On 2014 Sep 24, Michael Schroda commented:

This system works extremely well and represents an outstanding improvement of the Chlamydomonas toolkit.

On 2015 Jun 29, Bill Cayley commented:

A good example of when Less is More: https://lessismoreebm.wordpress.com/2015/06/29/efficacy-and-safety-of-steroid-injections-for-shoulder-and-elbow-tendonitis-a-meta-analysis-of-randomised-controlled-trials/

On 2014 Mar 05, Jacob Puliyel commented:

IT IS EXPEDIENT BUT IS IT PRUDENT TO LABEL ADVERSE EVENTS FOLLOWING IMMUNIZATION AS 'NOT AN EVENT OF [AEFI]'?

The old scheme of monitoring signals for vaccine safety (adverse events following immunization – AEFI monitoring), of the Advisory Committee on Causality Assessment Collet JP, 2000 has been overtaken by the Revised WHO Classification of AEFI. The changes have been described in 4 PubMed articles Tozzi AE, 2013, Bonhoeffer J, 2009, Halsey NA, 2012, Williams SE, 2013.

I wrote two very detailed comments to the article by Tozzi et al Tozzi AE, 2013 on the PubMed Commons which is envisaged as a forum for open constructive criticism and discussion of scientific issues. To facilitate meaningful discussion it has a link to 'Invite an author to comment'. Tozzi and colleagues have not responded so far. PubMed suggests that the main reason for not getting a response is a changed email contact address.

As this is a matter of patient safety I think it is important that the experts who understand the new scheme must explain why the revision was needed and that it is an improvement over the old scheme - that it will not miss opportunities of picking up new signals by classifying AEFI as 'Not a case of [AEFI]'. I will not repeat the posting but it may be viewed here

The purpose of this posting is to invite the learned authors of this article on causality assessment Bonhoeffer J, 2009 to respond. The article by Bonhoeffer and colleagues mostly describes a guideline for collection of data which is unexceptional, but the subsequent 'analysis and presentation of vaccine safety data in the surveillance system' may cause signals to be ignored because they are classified as ‘Not a case of [AEFI]’. Would the new scheme have picked up and flagged signals of adverse-effects like the RotaShield-reactions, had the scheme been in use in 1998?

On 2017 May 12, Kevin Hall commented:

In the copy editing process, it appears that several typographical errors were introduced in equations 5, 10, 14, and 15. The corrected equation 5 is:

DeltaBW = [(1-beta) x DeltaEI -Deltadelta x BWinit -(gammaFFM -gammaFM) x FM_init]/(gammaFFM +deltainit +Deltadelta) +[C x (gammaFFM -gammaFM)/(gammaFM +deltainit +Deltadelta)] x LambertW{[(gammaFM +deltainit+Deltadelta) x FMinit]/[C x (gammaFFM +deltainit +Deltadelta)] x Exp[[(gammaFM +deltainit +Deltadelta) x FMinit]/[C x (gammaFFM +deltainit +Deltadelta)]] x Exp[[(1-beta) x DeltaEI - Deltadelta x BWinit]//[C x (gammaFFM +deltainit +Deltadelta)]]}

The corrected Equation 10 is:

DeltaEI = Deltadelta x BWinit/(1-beta) + C² x (gammaFFM-gammaFM) x FMinit/(1-beta) + DeltaBW x (gammaFFM-gammaFM) x C² /(1-beta) x [1+(gammaFM +deltainit +Deltadelta)/(gammaFFM-gammaFM)]-C x (gammaFFM-gammaFM)/(1-beta) x LambertW{C x FMinit x Exp[C x (1 +FMinit) +DeltaBW]}

The corrected Equation 14 is:

DeltaBW=[(1-beta) x DeltaEI -Deltadelta x BWinit]/[gammaFFM +deltainit +Deltadelta-(gammaFFM -gammaFM) x Phi]

The corrected Equation 15 is:

d/dPhi{DeltaBW/DeltaEI} = (gammaFFM -gammaFM) x (1-beta)/[gammaFFM +deltainit-(gammaFFM -gammaFM) x Phi]² > 0

On 2013 Oct 28, Jamie Horder commented:

An independent group (Shumway S, 2012) confirmed the validity of the Calibrated Severity Score in 2012.

On 2014 Aug 31, Ivan Oransky commented:

This paper has been retracted: http://retractionwatch.com/2014/08/29/second-retraction-for-ob-gyn-in-ori-probe/ It's the second retraction for the last author: http://retractionwatch.com/2012/10/29/ori-investigating-university-of-florida-ob-gyn-researcher-accused-of-misconduct/

On 2016 Jan 23, Kenneth Witwer commented:

The link under "Availability" now opens a page in Japanese that does not appear to cover microarrays. Might this information be available elsewhere?

On 2016 Apr 12, Wolfgang Huber commented:

Dear Kenneth

Thank you for pointing this out. Apologies for the two months delay in response, I only saw your post today. The main online reference to the package remains the Bioconductor project: https://bioconductor.org/packages/arrayQualityMetrics . Running the code in the package vignette produces all the example reports mentioned in the above abstract. Moreover, we are also hosting a copy of these reports here: http://www-huber.embl.de/arrayQualityMetrics

The now defunct URL http://www.microarray-quality.org was associated with a grant-funded project (European Commission FP6) that achieved a lot of excellent outcomes but eventually reached the end of its life cycle (http://publications.jrc.ec.europa.eu/repository/handle/JRC60783).

On 2013 Nov 25, Dennis Eckmeier commented:

We did a follow-up electrophysiology study, which was published with some delay in 2013: Encoding of naturalistic optic flow by motion sensitive neurons of nucleus rotundus in the zebra finch (Taeniopygia guttata).

On 2013 Jun 15, Steven Salzberg commented:

This is a terrific article that rebuts the bad science promulgated by a popular children's doctor, who has been pushing an anti-vaccination message for years. Offit and Moser go through Sears' claims point-by-point and show how each one is misleading or simply wrong. Every pediatrician should read this.

On 2015 Jul 16, Mohamed Fahmy commented:

I wish to share in this valuable study, I think I had some exerince in this field

On 2015 May 07, Jeff Kiefer commented:

DAVID is continuously being used as evidenced by its numerous citations in current biomedical literature http://bit.ly/1FS1JgT. However, the data resources used by DAVID appear to not have been updated since 2009 http://david.abcc.ncifcrf.gov/helps/update.html. The fact that DAVID has not been updated going on 5 years calls into question the current utility of using this tool.

On 2016 May 26, Jeff Kiefer commented:

It looks like DAVID has been updated May 2016 https://david-d.ncifcrf.gov/content.jsp?file=release.html.

On 2017 Jul 11, Robin P Clarke commented:

"..why we are now seeing so many of these progressive diseases..."

One possibility could be that increased dietary vitamin C is causing increased iron absorbtion leading to progressive excess - even though obviously the vitamin C has benefits too (in the shorter term?).

On 2014 May 10, Ivan Oransky commented:

This paper has been retracted: http://retractionwatch.com/2014/05/09/more-retractions-for-researcher-who-says-he-will-no-longer-publish/

On 2017 Dec 06, Alexander Kraev commented:

The authors of this paper claim to have generated mouse strains that carry a PLN(R9C) transgene and 2, 1, or 0 endogenous PLN alleles. However, the mutant PLN resides on a transgenic array, with multiple copies the number of which the authors chose not to determine. It was independently found (https://doi.org/10.1101/075671), that the mutant PLN gene, assuming the transgene does not re-arrange during breeding, is present in 13 copies. This work also did not determine the actual mutant to wildtype PLN ratio at the mouse age, when the expression of the transgenic promoter is maximal (1 month), which would have estimated the scope of the overexpressed protein "bolus injection" that each strain received. Therefore, the conclusions of this paper should be interpreted with extreme caution, especially as such gene combinations never occur in human patients carrying PLN mutations.

On 2014 Apr 22, TS Shanmugarajan commented:

arun.laureate@gmail.com

On 2014 Nov 25, Harri Hemila commented:

The reasons for the retraction of this paper are described in: http://www.mv.helsinki.fi/home/hemila/PPH/CTA/CTA.html

On 2014 Jan 08, Tom Kindlon commented:

The inclusion of more quotes and qualitative information in the paper would have been useful

I think this is an interesting issue. However I think the paper would have benefited from quotes from what the participants said and generally more qualitative information. If healthcare providers are to improve on the situation, they need as much information as they can get about what exactly are the barriers.

In particular, I feel more qualitative information on "Knowledge, Attitudes, and Beliefs (KABs)" and "Healthcare System" would have been useful. Perhaps the data could be used to write another paper.

By the way, I find the use of the phrase (and acronym) "while those with insufficient fatigue (ISF)" in the abstract to be far from satisfactory. It seems to put fatigue onto a pedestal as the primary part of the definition of CFS. People for example may be in the ISF category because they don't have four of the case defining symptoms (while at the same time having "sufficient fatigue" i.e. the fatigue satisfies the entry criteria for CFS).

On 2015 Aug 19, Bill Cayley commented:

A good example of when "Less" is "more": https://lessismoreebm.wordpress.com/2015/08/03/episiotomy-for-vaginal-birth/

On 2015 Apr 02, Harri Hemila commented:

Errors in the Cochrane review (2009) on vitamin C for asthma by Kaur B, 2009.

In 2009, I found that the Cochrane review on vitamin C for asthma by Kaur B, 2009 had severe errors in the extraction and analysis of data. I wrote a Feedback to the Cochrane review and it is part of the 2009 Cochrane review, DOI, but the Feedback is also available as a separate document. Then I found out that the errors originated in the first Cochrane review version by Kaur B, 2001, see Pubmed Commons. Those errors were repeated in the updates by Ram FS, 2004 and by Kaur B, 2009, until the review was withdrawn by Kaur B, 2013. Because of the severe errors, the Cochrane review “vitamin C for asthma” misled readers for over a decade. This below is the Feedback (2009).

The Feedback (2009) on the Cochrane review by Kaur B, 2009

Schachter EN, 1982 carried out a trial with participants who had exercise-induced bronchoconstriction (EIB) so that each of the 12 participants was administered placebo and vitamin C at different times. Thus, each participant served as his or her own control (crossover). In Table III Schachter reported pre-post-exercise change of FEV1, so that the later FEV1 was measured 5 minutes after the exercise. Because two observations are measured from the same participant, the placebo period and vitamin C period difference in FEV1 change should be analysed using the paired t-test. The FEV1 data in Schachter’s Table III gives the mean difference between the vitamin C and placebo periods as 0.20 (SD 0.33) litres/s. Schachter EN, 1982 calculated t=2.13 in their paper, corresponding to P[1-tail]=0.028.

The Cochrane review by Kaur B, 2009 presents Schachter’s FEV1 changes in Analysis 1.2. However, data in Analysis 1.2 were extracted from Schachter’s Table II, which presents post-exercise FEV1 value measured immediately after the exercise. In EIB the fall in FEV1 occurs 5 to 20 minutes after the end of exercise, Rundell KW, 2008. Even Schachter EN, 1982 reported that, on the screening day, there was no fall in FEV1 immediately after exercise, but a significant fall 5 minutes after the exercise (Schachter Fig. 2). Therefore, extracting the FEV1 changes from Schachter’s Table II (FEV1 immediately after the exercise) is not reasonable if the purpose is to examine the effect of vitamin C on EIB.

Cohen HA, 1997 carried out an EIB trial with 20 participants who were administered placebo and vitamin C at different times (crossover). Post-exercise FEV1 was measured 8 minutes after the end of the exercise. The observations are paired also in this case and the results should be analysed using a paired test. 9 participants had FEV1 decrease >15% on both vitamin C and placebo treatments. 11 participants had >15% FEV1 decrease on placebo but <15% FEV1 decrease on vitamin C (Cohen 1997 Fig. 2). None of the participants had the opposite effect: <15% FEV1 decrease on placebo and >15% FEV1 decrease on vitamin C. In the paired 2x2 table analysis, the question is whether the difference between the corners (here 11 and 0) is statistically significant. This difference gives z=(11-0)/sqrt(11+0)=3.31, corresponding to P[1-tail]=0.0005.

A basic principle in controlled trial analysis requires that all randomized participants should be included in the analysis, the ITT principle. However, the Cochrane review by Kaur B, 2009 does not give the results for all 20 participants of (Cohen Fig. 2); Analysis 1.2 gives the results for only the 11 participants who had benefit of vitamin C (Cohen Table 2).

Furthermore, the Cochrane review by Kaur B, 2009 presents the average of post-exercise FEV1 values and not the pre-post-exercise difference in FEV1 in analysis 1.2. The post-exercise averages for Cohen’s Table 2 are 1.66 (SD 0.80) litres/s in the placebo period and 1.93 (SD 0.78) litres/s in the vitamin C period, P=0.42. However, given that the EIB is defined by the pre-post change in FEV1, the measurement of the effect on EIB should be based on the pre-post-exercise difference in FEV1, Rundell KW, 2008.

Furthermore, the relative effect calculated by Cohen HA, 1997 (Table 2; in %-units) is a better measure than the absolute value (in litres/s) because the relative effect adjusts for the great variation in baseline FEV1; the relative decrease in FEV1 is also used in guidelines, Rundell KW, 2008. Cohen HA, 1997 reports that the average relative fall in FEV1 is 25% in the placebo period and 5% in the vitamin C period (Table 2). Because the observations are paired, the paired t-test should be used. The average of the differences is 20% (SD 12%, SE 3.7%), which gives t=5.57, corresponding to P[1-tail]=0.00012. Thus, although the Cochrane review by Kaur B, 2009 presented only the 11 participants in which vitamin C was beneficial, their calculation suggests that even in this subgroup vitamin C was without effect, P=0.42, whereas a correct calculation gives a much smaller P-value.

In their EIB trial, Tecklenburg SL, 2007 studied 8 participants who were administered vitamin C and placebo at different times. They measured post-exercise FEV1 at 1, 5, 10, 15, 20, and 30 min after the exercise. Tecklenburg 2007 reported that the decrease in FEV1 in the vitamin C period was 6.4% (SE 2.4%) and decrease in the placebo period was 12.9% (SE 2.4%). Tecklenburg did not publish the paired comparison, nor original data so that the paired t-test could be calculated. Nevertheless, these averages give unpaired t=1.91, corresponding to P[1-tail]=0.038, which is conservative, the paired test P-value would be smaller.

Thus, three trials included in the Cochrane review by Kaur B, 2009 found benefit of vitamin C supplementation against EIB at 5 and 8 minutes after the exercise, Cohen HA, 1997, Schachter EN, 1982, or at the time of maximum fall in FEV1, Tecklenburg SL, 2007. The three P-values calculated above (0.028, 0.0005, 0.038) can be combined by using the Fisher's method. The combined P = 0.00007 provides evidence that the effects of vitamin C on EIB in these three trials are not explained by random fluctuations.

Analyses 1.1, 1.3 and 1.5 by Kaur B, 2009 present baseline data of two EIB trials discussed above (Cohen 1997; Schachter 1982). However, when a trial specifically examines the effect of vitamin C on EIB, the relevant outcome is the difference between the baseline and the 5-10 minutes post-exercise FEV1 values (the pre-post change), and not the baseline FEV1 value alone.

Finally, diagnosis of EIB by the change in FEV1 is well established Rundell KW, 2008. Therefore Kaur B, 2009 should have considered whether there is any benefit for readers from making additional analyses of the FVC and PEF values of the oldest trial by Schachter 1982. The more recent trials by Cohen 1997 and Tecklenburg 2007 did not report changes in FVC and PEF.

Postscript in 2015

Three years after my Feedback (above), in 2012, the Cochrane review authors replied to my criticism. Since their response had further errors, I wrote a second Feedback in 2013. The second Feedback was rejected by the Cochrane Airways group. Their rejection was inconsistent with the Principles of the Cochrane Collaboration (accessed April 2015). Eight principle is about “Ensuring quality: by applying advances in methodology, developing systems for quality improvement, and being open and responsive to criticism” [bold added]. The second Feedback (2013) is available as a separate document.

The above Feedback (2009) was extended to full length papers by Hemilä H, 2013 and Hemilä H, 2014.

On 2014 Apr 16, Tom Kindlon commented:

Prevalence estimates have been inflated due to the female predominance in the samples

(I previously posted this as a comment on the Br J Psych http://bjp.rcpsych.org/content/194/2/117.abstract/reply#content-block but not everyone may see it there)

We are not given information on the gender breakdown of Chronic Fatigue Syndrome (CFS) in this study but if it is in-line with other studies in the field, females would be much more likely to have CFS. Given a much larger percentage of the cohorts are female compared to the general population, this would mean that the (adjusted) prevalence rates for each country would be lower.

The total number of CFS cases found in a particular country cohort = Number of women with CFS + Number of men with CFS = P(CFS|F)N(F)+P(CFS|M)N(M) where F=Female, M=Male, N(F)=Number of Females, P(CFS|F)=Probability of a female having CFS, etc.

If one takes P(CFS|M)=0.25*P(CFS|F), which would be comparable to an approximate average of previous studies (for example, [1-4]), and assumes the number of men and women are equal in the 18-45 age bracket, the prevalence rates for CFS in the UK and Brazil are 1.65% and 1.21% respectively.

These figures in themselves are an upper bound on the true prevalence rates, given individuals in neither group went through rigorous and thorough individual assessments to exclude other conditions.

References:

[1] Bazelmans E, Vercoulen JH, Swanink CM, Fennis JF, Galama JM, van Weel C, van der Meer JW, Bleijenberg G. Chronic Fatigue Syndrome and Primary Fibromyalgia Syndrome as recognized by GPs. Fam Pract. 1999 Dec;16(6):602-4.

[2] Jason LA, Richman JA, Rademaker AW, Jordan KM, Plioplys AV, Taylor RR, McCready W, Huang CF, Plioplys S. A community-based study of chronic fatigue syndrome. Arch Intern Med. 1999 Oct 11;159(18):2129-37.

[3] Kim CH, Shin HC, Won CW. Prevalence of chronic fatigue and chronic fatigue syndrome in Korea: community-based primary care study. J Korean Med Sci. 2005 Aug;20(4):529-34.

[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 Intern Med. 2003 Jul 14;163(13):1530-6.

On 2016 Nov 25, Egon Willighagen commented:

Many of the conversions of nicotine outlined in Figure 3 are available as machine readable data in WP1600 in WikiPathways: http://www.wikipathways.org/index.php/Pathway:WP1600

On 2015 Sep 11, Bill Cayley commented:

A good example of when "Less" is "more" in evaluating foot and ankle injuries: https://lessismoreebm.wordpress.com/?s=ankle

On 2014 Oct 23, Khalid Hassan commented:

One of my students did a similar study for her dissertation (currently in press). She found that the consumption of alchohol is the single biggest cause for car crashes in Turkey (35% of all crashes were associated with alcohol use). This finding is no suprise by itself and complements numerous previous studies. However, she did find a very interesting new correlation. Since her group uses anonymized data from insurance companies, they were able to test several hypothesis which were in coordance with car crashes caused by the consumption of alcohol. For example, she found that certain car brands are associated with a 75% increase in alcohol related car crashes. While this is most likely just correlational and not caused because these cars are harder to drive when under influence, she did find another correlation which might be very intruiging to study further.

Because most of her data was provided by insurance companies, they were very detailed and trustable. For example, they included police reports were applicable. Because of this data they were able to establish wether the alcoholic user was the perpetrator of these crashes or wether (while driving under influence is technically illegal) were the culprit of these crashes. In the vast majority of cases the drivers under the influence of alcohol were indeed the perpetrator (85%). However she did a very intruiging finding when digging deeper in the data that was provided by insurance companies. The use of dashcams Wikipedia has gained a lot of popularity in Turkey in recent years. This is caused by multiple factors, one of which has to do with reduced insurance costs by car insurance companies. When my student corrected for the use of a dashcam, she found dat the pepetrator/culprit(85%/15%) ratio decreased significantly to 55/45%. Of course this is a very intruiging finding which can be caused be several factors. This is the first research to examine the use of a dashcam in relation to the amount of alcohol related car crashes. We're currently looking to see wether these results hold up in a bigger sample size. While this is the first study to find this correlation, there is a previous Dutch one (Website) which found that the use of a dashcam is associated with a reduction of the involvement in general car crashes of 34%. Incidentally, our study showed the same result in alcohol related crashes, but further study is now urgently needed.

On 2015 Jun 02, thomas samaras commented:

Additional information on height, body size and longevity is available from:

Samaras TT. Evidence from eight different types of studies showing that smaller body size is related to greater longevity. Journal of Scientific Research & Reports. 2014: 3 (16): 2150-2160, 2014; article no. JSRR.2014.16.003.

Samaras TT. Human Scaling and Body Mass Index. In: Samaras TT (ed): Human Body Size and the Laws of Scaling: Physiological Performance, Growth, Longevity and Ecological Ramifications. New York: Nova Science Pub; 2007: pp 17-32.

He Q, Morris BJ, Grove JS, Petrovitch H, Ross W, Masaki KH, et al. Shorter men live longer: Association of height with longevity and FOXO3 genotype in American men of Japanese ancestry. Plos ONE 9(5): e94385. doi:10.1371/journal.pone.0094385.

Salaris L, Poulain M, Samaras TT. Height and survival at older ages among men born in an inland village in Sardinia (Italy), 1866-2006. Biodemography and Social Biology, 58:1, 1-13.

Bartke A. Healthy Aging: Is Smaller better? A mini-review. Gerontology 2012; 58:337-43.

On 2014 Sep 12, Ivan Oransky commented:

This study reported that vials cost 71% more in June 2008 than they did in January 2007. That increase has continued unabated, as we report at MedPage Today: http://www.medpagetoday.com/Endocrinology/Diabetes/47603

On 2014 Mar 30, Tero Kivelä commented:

Figure 4 in this paper raises a few questions:

1: The graph has 2 steps indicating 2 patients who died, and 5 ticks indicating 5 censored observations; this adds to 7, but 11 patients entered the study.

2.1: According to the text "Three patients have died from extrahepatic metastases at 2.5, 3, and 18 months posttreatment". The one who died at 3 months is not plotted.

2.2: According to the text "One patient was lost to follow-up after 2.5 months". This patient is not plotted.

2.3: If we add these two apparently non-plotted patients, the plot seems to account only for 9 of the 11 patients.

2.4: Adding these 2 patients to the plot would drop 1-year survival to 25%, and 50% mortality would be reached around 18 months.

3: According to the text "Of the remaining 8 patients in follow-up, 1 patient developed new hepatic lesions at 14 months posttreatment". If we deduct from the 11 patients who entered the study the 3 who died and the 1 who was lost to follow-up, only 7 patients remain.

On 2017 Jul 07, Morten Oksvold commented:

This article should have been retracted after an investigation by The University of Maryland found this article to contain "compromised" data (a total of 26 articles in 11 journals were affected). The journal Clinical Cancer Research was informed in February 2017, according to Retraction Watch.

http://retractionwatch.com/2017/04/26/university-asked-numerous-retractions-eight-months-later-three-journals-done-nothing/

On 2014 Nov 23, Harri Hemila commented:

A manuscript version is available at handle

On 2013 Dec 28, Tsuyoshi Miyakawa commented:

"ImageEP", an image analysis appilcation software shown in this video article, is now freely availble from http://www.mouse-phenotype.org/software.html.

On 2014 May 05, Martine Crasnier-Mednansky commented:

Data by Wanner BL, 1978 did not indicate β-galactosidase activity is inversely proportional to the specific growth rate. In fact, data from Wanner Figure 1A indicated a large variation in β-galactosidase activity occurred in media supporting similar growth rate (thus synthesis rate is not constant). In addition, data from Wanner Figure 2B did not indicate addition of exogenous cAMP increased β-galactosidase activities less than two-fold. Wanner et al. stated "Media in which there was marked growth rate inhibition by cAMP also showed large stimulation of β-galactosidase synthesis; a growth rate inhibition, however, was not a necessary condition for an increase in the enzyme activity". In the presence of cAMP however, even though much of the variation was eliminated, repression remained which was carbon source dependent and growth related. Whether it [the remaining repression] is mediated by cAMP is uncertain - concluded Wanner et al.

On 2014 Dec 10, Kath Wright commented:

Other search filters are available from the InterTASC Information Specialists' Sub-Group Search Filter Resource at https://sites.google.com/a/york.ac.uk/issg-search-filters-resource/home

On 2016 Mar 31, Margaret Sampson commented:

Please see the updated version of PRESS: McGowan J, Sampson M, Salzwedel DM, Cogo E, Foerster V, Lefebvre C. PRESS Peer Review of Electronic Search Strategies: 2015 Guideline Statement. J Clin Epidemiol. 2016 Mar 18. pii: S0895-4356(16)00058-5. doi: 10.1016/j.jclinepi.2016.01.021. [Epub ahead of print] PubMed PMID: 27005575.

And the revised Explanation & Elaboration document: McGowan J, Sampson M, Salzwedel D, Cogo E, Foerster V, Lefebvre C. PRESS – Peer Review Electronic Search Strategies: 2015 Guideline Explanation and Elaboration (PRESS E&E). Ottawa: CADTH; 2015 Jan. https://www.cadth.ca/sites/default/files/pdf/CP0015_PRESS_Update_Report_2016.pdf

On 2016 Nov 20, Morten Oksvold commented:

An investigation committee at Wayne State University (WSU) recommends that 42 articles from Fazlul Sarkar to be retracted (report finished August 31, 2015). This article represents one of them.

This information was published by Retraction Watch (November 17, 2016) and you can find a link to the full report here:

http://retractionwatch.com/2016/11/17/details-of-investigative-report-into-sarkar-released-by-aclu/

This article should therefore no longer be cited.

On 2014 Dec 17, Sean Ekins commented:

Find out about CDD Vault here https://www.collaborativedrug.com/

On 2016 Apr 01, Egon Willighagen commented:

The pathway in Figure 2 is now available from WikiPathways: http://www.wikipathways.org/index.php/Pathway:WP3627

On 2014 Apr 28, Francisco Xavier Castellanos commented:

This line of work represents an important advance in seeking to identify the nature of the timing-related processing abnormalities that are regularly reported in ADHD and related conditions. As recently summarized by Kofler et al. (2013; PMID 23872284), reaction time variability is robustly associated with ADHD, but this is not specific to ADHD, as other psychiatric conditions also exhibit markedly elevated response time variability. Similarly, timing abnormalities have been noted at multiple time scales in ADHD (e.g., Noreika, Falter, Rubia, 2013; PMID 23022430) which likely reflects involvement of multiple brain systems. Gilden and colleagues are focusing on a specific frequency band/temporal window, which may allow tighter specification of the neurobiological correlate. In this regard, see their most recent paper, which is not yet allowing comments (Marusich and Gilden, 2014, Neuropsychology) PMID 24708046.

On 2014 Nov 23, Harri Hemila commented:

A comment is available at: http://hdl.handle.net/10138/16982

On 2014 Jan 11, Brett Snodgrass commented:

Dear Authors,

Thank you for the refreshing article that prudently identifies the Thebesian veins as veins, structures distinct from both the arteriosinusoidal (vessels-arteries) and the arterioluminal (vessels-arteries).

Please consider the excerpt:

"Arteriosinusoidal vessels connect arterioles to the chambers and Thebesian veins connect capillaries to the chambers. Beside these two vessel types, few small arterioluminal arteries drain directly into the chambers*

The definition of Thebesian veins connecting to the chambers may be correct, but might be more descriptively stated as by Pratt as they also include connections larger than capillaries. It is possible that the Thebesian veins do not always directly connect the venular end of a capillary bed to the heart chamber, but may occasionally connect a small vein to the heart chamber.

http://bit.ly/ThebesianByPratt

Please consider that both the arterioluminal and arteriosinusoidal vessels (vessels of Wearn) drain to the heart chambers from the coronary arteries.

The arteriosinusoidal vessels connect {small arteries &/or arterioles} to [myocardial sinusoids] which connect to the (heart chambers).

The arterioluminal vessels connect {small arteries &/or arterioles} to (heart chambers). http://bit.ly/JTWearn Wearn examined the celloidin casts of the arterioluminal vessels and noted that they exhibit vessel diameters that range from 0.2 mm to 1.0 mm. The diameter of the lumina as measured in the collapsed state ranged from 0.04 to 0.2 mm. (http://bit.ly/JTWearn page 158).

Wearn was probably too humble to name the vessels after himself. However, he referred to both the arteriosinusoidal & arterioluminal vessels collectively as "arterioluminal." An analogy for this difficult nosology is appreciated by consideration the drum and drumset termed "Tabla." A wise professor once told of a drumset where both drums were collectively called “Tabla,” and the drum on the right was also called “Tabla.”

In this analogy, the term “Tabla” is comparable to the term “arteriosinusoidal vessel.”

In summary, using the same word to represent two different concepts or two different things can probably be confusing. When uncertain of the specific type of arterial-vessel as defined by Wearn, the term “vessels of Wearn” may be appropriate. The eponym vessels of Wearn is the only specific noun that has been appropriately applied to these connections.

The vessels of Wearn connect coronary arteries to each of the four heart chambers. The term "ventriculocoronary connection,"(VCC) is certainly appropriate when referring to isolated ventricular connections. However, using the term VCC could also be applied to traumatically induced fistulae and therefore it does not reflect the normal nature of these connections. Thus the noun "vessels of Wearn," is appropriate in a manner similar to the term "distal convuluted tubule" is appropriate for those specific tubules. Thus, an eponym vessels of Wearn may be appropriate for these normal connections between the coronary arteries and heart chambers.

Thank you again for the excellent article.

Comments and suggestions are kindly requested. My aim is to follow the plea of Dr. Lurie and work with others to help produce accurate cardiac nomenclature.

Thank you very much.

On 2013 Nov 24, John Sotos commented:

Desai et al (1) describe a tragic case of panhypopituitarism diagnosed only when the patient developed cardiogenic shock and required two weeks of mechanical and pharmacological inotropic support, plus an implanted defibrillator.

Because they focus chiefly on the final outcome, the authors consider the patient’s management as a success. Instead, they should have used techniques of aviation mishap investigation to question how this patient’s close, 21st-century medical care over the preceding year could have allowed an eminently treatable disease to reach Dickensian severity.

Why did the review of systems upon admission not disclose the patient’s symptoms of hypothyroidism? Why did the admission physical miss the obvious hair and skin signs? Why was the neurological examination deemed “unremarkable” when this patient very likely had markedly delayed relaxation of tendon reflexes (2,3,4)? Evaluating such suspicious findings could have advanced hormone replacement and averted complications.

Aviators live and die by their checklists — literally. Thorough patient histories and physical exams are medicine’s ultimate checklist. We shortcut them at our peril, and at the peril of our patients.

(1) Desai NR, Ceng S, Nohria A, Halperin F, Giugliano RP. When past is prologue. N Engl J Med. 2009; 360: 1016-1022. Pubmed 19264691 doi: 10.1056/NEJMcps0805508

(2) Jonckheer M, Blockx P, Molter F. Use of the Achilles-tendon reflex in thyroid clinical investigation. Acta Endocrinol (Copenh). 1970; 63: 175-184. Pubmed 5467016

(3) [No authors listed] The Achilles heel of the ankle jerk. Journal of the American Medical Association. 1967; 199: 39. Pubmed 6071124

(4) Chaney WE. Tendon reflexes in myxoedema: valuable aid in diagnosis. Journal of the American Medical Association. 1924; 82: 2013-20166.

On 2015 Jun 06, Preben Berthelsen commented:

On page 136, Ristagno et al state that the Danish anaesthesiologist Bjørn Ibsen’s involvement in the Copenhagen poliomyelitis epidemic 1952-3 was not the beginning of critical care medicine. I beg to differ. It was the respect of his peers - gained from his pivotal engagement in the polio epidemic - that made it possible for Ibsen to inaugurate the first multidisciplinary intensive care unit in the world at Kommunehospitalet in Copenhagen December 21, 1953. (Berthelsen PG, Cronquist M. The first intensive care unit in the world: Copenhagen 1953. Acta Anaesthesiol Scand 2003;47:1190-5).

On page 138, the Norwegian Kristian Igelsrud is credited for the first successful open-chest cardiac massage in 1901. The account of the resuscitation, however, only appeared in the lay press so few clinical details are known. (There is a second-hand account in Keen ref. 43). In 1900, the Danish surgeon Hjalmar Maag used open-chest cardiac massage in a 27-yr-old man whose heart had stopped during chloroform anaesthesia (24 October, 1900). The beat of the heart was restored by Maag’s massage but cerebral damage was so severe that the patient died 10 hours later. (Maag H. Ein Versuch der Wiederbelebung (a.m. Prus) eines in Chloroformnarkose gestorbenen Mannes. Centralblatt fur Chirugie 1901;1:20-2).

P.G. Berthelsen, MD. Charlottenlund, Denmark.

On 2017 Sep 02, thomas samaras commented:

A recent paper indicates that shorter, smaller people have lower cardiovascular risk factors than taller people: Samaras T: Biological parameters explain why shorter, smaller people have lower cardiovascular disease and greater longevity. JSRR 15(1): 1-16, 2017; article no. JSRR.34729. The article identifies 36 parameters and factors that support the biological advantages of shorter, smaller bodies.

Some additional factors to consider in determining conflicting evidence on the cardiovascular risks of short and tall people follow:

1. The top developed countries with the lowest risk of heart disease are both short and tall. They include S. Korea, France, Japan, Luxembourg, Ihe Netherlands and Portugal.

2. No developed country is free of coronary heart disease (CHD) and stroke but many short populations were during the 20th century;e.g.,Solomon Islands, Papua New Guinea, Kalahari Bushmen, Congo Pygmies, and Kitavans.

3. Before 1970, taller upper class males had higher rates of heart problems compared to shorter working class. After 1970, it reversed.

4. In 1900, CHD was low compared to today. Yet, the average height was about 3 inches shorter in 1900.

5. In 1960s, Greece had one of the lowest CHD rates in Europe and was shorter than central and northern Europe. Today, Greek men are several inches taller and are seeing an alarming increase in CHD.

6. Osika found that within the low income segments of society, tall people had ~40% higher risk of heart attacks compared to shorter ones.

7. Tall dogs have 60 times the risk of heart failure as short dogs.

8. Chronic diseases (including CHD) were rare, even in elderly people, until recently according to the WCRF Report of 2007. People were also shorter then. (The report also stated that chronic disease were rare before the industrial revolution.)

9. Two recent large studies found short people had lower heart disease than taller ones. (Shapiro, et al. 2015; Elsayed et al.2015)

10. Women are shorter than men and have lower heart disease mortality.

The biological aspects of shorter, lighter stature favor lower heart disease and greater longevity. (Biologists and other scientists have found that within a species, smaller individuals tend to live longer.) The reasons for findings showing shorter people have more heart problems need to be explored more deeply.

On 2016 Aug 21, Morten Oksvold commented:

Please note that this article represents one of eleven publications which were found to contain false data, after an investigation led by ORI in 2015:

https://ori.hhs.gov/content/case-summary-dasmahapatra-girija

This article should therefor not be cited.

On 2016 Oct 03, Morten Oksvold commented:

Please note that after an investigation at the University of Cologne, six articles where T. Wenz figures as first or senior author were found to contain questionable data due to scientific misconduct. This article is one of these six articles.

The conclusion from the report was ready June 28, 2016, please see the link (in German):

http://www.portal.uni-koeln.de/9015.html?&tx_news_pi1[news]=4335&tx_news_pi1[controller]=News&tx_news_pi1[action]=detail&cHash=1deb8399d7f796d65ca9f6ae4764a1ce

On 2014 Nov 23, Harri Hemila commented:

The study has been commented on at the home page of the journal http://atvb.ahajournals.org/content/29/9/1304/reply#atvbaha_el_80

On 2017 Aug 29, Gary Mirams commented:

Some typos have been found in this paper, here is a list of errata and further details on the simplified model, and here is a corrected version of the paper.

On 2013 Dec 30, Tom Kindlon commented:

I had a response published: "Many questions remain about treatments for CFS"

I submitted a response to this article entitled, ""Many questions remain about treatments for CFS". It can be read at: http://www.bmj.com/rapid-response/2011/11/02/many-questions-remain-about-treatments-cfs

A version of it was subsequently published in the BMJ (1).

References:

[1]. Kindlon TP. Chronic fatigue syndrome. Many questions remain about treatments for CFS. BMJ. 2009 Apr 7;338:b1371. doi: 10.1136/bmj.b1371.

On 2018 Jan 19, Barak Rotblat commented:

Great method. Just be careful when you are measuring protein synthesis under metabolic stress. Using mammalian cells, we found that puromycin labeling dose not work for measuring mRNA translation under these conditions. https://www.nature.com/articles/s41419-017-0056-x

On 2013 Oct 31, John Cannell commented:

The authors stated that markers of oxidative stress are present in autism spectrum disorder (ASD). I wonder if the authors are aware that the genes for the antioxidants superoxide dismutase and thioredoxin reductase are directly up-regulated by the secosteroid 1,25 di-hydroxy vitamin D3 (calcitriol). I believe both genes also harbor a vitamin D response element.

Peehl DM, Shinghal R, Nonn L, Seto E, Krishnan AV, Brooks JD, Feldman D. Molecular activity of 1,25‐dihydroxyvitamin D3 in primary cultures of human prostatic epithelial cells revealed by cDNA microarray analysis. J. Steroid Biochem Mol. Biol 2004;92:131–141. PMID:15555907>

Calcitriol also directly up-regulates glutathione reductase and increases glutathione levels.

Jain SK, et alo. Vitamin D upregulates glutamate cysteine ligase and glutathione reductase, and GSH formation, and decreases ROS and MCP-1 and IL-8 secretion in high-glucose exposed U937 monocytes. Biochem Biophys Res Commun. 2013 Jul 19;437(1):7-11. doi: 10.1016/j.bbrc.2013.06.004. Jain SK, 2013

Also, supplemental vitamin D significantly reduces oxidative stress in humans.

Nikooyeh B, et al. Daily intake of vitamin D- or calcium-vitamin D-fortified Persian yogurt drink (doogh) attenuates diabetes-induced oxidative stress: evidence for antioxidative properties of vitamin D.J Hum Nutr Diet. 2013 Jul 5. doi: 10.1111/jhn.12142. Nikooyeh B, 2014

Asemi Z, et al. Vitamin D supplementation affects serum high-sensitivity C-reactive protein, insulin resistance, and biomarkers of oxidative stress in pregnant women. J Nutr. 2013 Sep;143(9):1432-8. doi: 10.3945/jn.113.177550. Asemi Z, 2013

Thus the vitamin D theory of ASD (vitamin D deficiency being the environmental risk factor for this highly heritable disorder) is consistent with the authors work. Three recent studies, using community controls, have found 25(OH)D levels are significantly lower in children with ASD. Two of the studies below (Mostafa et al and Gong et al) also found ASD severity, as rated on standard ASD rating scales, is inversely correlated with 25(OH)D levels. Mostafa et al found an R value of -.86 for the association of serum 25(OH)D with ASD severity.

Gong ZL, Luo CM, Wang L, Shen L, Wei F, Tong RJ, Liu Y. Serum 25-hydroxyvitamin D levels in Chinese children with autism spectrum disorders. Neuroreport. 2013 Oct 1. Gong ZL, 2014

Meguid NA, Hashish AF, Anwar M, Sidhom G. Reduced serum levels of 25-hydroxy and 1,25-dihydroxy vitamin D in Egyptian children with autism. J Altern Complement Med. 2010 Jun;16(6):641-5. Meguid NA, 2010

Mostafa GA, Al-Ayadhi LY.Reduced serum concentrations of 25-hydroxy vitamin D in children with autism: relation to autoimmunity. J Neuroinflammation. 2012 Aug 17;9:201. Mostafa GA, 2012

There is a plethora of basic science explaining why low gestational or early childhood 25(OH)D levels would adversely effect brain development.

Eyles DW, Feron F, Cui X, Kesby JP, Harms LH, Ko P, McGrath JJ, Burne TH. Developmental vitamin D deficiency causes abnormal brain development. Psychoneuroendocrinology. 2009 Dec;34 Suppl 1:S247-57. doi: 10.1016/j.psyneuen.2009.04.015. Epub . Review. Eyles DW, 2009

DeLuca GC, Kimball SM, Kolasinski J, Ramagopalan SV, Ebers GC. Review: the role of vitamin D in nervous system health and disease. Neuropathol Appl Neurobiol. 2013 Aug;39(5):458-84. doi: 10.1111/nan.12020. DeLuca GC, 2013

Eyles DW, Burne TH, McGrath JJ. Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease. Front Neuroendocrinol. 2013 Jan;34(1):47-64. doi: 10.1016/j.yfrne.2012.07.001. Epub 2012 Jul 11. Review. Eyles DW, 2013

Furthermore, the vitamin D theory of autism explains most of the epidemiological facts of ASD.

Cannell JJ. On the aetiology of autism. Acta Paediatr. 2010 Aug;99(8):1128-30. Cannell JJ, 2010

Cannell JJ. Autism and vitamin D. Med Hypotheses. 2008;70(4):750-9. Cannell JJ, 2008

70% of American toddlers do not take

On 2015 Sep 14, Bill Cayley commented:

Sometimes in diabetes care, "Less" is more: https://lessismoreebm.wordpress.com/?s=diab

On 2015 Mar 27, Daniel Haft commented:

This landmark paper stopped short of determining the biologically relevant substrates of VanH and VanA. For the next step, see Handwerger, et al. (PMID:1522072), which clarified that D-ala-D-ala is replaced by D-Ala-D-lactate at the terminus of the peptidoglycan precursor molecule in vancomycin-resistant Enterococcus faecalis. VanH is now described as a D-lactate dehydrogenase (EC 1.1.1.28) and VanA as a D-alanine--(R)-lactate ligase (EC 6.1.2.1).

On 2014 Apr 22, John Roger Andersen commented:

Green Open Access to the authors final version: click here.

On 2017 Jan 24, Misha Koksharov commented:

Nice negative results. We need more reports like this in the biomedical field.

On 2014 Apr 22, John Roger Andersen commented:

Read publishers pdf version in ReaderCube for free: click here.

Green Open Access to the author's final version: click here.

On 2014 Dec 10, Kath Wright commented:

Other search filters are available from the InterTASC Information Specialists' Sub-Group Search Filter Resource at https://sites.google.com/a/york.ac.uk/issg-search-filters-resource/home

On 2014 Apr 16, Tom Kindlon commented:

Some comments:

In this study, CFS/ME (or CFS in the abstract) is defined in this extremely strange way:

"Identification of fatigue syndrome cases A list of fatigue syndrome diagnoses was collated from the library of diagnostic codes within the GPRD (Gallagher et al. 2004). Patients aged >16 years with a new fatigue syndrome diagnosis in their records for the calendar years 1988-2001 were identified: only patients with a complete record for the 3 years before the date of diagnosis (the index date) were studied. Two subgroups of fatigue syndrome cases were studied: those with a diagnostic label that included the word ' post-viral ' or ' post-infectious ', which we call PVFS here, and the remainder, composed of CFS or ME, which we call CFS/ME."

Peter White (the corresponding author) knows that this is not how CFS/ME is defined of course (i.e. CFS/ME includes many post-viral or post-infectious cases).

Most of the paper actually isn't about comparing the PVFS group vs the CFS/ME and there is no table given for making the comparison. We just really have the text:

"Differences in risk markers between the two subgroups of fatigue syndrome, CFS/ME and PVFS, were assessed by testing for interaction terms in the models presented in Table 3. The presence of prior fatigue symptoms or prior depressive disorders was more common in patients labelled with CFS/ME. Prior infections, particularly viral ones (but not influenza), were more common in patients labelled with PVFS. The interaction terms all had p values of <0.001 in likelihood ratio tests, except for depressive disorder in the fatigue syndrome versus OA analysis, where p=0.04. The multivariable models for CFS are presented in Table 4. Fatigue and depressive disorders predicted CFS in both models, but different recent infections differentiated CFS from IBS in particular."

Discussion: "The data also suggested that there are subgroup differences in the risks for particular fatigue syndromes. The symptom of fatigue, mood and symptom- based diagnoses were all specific risks for a diagnosis of CFS/ME compared to PVFS, whereas almost all infectious groups were specific to PVFS in contrast to CFS/ME. CFS/ME was more similar to IBS than PVFS with regard to its risk markers. Even so, depressive diagnoses were a greater long-term risk marker for CFS/ME than IBS, and, as expected, systemic and gut infections also differentiated the two syndromes."

Just before the very end of the paper, they come out with this: "These data also suggest that fatigue syndromes are heterogeneous (Vollmer-Conna et al. 2006), and that CFS/ME and PVFS should be considered as separate conditions, with CFS/ME having more in common with IBS than PVFS does (Aggarwal et al. 2006). This requires revision of the ICD-10 taxonomy, which classifies PVFS with ME (WHO, 1992). The duration of PVFS of the same patients in this study was considerably less than CFS/ME, supporting this distinction (Hamilton et al. 2005)." [Remember PVFS is the group where a GP said it was a post-viral or post-infectious case and CFS/ME are the other cases. The paper doesn't even mention that CFS is linked to G93:3 or even that he's talking about G93;3]

One basic flaw is that all this shows is that a GP may be more inclined to give a "post-viral" or "post-infectious" diagnosis if they have viewed/"experienced" a patient in a certain way before attending, and give an alternative diagnosis if a patient has already had depressive symptoms (or the GP decided they were depressive symptoms) or fatigue in the past otherwise. It doesn't prove that the actual conditions the patients have are different i.e. it doesn't prove that the symptoms in the second group aren't post-viral/post-infectious.

Also the suggestion that CFS/ME and PVFS be separated by the WHO involves a few assumptions:

• It would have to be said that CFS/ME does not include PVFS/Post-infectious fatigue. What they did in the study was define CFS/ME as CFS/ME minus PVFS and minus PIFS.

• This was a prospective study. If a patient comes in with symptoms after being ill for 1/2/3+ years of being ill, how would a doctor/other know which WHO category to put the patient in? They would need to show that there was a good objective way of separating patients into either the PVFS/PIFS and CFS/ME (which is CFS/ME minus PVFS/PIFS). They haven't shown this.

On 2014 Dec 22, James G Thornton commented:

I appreciate that this review is about the effect of male circumcision on heterosexual acquisition of HIV in men, but the effect on the risk of female acquisition of HIV is surely relevant, and since there is no Cochrane review of that, I am commenting here.

The only randomised trial (Wawer et al 2009) showed 17/93 (18%) HIV acquisition in male circumcision female partners v 8/70 (11%) in control female partners. The difference might have occurred by chance (hazard ratio 1.58, 95% CI: 0.68–3.66, p=0.287), but the point estimate is almost exactly the same size harmful effect as the beneficial effect in men. Unfortunately the trial was stopped early for futility because the conditional power to detect 60% efficacy, was only 4.9%.

The trial authors have never adequately explained why stopping for futility was appropriate, given that the evidence in men was regarded as sufficient to encourage male circumcision.

Can I suggest that until there is a separate Cochrane review for the effect on women, that the outcome "heterosexual acquisition of HIV in female partners" be included in this review?

Wawer MJ, Makumbi F, Kigozi G, et al. Circumcision in HIV-infected men and its effect on HIV transmission to female partners in Rakai, Uganda: a randomised controlled trial. Lancet 2009;374:229-37.

On 2015 Oct 27, Peter Gøtzsche commented:

The authors report that escitalopram was significantly more effective than citalopram but caution against the “potential for overestimation of treatment effect due to sponsorship bias.” Indeed. Both substances were patented by Lundbeck, and the rejuvenated “me-again” drug, escitalopram, is merely the active half of the “old me” stereoisomer drug, citalopram.

One would not expect a molecule to be better than itself. I therefore suggest that the Cochrane review mention the results of a 2012 meta-analysis (1), also in the abstract and plain language summary. Independent researchers confirmed the Cochrane review’s findings that escitalopram was better than citalopram in head-to-head trials. All seven trials found this, apart from the single one that was not sponsored by Lundbeck or its affiliates. These researchers also did an indirect comparison of the two drugs based on 10 citalopram and 12 escitalopram placebo controlled trials (1), and now the effect of “me-again” and “old me” was very similar (odds ratio 1.03; 0.82 to 1.30).

Usually, direct comparisons are more reliable than indirect comparisons, but the drug industry routinely distorts its research to such an extent (2) that the indirect comparisons are sometimes the most reliable ones, which I believe is the case here. Lundbeck did not have any particular incentive to manipulate its placebo controlled studies more with escitalopram than with citalopram.

The Cochrane authors note that cost-effectiveness information is also needed in the field of antidepressant trials. Indeed. Even if we take Lundbeck’s results in its head-to-head trials at face value, there is no meaningful difference between the two versions of the drug. In one of Lundbeck’s own meta-analyses, the difference after eight weeks was 1 on a scale that goes up to 60 (2,3), which is totally irrelevant (4).

When I checked the Danish prices in 2009, Cipralex (escitalopram) cost 19 times as much for a daily dose as Cipramil (citalopram). This enormous price difference should have deterred the doctors from using Cipralex, but it didn’t. The sales of Cipralex were six times higher in monetary terms than the sales of citalopram both at hospitals and in primary care. I have calculated that if all patients had received the cheapest citalopram instead of Cipralex or other SSRIs, Danish taxpayers could have saved around €30 million a year, or 87% of the total amount spent on SSRIs.

1 Alkhafaji AA, Trinquart L, Baron G, et al. Impact of evergreening on patients and health insurance: a meta analysis and reimbursement cost analysis of ci¬talopram/escitalopram antidepressants. BMC Med 2012;10:142.

2 Gøtzsche PC. Deadly medicines and organised crime: How big pharma has corrupted health care. London: Radcliffe Publishing; 2013.

3 Gorman JM, Korotzer A, Su G. Efficacy comparison of escitalopram and citalopram in the treatment of major depressive disorder: pooled analysis of placebo-controlled trials. CNS Spectr. 2002; 7(4 Suppl. 1): 40–4.

4 Leucht S, Fennema H, Engel R, et al. What does the HAMD mean? J Affect Disord 2013;148:243-8

On 2014 Mar 11, Daniel Haft commented:

The CXX repeat proteins described in this paper are almost certainly modified post-translationally, with the side chains of multiple Cys residues bridged to their preceding residues to form thiazole-type heterocycles. In retrospect, the paper should have avoided overconfident use of the term "bacteriocin," given the lack of evidence then that these heterocycle-containing natural products were toxins rather than, say, peptide pheromones. The term "ribosomally synthesized and post-translationally modified peptide," or RiPP, was introduced in 2013 (see PMID:23165928), and addresses the linguistic hole for natural products that resemble bacteriocins in structure but may have another function. In the absence of convincing evidence for toxin activity, the broader term RiPP should be used.

However, Chopra, et al. have just published a description of sonorensin, a member of the heterocycloanthracin family from a marine isolate, Bacillus sonorensis MT93. They purified the product to homogeneity, and found broad spectrum antibiotic activity, affecting both Gram positive and Gram negative bacteria. (see http://aem.asm.org/content/early/2014/03/03/AEM.04259-13.abstract). Consequently, it now seems likely that additional members of the protein family defined by TIGRFAMs entry TIGR03601, including heterocycloanthracin itself (from Bacillus anthracis), indeed are active as bacteriocins.

On 2015 Jul 11, James Tsung commented:

Link to case video: https://youtu.be/ufl6VgfUWrc

On 2014 Jan 08, Jean-Jacques Orban de Xivry commented:

In this paper, Hunter and colleagues claim that anodal tDCS on M1 improves motor adaptation to force-field perturbation (Shadmehr R, 1994).

In force-field adaptation, one critical aspect of the task is to control movement speed as the magnitude of the perturbation depends on the velocity of the hand. Indeed, the magnitude of the force pushing the hand away of its trajectory is equal to the velocity of the hand times the magnitude of the field. Unfortunately, I don't think that hand velocity was properly controlled in the paper by Hunter and colleagues. Here are two results that suggest that changes in hand velocity might be a confounding factor:

1) In the present study, anodal tDCS, but not sham tDCS, appears to modulate the velocity of the hand although this effect did not reach significance (p.2995, movement time differences: p=0.07; last panel of Fig.4). (Note that the values in Table 1 do not seem to correspond to the paragraph on movement times on p.2995 or to the last panel of Fig.4). Therefore, one wonders if the larger adaptation with anodal tDCS reported by the authors is not due to a larger perturbation being experienced during anodal tDCS.

2) In force-field tasks, it is well documented that the after-effect observed when the perturbation is suddenly removed at the end of the perturbation period is equal to or slightly lower than the deviation observed after the initial introduction of the observation. Here, for the anodal group, the after-effect appears to be larger than the initial deviation due to the perturbation (Fig.3B and first panel of Fig.5). This is only possible if the magnitude of the perturbation is larger during N5 than during F1. That is, it is only possible if hand velocity is larger during N5 than during F1. Again, this effect appears to be specific to the anodal tDCS groups.

Taken together, these two facts suggest that anodal tDCS but not sham tDCS might influence movement speed in the study by Hunter and colleagues. The larger hand velocity of the anodal tDCS group results in a larger perturbation. A larger perturbation required the subjects to adapt more to it.

To solve the problem of changes in velocity apparently due to anodal tDCS, the authors should 1) provide graphs on peak hand velocity over the course of trials 2) perform an analysis that directly takes into account changes in movement speed. I suggest that the authors use an ANCOVA analysis with Delta Summed Error or Delta Signed Error as dependent variables, group as discrete predictor and movement speed as continuous predictor.

In conclusion, I think that it is safe to conclude that until the authors provide the appropriate analyses, this paper does not provide strong evidence that anodal tDCS enhances adaptation to force-field perturbation. Rather, it suggest than anodal tDCS might modulate movement speed specifically. At least two papers did not demonstrate an improvement in motor adaptation with anodal tDCS (Orban de Xivry JJ, 2011;Galea JM, 2011) (Disclosure: I co-authored both of these papers).

On 2017 Jan 12, James Burkett commented:

This article was NOT withdrawn, but rather was errated and the updated article is listed in PubMed at this link:

https://www.ncbi.nlm.nih.gov/pubmed/19539647

On 2014 Nov 30, Alberto Halabe Bucay commented:

This is the first article published in all History about a patient with cancer who improved only with citric acid (citrate) as his treatment.

On 2017 Apr 21, Vera Sharav commented:

A warning to doctors who have relied on the claimed safety and efficacy of rivaroxaban (trade name Xarelto) based on reports about the RECORD trials such as this one, published in The Lancet.

Please read “C. Seife. Research Misconduct Identified by the US Food and Drug Administration: Out of Sight, Out of Mind, Out of the Peer-Reviewed LiteratureJAMA Internal Medicine, April 2015.” The JAMA report identified the Lancet report as failing to disclose that the FDA inspections had found serious violations at 8 of the 16 sites at which the RECORD 4 trial was conducted. The violations, including “systemic discarding of medical records, falsification, improprieties in randomization,” were so serious that “the entire study, RECORD 4 […] was deemed unreliable by the FDA.”

Among the findings by the FDA Compliance Review: Xarelto (rivaroxaban), May 24, 2011, include: "violation of good clinical practice including prospective randomization, falsification, missing records…Although issues with clinical trial monitoring inadequacies were present in all four RECORD trials, the deficiencies were most frequent in RECORD 4.”

FDA cites unreported serious adverse events (SAEs) “defined by the necessity of expeditious medical evaluation or involving bleeding or hepatic events."

“There were 8 unreported SAEs noted in the audits, all in RECORD 4. When the unreported AEs were individually examined for significance as defined by the necessity for expeditious medical evaluation, or were AEs involving bleeding or hepatic events, there were 16 in RECORD 1, 24 in RECORD 2, and 265 in RECORD 4; RECORD 3 could not be tabulated due to failure to list individual laboratory abnormalities.

During the data verification process of RECORD 4, 504 unreported AEs were noted, as were 28 previously unreported SAEs. The audits identified more than twice as many AEs in RECORD 4 than in the other RECORD studies, and all of the unreported AEs were from RECORD 4”.

Seife reported that of the 78 publications that resulted from trials in which the FDA found significant violation – only 3 (4%) – mentioned the violations or serious objectionable practices found during the inspection. “No corrections, retractions, expressions of concern, or other comments acknowledging the key issues identified by the inspection were subsequently published.”

A retraction of this grossly misleading report by AG Turpie & 171 collaborators is long overdue.

Vera Sharav President, Alliance for Human Research Protection www.ahrp.org veracare@ahrp.org

On 2014 Jun 11, M S Muthu commented:

It is free article. Collect from Publisher's website.

On 2017 Sep 11, Artem Pankin commented:

The tool is not available via the URL published in the paper anymore.

On 2016 Aug 24, Ben Goldacre commented:

This trial has the wrong trial registry ID associated with it on PubMed: both in the XML on PubMed, and in the originating journal article. The ID given is NCT100457106. We believe the correct ID, which we have found by hand searching, is NCT00457106.

This comment is being posted as part of the OpenTrials.net project^[1] , an open database threading together all publicly accessible documents and data on each trial, globally. In the course of creating the database, and matching documents and data sources about trials from different locations, we have identified various anomalies in datasets such as PubMed, and in published papers. Alongside documenting the prevalence of problems, we are also attempting to correct these errors and anomalies wherever possible, by feeding back to the originators. We have corrected this data in the OpenTrials.net database; we hope that this trial’s text and metadata can also be corrected at source, in PubMed and in the accompanying paper.

Many thanks,

Jessica Fleminger, Ben Goldacre*

[1] Goldacre, B., Gray, J., 2016. OpenTrials: towards a collaborative open database of all available information on all clinical trials. Trials 17. doi:10.1186/s13063-016-1290-8 PMID: 27056367

* Dr Ben Goldacre BA MA MSc MBBS MRCPsych<br> Senior Clinical Research Fellow<br> ben.goldacre@phc.ox.ac.uk<br> www.ebmDataLab.net<br> Centre for Evidence Based Medicine<br> Department of Primary Care Health Sciences<br> University of Oxford<br> Radcliffe Observatory Quarter<br> Woodstock Road<br> Oxford OX2 6GG

On 2013 Oct 28, Jamie Horder commented:

The story behind this paper, and the remarkable media coverage it received, was covered by Ben Goldacre.

On 2014 Jan 07, Tom Kindlon commented:

Does reduced similarity across timescales really mean reduced complexity?

Despite a good familiarity with the CFS literature and despite taking many mathematics courses in university, including a methods course which included some coverage of non-linear dynamics, I will admit to not fully understanding this paper. However, I think I will not be alone in that and so will put my head above the parapet and ask the following: This study found CFS cases (compared to controls) showed reduced dissimilarity within timescales as well as reduced similarity across timescales. This is summarised by the authors as CFS patients showing a reduction in complexity. But does the second finding not show the CFS cases demonstrated increased complexity compared to controls for that measure? For measurements within a timeframe, the controls are closer to the scores one would see with random patterns (4.75). For measurements across timescales, the scores of the CFS patients are closer to the scores one would see with random patterns (1.5).

On 2016 Apr 02, Daniel Tsin commented:

The first report of human transvaginal cholecystectomy, carried out during a vaginal hysterectomy, was done on August 20, 1999 and published in 2003 by Tsin et al. ( Culdolaparoscopic cholecystectomy during vaginal hysterectomy. Tsin DA, Sequeria RJ, Giannikas G JSLS. 2003 Apr-Jun; 7(2):171-2.) PMID 12856851

On 2013 Dec 30, Keizo Takao commented:

The URL of the gene-brain-phenotyping database has now changed to http://www.mouse-phenotype.org/ (the Mouse Phenotype Database). "ImageLD", "ImageEP", and "ImageFZ", image analysis application softwares used in this article, are now freely available from http://www.mouse-phenotype.org/software.html.

On 2014 Apr 16, Tom Kindlon commented:

Unusually low rate of sudden onset of fatigue for a CFS cohort

Only 4.5% (2/44) (Table 1) had reported "sudden onset of fatigue". This is low, as I commented on the PLoS One site: http://www.plosone.org/annotation/listThread.action?root=10453

On 2017 Dec 02, Hilda Bastian commented:

Another major area of research waste is the high rate of trials abandoned for poor recruitment. Briel M, 2017 suggests that about a quarter of all trials in Switzerland are stopped, generally because of poor recruitment. A study of phase II and III trials closed in 2011 in ClinicalTrials.gov found that 19% "either terminated for failed accrual or completed with less than 85% expected enrolment, seriously compromising their statistical power" (Carlisle B, 2015).

Bower P, 2014 point to the need to develop more effective methods to increase recruitment and retention of participants. That is critical. We still don't know how to prevent all the waste associated with poor recruitment to clinical trials. However, the Swiss study of stakeholders makes it clear that there are serious inadequacies in coordination and preparedness for many trials (Briel M, 2017). The authors point to clear areas of responsibility for funders of trials and others. The NIHR's 70-day rule, a benchmark for time to recruiting the first patient is one example of a funder trying to reduce this area of waste (NIHR).

Briel M, 2017 also point to the contribution public negativity about clinical trials makes to poor recruitment. That is a problem for clinicians as well, and, too often, members of IRBs/research ethics committees. In every direction, the clinical trial project still has a lot of basic education to do.

On 2017 Dec 17, Iain Chalmers commented:

We agree with Hilda Bastian that poor recruitment leads to waste in research, and work to reduce barriers and improve recruitment is needed. We point this out in the book we co-authored for the public - Testing Treatments, http://en.testingtreatments.org/book/what-can-we-do-to-improve-tests-of-treatments/regulating-tests-of-treatments-help-or-hindrance/do-regulatory-systems-for-testing-treatments-get-it-right/. We wrote "And for researchers planning clinical trials, it can take several years to get from a trial idea to recruiting the first patient, and even then recruitment to trials can be slowed by regulatory requirements. But while researchers try to get studies through the system, people suffer unnecessarily and lives are being lost."

These same barriers also act to inhibit even considering attempts to undertake trials to address uncertainties. With the result that "clinicians are discouraged from assessing treatments fairly, and instead can continue to prescribe treatments without committing to addressing any uncertainty about them."

As Hilda rightly concludes, "the clinical trial project still has a lot of basic education to do". But informed recruitment to and retention in clinical trials will depend on far greater general knowledge about why it is important to address uncertainties about the effects of treatments, the adverse effects of failing to address uncertainties, and how uncertainties should be addressed. This implies responsibility for the educational challenge being taken up by educators way beyond "the clinical trials project" (see www.informedhealthchoices.org).

On 2016 Nov 20, Morten Oksvold commented:

¨An investigation committee at Wayne State University (WSU) recommends that 42 articles from Fazlul Sarkar to be retracted (report finished August 31, 2015). This article represents one of them.

This information was published by Retraction Watch (November 17, 2016) and you can find a link to the full report here:

http://retractionwatch.com/2016/11/17/details-of-investigative-report-into-sarkar-released-by-aclu/

This article should therefore no longer be cited.

On 2016 Aug 30, Ben Goldacre commented:

This trial has the wrong trial registry ID associated with it on PubMed: both in the XML on PubMed, and in the originating journal article. The ID given is NCT00123456. We have contacted the corresponding author, who has told us that the trial was not registered on ClinicalTrials.gov.

This comment is being posted as part of the OpenTrials.net project^[1] , an open database threading together all publicly accessible documents and data on each trial, globally. In the course of creating the database, and matching documents and data sources about trials from different locations, we have identified various anomalies in datasets such as PubMed, and in published papers. Alongside documenting the prevalence of problems, we are also attempting to correct these errors and anomalies wherever possible, by feeding back to the originators. We have corrected this data in the OpenTrials.net database; we hope that this trial’s text and metadata can also be corrected at source, in PubMed and in the accompanying paper.

Many thanks,

Jessica Fleminger, Ben Goldacre*

[1] Goldacre, B., Gray, J., 2016. OpenTrials: towards a collaborative open database of all available information on all clinical trials. Trials 17. doi:10.1186/s13063-016-1290-8 PMID: 27056367

* Dr Ben Goldacre BA MA MSc MBBS MRCPsych<br> Senior Clinical Research Fellow<br> ben.goldacre@phc.ox.ac.uk<br> www.ebmDataLab.net<br> Centre for Evidence Based Medicine<br> Department of Primary Care Health Sciences<br> University of Oxford<br> Radcliffe Observatory Quarter<br> Woodstock Road<br> Oxford OX2 6GG

On 2013 Dec 30, Keizo Takao commented:

The URL of the gene-brain-phenotyping database has now changed to http://www.mouse-phenotype.org/ (the Mouse Phenotype Database). "ImageLD" and "ImageEP", image analysis application softwares used in this article, are now freely available from http://www.mouse-phenotype.org/software.html.

On 2016 Nov 20, Morten Oksvold commented:

An investigation committee at Wayne State University (WSU) recommends that 42 articles from Fazlul Sarkar to be retracted (report finished August 31, 2015). This article represents one of them.

This information was published by Retraction Watch (November 17, 2016) and you can find a link to the full report here:

http://retractionwatch.com/2016/11/17/details-of-investigative-report-into-sarkar-released-by-aclu/

This article should therefore no longer be cited.

On 2013 Dec 02, Dmytro Demydenko commented:

Abstract states: "This review summarizes the data available to date on galectin-1 expression in human malignancies". However on page 76 in chapter "Skin" paper using mouse model of melanoma was cited (47. Rubinstein N, Alvarez M, Zwirner NW, et al. Cancer Cell 2004; 5: 241–51.) It was mentioned in original version of manuscript that "this is the only study in mice cited in the manuscript due to its importance". The mentioning was removed prior publication without my agreement.

Working link to the article 21.VI.2017: http://exp-oncology.com.ua/wp/wp-content/uploads/magazine/752.pdf?upload=

On 2015 Nov 19, Peter Gøtzsche commented:

The authors conclude that "most suicidal events occurred in the context of persistent depression and insufficient improvement without evidence of medication-induced behavioural activation as a precursor." As 17 of the 18 suicide attempts occurred in adolescent patients on fluoxetine (see fig. 1 in the article), we interpret this study quite differently. Like all other SSRIs, fluoxetine increases the risk of suicide in adolescents.

Robert Whitaker and Peter C. Gøtzsche

On 2015 Aug 27, Bernard Friedenson commented:

For more information please see the article entitled "Mutations in Breast Cancer Exome Sequences Predict Susceptibility to Infection and Converge on the Same Signaling Pathways" This article is available at http://la-press.com/article.php?article_id=5029

On 2017 May 20, Egon Willighagen commented:

An update was published last month in the Journal of Cheminformatics: "Scaffold Hunter: a comprehensive visual analytics framework for drug discovery" https://jcheminf.springeropen.com/articles/10.1186/s13321-017-0213-3

On 2014 Jan 07, Tom Kindlon commented:

Figures quoted should be considered lower bounds given they have not been adjusted for refusals, etc

This is a useful contribution to the field and again shows that viruses (in this case EBV) can trigger Chronic Fatigue Syndrome (CFS).

One point which I don't think is sufficiently clear to anyone who just reads the abstract is that these figures have not been adjusted for refusals, etc. In epidemiology in particular, numbers matter. All the percentages were calculated on the basis of the initial 301 patients but we do not have information on a percentage of these. For example:

• "Six months after their IM diagnosis, 286 (95%) completed a telephone screening interview." (i.e. 5% did not)

• "On the basis of the screening interview, 70 of these adolescents (24%) were considered not fully recovered. A clinical evaluation was completed for 53 (76%) of these 70 not fully recovered adolescents; 12 refused, 3 had exclusionary diagnoses (primary depression, transverse myelitis, or anorexia), and 2 did not meet the study criteria (the fatigue predated the IM or the subject was not able to complete the 6-month evaluation in a timely manner)"

• I am not going to break down the list of others lost to follow-up as Figure 1 does it quite clearly: in total, of the 53 (of 70 who were considered not fully recovered), there was a cumulative loss of 10 at 24 months.

Figure 1 has the caption, "Follow-up summary for screened nonrecovered participants (n=70). Three-digit numbers represent unique patient identifiers that were used throughout the study.". However in fact, it only includes information on 53.

Note, this is not a criticism of patients being lost to follow-up, just demonstrating that the figures could be adjusted.

For example, if we look at the 12 who refused clinical examination at six months and also include the patient who was not able to complete the 6 -month evaluation in a timely manner, we have a total of 13 patients. If the same proportion of them had CFS (i.e. 39/53) as the group that was evaluated, then a further 9.57 on average would have CFS on average. (Of course, one can't have half a person but given we do not know the exact figure, I will use the unrounded figure). This would give a figure of (39+9.57)/301 or 16.13% at 6 months rather than the 13% quoted. Other figures would also proportionally increase on average. If one used the percentage who completed the initial telephone screening instrument, the percentage would actually be (39+9.57)/286 or 16.98% (i.e. 17%) at 6 months.

On 2014 Dec 18, CREBP Journal Club commented:

Interestingly, recurrent acute otitis media (AOM) occurred more often in children originally treated with amoxicillin. However, the corresponding confidence intervals are wide and the results should be interpreted with caution. It is necessary to conduct similar long term follow-up studies to gain more knowledge about the long term effect and possible harms of antibiotic treatment. The authors identified possible confounders such as sex, allergy, and history of recurrent AOM. It might have been relevant to ask the parents “Has your child had antibiotics since after the trial”, and taken this possible confounder into account as well. The article does not give any information on subsequent antibiotic use after the first six months of the post-trial follow-up period. Sensitivity analysis for the primary outcome measure, comparing only children in each group who did not receive antibiotics in the first 6 months of the post-trial follow-up period, showed a risk difference of 32% (95% confidence intervals 13% to 51%).A sensitivity analysis, comparing those who were treated with antibiotics after the six months with those who did not receive any antibiotics after the six months follow-up period, could also have been performed. A Cochrane review on antibiotic treatment of children with AOM3 did not find any differences in AOM recurrence in children treated with antibiotics versus placebo (risk ratio 0.93 95% confidence intervals 0.78-1.10). The included trials in the review all had shorter follow-up periods – up to one year. An update of this Cochrane review should preferably include this present study by Bezáková et al as a long term outcome of antibiotic treatment. As the authors state, the use of antibiotics early in an episode of AOM may impair the natural immune response and weaken the protection against further episodes or may cause an unfavourable shift towards colonisation with resistant pathogens, which are likely to promote recurrence of infection. However, for the first six months of follow-up, recurrence rates in the amoxicillin and placebo group were similar (51% vs 50%, risk difference 1%, 95% confidence intervals -12% to 15%).We find it hard to believe that previous antibiotic treatment of AOM causes late recurrences of AOM – but not early recurrences. It is worthwhile conducting a similar study of both the long (up to one year) and very long (several years) term effects, as more information is needed both of the possible long term benefits and harms of antibiotic treatment of children with AOM. For more information see CREBP Journal Club

On 2013 Dec 31, Tom Kindlon commented:

My published response: Stratification using biological factors should be performed in more CFS studies

I had a response published. I've no idea why the journal published it in print edition the month before the paper itself was in the print edition.

Psychol Med. 2010 Feb;40(2):352. doi: 10.1017/S0033291709991322. Epub 2009 Oct 12. Stratification using biological factors should be performed in more CFS studies. http://www.ncbi.nlm.nih.gov/pubmed/19818203

Kindlon T, 2010

Tom Kindlon (https://www.researchgate.net/profile/Tom_Kindlon2/publications/)

On 2013 Dec 06, Tom Kindlon commented:

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

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

On 2014 Mar 07, Arnaud Chiolero MD PhD commented:

A great commentary on the difficulty of childhood prevention of hypertensive disorders - especially in clinical setting

On 2016 Sep 12, Morten Oksvold commented:

Please note that this article has been retracted and should therefore not be cited.

On 2014 Dec 10, Kath Wright commented:

Other search filters are available from the InterTASC Information Specialists' Sub-Group Search Filter Resource at https://sites.google.com/a/york.ac.uk/issg-search-filters-resource/home

On 2017 Jul 10, Robert Speth commented:

Recently there has been a spate of advertisements for a new cognition enhancing “proven results, improving memory & performance” dietary supplement, Natrol Cognium®. The advertising says that it has been clinically proven to be effective in 9 clinical trials. One of the trials cited on the website of the manufacturer of Natrol Cognium® is from this 2009 article in J. Med Food.<br> Upon reviewing this paper, I find the results to be suspect and not supportive of the claims that the active ingredient in Natrol Cognium® significantly enhances cognitive performance. In the only comparison with the placebo control group shown in this manuscript, the Natrol Cognium® ingredient-treated group actually performed slightly worse than the placebo group in the CTT-2 test: 74.8 (30.6) versus 74.5 (20.1) seconds, respectively, after a 4-week treatment! It is well-established that placebo treated groups show improvements in double-blind studies. This is why it is necessary to show that the experimental treatment group performs significantly better than the placebo group at the endpoint of the study. In this study there was no significant difference in the reported endpoint performance between the Natrol Cognium® ingredient-treated group and the placebo control group.<br> An additional question of the validity of the statistical analyses in this paper is the claim of a statistically significant (p<0.05), 1.7% improvement in CTT-1 time after taking Natrol Cognium® for 4 weeks. Given the large error variances 41 and 36% of the mean values before and after Natrol Cognium® ingredient-treatment, respectively, (the variance of the mean of the individual before and after difference for a paired comparison analysis is not provided in the manuscript), it is difficult to believe that a 1.7% improvement would be statistically significant or clinically meaningful. Therefore, this report does not support the advertising claims that Natrol Cognium® is clinically shown to improve cognitive performance.

On 2016 Feb 22, thomas samaras commented:

A report by the World Cancer Research Fund indicated that since the industrial revolution chronic diseases have increased along with our height, weight. The authors of the report also associated the Western diet with the increase in chronic diseases. Silventoinen also observed that the Western diet promotes both increased height and coronary heart disease. Trowell, Nazmi and Monteiro reported that pre-Western populations were free of common Western chronic diseases until they transition to the Western diet. Popkin also observed that the food system developed over that 100 years has been devastating to our health.

My point is that increasing height and weight is connected to poorer health. Yes, our life expectancy has increased due to improved sanitation, health care, reduced injuries due 60-70 hours of hard physical work, child and adult labor laws, and immunization programs. However, the increase in longevity at older ages has been insignificant. For example, a 75-year old in 1900 had a remaining life expectancy of 8.5 years. In 2000, a 75-year old had a life expectancy of 10 years. A 1.5 year increase in life expectancy is small considering the huge advances in medical science and care as well as a much improved standard of living.

The association of height with health is a valid within the developed world. However, it is not the cause of our increased life expectancy or reduced mortality from CHD. Most studies showing taller people have lower CHD compared to shorter people are not based on inherent benefits of increased height per se. This is clearly shown by the following evidence. In fact, recent research indicates that lower socio-economic status is an independent risk factor for CHD. And we know that more shorter people populate the lower economic classes than the upper classes.

1. Pre-Western populations, with poor medical care, often are free of CHD and other chronic diseases (Trowell, Burkitt, Walker, Nazmi, Cordain, etc). In fact, many populations studied in the mid 20th Century were entirely free of CHD and stroke. These included Solomon Islands, Papua New Guinea, Kalahari bushmen, and Congo pygmies. Others who had no or little CHD/CVD include Kitavans, Tarahumara Indians, Xingu Indians, Yanomamo Indians, rural black South Africans, and Vilcabambans. All these groups had males that averaged from below 5' to about 5'5".

2. In the early 1900s, Americans and Europeans had very low deaths from CHD but were a few inches shorter than we are today with much higher levels of CHD in spite of major advancements in heart care and treatment.

3. A US study of ethnic groups found that Asians had the lowest CHD mortality compared to other ethnic groups. The Whites and Blacks, had about twice the mortality rate of Asians. Latinos and Native Americans were in between these two groups in mortality. Asians are the shortest group and Latinos and Native Americans are shorter than Whites and Blacks. The source for mortality rates was Health US, 2001. It provided data from 1985 to 1999 and was based on millions of deaths.

4. Okinawans are shorter than mainland Japanese and have a 40% lower mortality from CHD. Japanese living in Hawaii are taller than mainland Japanese and have higher CHD mortality. Japanese in California are the tallest and have the highest CHD mortality compared to the shorter groups.

5. The Japanese average about 5'7" and in the recent past had the lowest death rate from CHD compared to European countries and the US. However, shorter Vietnamese women have lower risk of CHD compared to taller Japanese women.

6. Davenport and Love found that taller WWI military recruits had more heart problems than shorter ones.

7. In the 20th C, southern Europeans had about 40% lower deaths from heart disease compared to taller northern Europeans. Northern French were taller and also had higher CHD compared to southern French.

8. Bavdakar reported that young and middle aged Indians are suffering from an epidemic of heart disease and type 2 diabetes. This epidemic has paralleled changes in diet and increased height.

9. S.Korean males are now 5'8.5" compared to about 5'4" or 5'5" in the 1960s. Although they have avoided a large increase in obesity, they have seen a 2800% increase in CHD (Oken).

10. Davey Smith has shown that there is a relationship among, socio-economic status (SES), height, all-cause mortality and CHD. And men who spent their entire lives in higher SES were the tallest and had the lowest mortality compared to those who spent their entire lives in a lower SES. Men who had mixed backgrounds were in-between in height and mortality. Osika also found that taller people in low income groups had an almost 40% higher risk of heart attacks.

11. The idea that small size promotes more heart disease is not consistent with dog research. For, example, Bonnett found that Great Danes had 60 times the risk of heart failure as miniature Dachshunds. There was a general pattern of increasing heart failure with increasing breed size.

The factors that promote increased height and weight need re-evaluation. Yes, reduced starvation and improved medical care and living conditions have helped on the one hand. But excessive food and the wrong foods have hurt us as well. The obesity epidemic is certainly a reflection of serious health practices clouded by our false belief that rapid growth, tallness and increased robustness are desirable trends.

On 2016 Feb 22, thomas samaras commented:

Some publications that provide a different viewpoint. Additional arguments favoring smaller height or body size are presented in the previous discussion.

He, et al.2014. Shorter men live longer: association of height with longevity and FOXO3 genotype in American men of Japanese ancestry. PloS ONE 9(5): e94385. doi:10.1371/journal.pone.0094385

Samaras 2014. Evidence from eight different types of studies showing that smaller body size is related to greater longevity JSRR, 3(16) 2050-2160, article no.JSRR.2014.16.003

Salaris et al. 2012. Height and survival at older ages among men born in an inland village in Sardinia (Italy), 1866-2006. Biodemograph and Social Biology,58:1, 1-13. http://dx.doi.org/10.1080/19485565.2012.666118.

Mueller & Mazur 2009. Tallness comes with higher mortality in two cohorts of US Army officers. Paper presented at the XXVI IUSSP International Population Conference 2009.

On 2016 Dec 13, UFRJ Neurobiology and Reproducibility Journal Club commented:

There are also issues in the statistical analysis, as a large number of behavioral measures are obtained, with relatively few significant results, which due to the amount of statistical comparisons (more than 20 in total) may well be just spurious effects. However, the authors never seem to discuss this possibility. Moreover, in the passive avoidance task the results mention Z scores and chi-square results, while the figure and methods mention that the analysis was performed with Mann-Whitney and Kruskal-Wallis tests, which should not yield either chi-square or Z scores. Finally, the conclusion of the authors that testosterone and DHT have different effects is not warranted, as even though each drug shows significant differences against placebo in different tests, in none of them a difference between both treatments was found. Moreover, the improvement in the water maze retention test in the testosterone group seems to have been inferred from intra-group comparisons between quadrants in these groups, but no comparison between groups was performed. The assumption of a difference between treatments is thus erroneous, as the statistical analysis does not compare the groups directly (for more information on this common statistical error, see Nieuwenhuis S, 2011).

On 2014 Feb 27, George W Hinkal commented:

The National Cancer Institute has been investing in the development of an online webportal of curated cancer nanotechnology data called caNanoLab. The numerical data, nanomaterial characterizations and composition information for the ten nanoparticles related to this publication have been added to the database and can be found at:

https://cananolab.nci.nih.gov/caNanoLab/characterization.do?dispatch=summaryView&sampleId=36601870&page=0&tab=ALL

https://cananolab.nci.nih.gov/caNanoLab/characterization.do?dispatch=summaryView&sampleId=36601871&page=0&tab=ALL

https://cananolab.nci.nih.gov/caNanoLab/characterization.do?dispatch=summaryView&sampleId=36601872&page=0&tab=ALL

https://cananolab.nci.nih.gov/caNanoLab/characterization.do?dispatch=summaryView&sampleId=36601873&page=0&tab=ALL

https://cananolab.nci.nih.gov/caNanoLab/characterization.do?dispatch=summaryView&sampleId=36601874&page=0&tab=ALL

https://cananolab.nci.nih.gov/caNanoLab/characterization.do?dispatch=summaryView&sampleId=36601875&page=0&tab=ALL

https://cananolab.nci.nih.gov/caNanoLab/characterization.do?dispatch=summaryView&sampleId=36601876&page=0&tab=ALL

https://cananolab.nci.nih.gov/caNanoLab/characterization.do?dispatch=summaryView&sampleId=36601877&page=0&tab=ALL

https://cananolab.nci.nih.gov/caNanoLab/characterization.do?dispatch=summaryView&sampleId=36601878&page=0&tab=ALL

https://cananolab.nci.nih.gov/caNanoLab/characterization.do?dispatch=summaryView&sampleId=36601879&page=0&tab=ALL

The left navigation links on these pages provide information about each sample (under Navigation Tree).

For general information on how to use caNanoLab, please visit https://cananolab.nci.nih.gov/caNanoLab/home.jsp

On 2014 Mar 12, George W Hinkal commented:

None

On 2014 Mar 12, Allison Stelling commented:

While SERS gives an advantage in depth penetration, I would be more comfortable with not using any labels in medical diagnostics. Raman spectroscopy can be done without needing any nanoparticles. For a newer study that uses Raman and florescence to do non-invasive, non-destructive tumor border margin assessment on-line during surgeries, see Kong K, 2013.

As to the depth penetration, spatially offset Raman studies are being done that address this question. Labels and dyes may always have a place at the diagnostic table- however, I think they should be a last resort after less expensive and invasive tests; for a review see: Matousek P, 2013.

On 2014 Nov 23, Harri Hemila commented:

A manuscript version is available at handle

On 2014 Apr 03, Naresh Kasoju commented:

This work was highlighted as the "Biomaterial of the Month" by the Society for Biomaterials news letter: http://www.biomaterials.org/week/bio43.cfm

On 2016 Oct 16, Jaime A. Teixeira da Silva commented:

There are concerns about the accuracy of the description related to the mutants in this study. http://imgur.com/7h7RS4p

On 2015 Oct 06, S Sundar commented:

The conclusion by Nanda et al on hormonal therapy use for prostate cancer and increased mortality is not only based on a small subset (5%) of a retrospective study but the study population consisted of patients whose primary treatment was Brachytherapy(1). By contrast multiple prospective randomised trials, which have shown significant survival benefits for hormone therapy, utilised external radiation (RT) as the primary treatment modality(2)(3). Hence extreme caution is needed before extrapolating the evidence generated by Nanda et al to routine clinical practice.(1.

Radiobiologically, Brachytherapy is different from external RT. Radiation Doses delivered by Brachytherapy are usually far higher than delivered by external RT. Unlike external RT which is given in daily fractions over many weeks, Seed Brachytherapy delivers continuous radiation and affects repair and repopulation of surrounding normal tissues including vascular structures. Furthermore, a significant proportion of Brachytherapy treated patients have distant vascular migration of radioactive seeds.(4) The long term effect of delivering unnecessary vascular radiation at distant places such as lungs remains to be elucidated.

Independent randomised studies combining modest doses of external RT with adjuvant hormonal therapy have shown substantial overall survival benefit. Hence, unless prospective data confirms the results of data mining by Nanda et al, prostate patients with co-morbidity, who are having external RT as their primary therapy, should not be deprived hormone therapy.

References:

1. Nanda A, Chen M-H, Braccioforte MH, Moran BJ, D’Amico AV. Hormonal therapy use for prostate cancer and mortality in men with coronary artery disease-induced congestive heart failure or myocardial infarction. JAMA. 2009 Aug 26;302(8):866–73.

2. Bolla M, Van Tienhoven G, Warde P, Dubois JB, Mirimanoff R-O, Storme G, et al. External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study. Lancet Oncol. 2010 Nov;11(11):1066–73.

3. Brundage M, Sydes MR, Parulekar WR, Warde P, Cowan R, Bezjak A, et al. Impact of Radiotherapy When Added to Androgen-Deprivation Therapy for Locally Advanced Prostate Cancer: Long-Term Quality-of-Life Outcomes From the NCIC CTG PR3/MRC PR07 Randomized Trial. J Clin Oncol Off J Am Soc Clin Oncol. 2015 Jul 1;33(19):2151–7.

4. Eshleman JS, Davis BJ, Pisansky TM, Wilson TM, Haddock MG, King BF, et al. Radioactive seed migration to the chest after transperineal interstitial prostate brachytherapy: extraprostatic seed placement correlates with migration. Int J Radiat Oncol Biol Phys. 2004 Jun 1;59(2):419–25.