692 e-Letters

  • There are plenty of problems, but paucity of evidence is not one of them

    Dear Sir,
    In their recent paper,1 Mamluk et al describe the results of a systematic review and meta-analyses of the association between low alcohol intake in pregnancy and several adverse birth outcomes and long-term outcomes in children. The authors conclude that there is “limited evidence for a causal role of light drinking in pregnancy, compared with abstaining, on most of the outcomes examined” and that their “extensive review shows that this specific question is not being researched thoroughly enough, if at all.”

    I sympathize with the thorough work performed by the authors. Even so, a word of caution is needed with respect to the second part of their conclusion. The authors defined the intake of interest as a maximum of 32 g of alcohol per week corresponding to 4 standard UK drinks/week. While this makes sense from a British point of view, the definition of a standard drink being 8 g of alcohol, this cut-off makes little sense in most non-British countries, where a standard drink is typically defined as containing 10-12 g. Hence, a large number of non-British studies using three or four drinks as their cut-off for low intake have not been included in the present review, only because their definition did not correspond with the British.

    Several meta-analyses in recent years have used slightly more embracing definitions.2 3 These meta-analyses included far more studies, simply because a limit of 32 g fits poorly with international definitions. Using...

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  • Letter in response: Clinical Trial Transparency: A re-assessment of industry compliance with clinical trial registration and reporting requirements in the United States

    Dear Editors,

    Thank you for the opportunity to respond to Lassman et al.’s re-analysis of our study titled, “Clinical trial registration, reporting, publication and FDAAA Compliance: A cross-sectional analysis and ranking of new drugs approved by the FDA in 2012”.1 Our original study assessed the clinical trial transparency of novel drugs approved by the FDA in 2012 that were sponsored by large drug companies. We assessed the drugs by two sets of transparency standards: U.S. legal requirements and an ethical standard that all human subjects research should be publicly accessible to contribute to generalizable knowledge.

    Our original analysis included a review of 15 drugs, sponsored by 10 large companies, involving 342 trials. Lassman and colleagues’ reassessment examined 69 of these 342 trials and focused on only the U.S. legal requirements standard. Lassman et al did not elaborate on why they limited their assessment to this subset of trials and on compliance with legal requirements. As a reminder, US clinical trial disclosure requirements are defined by the Food and Drug Administration Amendments Act (FDAAA), passed in 2007.2

    We applaud efforts to replicate studies. We are glad that our policy of publicly sharing data through the Dryad Digital Repository enabled replication and re-analysis.3 Additionally, we generally agree with the Lassman and colleagues re-assessment of our study using today’s new and updated knowledge base and world-view....

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  • Prevalence of diabetic retinopathy in China

    We have read the article by Cui et al.[1] with interest, however we believe that some issues should be clarified. The authors present a cross-sectional study aimed to determine the risk factors for diabetic retinopathy (DR) in the Chinese population.

    On a cohort of 17 985 individuals from Beijing, China, the prevalence of DR was 1.5% in the general study population and 8.1% among individuals with diabetes mellitus (DM). It is presented that since the Beijing population is composed of Han people as well as minorities from the country, it could be considered as representative of the Chinese population. It should be underlined that the assessed prevalence is far lower than that of other studies, including those from Asian countries. For example the prevalence of DR among primary care Chinese patients with DM in Hong Kong was 39.0% [2], and 37% among Chinese patients aged over 40 years with a self-reported diagnosis of diabetes in the Beijing Eye Study [3].

    Thus, questions about the methodology can be raised. The American Diabetes Association clearly states the criteria for the diagnosis of diabetes: 1) fasting plasma glucose ≥ 126 mg/dL (≥ 7.0 mmol/L) 2) 2-hour plasma glucose after a 75-g oral glucose tolerance test ≥ 200 mg/dL (≥ 11.1 mmol/L) 3) A1C ≥ 6.5% 4) In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥200 mg/dL (11.1 mmol/L) [4]. Thus, it should be clarified if the diagnosis of diabetes in this study w...

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  • The Importance of Methodological Rigor and Communication of Information

    Dr. Mamluk and colleagues’ recent systematic review and publication in BMJ Open (1) carries with it a provocative title and over the past week its conclusions have garnered substantial attention by news organizations such as CNN (2), Newsweek (3), and the New York Post (4). Although we agree completely with the authors’ assertion that there is a significant gap in the literature concerning low levels of maternal alcohol consumption during pregnancy, we have some substantial concerns regarding misleading statements in the paper and inconsistencies between the methodology that was stated versus that which was conducted.

    First, in the introduction, the authors claim that “Internationally, clinical guidelines recommend that pregnant women should abstain from heavy or ‘binge’ drinking”. Although technically correct, it is misleading since the messaging reported in the authors’ cited reference actually shows that nearly every country advises abstaining from any alcohol consumption during pregnancy – not just heavy or binge drinking. Furthermore, the authors state that “…UK guidelines advised women to avoid drinking alcohol while trying to conceive, and in the first trimester, but at the same time indicated that consumption should be restricted to within ‘1 to 2 UK units, one or twice a week.” Their statement makes it seem as though the UK message is contradictory regarding maternal alcohol consumption during pregnancy – it is not. In the 2016 UK Chief Medical Officers’ Lo...

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  • Comments on PROMISE data interpretation in Siemieniuk meta-analysis from PROMISE team

    To the BMJ Editor:

    A recent analysis in BMJ Open accompanied by a clinical practice guideline on antiretroviral therapy (ART) in pregnant women living with HIV by Siemieniuk et al has concluded that “tenofovir/emtricitabine is likely to increase stillbirth/early neonatal death and early premature delivery compared with zidovudine/lamivudine” (1,2). While the clinical practice guideline was based on a systematic review, in reality, the conclusion was based solely on results of the PROMISE study (3). Evidence from large observational studies did not support this recommendation, but was viewed as too low quality to consider in making recommendations. As coauthors of the PROMISE study, we would like to comment on the authors’ conclusion.

    The objective of the PROMISE trial was to compare the efficacy of zidovudine/single-dose nevirapine (AZT-alone) with protease inhibitor-based (lopinavir-ritonavir) combination ART (AZT-based ART [AZT-ART] or tenofovir-based ART [TDF-ART]) to prevent mother-to-child transmission in women with CD4 cell count >350 cells/mm3 (3).The study enrolled during two periods, and the comparisons of the TDF-ART arm to the other arms are restricted to the women who were concomitantly randomized among the three study arms, which occurred only in the second period of the study. In Period 1 – accounting for about two-thirds of enrollment - only hepatitis B virus (HBV)-coinfected women (~1% of overall enrollment) were randomized to TDF-ART vs...

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  • Challenges in reviewing methamphetamine-associated psychosis

    Stuart and colleagues protocol for a systematic review of psychological treatment for methamphetamine use [1] is a timely and relevant response to a significant gap in guidance for treatment of psychological sequelae arising from psychostimulant use. Given that levels of psychological distress and clinical mental health symptoms are very common in people who use methamphetamine, there is an urgent need for psychological treatment guidelines for this population.

    While many psychological interventions to date have also targeted comorbid anxiety and depressive symptoms, psychotic symptoms are also highly prevalent, clinically challenging and often poorly addressed. Methamphetamine-associated psychosis has been associated with significant morbidity, including increased agitation and violence, presentation to acute health services, and considerable health service burden [2]. A subset of individuals may also be at risk of developing more persistent psychotic symptoms, later transitioning to a diagnosis of chronic psychotic disorder.

    To date, the presence of psychotic symptoms has either been excluded, or not routinely screened for, in the majority of studies of psychological treatment for methamphetamine use. For instance, some studies have excluded participants with recent antipsychotic medication use[3], while measurement of psychotic symptoms or clinical assessments of psychotic disorder are typically absent [4-7]. On the other hand, many pharmacological inte...

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  • Liquor lobby cited (incorrectly) in article

    It is concerning to read on page 1 of the introduction that “Internationally, clinical guidelines recommend that pregnant women should abstain from heavy or ‘binge’ drinking'". The reference cites the liquor industry social aspects organisation [http://www.iard.org/] as their source, which we admit find rather unusual. What is more unfortunate is the authors then misrepresent the content found on the industry website. Rather than the guidelines recommending the avoidance of heavy drinking, all of the 54 countries’ guidelines for alcohol and pregnancy advise abstinence, and the only exception is Bulgaria which offers a low-risk level for pregnant women who do choose to consume. This appears contradictory to the statement made by the authors in their introduction.

  • The burden of respiratory infections in primary care – the missing piece of the puzzle?

    We would like to thank the authors for their informative and innovative research, which interrogated electronic medical record free text, to demonstrate the significant impact of childhood respiratory illness on primary care workload in New Zealand. The findings indicate that almost half (46%) of all child-general practitioner consultations between January 2008 and December 2013 were attributed to the management of respiratory conditions.

    The findings of this research are not surprising given that children in developed and developing countries report six to eight episodes of acute respiratory tract infection every year (1). The high rate of consultations may be partly explained by the fact that there is no cure for acute respiratory infections, only symptomatic relief (1). For some parents, this might necessitate frequent and repeat consultations with general practitioners.

    While this research sheds light on the role of general practitioners in the management of childhood respiratory illness, there continues to persist ongoing knowledge gaps in an equally important field. There is some evidence to indicate that many parents manage their child’s acute respiratory infections at home, using a range of therapies, including complementary and alternative medicines (CAM)(2). With the increasing popularity of CAM and emerging high level evidence to support the role of CAM therapies for acute respiratory tract infection (e.g. Sambucus nigra (3), Pelargonium sidoides...

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  • Response to Vibha Jaiswal, Barriers to real world deployment of HPV consultation guides by ENT surgeons

    On behalf of the authors: We thank Dr Jaiswal for her generous and supportive comments about our article, ‘Talking about human papillomavirus and cancer: development of consultation guides through lay and professional stakeholder coproduction using qualitative, quantitative and secondary data’. We are pleased that reading it prompted her to conduct a rapid assessment of our consultation guides.
    We were delighted to discover the close similarities between the comments expressed by the clinicians in our study and the doctors who took part in Dr Jaiswal’s assessment exercise, and gratified that they found the consultation guides useful and would give the information leaflets to their patients. That the number of doctors fairly or very confident discussing HPV in the context of a Head and Neck consultation rose from 56% to 100% is very encouraging. This further strengthens our confidence in these tools. We would be pleased to receive continuing feedback from clinicians on their use of the guides or the patient information leaflets.
    The main barriers to deployment of the consultation guides in the real world are the practical ones of dissemination and implementation. How can we inform the appropriate clinicians of their existence, and make these resources more easily accessible to them? At present they are available to download; we would like to see them produced as print versions that could be more readily to hand in a consultation. We also believe that the...

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  • Comment on statistics

    Poisson regression is unsuitable for analysing data from Likert scales, even in aggregate (see http://rcompanion.org/handbook/E_01.html).

    Summing enough Likert scales (as when summing enough random variables) might result in summary data which are suitable for least squares regression, via the central limit theorem. But, Poisson regression is suitable for count data where the variance is equal to the mean (count data that violate this equality may require negative binomial regression).

    Since the statistical analysis is inappropriate, the Results and Conclusions may be unsound.

    Multi-level IRT is probably an appropriate way to analyse multiple Likert scales (e.g. Luo & Wang, Stat Med. 2014 Oct 30; 33(24): 4279–4291)