Day Three, and Searcher continued to deliver the goods. We hear about the PANDORA national survey results, a very big familial case study from Spain, results from the Canadian Community Health Survey, more results from epidemiological studies (and a look at treatments and comorbidities), then perhaps the key section of the day: the science of exercise testing and post-exertional malaise…
It’s Day Three (March, 22, 2014), of the IACFS/ME four-day conference and another packed research presentation agenda. Our summation continues from mid-morning after Searcher took a well-deserved break to try and recover some lost energy.
Additional notes for those sessions that she was unable to cover in the afternoon, have been very kindly provided by Hope – another patient – including those relating to exercise testing.
You can read the complete agenda for the day’s presentations – and a list of all of the many papers that were being discussed, here: IACFS/ME Professional Agenda.
We hope to be able to provide you with a more detailed look at the posters that were presented shortly, along with a more detailed review of some of the presentations, once we have been able to listen to the recordings and perhaps contact the authors for follow-up interviews.
Saturday, March 22nd
Expanding Access to Knowledgeable Healthcare for Neuro-endocrine-immune Diseases in Alabama – A Case Study
Tina M. Tidmore1, Lori Chapo-Kroger, RN2
1Tidmore Communications, 2PANDORA Org
“They mentioned that there aren’t any medical groups that say they treat ME/CFS in Alabama.
“PANDORA did a 1200+ respondent national survey to find out if patients are satisfied with current care and whether they are mostly on Medicaid, per a request from a CEO of a 5-hospital system in central Alabama.
“After they saw their results they set up two CME courses, including paying Komaroff to help in one.
“The doctors mentioned some obstacles including that:
“Patients require long visits and insurance doesn’t reimburse adequately”
“Patients keep coming back, need lots of attention”
“More than 60 of the doctors attending the CME received the IACFS/ME primer
“They would like to set up an NEI clinic after more research on viability
Phoenix Rising and the California Conferences 2014:
You can review all our previous coverage of these conferences, from Stanford through to IACFS/ME in San Francisco, in date order below:
Stanford Symposium, Wednesday, March, 19, 2014: summary article (with added content): HERE or the original live blog: here.
IACFS/ME Conference, Thursday, March, 20, 2014: summary article (with added content): HERE and the original live blog: here.
IACFS/ME Conference, Friday, March, 21, 2014: summary article (with added content): HERE and the original live blog: here.
And you can always review our Twitter feed to see what we posted on each of the days.
Family Aggregation Studies in CFS
Alegre J, Castro-Marrero J, Ribases M, Aliste L, Saez N, Calvo N, Marquino A, Fernandez de Sevilla T and Fibromyalgia and CFS Spanish Genetic and Clinical Data Bank (FSGCDB Group) and Foundation FF.
Chronic Fatigue Group. Vall d´Hebron University Hospital Research Institute. Universidad Autònoma de Barcelona. Barcelona. Spain
“Dr Jesus Castro Barcelona…
“There was a family study of 1140 Spanish CFS cases, consisting of 114 men and 1026 women
“They were looking for familial connections
- Increasingly strong evidence that CFS is heritable
- CFS/ME runs in families where more than one person is affected
- There is currently little agreement on the susceptibility genes and environmental factors
- Familial aggregation can’t separate out genetic and environmental contributions
Part II Session Public Health Research
Chair: Elizabeth Unger, M.D., Ph.D. Chief, Chronic Viral Diseases Branch, Division of High-Consequence Pathogens and Pathology National Center for Emerging and Zoonotic Diseases, Centers for Disease Control and Prevention
Prevalence and Health-related Characteristics of ME/CFS, FM and Environmental Sensitivities/MCS: Results from the Canadian Community Health Survey (CCHS) 2005, 2010 and 2012
M. Parlor, National ME/FM Action Network, Halapy E, Ontario Centre of Excellence in Environmental Health Business Case Project
“They sampled ordinary Canadians over age 12 and were looking at long-term health condition that have lasted more than 6 months
“In 2010, diabetes was most common. 1.4% of the target population had ME/CFS, which was less than FM.
“Of all the illnesses, only people with strokes had more functional impairment people with CFS. This was defined as what % of people needed help with tasks.
“According to the 2010 study, CFS patients were most likely to visit their family doctor or see specialists more than 5 times in a year. Despite all these visits, FM and CFS patients were most likely to have reported unmet health care needs.
“CFS patients and MCS patients were most likely to have low incomes. MCS, CFS, and FM patients were at the highest risk to have food security, defined as lack of access to health foods. This could be due to income or the inability to make healthy foods.
“It is massive what needs to be done.”
Summary: CFS is chronic and disabling, with little change in symptom severity over time
- Those with the most severe initial symptoms seem to have a higher likelihood of symptom improvement, although improvement does not necessarily mean recovery or markedly improved functioning
- Severe initial post-exertional malaise may be an important marker of functional outcomes and long term health status
- Onset type is not important in the long term course of CFS
- Episodic remissions occur in a reasonable proportion of CFS
- Patients have number of comorbid, chronic conditions
- Acknowledgement of the chronic fatigue initiative clinical epidemiology study subjects by Stella Lee, Dr Komaroff, Dr Bateman
Aims: study prevalence of cancer in patients with CFS
- Specific conditions including fibro, sleep apnea, bunch of other comorbidities
- Chi-square analysis, principal factor analysis (14 conditions → 4 comorbidity factors): Anxiety, depression, PTSD Hypothyroidism, autoimmune disease
- Narcolepsy → Neurological disease
- Cancer Correlation and regression analysis
- Top 4 conditions: Fibro, depression, anxiety, hypothyroidism
- Comorbidities decrease odds of better health over time, and their participation of extracurricular activities, school, etc.
- Comorbidities increase odds of CFS symptoms worsening over time
The Natural Course of Chronic Fatigue Syndrome: Evidence from a Multi-Site Clinical Epidemiology Study
Dana March, Ph.D., Assistant Professor, Department of Epidemiology, Columbia University Mailman School of Public Health
(Some of this is a repeat from yesterday’s CFI session.)
“They had 960 completed surveys done by patients at top clinicians in Florida, Nevada, New York, and Utah.
“Looked at many factors, including current CFS status, duration of illness, symptoms clusters, functioning, current health relative to illness onset, and patient-identified effective treatments.
“The patient-identified effective treatments’ question was “Is there anything that has significantly improved your CFS symptoms over time?” This was an open-ended question asking for top 5 treatments.
“The stats from yesterday about deceased patients– 37.8% cancer, 18.9% heart disease, 18.9% suicide– was out of a total of 59 deceased patients.
“Of the four sites, there was a longer CFS duration for Nevada and New York samples, which is a function of how long-standing Dr Peterson’s clinic is.
“57.3 had sudden-onset. “For every one-point increase in severity of initial post-exertional malaise, odds of reporting sudden onset increased by 63%.”
“In general patient’s symptoms didn’t change much over time and the mean CFS duration was 15 1/2 years.
“Current health status was not associated with onset type. Those with the most severe initial symptoms were most likely to report improvement.
“A few of the key points in the summary in the CFI Clinical Epidemiology study:
- CFS is chronic and disabling with little change in symptom severity over time.
- Severe initial PEM may be an important marker of functional outcomes and long-term health status.
- Episodic remissions occur in a reasonable proportion of CFS.
“15.6% of the patients had one or more cancers at some point.”
What Treatments Alter the Course of Chronic Fatigue Syndrome? Evidence from a Multi-Site Clinical Epidemiology Study
Lucinda Bateman, M.D., Adjunct Assistant Professor, Department of Anesthesiology, University of Utah
“Dan Peterson’s patients listed traditional medicine as their most effective treatments, and Lucinda Bateman’s patients were more likely to list self-help strategies. This likely reflects their interests.
Patient-identified effective treatments
Initial and current severity of 9 CFS symptoms from Fukada criteria + orthostatic intolerance
- Self-help strategies 65% (rest including efforts to improve sleep and pacing, diet, exercise like strength conditioning)
- Traditional medicine 53% prescription medications and vitamins, OTC medications, herbal remedies, acupuncture, massage
- Dan’s clinic: traditional medicine listed as the more effective treatment of major symptomology of illness v. Bateman clinic: empower patients to live with this illness (self-help strategies, value and manage health over time):
- Variables that may reflect the clinic differences including patient age, stage of disease, location?
- Autoimmune diseases (including hypothyroidism) more associated with traditional medicine (since that seems to help them the best)
- Neurological diseases –> complementary medicine
Summary: self help and traditional medicine are the most effective treatment types in CFS patient population but vary in magnitude by site
Treatment type effectiveness varies by:
- Severity of initial symptoms
- Initial symptom cluster severity
- Current health status and functioning
- Remission (ever)
- Number of comorbid conditions
- Cancer diagnoses by system: skin, blood, nervous system, thyroid, colon/liver/pancreas, kidney/bladder, breast, cervix/uterus/endometrium/ovary, prostate
- Prevalence of any cancer: 15.5%
- Excluding skin cancer, prevalence of any cancer: 8.1%
- Prevalence of any cancer in US: 4.1%
Question and Answer session:
Q: How do comorbid conditions related with CFS compare to the percentages of the normal healthy population?
A: great question and study will result soon
Q: On neurological symptoms?
A: slides depicted mild improvements across wide range of the symptoms (including neurological ones); other epidemiology studies with more granular information about neurological symptoms are taking place beyond CFS community, but they can’t definitively make any statements about neurological symptoms specifically
Q: Why does it seem that most of the highest improvements corresponds with the type of clinic (Peterson’s traditional medicine v. Bateman’s lifestyle and symptom management example)?
A: It’s probably just the nature of medicine and how we treat patients and practice medicine
Chronic Fatigue Syndrome and Comorbid and Consequent Conditions: Evidence from a Multi-Site Clinical Epidemiology Study
Salima Darakjy, MPH, Ph.D. Candidate, Department of Epidemiology, Columbia University
Question and Answer session for the epidemiology panel (these aren’t all the questions that were asked):
Q: What % of patients have a comborbid diagnosis of Anxiety, PTSD, bipolar disorder, or depression?
A: We need to look more at the data to determine this because of potential patients with multiple diagnoses. And the reports are self-diagnosed, so many patients could say they have depression but don’t actually have a diagnose.
“It was a long and informative day. We have an amazing set of researchers on our side, so I think we will see real progress soon. I had an amazing conversation with Mady Hornig that I will try to write up in the next few days.
There are going to be some good brain-related sessions tomorrow. Some is a repeat from Stanford but I should be able to provide more detail from tomorrow’ sessions.”[/box_right_wide]
Q: Is CFS less common in the black population or is there a potential bias in the study population?
A: paraphrase: This is a perpetual question. Many community studies, including Lenny Jason’s, showed higher percentages of minorities who have CFS than their population percentage. So this could be reflective of who are at these study sites. This doesn’t negate the value of this data even though we would love to have a more representative patient population.
Q: With regards to comorbid conditions how did the percentage of people with comorbid conditions compare with the normal population?
A: Great question. We don’t have an answer but are looking into it.
Q: How do neurological symptoms change over time?
A: We don’t have granular enough data to answer that question.
Session: Provocation Studies
Chair: Staci Stevens, M.A. Vice President, IACFS/ME, Work Well Foundation, Founder
Superior Ability of a Two-Day CPET Protocol to Detect Functional Impairment in ME/CFS Compared to Either a Single CPET, A Submaximal Exercise Test, or a VO2 Prediction Equation
Betsy A. Keller, Ithaca College, Dept. of Exercise and Sport Sciences, Ithaca NY
Additional notes from Hope:
CFS frequently use these types of energy: they require frequent rest breaks
Short-term anaerobic (to get up with fire alarm calls, brief)
Long-term anaerobic (15-75 sec)
VO2 peak measured directly during CPET is valid, standardized, reliable in health and diseased patients:
Maximal effort CPEP exacerbates symptoms of PEM so use of submaximal test is of interest → get the necessary info without max testing them and crashing them
- CPET 1: measures baseline functional capacity Vo2 peak and ventilator (anaerobic threshold), induces PEM
- CPET 2: determine if patient can reproduce CPET 1 results within well-established normative data variability (not compared to a matched healthy control); very well established that these are repeatable tests
Accuracy of predicting Vo2 peak:
- Linear relationship between HR and oxygen consumption (as workload increases, HR increase, O2 consumption increases in a linear fashion)
- Predicted maximum HR = valid for all subjects (200 – age)
- Constant work economy and mechanical efficiency during exercise
- Normal day to day HR variation exhibited by patients
- Prediction accuracy using submaximal HR has a standard deviation (standard error)
- Detecting functional impairment requires accurate measures of functional capacity
- Can functional impairment accurately be detected by Vo2 during 1 and 2 CPET tests?
- Summary: measured vo2 peak using 1 CPET, 2 CPET, predicted Vo2 using validated ACSM cycle ergometer equation, predicted VO2 from submax HR
Subjects and Procedures:
- Oxygen consumption (VO2), heart rate (HR), workload (work), respiratory exchange ratio (RER > 1.1), functional impairment determined
- Predicted VO2 peak was higher than actual VO2 peak for both CPETs
- CPET VO2 actual tests dropped significantly
- Predicted higher than actual VO2 peak for both CPETS
- Compared to health controls, PEM really lowers our ability to reproduce the tests
Summary: Validated prediction equation consistently over predicts the VO2 max in Me/CFS patients
- Interesting point: HR at three submax workloads are same for CPETS 1, 2
- The linear relationship between HR, Work, VO2 are not maintained in Me/CFS with PEM
- Regression showed poor ability to predict VO2 peak from any single or combination of variables
- Submax HR-work relationship during CPET 2 did not reflect the 13% decrease in Vo2 peak (probably due to PEM)
Cardiac failure experiment – tried to test severity of impairment:
- 43 % of sample appeared to have some degree of functional impairment on day 1 of SPECT, but when they were tested the 2nd day, 67% met functional impairment criteria
- Takeaway: using only 1 CPET, it failed to detect 15% of those with functional impairments – then the speaker said 55% (so confusing)
- It’s dangerous to over predict VO2 because patient can overexert, or patient’s exercise therapy can be overprescribed
- 2 CPETS are required to accurately detect functional impairment in ME/CFS
- 1 CPET is sufficient to characterize functional capacity of ME/CFS or correlate functional capacity with other objective measures
- However, assessment based on 1 CPET should acknowledge the inability of 1 CPET to detect deleterious effects of PEM on functional capacity in ME/CFS
- DANGERS OF PREDICTING VO2 PEAK
- It’s not linear so might over predict VO2 peak from heart rate → very dangerous for reasons such as the patient over working, the physical therapist making the patient push beyond limits
Diminished Pulmonary Ventilation in CFS Patients – Effects of Deconditioning and Post-Exertional Malaise
J. Mark VanNess, Ph.D. Associate Professor, University of the Pacific
Additional notes from Hope:
Definition of ventilation: when one breathes in O2 and subsequently removes CO2:
- Results from exercise test day one and retest day two
- Huge similar reduction in ventilation at peak exercise and at the anaerobic threshold
- Greater reduction in ventilation on test 2, especially at the anaerobic threshold → shows the PEM effect on CFS patient’s ability to exchange air
- Ventilator anomalies in CFS – what are they attributed to?
- Skeletal muscle fatigue? Oxidative deficiency?
- Autonomic drive? Related to dysautonomia
Submaximal Exercise Testing Using Near Infrared Spectroscopy (NIRS) May Not Differentiate Those With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) From Healthy Controls
Miller, RR1; Reid, WD2; Mattman, A1; Yamabayashi, C2; Steiner, T1; Parker, S3; Tang, P1; Gardy, JL1; Patrick, DM1 for the Chronic Complex Disease (CCD) Study Team
1University of British Columbia 2Dept of Physical Therapy; RAMP Lab, Vancouver Coastal Health Research Institute 3Centre for Health Evaluation and Outcome Sciences, Providence Health Care
Additional notes from Hope:
Potential value of exercise testing in ME/CFS
Identification of measurable physiological markers to aid or confirm diagnosis or to help classify disability:
- A drop in anaerobic threshold on the second day of exercise testing was present in ME/CFS but not in controls
- Goal is to identify discrete subtypes within ME/CFS
- Why submaximal exercise testing was used: screening for other disorders such as mitochondrial dysfunction, maximal cardiopulmonary exercise tests, test people without inducing a flare (CPET consistently causes flare)
Conclusion: Submaximal exercise testing procedure didn’t clearly distinguish between ME/CFS cases and healthy controls:
- Subset of 19% of ME/CFS patients met criteria
- Greater level of self-assessed exertion at lower exercise intensity experienced in ME/CFS might be explained by central perceptions (neurology component?)
- Even submaximal testing was intolerable for a subset
Oxygen Extraction and Lactate Are Low during Cardiopulmonary Exercise Test in Patients with Chronic Fatigue Syndrome
RCW Vermeulen, WG Vermeulen – van Eck and I.V. de Jong – Medvetska
Head of Research, CVS Centrum Amsterdam,
Specific Fitness Profile to Effort in CFS
Alegre J1, Suarez A2, García-Quintana AM2, Castro-Marrero J1, García-Quintana J2.
1Chronic Fatigue Group. Vall d´Hebron University Hospital Research Institute. Universidad Autónoma de Barcelona. Spain. 2CFS Unit. Centro Médico Delfos. Barcelona. Spain
Additional notes from Hope:
Examining exercise tolerance in CFS patients
Retrospective study of 6 year exercise testing:
- Cardiac output was monitored (pulse contour analysis)
- Lactate levels
- Peak O2 uptake is low in CFS patients
- Circulation is not different
- What explains the low values?
What’s the underlying reason for this?
- ADP, Pi, and H+ are recycled in the mitochondria
- Low lactate after exercise in several patients –similar to another doctor’s work
- Perhaps the cause of PEM is that several complex biological pathways might possibly go wrong:
- down-regulation of the entire system – lowering of lactate and H+
- a block in the system resulting in lower lactate and higher H+ production
- or something goes wrong in the mitochondria and the system compensates by overproducing H+ (protons)
Question and Answer session:
Q: what are your thoughts about a portable CPET machine to observe an individual’s given HR and VO2 max at any time while traveling, or during the specific moment of PEM after a particular exertion?
A: The researcher owns such machine which cost $30,000 !!!
Q: do other patients outside of CFS have PEM?
A: Danish Dr. Vermeulen treated a HIV patient had PEM as well – second test a lot worse than the first test
Q: do you see other patients with PEM?
A: No, and we have tested many patients with cardiovascular conditions etc, and they have nothing like CFS patients – both high and low functioning (yet the closest to the PEM was the HIV patient from that Dr. Vermeulen)
Q: What defines the minimal exercise threshold that induces PEM?
A: the patient – it has to be a very individualized approach to physical activity guidelines
Q: there are potent PEM responses to CPET 1 and 2 testing…
A: Researchers agreed that there was a concern:
- Some patients relapsed for 1 month
- All docs need to be very cautious about the possibility of PEM
- Patients need to expect a relapse and to be surprised if there is none
Additional researcher comments:
- Lung-wise there was nothing wrong with the pulmonary function before the exercise
- It’s the diminished functional capacity of the lungs itself with PEM after the exertion