2]. Focusing on low back pain, which physical therapists and physicians frequently encounter and treat in clinical settings, practical cases of FM® for musculoskeletal dysfunction are mentioned through 2 case reports in this article.

Practical cases of FM®

Case 1 – Ascending Fascial Compensation

General information

A 32-year-old woman, a care worker, has started playing badminton since her age of 10 years.  At present she plays badminton about once a month.  The physician who examined the patient made a diagnosis of myofascial low back pain, as any distinct finding on X-ray or MRI image was observed, and treated the patient by physical therapy.

Inquiries

The chief complaint of the patient was left low back pain (at the level of the 4th-5th lumbar vertebrae).  She had the pain 6 months ago without manifestation by any overt symptom.  It was caused by the long-time standing position and assistance for transfer activities during the work.  She had no pain in her sitting or lying position.  The most severe pain showed score 7 based on the Numerical Rating Scale (NRS). The patient has always been feeling physical disorder at her medial left scapula since 3 months ago (NRS: 1-2).

Inquiries about past histories revealed that the patient had fracture of the distal end of the right radius one year ago and received the 4-week treatment by plaster fixation.  She had pain in the lateral region of the left elbow joint 10 years ago.  The longest past history was left ankle joint inversion sprain 17 years ago.  It was treated by plaster fixation for 3 weeks, and it needed 4 months to have fully recovered. The patient had no dysesthesia at any terminal point (head, fingers, or toes), surgical history, or non-contributory internal past history. 

Hypothesis

In FM® a hypothesis is built up regarding a route to fascial compensation from temporal/spatial viewpoints on the basis of the results of inquiries [1]. Figure 1 shows a timeline of information, which was collected on inquiries about the chief complaint (the most severe pain at present), its associated pain, and past histories of he patient.  Figure 2 shows a body chart including the same information as that in Figure 1.

IJOT 19 SI - 102_Daisuke Ogawa_F1

Figure 1. A timeline (case 1).

IJOT 19 SI - 102_Daisuke Ogawa_F2

Figure 2. A body chart (case 1).

Several hypotheses can be built up about the route to fascial compensation from Figures 1 and 2.  When the occurrence of low back pain as chief complaint in a standing position is taken into consideration, however, insufficient sliding of the deep fascia may have been induced by long-term plaster fixation of the left ankle during the treatment of ankle inversion sprain [1], probably leading to the ascending fascial compensation and left low back pain in the patient.

Evaluation by the therapist

(1) Exercise test

On the basis of the above-mentioned hypothesis, two segments, i.e., pelvic girdle (PV) and ankle joint (TA), were selected for exercise test.  As a result, the same type of pain (NRS: 6) as the chief complaint, was induced to PV by pelvic anterior tilt movement in a standing position, while no marked finding was observed in TA. 

(2) Palpation test

The segments selected first for palpation test were PV, i.e., segment of the chief complaint, TA, i.e., the origin of the fascial compensation, and the hip joint (CX) localized between the PV and TA segments.  As for these segments, all CC points (anterior, rearward, inward, outward, internal rotation, and external rotation) were palpated. As a result of palpation test for CC, there was no difference in the number of the points at which findings of high density were observed, or the degree of high density among sagittal planes (anterior/rearward), frontal planes (inward/outward), and horizontal planes (internal rotation/external rotation), suggesting that fascial diagonal or fascial spiral, rather than fascial arrangement, is involved with fascial compensation.  Therefore, palpation test for CF points of the above-mentioned three segments was conducted, revealing that CF of left RE-LA-PV1 (Figure 3) showed a large area of high density and had remarkable pain associated with irradiating pain.  As other findings, left RE-LA-TA2 and left Re-LA-CX showed moderately high density. 

IJOT 19 SI - 102_Daisuke Ogawa_F3

Figure 3. Palpation and treatment for RE-LA-PV1 CF.

It was considered from the results of palpation test for the PV, TA, and CX that a left RE-LA diagonal or a left AN-ME spiral was involved with the patient’s chief complaint.  Faced with this situation, CF points were palpated at RE-LA and AN-ME of segments of toes (PE) and knee joint (GE) on the left side and low back (LU), and thorax (TH) on both sides.  As a result, left RE-LA-TH showed findings of a large area of high density, and left RE-LA-PE3 and RE-LA-LU on both sides showed findings of moderately high density.  It was judged from these findings that a left RE-LA diagonal was mostly involved with the patient’s chief complaint.  Then, the patient was treated based on the evaluation. 

Treatment

In FM® the CC/CF points treated are selected, and routes to fascial compensation are taken into consideration even on determining the treatment order [1, 2].  In general, since CC/CF points of segments with the chief complaint frequently show serious pain, the treatment rarely starts with the segments. In this patient the treatment started with RE-LA-PE3 (Figure 4) and RE-LA-TA2 (Figure 5), which were localized at the left ankle joint, i.e., the estimated origin of fascial compensation.  As a result of the judgment of the efficacy of the treatment of these CF points from the exercise test results, pain on the pelvic anterior tilt movement was reduced to 50% of that before the treatment.  Consequently, the hypothesis built up was judged to be valid, and the treatment of the RE-LA diagonal was advanced.  

IJOT 19 SI - 102_Daisuke Ogawa_F4

Figure 4. Palpation and treatment for RE-LA-PE3 CF.

IJOT 19 SI - 102_Daisuke Ogawa_F5

Figure 5. Palpation and treatment for RE-LA-TA2 CF.

CF points of the left RE-LA-PE3 were treated first, followed by those of the left RE-LA-TA2, left RE-LA-TH, left RE-LA-LU, left RE-LA-CX, left RE-LA-PV, and right RE-LA-LU, in that order.  After all these CF points were treated, exercise test was conducted again.  As a result, the left low back pain on pelvic anterior tilt movement was fully resolved, and the patient had no pain on any other low back movement. 

Case 2 – Descending Fascial Compensation

General information

A 54-year-old man, a viola player, has been practicing the viola for 4-8 hours almost every day since he was a child.  According to his reminiscence, he has taken the same posture, i.e., putting the viola on his left shoulder and settling it with his neck, for a long time.  The physician who examined him recognized the narrow intervertebral space of L3/4 and L4/5 on X-ray images, made a diagnosis of lumbar disc disease, and treated the patient by physical therapy. 

Inquiries

The chief complaint of the patient was left low back pain (at the level of the 1st-3rd lumbar vertebrae).  He had the pain 6 years ago without manifestation by any overt symptom.  He had the pain particularly during getting up at the time of rising from his bed and in a long-time sitting position.  The most severe pain showed score 5 based on NRS. 

The patient has been suffering from left shoulder pain (NRS: 4) since 7 years ago, as well as the left low back pain. Inquiries about past histories revealed that the patient had left elbow joint pain 10 years ago, right elbow joint pain 12 years ago, and neck pain 20 years ago.  He had no past history of either lower extremity. He had no headache or numbness in any finger/toe.  He had no surgical history or noncontributory internal past history.

Hypothesis

Figure 6 shows a timeline of information, which was collected on inquiries about the chief complaint, its associated pain, and past histories of the patient.  Figure 7 shows a body chart including the same information as that in Figure 6. In this patient, his past histories were restricted to his upper body, and he had low back pain as the chief complaint in such an occasion as that without body weight bearing on lower extremities; it occurred during getting up and taking a sitting position for a long time.  Based on these situations, it was considered that the patient took a specific posture because of playing a viola and the overuse of the neck and upper extremities led to insufficient sliding of the deep fascia [1], which was responsible for the descending fascial compensation.

IJOT 19 SI - 102_Daisuke Ogawa_F6

Figure 6. A timeline (case 2).

IJOT 19 SI - 102_Daisuke Ogawa_F7

Figure 7. A body chart (case 2).

Evaluation by the therapist

(1) Exercise test

On the basis of the above-mentioned hypothesis, two segments, i.e., low back region (LU) and shoulder joint (HU), were selected for exercise test.  Consequently, low back pain was induced as a chief complaint by extension movement and right flexion movement of the low back region.  On the other hand, shoulder pain was induced to the same site as that where the patient felt pain during abduction movement of the left shoulder.  ROM on active movement was 120°.

(2) Palpation test

The segments selected first for palpation test were LU, i.e., the segment of chief complaint, the cervical vertebra (CL) involved with the longest past history, and HU, i.e., the segment of its associated pain.  As for these segments, all 6 CC points were palpated. As a result of palpation test, RE-CL on both sides (Figure 8) and left RE-LU (Figure 9) showed high-density areas, and had remarkable pain associated with irradiating pain.  As other findings, RE-HU and AN-LU on the left side and right RE-LU showed moderately high density.  When the frequency of high density was compared among the sagittal, frontal, and horizontal planes, it was highest on the sagittal planes.

IJOT 19 SI - 102_Daisuke Ogawa_F8

Figure 8. Palpation and treatment for RE-CL CC.

IJOT 19 SI - 102_Daisuke Ogawa_F9

Figure 9. Palpation and treatment for RE-LU CC.

From the results of palpation test for LU, CL, and HU, it was judged that left fascial arrangement on the sagittal plane was most involved with the patient’s chief complaint.  To find latent CC points, anterior (AN) and rearward (RE) CC points of segments of the shoulder girdle (SC), thorax (TH), and pelvis (PV) on both sides were palpated.  As a result, RE-TH, RE-SC, and AN-PV on the left side showed findings of moderately high density.

Treatment

The treatment started with the CC points of the RE-TH of the adjacent TH segment (Figure 10) because of remarkable tenderness in CC points of CL (RE-CL on both sides), i.e., the estimated origin of fascial compensation.  The exercise test following the treatment of the CC points revealed that the pain on low back extension and right low back flexion decreased to 50% of that before treatment.  Furthermore, the pain during shoulder abduction movement was reduced to 20% of that before treatment, and the restricted ROM was almost resolved.  From the results, the built-up hypothesis was judged to be valid, and treatment of the points on the sagittal planes was advanced. CC points of the left RE-TH were treated first, followed by those of the left RE-SC, RE-CL on both sides, left RE-HU, RE-LU on both sides, and left AN-LU, in that order.  When RE-CL points were palpated again after the treatment of the RE-SC, tenderness was reduced.  Therefore, they were included in the subjects of treatment. After all the above-mentioned CC points were treated, exercise test was implemented again.  As a result, the patient had no pain in his low back or shoulder during any movement.

IJOT 19 SI - 102_Daisuke Ogawa_F10

Figure 10. Palpation and treatment for RE-TH CC.

Conclusion

In this article the treatment using FM® for 2 patients with low back pain was surveyed.  They had left low back pain in common.  Particularly noteworthy is the fact that they were different from each other regarding the segments evaluated and the CC/CF points treated despite the feature common to them.  It is important for implementation of the treatment appropriate for the individual patient to collect information about pain at present and in the past as accurately as possible on inquiries.  On the occasion of information collection, specific attention should be paid to trauma, immobilization, and overuse, because they may lead to increased mucosity associated with aggregation (high density) of hyaluronic acid in the deep fascia ad to adversely influence the sliding system of the deep fascia [1].  It should also be mentioned that setting-up of the hypotheses about routes to fascial compensation on the basis of information collected on inquiries before the start of exercise test and palpation test was important for evaluation and treatment to proceed smoothly. This article did not describe any concrete method of exercise or palpation test or position of each point of CC/CF as space is limited.  The author would be obliged if the readers would be confirmed in FM®-related publications.

References

  1. Luigi Stecco, Antonio Stecco (2018) Fascial Manipulation Practical Part – First Level. Padova: Piccin Nuova Libraria S.p.A.
  2. Luigi Stecco, Carla Stecco (2019) Fascial Manipulation Practical Part – Second Level. Padova: Piccin Nuova Libraria S.p.A.

Manual Physiotherapy of Fascia -Introduction to Muscle Pain Relief, Myofascial Release, and Myofascial Manipulation

Fascial Dysfunction

Fascial degeneration can be caused by various factors (Table 1). Injury, disuse, lack of exercise due to circulatory failure, repetitive movement, and persistent poor posture can cause twisting of collagen fiber bundles and densification of the fascia, eventually leading to dehydration, hardening, and gelation of the fascial matrix. Aggregation of hyaluronic acid due to overuse and sustained muscle contraction can also limit myofascial gliding [1–3]. Generally, fascial dysfunction is caused by 1) densification of the fascia, 2) gelation of the fascial matrix, and 3) aggregation of hyaluronic acid. Fascial dysfunction reduces the gliding property and mobility of the fascia and all underlying tissues such as muscles, thereby limiting the maintenance of antigravity posture as well as smooth, functional, and efficient movements. Fascia is composed of the superficial fascia, deep fascia (aponeurotic fascia), epimysium, perimysium, and endomysium (Figure 1). The superficial fascia is in the subcutaneous tissue while the deep fascia covers muscles and connects the whole body in 14 different arrangements. The epimysium is a thin membrane that covers muscles; it connects to the perimysium to cover muscle bundles and to the endomysium to cover muscle fibers. Muscle fibers enter from the epimysium into the deep fascia and connect muscles across joints along 14 different arrangements (Figure 2). Because the epimysium, perimysium, and endomysium are connected to each other, muscle spindles attached to the endomysium are over activated, resulting in increased alpha-motor neuron excitability. Moreover, poor gliding of muscle fiber results in reduced muscular flexibility and output.

Table 1. Causes of fascial degeneration.

Mechanical

Acute: sprain, fractures, direct trauma

Chronic: excessive use, posture, work, sports

Physical

Temperature: heat, cold, wind, humidity

Mental strain: anguish, conflict, depression

Chemical

Nutrition: overnutrition, unbalance, addiction

Endocrine: hormones

Infection

Metabolism

Immobilization:

Development of abnormal small networks between collagen fibers

Alteration of collagen turnover mechanics (synthesis and degradation)

Cleavage of new collagen fibers

Change in quantity and quality of amorphous substance due to reduced water and glycosaminoglycans (GAGs)

IJOT 19 SI - 101_Hitoshi Takei_F1

Figure 1. Superficial fascia, deep fascia, epimysium, perimysium, endomysium

IJOT 19 SI - 101_Hitoshi Takei_F2

Figure 2. Muscle fibers enter from epimysium into the deep fascia

All traction forces exerted by muscle spindles on the endomysium converge simultaneously on the epimysium. In the simplest fascial unit, traction forces are transmitted along the same muscle and converge on the midpoint. Even in a more complex fascial unit formed by many different muscle motor units, these forces converge on a single point. This exact point on the epimysium where muscle force vectors converge is referred to as the Center of Coordination (CC). The point where vectors from two adjacent fascial units converge in a multiplanar, diagonal, composite motion method (anterior-lateral, anterior-medial, and rear-lateral, rear-medial) is referred to as the Center of Fusion (CF). The human body can be divided into 14 segments: scapula (sc), humerus (hu), elbow (cu), carpus (ca), and fingers (di), which constitute the upper limbs; head (cp), neck (cl), thorax (th), lumbar (lu), and pelvis (pv), which constitute the trunk; and hip (cx), knee (ge), talus (ta), and toes (pe), which constitute the lower limbs. Abbreviations for body segments are written in Latin [1,2] (Table 2).

Table 2. Body segments and terms used to represent their abbreviations.

Japanese

Latin

Latin

English

Anatomical parts included

手指

DI

Digiti

fingers

Intercarpal and interphalangeal joints, interosseous muscles of the hand

手根

CA

Carpus

wrist

Radiocarpal joint, extensor carpi radialis muscle, and extensor carpi ulnaris muscle

CU

Cubitus

elbow

Elbow joint, brachial fascia, biceps brachii muscle, triceps brachii muscle, brachioradial muscle

上腕

HU

Humerus

shoulder

Glenohumeral joint, deltoid muscle, biceps brachii muscle, supraspinous muscle

肩甲骨

SC

Scapula

scapula

Scapulothoracic and collar joints, trapezius muscle, serratus anterior muscle, rhomboideus muscle

頭部

CP

Caput

head

Skull and temporomandibular joint, eye muscles, temporalis muscle

Neck

CL

Collum

neck

Cervical spine, cervical fascia, iliocostalis cervicis muscle

胸郭

TH

Thorax

thorax

Thoracic spine, thoracolumbar joint, iliocostalis thoracis muscle, pectoral muscles

腰部

LU

Lumbi

lumbar

Lumbar spine, fascia, iliocostalis lumborum muscle, rectus abdominis muscle

骨盤

PV

Pelvi

pelvis

Sacroiliac joint, pubic symphysis, gluteal muscles, abdominal oblique muscle, rectus abdominis muscle

CX

Coxa

thigh

Hip joint, thigh, internal obturator muscle, pubic muscle, piriform muscle

GE

Genu

knee

Knee joint, femoral fascia, quadriceps femoris muscle, biceps femoris muscle

距骨

TA

Talus

ankle

Ankle joint (talocrural joint), lower leg fascia, gastrocnemius muscle, tibialis muscle

足趾

PE

Pes

foot

Intertiparal and interphalangeal joints, fascia, interosseous muscles of foot

There are 6 arrangements of CCs and 8 arrangements of CFs connecting these segments; thus, at least one of these 14 arrangements is affected in fascial dysfunction. The wavy collagen fibers of the epimysium and perimysium/endomysium connect to the tendon. When the tendon stimulates mechanoreceptors and nociceptors in a joint, the patient feels pain around the joint. The area where the patient feels or perceives pain is referred to as the Center of Perception (CP). Thus, therapists should be aware that the problem is not in the joint, but in the fascia. Successful treatment of fascial dysfunction relieves muscle/fascial pain and improves muscular output/flexibility and motor paralysis, resulting in improved exercise performance and activities of daily living.

Treatment of Fascial Dysfunction

Treatment for fascial dysfunction includes muscle pain relief as an indirect approach, and myofascial release and Fascial Manipulation® (FM) as direct approaches (Table 3). General assessments include current history of pain and concomitant pain, detailed history taking, alignment, Range of Motion (ROM) during exercise, muscle strength, abnormal sensation, and determination of the site of pain by palpation. Motion assessment (active/passive motion, stretching, resistance exercise) is then performed to determine whether there is any pain, ROM restriction, and/or muscle weakness. These assessments are combined with assessment of CCs and CFs by palpation to assess each segment and arrangement. Balance between agonist and antagonist muscles should also be considered when performing treatment.

Table 3. Therapeutic techniques for fascial dysfunction.

Procedure

Description

Muscle pain relief (MPR)

 

A myofascial treatment technique based on strain-counterstrain with some original modifications developed by Takei taking into account the fascial arrangement. This technique is effective for relieving pain in center of coordination (CC) on epimysium where vectors of muscle strength converge, by having a patient passively take an easy posture that is least painful and thereby causing the muscle spindle to be shortened passively to reduce or suppress inappropriate proprioceptive activity.

Myofascial release

 

This technique is intended to influence the fascial tissue all over the body and aims to release and unravel twisted fascia, change the viscosity of the fascial matrix, and adjust muscular/fascial balance, rather than simply stretching the fascia. Concepts of CC and fascial arrangement have further improved its therapeutic effect.

Fascial manipulation®

fascial manipulation®

Therapeutic targets are the CC and the center of fusion (CF), which is a wider region or a point where forces from multiple fascial units converge. For a densified CC, assessment and treatment should be performed along the fascial arrangement. Take sufficient time to rub each CC to correct the viscosity of matrix. Balance between agonist and antagonist muscles should also be taken into consideration.

CFs are involved in the coordination of complex movements. Assessment and treatment should be performed along the diagonal and spiral fascial lines. Apply lower pressure than for CCs to increase friction glide.

Muscle Pain Relief

Muscle Pain Relief (MPR) is a technique based on the therapeutic principle of Strain-Counterstrain (S-CS) with some original modifications. The technique was developed by Takei as a treatment for muscle/fascial pain, taking into account the fascial arrangement. S-CS, also referred to as ‘positional release,’ is a technique used to relieve pain by moving a body part affected by somatic dysfunction to an easy, less painful position to reduce or suppress the inappropriate proprioceptive activity responsible for the somatic dysfunction [4–12]. However, this technique does not involve whole-segment assessment/treatment along the anatomical fascial arrangement and focuses on treating muscle pain at each part. Moreover, in S-CS, “tender points” are considered to indicate somatic dysfunction, whereas the therapeutic targets of MPR are CCs on the epimysium where muscle force vectors converge. CCs are scientifically defined points based on the anatomical fascial arrangement [1,2].

Therapeutic Principle

A muscle spindle is located in parallel with the course of muscle fibers and senses the length of a muscle and the degree of change thereof [13,14]. In the middle and adjacent parts of the muscle spindle are sensory receptors known as the primary and secondary endings, which are innervated by group Ia and II sensory nerve fibers, respectively. The middle part of the muscle spindle is non-contractile and contains a receptor formed by annulo-spiral endings while both its ends form a contractile intrafusal muscle fiber that connects to an extrafusal muscle fiber. The intrafusal muscle fiber at both ends is innervated by gamma-motor neurons, which only innervate intrafusal muscle fibers, and beta-motor neurons that innervate both the extra- and intrafusal muscle fibers via a single axonal branch. Activation of these neurons causes both ends of the spindle to contract. This force is too weak to cause muscle tension but does increase the tension of the muscle spindle, thereby enhancing its sensitivity as a receptor. Excitation of the muscle spindle or gamma efferent fibers and subsequent muscle contraction results in increased impulse from the primary endings (group Ia fibers). Taking a joint position that allows this strained and activated muscle spindle to be shortened passively leads to decreased afferent firing from the primary endings and decreased alpha- and gamma-motor neuron firing in the central nervous system, resulting in relaxation of the extrafusal muscle fibers [4–8, 15–17].

General principles of treatment

Therapists with minimal experience should try various postures and identify those which are comfortable and uncomfortable based on feedback from the patient. The optimal posture should relieve pain. If pain/tenderness is successfully relieved, the patient will perceive it distinctly. As more experience is gained, it will be easier to feel changes with the fingertips and find an ideal posture. Therapists with more experience can tell that the ideal posture has been achieved even when the patient is still in pain. Even such patients are likely to have pain relief in about 30 seconds.

Actual treatment procedure

The MPR techniques are applied to CCs all over the body. In MPR, tender points in specific areas of the musculoskeletal system are identified and used for both diagnostic and therapeutic monitoring purposes. Once a CC is identified, it is necessary to find a position that can reduce both tenderness and the sensitivity of the tissue felt by the therapist. What is important here is to understand the action of each muscle three-dimensionally. It is important to find a position that can reduce pain three-dimensionally, taking into account composite factors such as flexion/extension, adduction/abduction, and external/internal rotation, rather than a position that simply shortens the muscle to the maximum extent. During treatment, keep the finger on the CC, but with a lighter touch than during diagnosis, to feel changes in the tissue. Feel with the fingertips that tension is released and ask the patient if pain/tenderness is released while pressing the point intermittently. Hold this posture for about 90–120 seconds. Then, slowly return the patient to the normal posture and perform reassessment. The following part of the section describes example treatment procedures for Antemotion (AN) of the upper limbs.

Example treatment cases

AN-SC: Pectoralis minor (Figure 3)

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Figure 3. MPR for AN-SC (pectoralis minor)

CC: Located inferior to the coracoid process and on the belly of the pectoralis minor and the coracoclavipectoral fascia.

CP: Pain in the shoulder, clavipectoral fascia, and acromioclavicular joint (CC and CP are close).

Treatment position: Supine position. The CC-side upper limb is placed across the front of the body. Scapula: Tilted anteriorly, rotated inferiorly, and depressed.

AN-CU: Biceps brachii (Figure 4)

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Figure 4. MPR for AN-CU (biceps brachii)

CC: Located just below the deltoid attachment and lateral to the belly of the biceps brachii.

CP: Pain at the anterior elbow, often at the epicondyle or distal biceps brachii tendon.

Treatment position: Supine position. Shoulder joint: Flexed to 90°, slightly to moderately abducted (or slightly to moderately adducted for the short head). Elbow: Moderately flexed. Forearm: Supinated.

Myofascial Release (MFR)

The purpose of MFR is to restore the normal function of muscles and other structures by reversing fascial twisting and to improve the mobility and stretchability between muscles or between muscles and other structures. The deepest fascial tissue forms a dural tube that wraps and supports the central nervous system and impaired dural mobility may limit the physiological movement of the skull and sacrum, causing various forms of dysfunction [18–21]. Because the fascial tissue forms a systemic network, MFR is often combined with cranio-sacral therapy [18]. Although similar therapeutic techniques have traditionally been applied in osteopathy, the MFR technique described here was systematically established by John F. Barnes et al. and is intended to release and unravel fascial twisting, rather than simply stretching the fascia [18,22–25]. Based on this technique, Takei et al. incorporated the concepts of CCs and fascial arrangement to establish their original therapeutic principles and techniques (Takei’s concept). This modification has made MFR a more effective technique.

What is “release”?

The objective of MFR, in particular, deep myofascial release, is to release densified and cross-linked collagen and elastin fibers and change the viscosity of the fascial matrix (intercellular material) from gel to sol. Barriers formed by the collagenous component cannot be corrected forcibly. Instead, applying gentle and sustained stretching and pressure can change the viscosity or density of the matrix and release the restriction caused by collagen fibers, resulting in a change in tissue length. First, apply pressure down to the deep fascia. Then, while keeping the pressure, apply gentle stretching motions to the site of fascial restriction, causing the elastic component to be stretched by the initial stretch applied to the fiber complex. The elastic element is slowly pulled like an elastic or spring coil until the hand applying the stretch stops at a tough barrier formed by the collagenous component. It should be kept in mind that elastin fibers have shape-memory properties and if stretching stops here, they return to their original length due to elasticity. Although barriers formed by the collagenous component cannot be corrected forcibly, applying sustained stretch can cause gradual stretching of collagen fibers due to the viscoelasticity of elastin fibers [26]. The stretched elastin fibers allow the tissue to regain its original shape and flexibility, resulting in restoration of the proper biomechanical alignment of the skeleton. Barriers formed by the collagenous fibers cannot be corrected forcibly. Lower load (gentle pressure) is more effective than higher load (fast, pressure applied) in changing the viscosity of the matrix [18]. Applying gentle and sustained stretching and pressure over 90 seconds to 3 minutes (5 minutes maximum) can change the viscosity or density of the matrix and release the restriction caused by collagen fibers, resulting in a change in the tissue length.

Precautions during release

After successful myofascial release, many patients experience an emotional change known as “somatoemotional release.” Just as emotional stress causes physical tension, physical stress causes emotional tension. Thus, releasing the fascial tissue from physical stress also results in emotional release [18,19,21].

Goal of myofascial release

The goal of myofascial release is to release fascial restriction and restore the overall musculoskeletal balance leading to a balanced posture. Acquisition of a structurally balanced posture will permit normalization of the center-of-gravity line and the symmetrical functioning of the entire musculoskeletal system. Applying gentle stretching to the fascial restriction elicits heat, which is a vasomotor response that increases blood flow in the affected area, improves lymph drainage, reorganizes the fascial tissue, and most importantly resets the sensory mechanism of soft-tissue proprioception [18,19–21]. This activity will reprogram the central nervous system, allowing a normal functional range of motion without eliciting old pain patterns [27]. The final goal is to achieve optimal function and performance with the least amount of energy. Because this technique is mild, MFR is applicable to various signs and symptoms. Systemic contraindications include malignant tumors/cancer, aneurysms, acute rheumatoid arthritis, and systemic/local infection; local contraindications include hematomas, open wounds, sutured wounds, and fracture sites during the healing process.

Actual treatment procedure

The three basic MFR techniques are 1) longitudinal release, 2) transverse release, and 3) pulling or traction (Fig. 5). Longitudinal release is a technique used to stretch the fascia while gently applying pressure so as to sandwich the CC, taking into account the fascial arrangement, and to keep stretching after feeling the restriction of elastin fibers until the restriction of collagen fibers is released and myofascial release is achieved. Transverse release is a technique used to release the fascia on the transverse plane while simultaneously feeling the ventral and dorsal connections of the deep fascia. Pulling is a technique that is used to easily move the upper or lower limbs in various directions while releasing the fascia distally. While performing release, the therapist should be relaxed and feel as if their palm or finger pulps were fused with the patient’s skin. While applying pressure down to the deep fascia while stretching the skin, the deep fascia is also stretched. In the initial phase of release, the elastic component is slowly pulled like a spring coil. Then, maintain the pressure for 90 seconds to 3 minutes (5 minutes maximum) to release the collagen component, causing the tissue to soften like melting butter. Pressure reaches the deeper layers gradually. The time required to complete the procedure will decrease with improved technique. Successful release will allow elastin, a constituent of elastin fiber, to help restore the original shape and flexibility of the tissue. The following part of this section describes representative treatment procedures for Lateromotion (LA) of the upper limbs.

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Figure 5. Three basic techniques for myofascial release

Representative treatment cases

LA-CX: Tensor Fascia Lata (Figure 6)

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Figure 6. Release of LA-CX (tensor fascia lata)

CC: Located inferior to the anterior superior iliac spine and on the tensor fascia lata.

CP: Pain in the lateral thigh around the tensor fascia lata. Numbness at a lower part of the lateral thigh.

Treatment position: Lateral position, with the lower leg placed forward and the upper leg placed slightly backward. Place your hands crossed over the CC (cross-hand technique) to apply pressure and stretch.

LA-TA: Extensor Digitorum Longus (EDL) (Figure 7)

CC: Located between the proximal one-third and middle one-third of the lower leg, anterior to the fibula and on the EDL. Another located on the peroneus tertius.

CP: Pain in the lateral ankle. Pain secondary to ankle sprain.

Treatment position: Lateral position. Apply pressure and stretch to the EDL at the middle one-third of the lower leg (slightly above the mid-point) and anterior to the fibula.

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Figure 7. Release of LA-TA (extensor digitorum longus)

Fascial Manipulation®

The therapeutic principle of FM consists of mechanical (movement – friction), physical (heat – inflammation) and chemical (metabolism – repair) elements. The therapeutic targets are CCs and CFs. CCs are located in the 6 fascial units that move various body segments in 3 spatial planes (anterior and rearward movements in sagittal plane, medial and lateral movements in frontal plane, and internal and external rotation in horizontal plane). CFs are involved in multiplanar composite movements on diagonal lines and spirals (anterior-lateral [AN-LA], anterior-medial [AN-ME], rear-lateral [RE-LA], and rear-medial [RE-ME]). Differences between CC and CF are shown in
table 4. FM is also effective in evaluating and treating the musculoskeletal system affecting internal dysfunction, including visceral, vascular, and glandular dysfunction; in treating sensory organs in the head, including the face; and in treating the superficial fascia for lymphatic/immunological, dermatological/thermoregulatory, fat/metabolism, and neurogenic/psychogenic disorders [28]. An alternative treatment approach for lymphatic/immunological, dermatological/thermoregulatory, fat/metabolism and neurogenic/psychogenic disorders is to divide each of the trunk, upper, and lower limbs into 4 areas (AN-LA, AN-ME, RE-LA, and RE-ME) and treat the superficial fascia in each area.

Table 4. Differences between center of coordination (CC) and center of fusion (CF)

CC

CF

Located on the muscle belly and coordinates fascial units through the epimysium, perimysium, and endomysium.

Located on the tendon and coordinates the motion method through the retinaculum and fascial spiral.

Located in body parts that correspond to the three spatial planes.

Located in the intermediate zone (diagonal line) between two planes near the joint.

Mobilized when force is required or when the muscle insertion into the fascia is tensioned (arranged).

Mobilized by retinacular tension applied either directly (via the tendon) or indirectly (via movement of the bone to which the retinaculum is attached).

Actual assessment procedure

Fascial dysfunction may occur on the fascial arrangements where fascial units in each segment involved in local pain are arranged on the frontal, sagittal, and horizontal planes (Figure 8); the fascial diagonal lines on these planes (Figure 9); and the fascial spirals involved in extensive pain (Figure 10). Motion assessment is performed to assess the entire bone-nerve-myofascial complex or individual fascial units instead of individual muscles, by moving each segment in a specific direction. Each CC is located slightly away from their corresponding CPs and pain is only detectable on assessment by palpation. Based on the results of motion and assessment by palpation, it is necessary to identify densified and degenerated fasciae, treat the fasciae to reverse fascial degeneration, and continue verifying hypotheses and results.

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Figure 8. Example fascial arrangement: Sagittal view of the fascial arrangement involved in backward movement of the lower limb (adapted from reference 1 with some modifications)

Center of coordination: IJOT 19 SI - 101_Hitoshi Takei_F8a  Center of perception (site of pain): IJOT 19 SI - 101_Hitoshi Takei_F8b

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Figure 9. Example diagonal lines: Centers of fusion (CFs) on rear-lateral diagonal lines2)

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Figure 10. Example fascial spiral: A RE-LA (rear-lateral) spiral originating from the rear lateral aspect of the hand and foot.

Actual treatment procedure

FM should be performed on a densified area that needs to be treated by applying deep pressure to the area (CC or CF) while applying friction for a sufficient length of time to generate heat. This heat helps correct the viscosity of the matrix and initiates inflammatory processes required for healing. This technique should be continued until fascial correction is achieved and pain resolves. Increased temperature promotes the gel-to-sol transition and results in a corrected fascial matrix. In general, the viscosity transition of a densified fascia can be achieved in several minutes. Sudden release of free nerve endings results in reduced densified loci, leading to improved motor coordination, normalized joint motion trajectory, and subsequent reduction of associated pain. This results in elimination of a fibronectin network that interferes with the functionality of CCs. Immediately after treatment, patients may perceive improvement in symptoms and local warmth around the treated area. With no swelling, they feel even better than before treatment. A small depression due to change in loose connective tissue may occur in this area. After 10 minutes, some patients may notice worsening of symptoms and local pain. This is due to increased blood flow to the area and swelling formed as a consequence of the exudation phase. FM prevents matrix binding to allow for a new orientation of fibroblasts. During several hours after the fascial inflammation phase, neutrophils appear following macrophages and are removed simultaneously with newly formed necrotic material. Myofibroblasts are activated and produce new type-III collagen fibers.

During the following 3 days, a small hematoma may appear at the treated area, which may worsen symptoms temporarily depending on predisposing factors. At this time, the use of anti-inflammatory compresses or medications should be avoided because they inhibit normal inflammatory reaction. Patients in good condition should also refrain from walking longer than usual or going shopping or to a fitness gym. By 5 days after treatment, reduced local pain, improved fascial tension balance, and resolution of symptoms and swelling should be observed. During the next 20 days, the initial type-III collagen fibers are gradually arranged along the traction line and are replaced by more stable type-I collagen fibers. It is important to inform patients in advance of the possibility of these reactions.

Example treatment cases

AN-GE: Lateral aspect of rectus femoris (Figure 11)

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Figure 11. Fascial manipulation on AN-GE (lateral aspect of rectus femoris)

CC: Located at half of the length of the thigh and on the vastus intermedius between the rectus femoris and vastus lateralis.

CP: Pain in the inguinal region and the medial thigh. Pain in the muscles attached to the pubic bone.

Treatment position: Supine. Apply pressure and friction with a knuckle or elbow placed on the fascia lata in the lateral aspect of the rectus femoris between the patella and the inguinal ligament.

RE-PV: Iliocostalis lumborum (Figure 12)

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Figure 12. Fascial manipulation on RE-PV (iliocostalis lumborum)

CC: Located at the L5 level and medial to the posterior superior iliac spine on the quadratus lumborum muscle originating from the iliolumbar ligament.

CP: Pain at a site medial to the sacrum, piercing in nature, may diffuse along the posterior thigh/lower leg.

Treatment position: Prone. Apply pressure and friction with the elbow placed between the fifth lumbar spine and the anterior superior iliac spine.

RE-LA-LU: Latissimus dorsi (Figure 13)

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Figure 13. Fascial mobilization on RE-LA-LU (latissimus dorsi)

CF: Located at the center of the latissimus dorsi at the costal attachment of the upper margin of the serratus posterior inferior and the iliocostalis.

CP: Back pain occurs on torsion, lateral bending, or extension.

Treatment position: Prone. Apply a lower pressure and a slightly broader friction than for CC treatment (fascial mobilization) to the center of the latissimus dorsi at the costal attachment of the upper margin of the serratus posterior inferior and the iliocostalis.

Three treatment techniques for fascial dysfunction were described. Of these, muscle pain relief is an indirect treatment technique and is less effective than others for physical improvement of fascial dysfunction. Still, causing no inflammatory reaction, this technique is effective for persons with low pain threshold, children, the elderly, and athletes scheduled to participate in an event on the same or following day. Myofascial release and FM are both direct treatment techniques, although the former is more effective for those people sensitive to pain and those athletes scheduled to participate in an event on the following day. FM is most likely to cause inflammatory reaction among these techniques, and therefore requires sufficient patient orientation and accurate assessment. Therapists should also be able to select the most suitable technique for each patient.

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