769 e-Letters

  • Figure clarification and data correction from the authors

    Readers of our article have indicated that the description of Figure 1 was insufficient to help them understand what it represents. Below, we further describe the figure, correct two minor errors, and provide a summary table.

    Figure 1 description:
    Figure 1 was designed to show two overarching pieces of information. First, the line plots allow the reader to see how the filtering process progresses for individual studies. Each line represents a single study going from one phase to the next. Each phase is centered on the midpoint of the range, giving it a Buchner funnel-like shape. The purpose of this representation, as opposed to having the x-axis anchored to 0 for instance, is that it better highlights the rank changes across phases. Just because a study has a large number of papers at one phase does not mean that it will have the largest number included at a subsequent phase, and this difference can sometimes be pronounced (as evidenced by steeply crossing lines).The second piece of information was summary statistics represented in boxplots overlaid at each phase, which are more self-explanatory.

    Figure 1 data processing:
    For the lineplots, four studies were excluded because their values were greater than 2.5 standard deviations above the mean for the ‘Total N Found’ variable. Had these four studies been plotted, all other lines would have been compressed to the left of the figure because of how far these four values would have extended the axis...

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  • D313Y variant: Evidence in favour or against its pathogenicity in Fabry Disease?

    Dear Editor,

    We read with interest the article by Koulousios et al. The authors report five patients with a presumed “definite” diagnosis of Fabry Disease (FD) out of a group of 17 Greek individuals with the D313Y variant of the a-galactosidase A (GLA) gene. The authors claim that they provide “strong evidence that the D313Y mutation could be pathogenic”. Beyond the obvious contradiction of being certain about an uncertainty, the study contradicts to overwhelming evidence from the literature, mainly due to a mechanistic interpretation of incomplete patient data without (in the majority of cases) the appropriate counseling and expertise by the medical specialties responsible for the management of the patients’ principal clinical manifestations. In particular, the authors claim that the “vast majority of patients with the D313Y mutation presented with neurologic symptoms and signs”. Nevertheless, none of the authors is a neurologist and it is obvious that a neurological perspective is missing from the manuscript.
    For the past two years, we have been following in our department Patient 4 (table 1) and her mother (Patient 5). Patient 5 had a history of slowly progressing spastic tetraparesis over at least 20 years, initially diagnosed in another institution as primary progressive multiple sclerosis. After all relevant investigations, our diagnosis was that of an undetermined moderate leukoencephalopathy. Plasma Gb3 levels were 4.7 nmol/mL (reference: 0.8-4.52). I...

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  • A possible explanation may be exposure to hydrocarbons

    As suggested by Kim et al. the association between decreased lung function and chronic kidney disease (CKD) implies that there must exist a common pathogenic mechanism. A likely one is exposure to organic solvents or other types of hydrocarbons because such exposure may cause both lung disease2-6 and CKD.7-10
    1. Kim SK, Bae JC, Baek J et al. Is decreased lung function associated with chronic kidney disease? A retrospective cohort study in Korea BMJ Open 2018.
    2. Angerer P, Marstaller H, Bahemann-Hoffmeister A et al. Alterations in lung function due to mixtures of organic solvents used in floor laying. Int Arch Occup Environ Health 1991;63:43-50.
    3. Harving H, Dahl R, Mølhave L. Lung function and bronchial reactivity in asthmatics during exposure to volatile organic compounds. Am Rev Respir Dis 1991;143:751-4.
    4. Spanier AJ, Fiorino EK, Trasande L. Bisphenol A exposure is associated with decreased lung function. J Pediatr 2014;164:1403-8.
    5. Padula AM, Balmes JR, Eisen EA et al. Ambient polycyclic aromatic hydrocarbons and pulmonary functionin children. J Expo Sci Environ Epidemiol 2015;25:295-302.
    6. Wang S, Bai Y, Deng Q et al. Polycyclic aromatic hydrocarbons exposure and lung function decline among coke-oven workers: A four-year follow-up study. Environ Res 2016;150:14-22.
    7. Ravnskov U, Lundström S, Nordén A. Hydrocarbon exposure and glomerulonephritis: evidence from patients' occupations. Lancet 1983;2(8361):1214-6....

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  • Note from Production

    The correct number of shifts measured was 62 (not 61), and 13 evening shifts (not 12). The measured hours in evening shifts were 7:15 h:m (not 7:25).

  • Response: Randomised trial of coconut oil, olive oil or butter on blood lipids and other cardiovascular risk factors in healthy men and women

    We would like to congratulate the authors: the pragmatic trial design is novel and interesting, and may have provided a better estimate of the ‘real-life’ effectiveness of the intervention than a conventional RCT. Nevertheless, there are certain aspects of the paper that we wish to highlight. As the authors acknowledge, there are concerns about uncontrolled confounders. However, we would also like to raise the following 3 points of concern to consider:
    1. The study lacked a control group (where no additional lipid was added/replaced in the diet). This is problematic as the article’s conclusion suggests that the changes seen in LDL-C are an effect of extra virgin coconut oil, whereas it might instead be the impact of additional butter (and without a control group we are unable to assess the impact of coconut oil alone).
    2. The study is unclear about whether participants consumed the 50ml of coconut oil or olive oil as cold oils, or whether they cooked them before consumption. Multiple studies have suggested that hot (cooked) vegetable oil has a negative impact on blood lipids and metabolic profiles, increasing LDL-C levels, inflammatory markers and blood pressure (1). We would therefore welcome clarification of this point from the study authors.
    3. Longer follow up may be warranted to determine whether ongoing use of coconut oil would result in significant weight gain. This is of particular concern if coconut oil is added to the diet instead of replacing...

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  • Response to query regarding use of the Morisky scale

    During the study design period, we planned to use a Chinese version of the Morisky scale to assess medication adherence. This version was previously validated and available for use in China. In 2017, we were informed by Dr.Morisky team that we need to pay to use the scale. After careful consideration, we opted not to use the Morisky scale and declined to pay the fee. These developments occurred during the submission and review process at BMJ Open. As such, the initial version of the manuscript noted the use of the Morisky scale to assess adherence, though this was deleted from the revised and published version. Instead, we will assess adherence using detailed medication information obtained during each follow-up visit.

  • Cardiac Rehabilitation Effectiveness? A response from the Canadian Association of Cardiovascular Prevention and Rehabilitation (CACPR)

    In the January 2018 issue of BMJ Open, Powell et al. published a review which pointedly challenges the effectiveness of cardiac rehabilitation (CR) in reducing mortality. This response is forwarded with: (1) respect for the quality of this study (although we might dispute inclusion of some of the trials),[1] (2) consideration of other recent reviews of CR efficacy in the modern era, [2-5] and (3) the desire to incite a balanced discussion of the merits of CR. CACPR invites readers to take into consideration a few important factors when reading Powell et al.’s article.
    First, Powell et al. identify the importance of CR dose and patient adherence and how it was not considered in their work. Actual dose received may often be too low, such that the impact of CR is reduced. [6] There is wide variation in exercise prescriptions and how they are progressed. [7] Degree of improvement and degree of cardiorespiratory fitness is one of the major mechanisms through which CR can reduce mortality,[8] yet often this is not described in trials. In future trials, these factors need to be better documented and considered statistically. Powell et al. recommend a nice framework (see their reference 63), and the TiDIER framework provides another option.[9]
    Second, CR is a “complex”, [10] multi-component intervention.[5,11,12] As Powell et al. state, many of the included trials were exercise-only, and for those that were comprehensive, there was substantial variation. Therefore, it...

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  • Comment on: Prevalence and distribution of hypertension and related risk factors in Jilin Province, China 2015: a cross-sectional study

    First I would thank Wu J et al, for publishing their research on prevalence of hypertension & its associated risk factors in your esteemed journal and this work is of high public health priority. There is no mention on the study setting where the blood pressure was actually measured, as the variability can be expected in settings like clinic where there is a chance of white coat hypertension which might not be there if measured at home by the health worker. Though the variability in blood pressure would be taken care by taking average of three readings, maintaining uniformity in study setting would offer high internal validity. In the methodology section, there is no mention on exclusion criteria and if pregnant women were included into the study as they are of different risk profile. Behavioral factors like smoking/alcohol intake were captured through face to face interview; hence social desirability can play a role in the risk factor ascertainment. Another interesting fact about this study was current tobacco smokers were estimated as 37% (in males) vs. 8% (in females) which is different to that of China’s national level estimate of 52% (in males) and 2.7% (in females) based on Global Adult Tobacco Survey (GATS, 2015). Though both GATS and this study adopted same interview technique in assessing smoking behavior, still this region estimates varies with the national level data. In discussion, authors have highlighted increased insurance coverage could have impacted o...

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  • Response from the British Association for Cardiovascular Prevention and Rehabilitation (BACPR) in collaboration with NACR, the Cochrane Heart Rehabilitation Review Coordination Centre and ACPICR

    Powell et al’s systematic review and meta-analysis acknowledges that previous meta-analyses have included trials undertaken in the 1970s and 80s that may overestimate the contemporary benefit of exercise-based cardiac rehabilitation (CR) in terms of mortality[1]. The authors recognise the impact of the improvement in the acute medical management of patients with coronary artery disease since the turn of the century, which has led to better survival. Whilst we advocate that more reviews should acknowledge the wider clinical context when evaluating interventions, this particularly broad-brushed approach to the overall effectiveness of CR warrants several counter responses.

    Most notably, it is disappointing that the article depicts mortality as the main barometer of the effectiveness of CR, and conveys the message that the contemporary approach to CR generates no effect. In their updated 2016 Cochrane Review and meta-analysis, Anderson et al[2] acknowledge a linear reduction in all-cause mortality effect over time (i.e., with publication date) but importantly stress that promotion of CR should now focus upon reduced hospital admissions and clinically relevant improvements in quality of life, rather than mortality[3]. This view is supported by Lavie et al[4] who reiterate that CR is known to improve cardiorespiratory fitness and quality of life, and reduce cardiovascular disease (CVD) risk factors, providing cost-effective secondary CVD prevention. Lavie et al[4] al...

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  • Non-disclosure by physicans of payments from the pharmaceutical industry

    This is an interesting piece. Pharmaceutical companies have to publish payments made to individual, named physicians. (These are available at http://www.abpi.org.uk/ethics/ethical-responsibility/disclosure-uk/.) However, recipients can choose to remain unidentifiable (PMCPA Clause 24.9). In the figures for 2016, published in Disclosure UK in June 2017, 35% of health care professionals chose to remain incognito. In the GMC's Good Medical Practice they only recommend that physicians consider the PMCPA code. Perhaps they could be firmer in their recommendation.