439 e-Letters

published between 2017 and 2020

  • 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.

  • Long-term work-related poor sleep and subsequent cognitive impairment

    Poor sleep has been considered as a risk of Alzheimer's disease incidence. Thomas et al. reported a protocol paper regarding the effect of long-term work-related poor sleep on cognition and amyloid accumulation in healthy middle-aged maritime pilots (1). The same authors reported some results in another journal (2). They investigated the effects of work-related sleep loss on subsequent cognitive impairment and early dementia symptoms in 50 male maritime pilots with a history of >25 years of work with irregular job schedules, which resulted in sleep loss. They concluded that long-term exposure to work-related sleep loss had no relation to subsequent cognitive decline or early dementia symptoms in retired maritime pilot. I have two concerns about their study.

    First, Diem et al. examined the association between objective sleep-wake measures and risk of incident cognitive impairment (3). Longer average sleep efficiency and latency, but not total sleep time, were significantly associated with higher odds of developing cognitive impairment. They conducted a prospective study with average follow-up of 4.9 years, and risk assessment by longer follow-up is needed by considering sex, age and other factors.

    Second, the authors cited a reference by kang et al. concerning the mechanism of the association between sleep and Alzheimer's disease in "Sleep Medicine Research", but this paper was retracted. I recommend a review of the same authors, which d...

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  • POFA trial study protocol. Opioid-free-anesthesia, really?

    Alexis Guillaume1, MD, Marc de Kock2, MD, PhD, Marco Ghignone3, MD, FRCPC, FCCP, Luc Quin-tin4, MD, PhD.
    Anesthesia/Critical Care, Polyclinique de Franche Comté1, Besançon, France, Centre Hospitalier de Wallonie Picarde2, Tournai, Belgique, JF Kennedy North Hospital3, West Palm Beach, Florida, USA, Hôpital d’Instruction des Armées Desgenettes4, Lyon, France.
    Correspondence: L Quintin, 120 Rue de la Pagère, 69500 Lyon-Bron, France, luc-quintinx@gmail.com

    Beloeil et al [1] should be commended for addressing the postoperative side-effects of anesthesia without opioids («opioid free anesthesia»: OFA). Nevertheless,

    1) The protocol is unclear to us: « Propofol 1.5-2 mg.kg-1, lidocaine 1.5 mg/kg…, ketamine 0.5 mg/kg…., cisatracurium 0.15 mg/kg…., dexamethasone 8 mg… and target-controlled infusion (TCI) of remifentanil (3–5 ng/mL) (control) or [our emphasis] intravenous dexmedetomidine 0.4–1.4 μg.kg-1» [1]. Does the control group receive lidocaine, ketamine and dexamethasone in addition to remifen-tanil? Would our understanding be correct, standard OFA [2] (alpha-2 agonist supplemented with multimodal non-opioid analgesics), is compared with opioid+multimodal anti-nociception. In this respect, enkephalins are one out of many transmitters involved in nociception [3]. Therefore, standard balanced anesthesia (hypnotic+myorelaxant+opioid) is to be compared to OFA (hypnot-ic+myorelaxant+multimodal nonopioid analgesi...

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  • Further clarifications to the comments of the authors

    Dear colleagues,

    We would like to respond to your comments.

    1. We were rather concerned to learn of your confusion regarding our reasons for stopping the COMPACT-2 trial. We will try to better clarify what happened. In our report communicating our intention to interrupt the trial, we openly reported the results of our interim analysis, which were also summarized in our comment to your paper. We reiterate that we observed a close to significant difference in the trial’s primary endpoint (last hospital mortality), suggesting higher mortality in patients randomized to CPFA (59.6% vs. 41.3%; p=0.076). We observed significantly higher 3-day mortality in patients randomized to CPFA (32.8% vs. 12.5%; p=0.02). We observed higher mortality in the CPFA group at the survival analysis performed in the first 90 days after randomization (Log Rank test, p=0.03; Pet test, p=0.01). On the basis of these results, we concluded that: “The interim analysis requested by the EDSMC shows higher mortality for the CPFA group compared to the controls, particularly in the first days of treatment. Although the absolute number of treated patients is relatively small, the results raise concern that the use of CPFA may cause harm or worsen the clinical condition of septic shock patients”. In our understanding, the aim of this conclusion was to report exactly what we observed (significantly higher mortality in the CPFA group, particularly in the first days of treatment), while underlining th...

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  • Authors' reply

    We appreciate the opportunity to address the concerns raised by D’Angelo and colleagues in relation to our recently published protocol for the Trans20 study [1]. While we certainly welcome feedback on our study, D’Angelo and colleagues focus much of their commentary on the clinical care of young people with gender dysphoria rather than on the Trans20 study protocol itself. In addition, the letter contains a number of inaccuracies and misconceptions that we feel must be clarified.
    Firstly, the authors claim not only that the study “intervenes in the developmental trajectories of all 600 expected participants” and that the model involves “a uniformly stepwise progression through the social and biological stages of transition”, but also that The Royal Children’s Hospital (RCH) Gender Service offers biological interventions to children as young as three. These assertions are incorrect. While patients and families attending the RCH Gender Service routinely receive mental health input to assess, explore and support their gender identity, the use of medical interventions occurs in only a minority of patients, reflecting the highly individualised approach to care. More specifically, a recent 10-year audit of the service from 2007-16 (up until the inception of Trans20) revealed that only 23% of patients received puberty blockers, while an even lower figure of 20% received gender-affirming hormones, and no patient under 10 years of age received either of these medical interven...

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  • Characterising ideal trainee working hours - A Response Letter to “Working hours, common mental disorder and suicidal ideation among junior doctors in Australia: a cross-sectional survey”

    Petrie et al. asks the interesting question of where optimal weekly work hours lie for junior doctors, which is ultimately the question policy makers and advocates want to answer, with the aim of safeguarding the wellbeing and promoting satisfaction of junior medical doctors. Having recently (Dec 2019) published a large study (n=4012) in Medical Education examining factors related to Australian specialist trainee doctors we thought that there were several points of discussion made that may be distilled by our findings.

    There are a number of salient points to discuss:

    1. Satisfaction and Mental Illness - Our study examined specialist trainee’s satisfaction rather than mental illness or suicidal ideation with the idea being that a shift in the drive for policy from illness avoidance to promotion of satisfaction may be considered. In our Australia wide study, we found that one in five respondents worked more than 56 hours per week and, corroborating Petrie et al., that they were 24% less likely to be satisfied than those working 45 - 50 hours (median working hours).

    2. Optimal work hours - In contrast to the findings of Petrie et al. we found that those working 51 - 56 hours were the most satisfied group, 21% more satisfied than those working 45 - 50 hours (p=0.006). The demands and priorities of a trainee undertaking a specialist pathway, which include: taking time with patients to build a sufficient case load to become proficient, taking time to study,...

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  • Response letter to Ravnskov U et al "Dyslipidemia is an unlikely cause of atherosclerosis"

    We appreciate the authors’ interest for our paper, and we would like to thank them for the opportunity to discuss the problems raised in their letter (1).

    First of all, we would like to emphasize that in our study we didn’t try to investigate the pathophysiology of atherosclerosis, but tried to see how the generally accepted risk factors of atherosclerosis correlate with significant coronary heart disease evaluated by CAD-RADS score in the Romanian population (2). The design of our research was cross-sectional, retrospective, therefore our purpose was not to establish the causality between dyslipidemia and cardiovascular disease. We agree with the authors that there is a difference between causality and association and our current study was based on evaluating the association between the presence of risk factors and the burden of atherosclerotic coronary disease evaluated using CCTA method. We chose dyslipidemia among the atherosclerosis risk factors studied based on the most current guidelines on cardiovascular disease prevention at the time (3).

    Regarding the pathophysiology of atherosclerosis, the role of lipids and lipoproteins in the development of atheromatous plaque is proven by many studies (4-7). This complex process, based on an inflammatory response, is initiated by the infiltration of apoB containing lipoproteins into the arterial wall, which cause wall injuries and promote infiltration of monocytes into the subendothelial space. Secondly, the ma...

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  • Authors' Response

    Thank you for your comments on our manuscript.
    Firstly, we applied meta-analysis to pool diagnostic accuracy for NBI, HAL and 5-ALA techniques for patients with NMIBC in comparison with WLC as the reference standard, which demonstrated the superior diagnostic performance of new imaging techniques in bladder detection compared with conventional WLC. These new imaging techniques are promising diagnostic interventions to improve clinical procedures in bladder cancer detection.
    We described The SROC curves for NBI, HAL and 5-ALA in Figure 3A and the pooled DOR for NBI, HAL and 5-ALA were 40.09 (95% CI, 20.08-80.01, Figure 2A), 78.14 (95% CI, 31.42-194.28, Figure 2B) and 18.14 (95% CI, 4.28-76.87, Figure 2C), showing significant diagnostic superiority compared with white light cystoscopy (WLC) at the lesion level. While SROC curves for NBI, HAL and 5-ALA were showed in Figure 3B, DOR for NBI and HAL were 358.71 (95% CI, 44.50-2891.71, Figure 2D) and 59.95 (95% CI, 24.30-147.92, Figure 2E), presenting better performance compared with WLC. Figure 3 showed HAL and NBI exhibits similar SROC curves in lesion level, NBI performed significant excellent SROC curve in patient level. For patient-level analysis, NBI showed highest median sensitivity (SSY) 100%, median positive predictive value (PPV) 90.75%, median negative predictive value (NPV) 100% and median false positive rate (FPR) 31.55% in supplementary Table 1. And supplementary Table 2 showed similar narrative outcome...

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  • Response

    Dear Editor,
    Socioeconomic status (SES) has long been found to be significantly associated with increased risk of morbidity and mortality. It is related to health at all levels (1). A weak association between SES and maternal health care is found in countries where females are more educated (2). In developing countries like Pakistan where maternal mortality is still high despite efforts been made (3). This poor maternal health care use leads to maternal depression leading to CMH (Child Mental Health) issues (4). Therefore, efforts should be targeted to improve maternal health care use in order to ensure physical and mental health of the future generation irrespective of their SES.
    1. Adler NE, Boyce WT, Chesney MA, Folkman S, Syme SL. Socioeconomic inequalities in health. No easy solution. Jama. 1993;269(24):3140-5.
    2. McTavish S, Moore S, Harper S, Lynch J. National female literacy, individual socio-economic status, and maternal health care use in sub-Saharan Africa. Social science & medicine. 2010;71(11):1958-63.
    3. Mumtaz Z, Salway S, Shanner L, Zaman S, Laing L. Addressing disparities in maternal health care in Pakistan: gender, class and exclusion. BMC pregnancy and childbirth. 2012;12(1):80.
    4. Maselko J, Sikander S, Bangash O, Bhalotra S, Franz L, Ganga N, et al. Child mental health and maternal depression history in Pakistan. Social psychiatry and psychiatric epidemiology. 2016;51(1):49-62.

  • How to improve diagnosis of non-muscle invasive bladder cancer?

    In their recent paper Chen et al. presented a meta-analysis on the diagnostic performance of image technique based transurethral resection for non-muscle invasive bladder cancer: They claim in their conclusion that narrow band imaging (NBI) showed the best diagnostic performance outcomes in a comparison to blue light cystoscopy with hexaminolevulinate (HAL) and 5-aminolevulinic acid (5-ALA). We cannot find the evidence for this in the result they present which deserves commenting.
    In the abstract it is written that NBI showed significant diagnostic superiority compared with white light cystoscopy (WLC) at the lesion level (Pooled sensitivity 0.94, 95% CI 0.82 to 0.98; Pooled specificity 0.79, 95% CI 0.73 to 0.85; Diagnostic odds ratio (DOR) 40.09, 95% CI 20.08 to 80.01; Area under the receiver operating characteristic curve 0.88, 95% CI 0.85 to 0.91). That HAL showed superior lesion level detection results in all measured parameters is not mentioned. It is further stated that NBI presented the highest DOR (358.71, 95% CI 44.50 to 2891.71) in the patient level. The subgroup analysis, evaluating diagnostic performance in studies with low to moderate risk of bias and in studies with more than 100 patients, is only presented in supplementary material and similarly show how HAL and 5-ALA achieve comparable or improved diagnostic performance compared to NBI. Despite these results, the authors emphasize and conclude on behalf of NBI throughout the paper.
    While the con...

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