BioMed Central - Latest comments

Differences in medication usage in the Wichita and Georgia cohorts could be due to the different methods of operationalizing the Fukuda criteria that were used

Tom Kindlon — 2009-12-04T00:00:00Z

Medication usage was not the same in the CFS populations found in the Wichita and Georgia populations.

The authors summarise the similarities and differences in the following paragraph:

“Our findings confirm those from a previous study of medication use in persons with CFS from Wichita, Kansas. Both studies found significantly higher usage of pain relievers, gastrointestinal drugs, antidepressants and benzodiazepines by persons with CFS compared to Well controls. Unlike the Wichita study, though, persons with CFS in Georgia were not significantly more likely than controls to use hormones and supplements but were significantly more likely than controls to use muscle relaxants and anti-allergy and cold/sinus medications. Overall, compared to persons with CFS from the Wichita study7, a smaller proportion of persons with CFS in Georgia used pain-relievers (65.5% in Georgia vs. 87.8% in Wichita), supplements/vitamins (44.3% vs. 62.2%), antidepressants (36.3% vs. 41.1%), antibiotics (7.1% vs. 16.7%), hormones (43.4% vs. 52.5%. among women only, 11.8% among all CFS), antihypertensive drugs (17.7% vs. 21.1%), muscle relaxants (8.9% vs. 12.2%), anti-asthma medications (7.1% vs. 12.2%), glucose-lowering drugs (0.9% vs. 4.4%.). Use of other prescription drug categories such as lipid-lowering drugs (11.5% vs.12.2%) and benzodiazepines (12.4%, vs. 11.1% respectively) was similar in Georgia and Wichita (Kansas). The relatively lower usage of most prescription drug medications by persons with CFS in Georgia compared to Wichita may reflect lower seeking of, or lower access to, health care.”

An alternative reason could be that the two sets of criteria for CFS used were not selecting the same type of patients.

The current study[1] uses the empiric definition for CFS[2]. As one can see from the paper that gives the criteria involved in the empiric definition, although it is also based on the Fukuda definition[3], a different number of patients satisfy the criteria [2] compared to how the authors used the definition in the initial study of the Wichita population.

This change looks more significant when one looks at the prevalence rates for CFS obtained in the two cohorts. In the Wichita study[4], the prevalence of CFS was 0.235% (95% confidence interval, 0.142%-0.327%). In the Georgia study[5], the prevalence of CFS was 2.54%, 10.8 times the prevalence in the Wichita study!

Concerns have been raised[6,7] about the newer method[2] of operationalizing the Fukuda definition[3] that were used in the current study[1]. In the only study[7] using the empiric criteria [2] that I am aware of that did not involve the CDC CFS team, 38% of those chosen as patients with Major Depressive Disorder but not CFS, were found to satisfy the new criteria[2] for CFS.

References

1] Boneva RS, Lin JM, Maloney EM, Jones JF, Reeves WC. Use of medications by people with chronic fatigue syndrome and healthy persons: a population-based study of fatiguing illness in Georgia. Health Qual Life Outcomes. 2009 Jul 20;7:67.

[2] Reeves WC, Wagner D, Nisenbaum R, Jones JF, Gurbaxani B, Solomon L, Papanicolaou DA, Unger ER, Vernon SD, Heim C. Chronic fatigue syndrome--a clinically empirical approach to its definition and study. BMC Med. 2005 Dec 15;3:19.

[3] Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome; a comprehensive approach to its definition and study. Ann Int Med 1994, 121:953-959.

[4] Reyes M, Nisenbaum R, Hoaglin DC, Unger ER, Emmons C, Randall B, Stewart JA, Abbey S, Jones JF, Gantz N, Minden S, Reeves WC: Prevalence and incidence of chronic fatigue syndrome in Wichita, Kansas. Arch Int Med 2003, 163:1530-1536.

[5] Reeves WC, Jones JF, Maloney E, Heim C, Hoaglin DC, Boneva RS, Morrissey M, Devlin R. Prevalence of chronic fatigue syndrome in metropolitan, urban, and rural Georgia. Popul Health Metr. 2007 Jun 8;5:5.

[6] Jason LA, Richman JA. How science can stigmatize: The case of chronic fatigue syndrome. Journal of Chronic Fatigue Syndrome 2008, 14, 85-103.

[7] Jason LA, Najar N, Porter N, Reh C. Evaluating the Centers for Disease Control’s empirical chronic fatigue syndrome case definition. Journal of Disability Policy Studies 2009, 20, 93-100. doi:10.1177/1044207308325995

Individual validity of patient reported outcomes: The use of the Clinical COPD Questionnaire (CCQ) in primary care

Jan Willem Herman Kocks — 2009-12-04T00:00:00Z

Individual validity of patient reported outcomes: The use of the Clinical COPD Questionnaire (CCQ) in primary care

JWH Kocks, T. van der Molen

Department of General practice, University Medical Center Groningen, Groningen, The Netherlands

JWH Kocks – j.w.h.kocks@med.umcg.nl – corresponding author
T van der Molen – t.van.der.molen@med.umcg.nl

Abstract
Response to Ställberg et al. Health and Quality of Life Outcomes 2009,7:26

Dear Editor,

With great interest we have read the article by Ställberg and colleagues[1] describing the validation of the Clinical COPD Questionnaire (CCQ) in primary care. As developer (TvM) and researcher (JWHK) of the CCQ we like to thank the authors for performing a study so relevant for clinical practice, but also like to comment on two essential results and interpretations by the authors. The authors use a different approach than commonly to determine the stability of the patient reported outcomes (test-retest reliability). Based on statistical analyses alone the authors conclude that the CCQ reliability might not be sufficient for individual patient monitoring.

The test-retest reliability is assesed using the St. George’s respiratory questionnaire (SGRQ) as indication for stability. The authors state in the discussion that they choose a long time- interval of: ??? to determine the test-retest reliability. A long time-interval indeed minimizes the problem of recall bias[2], but adds difficulty determining the stability using the intra class coefficient. The authors choose an other widely used health status questionnaire to determine change. The use of the SGRQ as method to determine stability raises two issues: 1. the cut off point of 4 points as the minimal clinically important difference is mainly based on the effectiveness of medication in a one year trial, which may not be sufficient bases to use it as a stability measure[3] and 2. The timeframe on which SGRQ “stability” was determined is “lately” as the authors describe in their methods. We suggest for future studies the use of the commonly used Global Rating of Change scale (GRC) in a shorter timeframe.

The authors state that the CCQ’s reliability may not be sufficient for the monitoring of individual patients. The result of the crohbach’s alpha (0.85) and the intra class coefficient (0.85) found in the study are indeed below the suggested threshold of 0.9 for individual monitoring. In previous studies the crohnbach’s alpha and the ICC’s of the CCQ were higher 0.89 to 0.99[4,5]. In the previous paragraph we already discussed the validity of the method to determine the ICC. Taken this into account to our opinion the authors can therefore not justify the conclusion on the individual patient monitoring in this specific study. Next to the statistical grounds, we previously proposed a new method to determine the individual validity of patient reported outcomes[6]. In short, we suggest to determine the concordance between the patient score and an in-depth interview with the patient. We performed a study using this method for the CCQ and the concordance (Lin’s concordance correlation confident (CCC)) in 44 patients was 0.88 (submitted). These results together with the feasibility to use in routine practice, we suggest the CCQ can be used in monitoring individual patients next to clinical trials and quality of care monitoring.

Authors contributions
JWHK and TvdM have written this letter together.

Reference List

1. Stallberg B, Nokela M, Ehrs PO, Hjemdal P, Jonsson EW: Validation of the clinical COPD Questionnaire (CCQ) in primary care. Health Qual Life Outcomes 2009, 7: 26.
2. Stull DE, Leidy NK, Parasuraman B, Chassany O: Optimal recall periods for patient-reported outcomes: challenges and potential solutions. Curr Med Res Opin 2009, 25: 929-942.
3. Schunemann HJ, Griffith L, Jaeschke R, Goldstein R, Stubbing D, Guyatt GH: Evaluation of the minimal important difference for the feeling thermometer and the St. George's Respiratory Questionnaire in patients with chronic airflow obstruction. J Clin Epidemiol 2003, 56: 1170-1176.
4. Damato S, Bonatti C, Frigo V, Pappagallo S, Raccanelli R, Rampoldi C et al.: Validation of the Clinical COPD questionnaire in Italian language. Health Qual Life Outcomes 2005, 3: 9.
5. Molen van der T, Willemse BW, Schokker S, Ten Hacken NH, Postma DS, Juniper EF: Development, validity and responsiveness of the Clinical COPD Questionnaire. Health Qual Life Outcomes 2003, 1: 13.
6. van der Molen T, Kocks JW: Do health-status measures play a role in improving treatment in chronic obstructive pulmonary disease? Expert Opin Pharmacother 2006, 7: 57-61.

Nomenclature of Hop proteins

David Studholme — 2009-12-04T00:00:00Z

Following an informal meeting among P. syringae genome researchers at the IS-MPMI meeting in Quebec 2009, it was agreed that validated Hop proteins (that is, effectors that are translocated across the host membrane) should be clearly distinguished from type-three secetion system (T3SS) helper proteins. The following proteins should properly be called T3SS helper proteins: HrpZ1, HrpW1, HrpK1, HrpAK1, HrpAJ1, HopP1 and HrpA2.

Validated Hop proteins should also be distinguished from candidate Hop proteins that have been shown not to be secreted and translocated. In this manuscript, we mention several candidate T3SS substrates that are not validated: HopAH2 (C1E_3507) can be translocated by the T3SS but has yet to be found in association with a hrp box. HopJ1 (C1E_5568), HopAJ2 (C1E_0586) and HopAN1 (C1E_1908) cannot be forced to translocate even under highly optimized conditions. I would like to clarify, therefore, that these proteins are not validated T3SS effectors.

I am grateful to Dr. Magdalen Lindeberg for drawing my attention to these issues.

Subluxation, Hill's Critera of Causation and EBM

James Demetrious — 2009-12-04T00:00:00Z

I read with interest the paper written by Mirtz et al, entitled, “An epidemiological examination of the subluxation construct using Hill's criteria of causation (Chiropractic & Osteopathy 2009, 17:13).” I have reservations regarding the authors’ conclusions pertaining to which they have editorialized the subject matter and applied Hill’s Criteria of Causation.

I would direct the authors to the paper written by Phillips and Goodman entitled, “The missed lessons of Sir Austin Bradford Hill (Epidemiologic Perspectives & Innovations 2004, 1:3) [1]. Phillips and Goodman report the following:

Making a good decision does not depend on having studies with confidence intervals that exclude the null. A best decision can be based on whatever information we have now, and indeed a decision will be made – after all, the decision to maintain the status quo is still a decision. Hill offered his clearest condemnation of over-emphasizing statistical significance testing, not when he discussed p-values, but when he concluded by saying: "All scientific work is incomplete – whether it be observational or experimental. All scientific work is liable to be upset or modified by advancing knowledge. That does not confer upon us a freedom to ignore the knowledge we already have, or to postpone the action that it appears to demand at a given time [1]."

This would release us from the trap of letting ignorance trump knowledge. Regulators often fail to act because we have not yet statistically "proven" an association between an exposure and a disease, even when there is enough evidence to strongly suspect a causal relationship. There is a growing movement to escape this mistake by making a similar mistake in the other direction: adopting precautionary principles, which typically call for restrictions until we have "proven" lack of causal association – a decision based on ignorance that merely reverses the default. If we can escape from the false dichotomy of "proven vs. not proven," facilitated by the non-existant bright line implied by statistical hypothesis testing and by the notion that causality can be definitively inferred from a list of criteria, then we can make decisions based on what we do know rather than what we don't [1].

The uncritical repetition of Hill's "causal criteria" is probably counterproductive in promoting sophisticated understanding of causal inference. But a different list of considerations that can be found in his address is worthy of repeating:

• Statistical significance should not be mistaken for evidence of a substantial association.
• Association does not prove causation (other evidence must be considered).
• Precision should not be mistaken for validity (non-random errors exist).
• Evidence (or belief) that there is a causal relationship is not sufficient to suggest action should be taken.
• Uncertainty about whether there is a causal relationship (or even an association) is not sufficient to suggest action should not be taken [1].

These points may seem obvious when stated so bluntly, but causal inference and health policy decision making would benefit tremendously if they were considered more carefully and more often. The last point may be the most important unlearned lesson in health decision making [1].

In fairness to those who do not appreciate these points even today, it over-interprets Hill's short paper to claim that he clearly laid out these considerations, or that he was calling for modern decision analysis and uncertainty quantification. But the fundamental concepts were clearly there (and the over-interpretation is not as great as that required to derive a checklist of criteria for determining causation). Several generations of advancement in epidemiology and policy analysis provide much deeper exposition of his points. But Hill still offers timeless insightful analysis about how to interpret our observations. Strangely, these forgotten lessons, which are only slowly and grudgingly being appreciated in modern epidemiology, are hidden in plain sight, in what is possibly the best known paper in the field [1].

It is my impression that Mirtz et al. have exercised an uncritical repetition of Hill's "causal criteria" that is counterproductive in promoting a sophisticated understanding of causal inference of the term, “subluxation.”

I would also caution the authors to carefully apply the tenets of evidence based medicine. Sackett et al. [2] conveyed the following thoughts:

• Evidence based medicine is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients.
• The practice of evidence based medicine means integrating individual clinical expertise with the best available external clinical evidence from systematic research.
• Good doctors use both individual clinical expertise and the best available external evidence, and neither alone is enough.
• Evidence based medicine is not restricted to randomised trials and meta-analyses. It involves tracking down the best external evidence with which to answer our clinical questions [2].

Finally, the opinion of Resnick [3] bears consideration: “Evidence-based medicine is a useful tool for summarizing and grading the evidence available in the literature for or against a particular treatment strategy. Its utility is limited by the quality of the primary literature, and the absence of proof cannot be equated with the proof of absence.”

When considering the term, “subluxation,” utilized by the chiropractic profession, it is my impression that stringent adherence to epidemiologic constructs and evidence based medical protocols must not over-shadow clinical experience. Authors must integrate clinical experience and the best available external evidence.

References

1. Phillips CV, Goodman KJ: The missed lessons of Sir Austin Bradford Hill. Epidemiologic Perspectives & Innovations 2004, 1:3.
2. Sackett DL, Rosenberg WMC, Gray JAM, Haynes RB, Richardson WS: Evidence based medicine: what it is and what it isn't: It's about integrating individual clinical expertise and the best external evidence. British Medical Journal 1996, 312(7023): 71-72.
3. Resnick DK: Evidence Based Spine Surgery. Spine 2007, 32(11): S15-S19.

James Demetrious, DC, FACO
Wilmington, NC

Statistical Concerns in Analysis of Adiponectin and Cortisol Data

Allan Walkey — 2009-12-03T00:00:00Z

We read with interest the report by Venkatesh et al investigating changes in adiponectin during critical illness. Results show a significant relationship between adiponectin concentration and cortisol levels in critically ill subjects (eg., an R2 of 0.32 with p=0.01 at day 3). Upon further review of the data we observed that one extreme outlier exists in the cortisol day 3 data set (level 2620 nmol/L, with all other values below 600 nmol/L). As the authors point out, this outlier skews the cortisol data to a non-parametric distribution. Thus, in this case, the use of a simple linear regression to analyze the relationship between adiponectin and cortisol violates the normality assumptions needed for valid linear regression analyses. More appropriate analyses of these data would include reporting the Spearman correlation coefficient (as mentioned in Methods section) or log-transformation of the data for linear regression analysis. Performing these analyses, we found the Spearman correlation coefficient for the relationship between adiponectin and cortisol to be 0.51 with p=0.17; alternatively, linear regression with log-transformed values led to an R2=0.06 with p=0.33. Results demonstrate that when using non-parametric statistical methods, the relationship between adiponectin and cortisol at day 3 is no longer statistically significant. Despite this, we agree with the authors conclusion that “the relation between adiponectin and the inflammatory response, organ dysfunction and outcome in critical illness” is a subject worthy of future investigations.

Sincerely,

Allan Walkey, MD

Ross Summer, MD

Not all mice are created equal!

Sergio Stagnaro — 2009-12-03T00:00:00Z

In spite of the fact that mice and men are really different, I cannot agree with article's conclusion, that sounds: "It is concluded from the present work that chronic exposure to either the leaded or the unleaded gasoline vapours impaired the levels of monoamine neurotransmitters and other biochemical parameters in different brain areas and modulated several behavioural aspects related to aggression in rats". In fact, there is a fundamental bias in such as study: like all others creatures, mice are not created equal! Whatever environmental risk factor can act exclusively when a specific INHERITED Real Risk is present, as it happens in diabetes, CVD, cancer (1-10). This Inherited Real Risk can be bedside recognized due to the relative, local, microcirculatory remodelling, characterized by newborn-pathological, type I, sub-type a) oncological , and b) aspecific, Endoarteriolar Blocking Devices (8).

References
1) Stagnaro S., Stagnaro-Neri M.Istangiopatia Congenita Acidosica Enzimo Metabolica. Gazz. Med. It.- Arch. Sci. Med. 144, 423, 1985.
2) Stagnaro S., Stagnaro-Neri M. Una patologia mitocondriale ignorata: la Istangiopatia Congenita Acidosica Enzimo-Metabolica. Gazz. Med. It. - Arch. Sci. Med. 149, 67 1990.
3) Stagnaro Sergio. Newborn-pathological Endoarteriolar Blocking Devices in Diabetic and Dislipidaemic Constitution and Diabetes Primary Prevention. The Lancet. March 06 2007. http://www.thelancet.com/journals/lancet/article/PIIS0140673607603316/comments?totalcomments=1
4) Stagnaro-Neri M., Stagnaro S., Cancro della mammella: prevenzione primaria e diagnosi precoce con la percussione ascoltata. Gazz. Med. It. – Arch. Sc. Med. 152, 447 1993
5) Stagnaro-Neri M., Stagnaro S. Introduzione alla Semeiotica Biofisica. Il Terreno Oncologico. Travel Factory, Roma, 2004. http://www.travelfactory.it/semeiotica_biofisica.htm
6) Stagnaro S., Stagnaro-Neri M., Oncological Terrain, conditio sine qua non of Oncogenesis, 2004: http://www.gutjnl.com/cgi/eletters?lookup=by_date&days=60
7) Stagnaro Sergio. "Genes, Oncological Terrain, and Breast Cancer" World Journal of Surgical Oncology., 2005, http://www.wjso.com/content/3/1/45/comments#205475
8) Stagnaro Sergio. Reale Rischio Semeiotico Biofisico. I Dispositivi Endoarteriolari di Blocco neoformati, patologici, tipo I, sottotipo a) oncologico, e b) aspecifico. Ediz. Travel Factory, www.travelfactory.it, Roma, Luglio 2009.
9) Stagnaro Sergio. CAD Inherited Real Risk, Based on Newborn-Pathological, Type I, Subtype B, Aspecific, Coronary Endoarteriolar Blocking Devices. Diagnostic Role of Myocardial Oxygenation and Biophysical-Semeiotic Preconditioning. www.athero.org, 29 April, 2009 http://www.athero.org/commentaries/comm907.asp
10) Stagnaro Sergio. Role of Coronary Endoarterial Blocking Devices in Myocardial Preconditioning - c007i. Lecture, V Virtual International Congress of Cardiology, 2007. http://www.fac.org.ar/qcvc/llave/c007i/stagnaros.php

Future of Cases Journal

Subramanian Vaidyanathan — 2009-12-02T00:00:00Z

I understand that Cases Journal has stopped accepting new manuscripts.
Whatever version replaces Cases Journal, the new online database or repository of doctor-patient narratives should be
1. Peer-reviewed
2. Indexed in Medline, PubMed, PubMed Central
3. Open acccess online medical repository, which is reliable
4. The article processing fee or its equivalent should be affordable; say, £99 plus VAT
5. Prompt publication

Thanks
Dr S Vaidyanathan

applause for your philosophy on the journal!

S. Calvin Li — 2009-12-02T00:00:00Z

Dear Honorable Editor Smith,

Reading your "Editorial, Standards of English in a democratic, mass publication journal." Your courage and vision have impressed me tremendously. You are making a historic breakthrough by doing what you are doing! I admire the following points.

"So where do we draw the line? How low will we go? As low as we can" is the answer."

I don't think that is a low standard as long as you can get the most raw materials - People preserve their own style of using English and their way of expression - a precious moment of inspiration in writing. Many cases in the history have showed that it was those not so sophisticated in writing discovered the most important facts. When those "language fanatics" found “infelicities of language in the journal” as you pointed out, however, they missed the real meaning of your journals, recording those “facts” – the raw precious materials. Even those "‘good books’ – Dickens, Trollope, Hemingway, Powell, Austen, Eliot, Conrad, James, Proust, Balzac, Roth, Updike, McEwan, and the like,” had inspired by “raw materials.”

The following idea of "dialogue" is an invention in the scientific publishing business.

"Then because Cases Journal is electronic we have the possibility of dialogue. Being misunderstood is routine even if your language is perfect. Wise doctors, for example, will ask patients to repeat back to them what they have understood. Often they find that patients have misunderstood even when they say they have understood clearly. So if readers cannot understand what authors have written then they should ask them to explain, and we will ensure that authors respond."

I applause for your philosophy on the journal! An article written with the depth and beauty is recognised more about its well-balanced thought and inspiration than its eloquent rhetoric. Simply state, facts are more important than rhetoric.

Respectfully,

A reader

What was the cause of death and impressed by the report of pain relief

Melvin Hayden — 2009-12-02T00:00:00Z

Thank you for sharing you interesting case report with calciphylaxis.

I thought the relief of pain was rather classical and seems to be a an exciting outcome for the pain is horrendous and actually horrific.

What was the cause of death in your patient as this was not discussed in your case report. Also what was the time interval between the onset of the eschar you shared and death?

How can we be certain that the sodium thiosulfate was not promoting wound healing if the patient died as it frequently takes 3-6 months for these lesions to heal. Do you have any images of the skin ulceration after 2 months as there could be evidence of healing at the wound margin.

I look forward to your comments and response.

If you prefer you may feel free to correspond with me by e-mail: mrh29@usmo.com

Thank you again for sharing this most interesting case report and I wish to thank Cases Journal and their editors for allowing case reports such as this case to be reported and shared with the readers of Bio Med Central. M.R. "Pete" Hayden, MD.

Regarding new thoughts and ideas in evolution. There is growing interest in the development of low levels of hepatic synthesized fetuin-A,which is surpressed concurrent with albumin when the innate immune system is activated due to redox stress and activation of NFkappaB by reactive oxygen species and subsequent downstream inflammatory cytokines. pete hayden

Is it a manifestation of immune deficiency?

aisha marsafy — 2009-12-02T00:00:00Z

I agree with you that splenic abscess is a relatively rare presentation.
I wished to know some data such as the details of the blood picture, if blood culture was done, if culture from the removed spleen was obtained,what was the organism?
Did you perform any immunological screening in this case?