IACFS/ME conference abstracts (2014)

[Bob]

IACFS/ME conference abstracts (2014):
http://www.iacfsme.org/DesktopModules/DigitalDownload/2014Syllabus25.pdf

Some heavy-duty science in these abstracts. I'm reading through it slowly.

 

[taniaaust1]

Yeah that is way heavy going, Ive got part throu and Ive been going throu it reading only the results and conclusions areas of many of the studies (but reading a little bit more of something if it really got my attention). Im going to finish reading the rest of the study results another another day.

A couple of things got my attention, the bit in the childrens part mentioned many ME/CFS children had issues with milk protein (Ive been sure for ages my body is having an issue with milk protein at times, my sister who has ME/CFS seems to have an issue with milk protein too). Neither of my healthy sisters have issues with milk or any of my other family (only my nanna who has FM). So I can see a link there.

One part I think would get the attention thou of most here is the following.

S
ESSION: PUBLIC HEALTH RESEARCH - PART I

Session Chair: Lily Chu, M.D.
CFS/ME and fatiguing illnesses: differential diagnoses from a community-based sample.
Nicoletta Carlo-Stella MD, PhD , free professional, Pavia, Italy
Introduction
: ME/CFS when diagnosed in a clinical setting is considered to be an exclusionary diagnosis, and

scientific literature frequently cites the diseases characterised by fatigue, which should be taken into account
when considering a diagnosis of CFS/ME. However data on the frequency of making an alternative diagnosis in
patients with fatigue are scarce.
Materials and Methods
: 89 consecutive self-referred patients complaining of PENE (post-exertional neuroimmune

exhaustion) (1) were seen in a private practice specializing in CFS/ME from 2007 to 2012. A thorough work-up
including history, clinical examination, lab testing and imaging, when necessary were undertaken.
Results
: 31,4% of the patients were male; 68,6% were female. The ages ranged from 20 to 60 years of age. A

diagnosis of CFS/ME was confirmed in 36 patients (40%); however rheumatological diseases (43%), endocrine
disorders (5,6%), psychiatric diseases (5,6%), gastrointestinal diseases (4,5%), haematological cancer (2,2%) and
urological bladder cancer (1,1%) accounted for the remaining 60 % of diagnoses of patients complaining of fatigue.
Conclusions
: notwithstanding the fact that these patients were mostly self-referred and moreover through

information gathered through the internet and social networks, 40% of them were correctly diagnosed as having
CFS/ME. However 60% of the patients were not. This is in accordance with a recent paper on conducting a pilot
registry in Bibb County, Ga (2). Thus caution is warranted before making a final diagnosis of CFS/ME.

This gives much food for thought "self-referred patients complaining of PENE (post-exertional neuroimmune exhaustion)" Why did it turn out that 60% of them had other illnesses and not ME/CFS seeing they had PENE or thought they did.

Can we not trust at all that PENE helps define this illness??? or is it the case of many who have ME/CFS not really understanding what PENE is and saying they have it when they do not at all? I want to know how PENE was defined to these people who said they had it.

 

[Bob]

This gives much food for thought "self-referred patients complaining of PENE (post-exertional neuroimmune exhaustion)" Why did it turn out that 60% of them had other illnesses and not ME/CFS seeing they had PENE or thought they did.

Can we not trust at all that PENE helps define this illness??? or is it the case of many who have ME/CFS not really understanding what PENE is and saying they have it when they do not at all? I want to know how PENE was defined to these people who said they had it.

It's curious, isn't it Tania. Thanks for highlighting.

They had probably been reading up on ME/CFS and thought that the symptom of PEM/PENE fitted their health experiences. Perhaps they'd been misdiagnosed with ME/CFS by a primary care practitioner. I think that 'PEM' and 'PENE' might be interchangable here, in that 'PENE' might be the author's favoured term rather than the patients' own description.

The abstract mentions that 43% were re-diagnosed with rheumatological diseases. I've heard before that people with arthritis have post-exertional flare-ups, and experience fatigue, so perhaps it isn't surprising that they identified with 'PENE' or 'PEM', and not entirely surprising if they'd previously been misdiagnosed with ME/CFS by incompetent general practicioners.

To keep this thread on-topic, I've posted more about this in another thread, here:
http://forums.phoenixrising.me/index.php?threads/is-cdc-out-to-bury-pem.31292/page-8#post-487660

 

[Bob]

Just bumping this because there are some really interesting abstracts. It's worth having a flick through, if you're interested, as it hopefully gives a taste what's to come in terms of future publishing re ME/CFS. It's difficult to analyse many of the abstracts without the full information, but there seems to be some interesting research in the pipeline. I don't think there are any stand-out papers that look like they are going to give us answers in the immediate future but, combined, this seems to be quite a substantial body of work, with plenty of overlapping research looking at the same systems. It includes abstracts by some scientific big-hitters.

 

[Forbin]

As someone who was once apparently erroneously diagnosed with chronic ulcerative colitis several years following the onset of ME (the "chronic" ulcerative colitis simply vanished after a month of treatment with azulfidine), the study below caught my attention:

Basically, the research finds that the gut microbiome of ME/CFS patients shows a shift characteristic of inflammatory bowel diseases such as Crohn's disease and acute ulcerative colitis.

[My personal history makes me wonder if there is something going on in ME that is so close to chronic ulcerative colitis that it can "mimic" it well enough to fool an experienced gastroenterologist.]

Altered Gut Microbiome in ME/CFS Patients in Comparison to Healthy Controls
Maureen R. Hanson1, Ludovic Giloteaux1, Julia K. Goodrich2, Susan M. Levine1,3, and Ruth E. Ley1,2
1 Cornell University, Dept. of Molecular Biology and Genetics, Ithaca NY, 2 Cornell University, Dept. of Microbiology, Ithaca NY, 3 Private Practice, New York City

Objectives. As well as the symptoms of fatigue, pain, malaise, immune dysfunction and exercise intolerance, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is associated with a variety of gastrointestinal complaints. In order to investigate the possible basis of this comorbid condition, we undertook a study to determine whether the gut microbiome in a ME/CFS population from the New York City area differs from healthy individuals.

Methods. We characterized the gut microbiota of a cohort of 48 patients with ME/CFS and 36 healthy controls from the New York City region by sequencing amplicons of the V4 region of 16S rRNA genes using the Illumina platform. Of the ME/CFS subjects, average age was 50.6 ± 13.3, 38 were female and 10 were male, while of the controls, average age was 46.5 ± 9.7, 29 were female, 7 were male. All patients fulfilled the Fukuda criteria for diagnosis of CFS. Levels of markers of inflammation, i.e. lipopolysaccharide (LPS), soluble CD14 (sCD14) and lactoferrin (LF) levels were also determined in plasma samples using standard assays.

Results. We obtained an average of 140,000 (± 86,000) high quality reads per sample. In both cases and controls, the most represented phyla were Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Comparisons between cases and controls indicated a shift of diversity in the patient cohort. Statistical analysis revealed significant differences between groups, i.e. a reduction in members of the Bacteroidetes and an increase in members of the Firmicutes in the patient population, also reported in Crohn’s disease and acute ulcerative colitis. Specific species, including reduction of butyrate-producer Roseburia faecis (p = 0.001, q = 0.03) and increase of Ruminococcus spp. (p < 0.001, q = 0.004), were detected in subjects with ME/CFS. The amounts of LPS, sCD14 and LF in plasma in our cohort were not statistically different from controls and fell within normal ranges. Our data do not corroborate prior reports of significantly higher levels of Lactonifactor, Alistipes and Enterococci in the feces of patients.

Conclusion. Subjects with ME/CFS in our cohort have a shift in overall microbial composition in comparison to healthy donors, a finding also characteristic of patients with inflammatory bowel disease. Our analyses highlight the contrast between the distribution of anti-inflammatory species, such as Roseburia species, which are more prevalent in healthy individuals, and potentially pro-inflammatory Ruminococcaceae, which are associated with irritable bowel syndrome and found to be more frequent in ME/CFS cases. Despite the differences in gut microbiome, three inflammatory markers did not differ between patients and controls in plasma. Whether deliberate manipulation of the composition of the gut microbiome in ME/CFS patients may ameliorate symptoms in some patients remains to be investigated.

Maureen R. Hanson, Ph.D., Liberty Hyde Bailey Professor, Dept. of Molecular Biology and Genetics, Biotechnology Bldg., Ithaca, NY 14853 USA, mrh5@cornell.edu

 

[Tom Kindlon]

Thought this was interesting:

ME/CFS: Trauma in the Context of Social Institutions

Geoffrey Hallmann, Dr Rosanne Coutts, Dr Yvonne Hartmann, Southern Cross University

Objectives:

To examine the nature and impact of trauma upon persons with ME/CFS when engaged in interactions with Social Institutions.

Method:

The initial phase of the research involved a thorough review of the available literature to establish the interaction of those with ME/CFS with social institutions.

A focus for this paper was made on the incidence of trauma that participants reported as having experienced during interactions within institutional settings and attention was paid to the effect of such experiences.

In the data collection phase, a pilot study involving an investigation of the Australian perspective of the experience of ME/CFS was obtained.

This was expanded in the main study and participants were provided the opportunity to reveal their stories.

Participants were required to have a diagnosis of CFS, ME or ME/CFS from a medical practitioner and self-select themselves as compliant to the Fukuda CFS Criteria, Canadian ME/CFS Criteria and Ramsay ME Criteria.

A background questionnaire was provided to give an insight into the history of the participant, particularly interactions with social institutions and pathways to diagnosis.

Social institutions are the complex social forms that are found within governments, family, universities, hospitals, incorporated entities, legal systems and other social structures and organisations.

The interview drew upon the questionnaire for guidance, with the primary questions derived from information gained from the literature review.

The interviews were transcribed, coded and the relationships and issues identified in order to guide the second phase of the research which was conducted further into the study.

The pilot study involved 3 participants, followed by a second, more comprehensive phase comprising 16 participants.

Stories emerged from within those interviews with respect to interactions with society and these were broken down to reveal particular themes relevant to those experiences.

Results:

A total of 19 interviews were conducted.

The average age of participants was 41.95 with all 14 females and 5 male participants.

The mean duration of the condition was 17.66 years, with 8.35 years from onset until diagnosis.

A number of issues arose, revealing an insight into the nature of the relationships that exist between persons with ME/CFS and various social institutions.

Relationships of power, politics, policies, practices and social relations were revealed to play an important role in the experience of ME/CFS.

Trauma appeared to occur across every facet of the participant’s lives, particularly in dealings with the medical profession, insurance companies, educators, employment, family, friends and the media.

Whilst apparently present such behaviour was often not named as such nor addressed.

Conclusion:

When interacting with social institutions, persons with ME/CFS are subject to attitudes, beliefs, policies and behaviours (including bullying), that directly or indirectly arise because of their diagnosis and the contested nature of the condition.

These experiences have an adverse impact upon the person – both physically and emotionally.

Participants revealed that traumatic encounters and issues can influence their dealings with people within social institutions and impact adversely upon their condition and manner in which they address future interactions.

Whilst trauma has at times been identified within the literature in the context of ME/CFS, there has been no thorough examination within an institutional context.

The ability to protect themselves against traumatic experiences is difficult although avoidance is employed at times to limit exposure.

Providing a more settled understanding of the condition and education within society is indicated as a counter measure to identify and counter traumatic experiences.


Geoffrey Hallmann
B.Bus.(Hons)(UNE-NR), LLB (Hons)(Newcastle), DipLegPrac (Newcastle), DipFinPlan (Deakin)
PhD Candidate
Southern Cross University
School of Exercise Science & Sport Management
PO Box 157
EAST LISMORE NSW 2480
+ 61 2 66241979
+ 61 4 14 014 365
geoffhallmann@yahoo.com

 

[Tom Kindlon]

Another abstract from the same team

ME/CFS: Social Security Accessibility and Experiences

Geoffrey Hallmann, Dr Rosanne Coutts, Dr Yvonne Hartmann, Southern Cross University

Objectives:

To examine the accessibility and experience of social security for persons with ME/CFS.

Method:

The initial phase of the research involved a thorough review of the available literature to establish the interaction of those with ME/CFS with social institutions.

A focus for this paper was made on the incidence of trauma that participants reported as having experienced during interactions within institutional settings and attention was paid to the effect of such experiences.

In the data collection phase, a pilot study involving an investigation of the Australian perspective of the experience of ME/CFS was obtained.

This was expanded in the main study and participants were provided the opportunity to reveal their stories.

Participants were required to have a diagnosis of CFS, ME or ME/CFS from a medical practitioner and self-select themselves as compliant to the Fukuda CFS Criteria, Canadian ME/CFS Criteria and Ramsay ME Criteria.

A background questionnaire was provided to give an insight into the history of the participant, particularly interactions with social institutions and pathways to diagnosis.

Social institutions are the complex social forms that are found within governments, family, universities, hospitals, incorporated entities, legal systems and other social structures and organisations.

The interview drew upon the questionnaire for guidance, with the primary questions derived from information gained from the literature review.

The interviews were transcribed, coded and the relationships and issues identified in order to guide the second phase of the research which was conducted further into the study.

The pilot study involved 3 participants, followed by a second, more comprehensive phase comprising 16 participants.

Stories emerged from within those interviews with respect to interactions with society and these were broken down to reveal particular themes relevant to those experiences.

Results:

A total of 19 interviews were conducted.

The average age of participants was 41.95 with all 14 females and 5 male participants.

The mean duration of the condition was 17.66 years, with 8.35 years from onset until diagnosis.

A number of issues arose, revealing an insight into the nature of the relationships that exist between persons with ME/CFS and various social institutions.

The ability to engage with the social security provider (known as Centrelink in Australia) was hindered by physical and administrative barriers making the process of benefit accessibility difficult for persons with ME/CFS.

Conclusion:

Persons with ME/CFS experienced difficulty in engaging in the process of accessing social security benefits, particularly the Disability Support Pension.

Physical barriers (eg public transport, odours, smells, furniture, lines, distance, etc) impeded or prevented the requirement to physically attend the Social Security offices.

The office set-ups were not appropriately designed for those with a physical disability like ME/CFS.

Use of standing lines, long waiting times, and exposure to perfumes and other airborne smells/odours exacerbated symptoms or prevented entry into offices.

Cognitive issues impacted the ability to interact with staff effectively.

Attendance of offices of medical assessors for the purposes of assessment were not adequately set up to accommodate persons with ME/CFS, with chairs within waiting rooms not suitable for sitting or lying down, exposure to environmental exacerbators such as fluorescent lighting, smells, chemicals, noise and persons with communicable airborne ailments.

Participants reported difficulty in engaging with Centrelink administrative requirements, including attendance at non-negotiable times that conflicted with the participants ability to function, excessive paperwork that they were unable to provide within the allotted time frame or without assistance, onerous medical requirements, assessments by persons with little knowledge of ME/CFS or preconceived and adverse beliefs about the condition, inappropriate methods of assessing disability/impairment unhelpful appeal processes and poor access to advocacy and assistance.

In contrast to select geographical locations with knowledge of ME/CFS provided through training from ME/CFS groups, other offices in other locations denied entitlement to disability benefits, forcing some participants onto benefits that required job search commitments or onto sickness benefits that provided less income and benefits.

The ability to respond to adverse decisions was limited by knowledge of process and procedure, the health constrictions that impact the ability to take action, the availability of advocates to assist in such action, and the knowledge of the condition of those taking the action or making decisions.

There are parallels between these findings and those for other disadvantaged/discredited groups who depend upon social security services and welfare, such as sole parents and those on disability pensions.

 

[Tom Kindlon]

3rd paper from same team

ME/CFS: Institutional Dependence

Geoffrey Hallmann, Dr Rosanne Coutts, Dr Yvonne Hartmann, Southern Cross University

Objectives:

To examine the nature and impact of dealing with social institutions for persons with ME/CFS in the context of institutional dependence.

Method:

The initial phase of the research involved a thorough review of the available literature to establish the interaction of those with ME/CFS with social institutions.

A focus for this paper was made on the incidence of trauma that participants reported as having experienced during interactions within social institution settings and attention was paid to the effect of such experiences.

In the data collection phase, a pilot study involving an investigation of the Australian perspective of the experience of ME/CFS was obtained.

This was expanded in the main study and participants were provided the opportunity to reveal their stories.

Participants were required to have a diagnosis of CFS, ME or ME/CFS from a medical practitioner and self-select themselves as compliant to the Fukuda CFS Criteria, Canadian ME/CFS Criteria and Ramsay ME Criteria.

A background questionnaire was provided to give an insight into the history of the participant, particularly interactions with social institutions and pathways to diagnosis.

Social institutions are the complex social forms that are found within governments, family, universities, hospitals, incorporated entities, legal systems and other social structures and organisations.

The interview drew upon the questionnaire for guidance, with the primary questions derived from information gained from the literature review.

The interviews were transcribed, coded and the relationships and issues identified in order to guide the second phase of the research which was conducted further into the study.

The pilot study involved 3 participants, followed by a second, more comprehensive phase comprising 16 participants.

Stories emerged from within those interviews with respect to interactions with society and these were broken down to reveal particular themes relevant to those experiences.

Results:

A total of 19 interviews were conducted.

The average age of participants was 41.95 with all 14 females and 5 male participants.

The mean duration of the condition was 17.66 years, with 8.35 years from onset until diagnosis.

A number of issues arose, revealing an insight into the nature of the relationships that exist between persons with ME/CFS and various social institutions.

In revealing their experience of “institutional dependency” all participants reported conduct and experiences that negatively affected them emotionally and physically when expressing interactions with various social institutions.

Intrusive requirements by various institutions placed the participants in a constant position of investigation, scrutiny, judgement and accountability on an ongoing basis.

Institutions such as social security, medical staff, insurers, educational bodies, allied health providers, housing, welfare services, the legal system, financial institutions, family and the like required a variety of reports, documents, verification checks, examinations, surveillance and the like to administer their particular dealings with the individual.

Conclusion:

Each ME/CFS participant reported a variety of encounters with social institutions.

All participants reported some form of obligation to or dependence upon more than one social institution.

The condition was continually scrutinised and often questioned.

Medical institutions required significant information, physical and personal invasiveness, and often questioned the validity and veracity of the condition, with many participants labelled with psychiatric attributions to causation.

Insurance companies were identified as particularly intrusive and onerous and often questioned or denied the validity of the diagnosis.

Paperwork, attendances to independent medical examiners, reporting of income, work hours, job search, family members, treatment regimes, medical attendances, symptoms and the like were a common experience.

Social security obligations were one of the most commonly reported institutional involvement, with paperwork requirements on a regular basis necessary to obtain benefits.

Financial entitlement necessitated close scrutiny and carried with it the threat of termination of benefits for noncompliance or adverse decision.

Educational institutions required reasons for non-attendance, accommodations, exam modifications, failure, special consideration, disability access and other entitlements. Medical certification was a regular and essential component.

Again entitlement was assessed by the instruction with an adverse outcome possible.

Participants reported experiences of dishonesty, misstatement, threats, trauma, bullying and harassment within this process of instructional accountability.

Such experiences were emotionally stressful and upsetting, whilst also causing exacerbation of the symptoms of the condition.

The more stressful the event, the greater the potential severity of the symptom exacerbation.

Institutional dependency of this type and duration has been shown to impact individuals and cause long term trauma.

 

[Esther12]

Ta Tom.

Does seem they're looking at areas most 'biopsychosocial' researchers have turned a blind eye to.

A number of issues arose, revealing an insight into the nature of the relationships that exist between persons with ME/CFS and various social institutions.

Relationships of power, politics, policies, practices and social relations were revealed to play an important role in the experience of ME/CFS.

Trauma appeared to occur across every facet of the participant’s lives, particularly in dealings with the medical profession, insurance companies, educators, employment, family, friends and the media.

Whilst apparently present such behaviour was often not named as such nor addressed.

Conclusion:

When interacting with social institutions, persons with ME/CFS are subject to attitudes, beliefs, policies and behaviours (including bullying), that directly or indirectly arise because of their diagnosis and the contested nature of the condition.

These experiences have an adverse impact upon the person – both physically and emotionally.

Participants revealed that traumatic encounters and issues can influence their dealings with people within social institutions and impact adversely upon their condition and manner in which they address future interactions.

 

[Tom Kindlon]

From Norway

CFS/ME is associated with the pandemic H1N1 influenza virus, but not with H1N1 vaccination.

Magnus P 1 ,Bakken IJ 1 , Gunnes N 1 , Ghaderi S 1 , Tveito K 2 , Trogstad L 1 ,Håberg SE 1 .

1 The Norwegian Institute of Public Health, Oslo, Norway.
2 The Journal of the Norwegian Medical Association, Oslo, Norway.

Objective:

To estimate the association between exposure to H1N1 influenza infection and/or H1N1 vaccination during the 2009 pandemic and later development of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) in the Norwegian population.

Methods:

Norway has nation-wide registries for infectious diseases, vaccination as well as attendance to health care.

We used regression methods to estimate the relative risk of CFS/ME in the years 2010-2012 according to exposure to influenza and/or vaccination with Pandemrix in the last months of 2009.

Results:

During 2010-2012, 3645 new cases of CFS/ME were registered in the specialized health care system. The odds ratio for CFS/ME according to vaccination was 0.95 (95 % CI 0.89-1.01).

Among the CFS/ME cases, 9 % had been registered with an influenza diagnosis in the primary health care system during the pandemic compared to 3.6 % for the rest of the population (OR=2.5, 95 % CI: 2.3-2.8).

A positive H1N1 viral detection was registered in the Norwegian Surveillance System for Communicable Diseases in a subgroup (0.27 %) of the total population.

For CFS/ME cases, the proportion registered was 0.57 %, giving an OR of 2.1 (95 % CI: 1.4-3.3).

Conclusion:

These relative risks suggest that infection with the pandemic influenza virus (H1N1) increases the risk of CFS/ME.

Vaccination does not appear to influence the risk.

The results are preliminary and will be analyzed in more detail prior to the conference.

This is only one particular vaccine of course.

 

[Tom Kindlon]

Another from Norway

Two age-peaks in the prevalence of CFS/ME in Norway. A registry study.

Bakken IJ 1 , Trogstad L 1 , Håberg SE 1 , Ghaderi S 1 , Gunnes N 1 , Tveito K 2 , Magnus P 1 .

1 The Norwegian Institute of Public Health, Oslo, Norway.
2 The Journal of the Norwegian Medical Association, Oslo, Norway

Objective:

To estimate the prevalence of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) in the Norwegian population according to sex and age.

Methods:

Diagnoses for all patients who are hospitalized or attend outpatient clinics in Norwegian specialized health services are reported to the Norwegian Patient Registry.

We estimated sex- and age-specific prevalences by using the whole population (sized about 5 million) as denominator and registry cases with CFS/ME (ICD-10 code: G93.3) as numerator.

We had access to registry data for the years 2008 through 2012.

Results:

During these years, 5775 individual patients were registered with a diagnosis of CFS/ME as outpatients or inpatients in Norwegian hospitals.

The overall prevalence was 0.133 % (95 % confidence interval (CI): 0.130-0.137).

The female-male prevalence ratio was 3.0 (95 % CI: 2.8-3.2).

The highest prevalence (0.416 %) was observed among women aged 15 to 19 years.

A second peak (0.348 %) was found among women aged 35-39 years.

Conclusion:

The estimates are most likely biased by forces of selection and variable use of the G93.3 diagnosis in clinical practice.

However, the sex ratio and the two age peaks point to biological regularities that demand explanation.

Presenting author: Lill Trogstad, MD, PhD, senior researcher, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, 0403 Oslo, Norway. E-mail: lill.trogstad@fhi.no

I would have been more interested in information on incidence as ME/CFS is a chronic illness.

The prevalence would likely be an underestimate as many people either never get diagnosed or it takes them years to get diagnosed (but some people also get misdiagnosed with CFS/ME).

 

[Tom Kindlon]

Reproducibility of Measurements Obtained During Cardiopulmonary Exercise Testing in Individuals With and Without Fatiguing Health Conditions: A Case Series

Benjamin M. Larson 1 , Todd E. Davenport 1,2 , Staci R. Stevens 2 , J. Mark Van Ness 1,2 , Christopher R. Snell 1,2,

1 University of the Pacific, Stockton, CA, USA
2 Workwell Foundation, Ripon, CA, USA

Purpose:

The reproducibility of measurements obtained during cardiopulmonary exercise testing (CPET) is a longstanding tenet of exercise physiology.

However, test-retest variation in CPET measures may be higher for individuals with chronic fatigue syndrome (CFS), which could explain the characteristic functional deficits of post-exertional malaise.

The purpose of this case series was to demonstrate the potential variability of test-retest CPET measurements in individuals with and without fatiguing health conditions.

Case Descriptions:

Subjects (n=7) who were matched to age, body mass index, and gender received 2 maximal CPETs 24 hours apart.

Cardiovascular, respiratory, and metabolic measurements were taken at both peak exertion and ventilatory threshold (VT).

Standard criteria were used to verify a maximal test took place.

Diagnoses included sedentary but non-disabled individuals (n=2), an active and non-disabled individual (n=1), multiple sclerosis (MS; n=1), human immunodeficiency virus (HIV; n=1), an individual with CFS who was low-functioning (n=1; Test 1 peak volume of oxygen [VO2]: 17.2 mL/kg/min), and an individual with CFS who was high-functioning (n=1; Test 1 peak VO2: 33.9 mL/kg/min).

Outcomes:

Subjects ranged in age from 33-46 years, and BMI ranged from 21.1-25.7.

Test-retest CPET measurement variability for most peak variables including oxygen consumption (VO2), workload (WL), heart rate (HR), and ventilation (VE) largely were reproduced, or even increased, between Test 1 and Test 2. However, both individuals with CFS showed significant decreases.

The low-functioning individual with CFS demonstrated decreases of 16%, 67%, and 9%, and 19% in VO2, WL, HR, and VE at VT, respectively.

The high-functioning individual with CFS showed decreases of 30%, 33%, and 14%, and 9% in VO2, WL, HR, and VE at VT, respectively.

Conclusions:

Variability in submaximal cardiac, pulmonary, and metabolic performance may be responsible for the waxing and waning symptoms and activity limitations in individuals with CFS.

The findings of this case study merit further verification in the context of adequately-powered measurement validation studies that compare test-retest CPET measurement characteristics across fatiguing health conditions.

Benjamin M. Larson is doctoral student in physical therapy, University of the Pacific, Department of Physical Therapy, 3601 Pacific Avenue, Stockton, California. Email address: b_larson2@u.pacific.edu.

 

[Tom Kindlon]

Cerebral Blood Flow Regulation, Orthostasis and N-Back evaluation in Chronic Fatigue Syndrome

Marvin S. Medow, Akash Pandy, Shilpa Sood, and Julian M. Stewart

Department of Pediatrics, New York Medical College, Valhalla, New York 10595

Chronic Fatigue Syndrome (CFS), associated with orthostatic intolerance is characterized by neurocognitive deficits, impaired working memory, concentration, and difficulty processing complex information.

We showed that in CFS/POTS subjects, upright tilting (HUT) caused decreased cerebral blood flow (CBF) related to hypocapnia and impaired cerebral autoregulation and increasing orthostatic stress during neurocognitive testing resulted in decreased cognition.

We also showed an increased respiratory chemoreflex response to hypoxia and decreased respiratory chemoreflex response to hypercapnia.

In CFS/POTS therefore, a lack of appropriate chemoreflex response to CO2 can account for the inappropriately sustained hypocapnia.

Objectives:

Orthostasis-related neurocognitive impairment in CFS may be due to decreased CBF as a direct effect of CO2, altered cerebrovascular regulation or a combination of these.

Methods:

We determined the effect of loading the baroreflex with sub-pressor dose phenylephrine to prevent hyperpnea, by normalizing CO2 with exogenous CO2 to prevent hypocapnia, or by administration of acetazolamide, to alter CBF during HUT.

We then performed N-Back testing of neurocognitive function.

Results:

HUT increased heart rate (HR) in 8 controls by 23 bpm, while in 15 CFS/POTS, HR increased by 36 bpm. HUT also caused CBF to decrease 8.7% in controls, but fell by 22.5% in CFS/POTS.

Exogenous CO2 to maintain eucapnea during HUT in controls mitigated the orthostasis-induced decrease in CBF (73.11±5.23 vs. 67.87±4.89 cm/s); baseline vs. treatment.

Phenylephrine (69.75±2.02 vs. 69.93±3.74 cm/s) and acetazolamide (76.93±4.44 vs. 79.52±4.06 cm/s); baseline vs. treatment, resulted in no CBF decrease with tilt.

The significant drop in CBF with tilt in CFS was prevented by CO2 (71.57±9.71 vs. 64.52±8.78 cm/s), phenylephrine (69.08±9.13 vs. 63.48±10.73 cm/s) and acetazolamide (67.13±7.86 vs. 71.58±10.93 cm/s); baseline vs. treatment.

CBF measurements indicate that compared to control, CFS subjects are both more sensitive to orthostatic challenge and to baroreflex/chemoreflex-mediated interventions.

These interventions can be used with N-Back testing to evaluate neurocognitive deficits with orthostasis in CFS subjects.

N-Back testing showed no difference in the normalized response time (nRT) of control subjects comparing supine to HUT (106.2±3.1 vs. 97.3±2.3 msec at N=4), and no difference comparing control to CFS while supine (97.1±2.3 vs 96.5±3.9 msec at N=4).

However, HUT of CFS subjects caused a significant increase in nRT (148.0±3.1 vs. 96.5±3.9 msec at N=4) compared to supine.

Phenylephrine administration significantly reduced the HUT-induced increase in nRT in CFS to levels similar to supine (116±2.4 vs 96.5±3.9).

Conclusions:

These interventions are effective in altering CBF.

In CFS subjects, mitigation of the HUT-induced CBF decrease with phenylephrine has a beneficial effect on N-Back outcome in CFS subjects.

Marvin S. Medow, Ph.D. Professor of Pediatrics and Physiology New York Medical College, Valhalla, NY 10595 Marvin_Medow@nymc.edu

 

[Tom Kindlon]

Psychological stress exacerbated low-grade fever in a chronic fatigue syndrome patient

Takakazu Oka 1 , Yoshio Kanemitsu 1,2 , Nobuyuki Sudo 1 , Haruo Hayashi 3 , Kae Oka 4 ,

1 Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University,
2 Psychosomatic Medicine, Department of General Medicine, Fukuoka Dental College.
3 Division of Psychosomatic Medicine, Department of Neurology, University of Occupational and Environmental Health,
4 Department of Pediatrics and Child Health, Kurume University School of Medicine,

Objective:

Low-grade fever is a common symptom in patients with chronic fatigue syndrome (CFS).

However, the mechanisms responsible for its development are poorly understood.

We hypothesized that psychological stress contributes to low-grade fever in some CFS patients.

The aim was to assess if psychological stress exacerbates low-grade fever and its mechanisms in CFS patients.

Methods:

A 26-year-old female CFS patient was admitted to our hospital.

She had been recording her axillary temperature (Ta) regularly and found that it was especially high when she felt stress at work.

To assess how psychological stress affects temperature and to investigate the possible mechanisms for this hyperthermia, we conducted a 1-hr stress interview and observed the changes in the following parameters: Ta, tympanic membrane temperature, fingertip temperature, systolic and diastolic blood pressures, heart rate, plasma catecholamine levels, and serum levels of pyretic cytokines, including interleukin (IL)-1βand IL-6 and anti-pyretic cytokines, including tumor necrosis factor-αand IL-10.

Results:

At baseline, her Ta was 37.2°C. It increased to 38.2°C by the end of the interview. In contrast, her fingertip temperature decreased during the interview.

Her heart rate, systolic and diastolic blood pressures, and plasma catecholamine levels increased during the interview; there were no significant changes in either pyretic or antipyretic cytokines during or after the interview.

Conclusion:

One-hr stress interview induced a 1.0°C increase in Ta in a CFS patient.

Negative emotion-associated sympathetic activation, rather than pyretic cytokine production, contributed to the increase in temperature induced by the stress interview.

This finding suggests that psychological stress may contribute to the exacerbation of low-grade fever and fatigue in some CFS patients.

 

[Tom Kindlon]

The prevalence and possible significance of thyroid disorders to Chronic Fatigue Syndrome patients diagnosed in CFS specialty clinics.

*Lucinda Bateman, Nancy Klimas, Daniel Peterson, Susan M. Levine, Donna Felsenstein, Gail H. Ironson and the CFI Study Group**

Objectives:

Examine the occurrence and/or treatment of thyroid conditions in CFS patients diagnosed in CFS specialty clinics.

Methods:

Data from the Chronic Fatigue Initiative (CFI) were analyzed to assess how many patients are diagnosed with a thyroid condition, taking levothyroxine, and/or have abnormal thyroid stimulating hormone (TSH) results compared to age, gender and regionally matched healthy control subjects.

The study cohort has 405 subjects, 203 with CFS and 202 matched controls, divided evenly across five CFS Clinics in the U.S (Salt Lake City, Miami, Incline Village, New York, Boston), collected between Dec 2011 and Dec 2012

Results:

Hypothyroidism is listed as a diagnosis in 30% versus 7% (p=.000), hyperthyroidism in 3% versus 0% (p = .014), and thyroiditis in 7% versus 0% (p = .001) of CFS patients versus matched healthy controls.

Levothyroxine is taken by 23% of CFS patients versus 5% of controls.

Of all subjects on levothyroxine (n=51), 23 reported they are significantly improved, 16 somewhat improved, 12 unchanged, and no one reported being somewhat worse or significantly worse on this treatment.

There was no difference in effectiveness of levothyroxine for CFS patients (n=42) vs. controls (n=9). (The effectiveness data are from the medication history in the core questionnaire).

TSH lab values are available from 199 CFS and 199 control subjects.

There is no difference between the mean TSH values of CFS patients and controls (including 42 CFS patients and 9 Control subjects taking levothyroxine).

Of the total cohort (on or off levothyroxine) 14% of the CFS patients had abnormal TSH (16 low, 12 high) and 7% of the health controls had abnormal TSH (7 low and 7 high).

Conclusions:

The diagnosis of thyroid disorders and treatment with thyroid hormone is much higher in CFS patients than the normal population.

This may be from the detection and treatment of subclinical hypothyroidism (defined as a TSH 5-10 with normal T4) during a vigorous diagnostic search for underlying chronic illness, but the background rate in the general population is 3-8%, as is reflected in our control subjects.

It is possible that patients are receiving chronic thyroid hormone supplementation without a true diagnosis of thyroid disease in an attempt to treat CFS symptoms, a practice that does not have established long term efficacy or safety.

The data may also suggest an underlying mechanism of illness in CFS that leads to primary or secondary hypothyroidism.

Because the main causes of hypo- and hyperthyroidism in the general population are auto-immune, further analysis of these findings may lead to better understanding of CFS pathophysiology and to more effective treatments.

*Lucinda Bateman, MD. Director, Fatigue Consultation Clinic. 1002 E. South Temple, Suite 408, Salt Lake City, Utah 84108. lbateman@fcclinic.com

**The CFI Cohort Recruitment Study Group includes:
Nancy Klimas, MD, Nova Southeastern University and Miami VA Hospital,
Lucinda Bateman, MD, Fatigue Consultation Clinic, SLC Utah
Dan Peterson, MD, Simmaron Research Institute, Nevada
Donna Felsenstein, MD, Harvard Medical School, Boston MA
Susan M. Levine, MD, New York City, NY
Anthony L. Komaroff, MD, Harvard Medical School, Boston MA
Mady Hornig, MD, Center for Infection and Immunity, Columbia University Mailman School of Public Health
W. Ian Lipkin, MD, Center for Infection and Immunity, Columbia University Mailman School of Public Health

Statistical team:
Gail Ironson, MD, PhD, University of Miami Elizabeth Balbin, University of Miami and Miami VA Hospital
Aundrea Carter, University of North Carolina, Greensboro
Korinne Chu, Physicians for Peace, Norfolk, VA

Serology
Mary Ann Fletcher, PhD, Nova Southeastern University and Miami VA Hospital

It would have been more interesting to know their score (TSH, etc.) before or off therapy.

 

[aimossy]

Allergy-related immune signatures and duration of illness in CFS

Susan Levine,1 Xiaoyu Che,2 Andrew F. Schultz,2 W. Ian Lipkin,2 Nancy Klimas,3 Lucinda Bateman,4 Dan Peterson,5 Donna Felsenstein,6 Elizabeth Balbin,7,8 Aundrea Carter,9 Korinne Chu,7 Mary Ann Fletcher,3 Anthony Komaroff,6 Gail Ironson7 and Mady Hornig2
1Private practice, NY, NY; 2Columbia U Mailman School of Public Health, NY, NY; 3Nova Southeastern U, Fort-Lauderdale-Davie, FL; 4Fatigue Clinic, Salt Lake City, UT; 5Simmaron Research Inst, Incline Village, NV; 6Harvard Med School, Boston, MA; 7U of Miami, Miami, FL; 8Miami VA, Miami, FL; 9U of North Carolina, Greensboro, NC; 10Physicians for Peace, Norfolk, VA

Objectives: Clinical features consistent with atopic and allergic disorders are reportedly more common among CFS patients. We sought to identify evidence for an enhanced allergic phenotype in CFS by comparing plasma levels of allergy-associated immune/inflammatory molecules in CFS patients with shorter vs. longer illness duration.

Methods: 293 CFS patients from two studies (NIH CFS and Chronic Fatigue Initiative studies) were pooled for analysis: 52 short duration (<3 years) and 241 longer duration subjects (>3 years). Plasma samples acquired at clinic visits were subjected to immune profiling analysis, and levels of allergy-related immune molecules were compared in short and long duration CFS.

Results: As compared with long duration CFS patients, patients with shorter illness duration had higher IL4 (p<0.001), IL13 (p=0.014), IL10 (p<0.001), IL6 (p=0.005), IL17A (p<0.001) and CCL5 (p<0.006). There was a trend toward lower eotaxin levels in the short duration subset (p=0.052). Short duration subjects also had elevations in other cytokines implicated in allergic responses, including IL1α, IL1β, IL1RA, IL8, MCP1, CXCL10, MIP1α, IL12p40 and TGFα (all p<0.002), as compared with longer duration CFS subjects.

Conclusion: Elevated levels of allergy-associated cytokines and chemokines in CFS of <3 vs. >3 years’ duration has led us to postulate a role for these mediators in producing allergic-type clinical phenotypes. Previous studies examining allergic disorders (asthma, allergic rhinitis) - often implicated as comorbid conditions in CFS - support the presence of elevated plasma IL4, IL5 and IL17. Our finding of elevated levels of molecules involved in the allergic diathesis, including IL4 and IL17A as well as IL6, IL8, IL10, and eosinophil-recruiting chemokines such as CCL5, lends support to the hypothesis of a Th2 shift with a distinct immune signature in a subset of CFS. IL4 produced by basophils following encounters with allergens leads to T cell differentiation and IL17A production; IL17A in turn recruits eosinophils, mast cells, neutrophils and other cell types that then produce IL6 and IL8 in addition to other allergic mediators.Elevated plasma eosinophil cationic protein has been reported in a group of CFS patients, but few other studies have investigated the role of allergic mediators. Our findings suggest pathways for possible therapeutic intervention and clinical trials. Leukotriene inhibitors used to treat asthma that reduce plasma IL-4 could potentially play a therapeutic role in certain CFS subsets. The unique immune signature found in our short duration subjects suggests at least one important pathophysiologic mechanism by which we can begin to understand the allergic CFS phenotype. The influence of eosinophil and basophil levels, age, level of disability, comorbidity, heritable conditions, ethnicity, sex and geographic site will be examined in addition to temporal and seasonal changes in the allergy-related cytokines/chemokines. Future studies should include determinations of levels of histamine, total and specific IgE, prostaglandin E2, tryptophan and serotonin, in addition to comparisons with healthy controls.

Presenting author: Susan Levine, MD; Physician in private practice, address: 115 East 72nd St, Suite 1A, NY NY 10021 USA; email:

I really like seeing the higher number in cohort from the CFI work.

 

[aimossy]

[QUOTEImmune signatures associated with cognitive dysfunction in CFS

Mady Hornig,1* Xiaoyu Che,1 Andrew F. Schultz,1 Susan Levine,2 W. Ian Lipkin1 and the CFI Study Group 1Columbia University Mailman School of Public Health, NY, NY; 2Private practice, NY, NY

Objectives: Mental fatigue, memory deficits and perceptual processing problems are major contributors to dysfunction in CFS, but the severity of cognitive disturbance varies both within individuals over the course of illness and across phenotypic subsets. Access to a robust biomarker of cognitive dysfunction in CFS would accelerate identification of patients responsive to select treatment strategies and also provide clues to pathogenesis. Although cytokine disturbances are reported in many CFS investigations, study populations and findings are heterogeneous, limiting their utility as biomarkers. We used feature selection and 51-plex immunoassays in an effort to define immune signatures associated with cognitive deficit in CFS.

Methods: Data from 298 CFS and 348 control subjects from the NIH CFS and the Chronic Fatigue Initiative studies, frequency-matched on age and gender, were pooled. High/low cognitive impairment subgroups were established using mean scores for 4 mental fatigue items from the Multidimensional Fatigue Inventory (MFI4, cases and controls; cutoff 1 SD > population mean): 142 high/147 low MFI4 cases; 29 high/312 low MFI4 controls. Plasma samples were subjected to immune profiling analysis. Principal components (PCA) and partial least square (PLS) feature selection approaches were applied to the 51-cytokine data set to derive latent variables for application as independent variables in logistic regression. Cytokines with odds ratios (OR) >1.1 or <0.9 (p<0.05) by PCA or PLS for the association with high MFI4 subgroups were included in the final logistic regression model along with age as a covariate.

Results: Elevated IFNγ levels were strongly associated with cognitive impairment in cases (high MFI4) (OR, 67.42; 95% CI, 5.34, 850.83; p=0.0011). Increased CXCL1 levels were also associated with more impaired case MFI4 (OR, 1.23; p=0.0285), with a trend in the same direction for IL13 (OR, 1.26; p=0.08). The pattern within controls was similar to that within cases for IL13, with elevated levels predicting greater cognitive impairment (OR, 1.71; p=0.0088); however, other cytokines associated with cognitive impairment among cases did not show a similar pattern among controls. Stratified analyses showed no relationship with sex.

Conclusion: Cognitive dysfunction in CFS is associated with specific patterns of elevated cytokines. Increased circulating levels of IFNγ have a striking relationship with cognitive impairment. Individuals with CFS but without cognitive dysfunction did not demonstrate these disturbances. These results suggest immune homeostasis may be dysregulated in the subset of subjects with CFS with prominent cognitive disturbance. IFNγ elevations among cases with cognitive impairment may point toward a subgroup with higher probability of viral triggers and/or persistent infection.][/QUOTE]

It didn't do the pink block for me this time, I feel like we are starting to get somewhere when cohorts like this get published with this type of work. These are posters - I just wish they were in Journals already!!