483 e-Letters

published between 2020 and 2023

  • Multifaceted Interaction Between Heart Rate, Blood Pressure, Comorbidities, and Sex

    Dear Authors and Editorial Team,

    The inverse association between resting heart rate (RHR) and longevity has been the subject of many studies, both in humans and across species [1]. The article by Zhao et al., titled, “Effect of resting heart rate on the risk of all-cause death in Chinese patients with hypertension: analysis of the Kailuan follow-up study” determines that resting heart rate > 76 beats-per-minute (bpm) is a predictor of mortality in Chinese hypertensive patients as well [2]. I applaud the authors for thoroughly adjusting for confounding factors and offering explanations for the association, but would like to bring to discussion key points that may help contextualize the findings.

    Firstly, several studies have established that women have higher RHR than men and tend to have weaker associations between RHR and mortality [3]. Thus, it may be important to develop sex-specific quintiles when categorizing heart rate as women paradoxically also have higher life expectancy than men. Fortunately, this study has a large proportion of men which reduces misclassification bias but may also in turn reduce generalizability of the results to women.

    There are peculiarities among the baseline characteristics by quintile of RHR that may warrant further attention. There seems to be markedly unequal sample sizes across the quintiles (e.g. Q2 = 7589 vs. Q1=10349), suggesting that there may be room to adjust the categories. Furthermore, there is a distinct...

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  • Sex ratio post stress event in Canada

    the difference between boys and girls 5 to 7 months post stress event is mentioned favoring the survival of girl fetuses. If true then historical data will show what were the happiest of the times when ( - minus 5 to 7 months) more boys were born. This can be a good anthropology historical tool to judge when people were happier.

  • Risk factors of central obesity in male firefighters

    Damacena et al. conducted a cross-sectional study to investigate the association of central obesity (CO) with sociodemographic, occupational, life habits, fitness and health status variables in 892 male firefighters (1). Adjusted odds ratios (95% confidence intervals) of the age range of 50 to 59 years old, low self-reported physical activity, low cardiorespiratory fitness, hyperglycaemia and hypertriglyceridaemia fasting status for CO were 2.93 (1.05 to 8.14), 1.95 (1.14 to 3.34), 5.15 (3.22 to 8.23), 1.70 (1.07 to 2.72) and 3.12 (1.75 to 5.55), respectively. I have two concerns about their study.

    First, Yook investigated the association between occupational stress, cardiorespiratory fitness, arterial stiffness, heart rate variability and sleep quality in 705 male firefighters aged 40-50 years (2). Pearson’s moment correlation coefficients between occupational stress and cardiorespiratory fitness, arterial stiffness or sleep quality were -0.082, 0.085, 0.276, respectively. Although mental factors affected health status in male firefighters, risk assessment of occupational stress for cardiovascular diseases should be specified by a prospective study with a multivariate analysis.

    Second, Kaipust et al. determined the association between sleep and on-duty injury among male career firefighters, stratified by body mass index (3). By multivariate analysis, more than half of on-duty injury reduction was observed by good sleep in obese firefighters. This significant...

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  • Re: Cannabis exposure as an interactive cardiovascular risk factor and accelerant of organismal ageing: A longitudinal study

    I have read with interest Reece and colleagues (2016) paper, but some questions remain.

    First, I think the authors have done a commendable job detailing most of their statistical methodology. However, some things are left to be desired, such as a description of the Statistical Power analysis. Using the Benjamini-Hochberg Procedure (a modified Bonferroni Procedure) on the data listed in their Supplementary materials, one can conclude that the authors' results were indeed statistically significant. What remains to be seen, however, is what the magnitude of these effects were, precisely, and what happened to the Power as these multiple comparisons were assessed, since Power decreases with increasing univariate statistical tests. One might assume Power to be sufficient given the N = 1,553, but these data have been parsed in many different ways, and it would be helpful to know the authors’ anticipated effect sizes and any Power analyses for these comparisons that were conducted prior to the start of the study.

    Second, due to issues with boundary conditions and computational modeling, the method used in this paper for the mixed-effects linear model may not be quite right [1, 2]. There is often a misapplication of traditional AIC selection criteria in linear mixed effects (LME) modeling, owing to poor justification for use in longitudinal data analysis, due in part to error variance estimates [2], which is partially how this seemed to have been used here, in th...

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  • Clinical quality registry for gynecological cancers: attention to staging

    Dear editor,

    We carefully read the study protocol proposed by Heriot et al (1), regarding the development of a prospective registry of gynecological cancers in Australia. In fact, it is a heterogeneous group of pathologies, with different clinical presentations, diagnostic characteristics and therapeutic proposals (2,3). Together, this oncological complexity can restrict the daily practice of the professionals involved in this context and even impair the treatment of the women affected.

    Oncological staging consists of a process to estimate the extent of the cancer present in the body of an affected person. Despite the particularities of each tumor site, it usually involves an evaluation obtained by physical examination associated with specific complementary examinations. However, in a real-world scenario, several factors can add limitations to this staging process (4).

    Considering the staging of gynecological cancers, the interobserver variation in tumor measurement and clinical evaluation of patients stands out. In this context, if the tumor palpation varies by a few centimeters, the patient's clinical staging and prognostic classification are also altered. In addition, the disease itself can evolve throughout the diagnostic process, which can involve several months depending on the geographic region and specific socioeconomic conditions. Thus, professionals with less experience can make mistakes in defining the clinical stage and, consequently,...

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  • Quality in breast cancer screening: the breast positioning matters

    Dear editor,

    We read the article by Yuan et al. with great interest, which highlights different quality criteria in two breast cancer screening models in Canada (1).

    Currently, mammographic screening for breast cancer is recommended by several medical institutions and government agencies (2,3), based on prospective studies that have shown reduced mortality and other favorable outcomes (4,5). However, in recent years, several authors have questioned the benefits of population screening due to the rates of overdiagnosis and overtreatment (6). Nevertheless, many of these questions are based in retrospective and population-based studies, whose methodological limitations restrict the extrapolation of data to the individualized clinical context.

    The study conducted by Yuan et al. addresses an important issue of mammographic screening: the quality of the exams. Even in Canada, a high-income country with a consolidated health system, there are significant differences in the quality of screening between the centralized system (Screen Test, Alberta Cancer Agency) and community radiology clinics (1). Throughout the article, the authors also discuss several aspects related to technical criteria, such as cancer detection rate and false positive rate. However, as in most similar studies, nothing is discussed about the clinical quality control of the tests performed on both models.
    Clinical quality control involves several criteria related to breast positioni...

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  • Why network meta-analysis cannot be used to determine the optimal method of anticoagulation in pregnant women with mechanical heart valves

    Dear editor,

    We read with interest, the study protocol by He. et al, comparing anticoagulation strategies in pregnant women with mechanical heart valves (MHVs)[1]. In their protocol, the authors propose the conduct of a network meta-analysis (NMA) to compare various strategies for anticoagulation in this population. The proposed protocol adds to a long list of recently-published systematic reviews on the topic, each of which adopted slightly different methodological approaches, resulting in the drawing of disparate clinical conclusions. The reason for this is the considerable clinical, methodological and statistical heterogeneity within published studies, most of which case series and small cohort studies[2]. Although this protocol has a number of strengths, which includes an exhaustive list of databases, clear definitions of outcomes and the use of GRADE methodology to assess the certainty in evidence and the strength of recommendations, there are a few concerns that must be addressed.

    The choice of anticoagulant in pregnant women with MHVs is often based on resource availability and clinical factors. For example, the use of low molecular weight heparin is cost-prohibitive in low-resource settings and where serial anti-Xa levels cannot be monitored. In settings where a choice of all methods is available, those at highest risk, still receive a vitamin-K-antagonist-based regimen. Further, clinical outcomes are considerably different in lower resource setting...

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  • Re: Cost-effectiveness analysis of cetuximab combined with chemotherapy as a first-line treatment for patients with RAS wild-type metastatic colorectal cancer based on the TAILOR trial

    Dear Editor,

    We read the original study by Wang et al1, published in the February 2020 issue of BMJ open, with much interest. In this study, the authors sought to evaluate the costs, quality-adjusted life-years (QALYs) and the incremental cost-effectiveness ratio (ICER) of cetuximab plus FOLFOX-4 when compared to FOLFOX-4 alone among Chinese patients with RAS wild-type metastatic colorectal cancer.1 The authors used a Markov model that was structured around 3 health states [i.e., progression-free survival (PFS), progressive disease (PD) and death], with transition probabilities obtained from parametric fitting of PFS and OS curves from the published TAILOR clinical trial.2 Costs were measured in the societal perspective and the medication costs were calculated assuming with the specific height (161cm), weight (62kg) and a body surface area (1.66 m). Health utilities were obtained from existing literature. Based on the ICER of US$ 16,4044 per QALY and a willingness-to-pay threshold of US$ 28,106 per QALY, the authors concluded that cetuximab plus FOLFOX-4 is not a cost-effective treatment in the Chinese health care setting.

    Although this paper contributes to a better understanding of the alignment between the price of cetuximab and its observed efficacy in the Chinese healthcare setting, we feel that further clarifications of the authors’ methodological choices are warranted for transparency and replication purposes. Below are 5 important points for the autho...

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  • Emerald trial disclaimer update

    CORRECTION/DISCLAIMER. As of the date of publication of the study protocol for a randomised, double-blind, placebo-controlled study evaluating the efficacy of cannabis-based Medicine Extract in slowing the disease progression of Amyotrophic Lateral sclerosis or motor neurone disease: the EMERALD trial (the “Study”), CannTrust Inc. (“CannTrust”) had received a Notice of Licence Suspension pursuant to the Cannabis Act (Canada). The Notice states that Health Canada has suspended CannTrust's authority to produce cannabis, other than cultivating and harvesting, and to sell cannabis. As such, the Notice constitutes a partial suspension of the Company's licence for standard cultivation and a full suspension of its licences for standard processing, medical sales, cannabis drugs and research issued under the Cannabis regulations. As a result, the EMERALD trial will proceed with another licensed provider of cannabis-based medicine extract.

  • Response to authors

    A recent article in The Times asks: "How will this play out in the next decade, as the first cohort on puberty blockers come to terms with their probable infertility? Such experimental paediatric medicine has been politicised and shrouded in secrecy for too long. It is time to ask serious questions.”1

    In the spirit of asking serious questions of the RCHGS Trans20 study, we stand by our previous claims and respond to the author’s comments, which clearly misrepresented our concerns. Based on our reading of the data, we are of the view that gender-affirming interventions, be they psychosocial or medical, do not have an adequate evidence base to warrant their widespread use as routine medical care in children and adolescents. In fact, the paper’s authors acknowledge this lack of evidence and highlight the “urgent need for more evidence to ensure optimal medical and psychosocial interventions”.

    In their response to our comments, the authors justify their claim that the Trans20 study is an observational study by referring to the NIH definition that an observational study is one in which “participants may receive interventions that are part of their routine medical care”. We do not agree that gender affirmative treatments, particularly medical interventions, constitute “routine medical care”, especially when there are only two small follow-up studies that report short term outcomes of young people who have undergone puberty blockade.2,3 This view is supported...

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