497 e-Letters

published between 2020 and 2023

  • On reducing infection risk via air purification

    We appreciate the authors for their interesting article, but we want to highlight issues regarding the interpretation and reproducibility of the research results. The key problems lie in the documentation of measurements and the reporting of essential aspects of the study.

    First, the article does not provide sufficient detail on how ventilation in the participating daycare centers is implemented – whether it is mechanical, gravity-based, or reliant solely on window ventilation. Fundamental information concerning the baseline ventilation is crucial for evaluating and reproducing the study results. When assessing the effectiveness of air purification against airborne infections, it is necessary to establish 1) what is the baseline ventilation capacity which dictates the reference airborne infection risk level and 2) what is the augmented ventilation capacity after introducing air purifiers which, in turn, dictate the expected reduction in the risk level (Rehva 2020; Auvinen et al. 2022; Buonanno et al. 2022). Without knowing the baseline ventilation rates and how they differ between intervention and control groups, it is impossible to assess whether the introduced air purification improves the overall ventilation performance sufficiently to bring the risk level low enough to justify expectations for an observable improvement. After all, it is possible that even after introducing air purifiers the infection risk levels remain high nonetheless (Rehva 2023).


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  • ALABAMA: Update to the Primary Outcome and Cost Effectiveness Analysis

    Dear Editor,

    RE. Penicillin allergy status and its effect on antibiotic prescribing, patient outcomes and antimicrobial resistance (ALABAMA): protocol for a multicentre, parallel-arm, open-label, randomised pragmatic trial. https://bmjopen.bmj.com/content/13/9/e072253

    The issue of incorrect penicillin allergy records and their impact on antibiotic prescribing remains an internationally important issue that lacks randomised controlled trials to guide optimal management.

    Since submission of this protocol paper, the funder (UK National Institute for Health and Care Research Programme Grants for Applied Research) has undertaken a review of trial progress and decided not to provide additional funds to compensate for slow recruitment caused by COVID-19. Although a steady rate of recruitment was achieved during the pandemic, it was not at the rate anticipated pre-COVID-19. The funder recognised the value of the trial but maintained that the financial climate has changed within the context of the UK Department of Health and Social Care’s wider ‘Research Reset’ initiative. As a result of this funding review a revised primary trial outcome has been agreed. This will allow us to provide a powered study with a revised (reduced) sample size.

    NHS Research Ethics Committee and Health Research Authority approval has been granted for the protocol amendment outlined in this correspondence and clinical tri...

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  • Further Research Needed to Enhance Mental Health Interventions for Adolescents in sub-Saharan Africa

    The authors have conducted a thorough analysis of the existing literature on this crucial topic and have provided valuable insights into the effectiveness of various interventions for improving mental health outcomes among adolescents in sub-Saharan Africa (SSA).
    The systematic review employed the Grades of Recommendation, Assessment, Development, and Evaluation approach, ensuring a robust evaluation of the evidence. The researchers conducted a comprehensive search across multiple databases, including Cochrane Library, MEDLINE, EMBASE, PSYCINFO, and Web of Science, and identified 30 studies for inclusion in the review.
    The findings of this review highlight the significance of multi-level interventions in addressing mental health disorders among adolescents in SSA. The synthesis of the studies revealed that interventions comprising economic empowerment, peer support, and cognitive behavioral therapy (CBT) were particularly effective in improving mental health outcomes among vulnerable adolescents. Moreover, community-level interventions delivered to community groups demonstrated significant positive changes in mental health outcomes.
    While the results of this review are promising, the authors acknowledge the need for further research to understand the reliability and sustainability of these interventions in different African contexts. They rightfully point out the variability in intervention components and study participants among the included studies, emp...

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  • Re: IV Iron before surgery

    We appreciate the interest and questions posed by Professor Richards regarding the FORGE trial. The PREVENTT trial was a well-designed and executed trial, however the primary limitation of the trial is the “Two-week rule” described by the author in their letter and discussed in our introduction. It is well known that the biochemical response to all iron replacement improves with time, with most studies noting a larger response at 3 to 4 weeks post infusion[1,2]. In the PREVENTT study, the median time from infusion to surgery was 14 days in the iron infusion group, with an interquartile range (IQR) of 12-21 days. This is perhaps an explanation as to why the study demonstrated a hemoglobin increase of only 4.7g/L while other studies with median time from infusion to surgery demonstrated greater responses[1]. The study by Derman and colleagues found that at 2 weeks only 30% of patients obtained an increase of hemoglobin concentration greater than 20g/L in response to IV ferric derisomaltose (FDI), while at 3 weeks this increased to nearly 50% of patients[2]. Similarly, the work by Froessler and colleagues in 2016 found only an 8g/L difference in hemoglobin when IV iron (ferric carboxymaltose) was administered a median of 8 days (IQR 6-13 days) prior to surgery[3].

    Although expedited surgery for malignancies is often the ideal, in many jurisdictions, this is not feasible, or advisable based on patient, disease, and health system factors. The COVID-19 pandemic afforded a...

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  • Schlußfolgerungen

    Eine interessante Studie mit einem klaren Ergebnis

    Zur Schlußfolgerung: "Es ist bekannt, dass die Ansteckung hauptsächlich über den direkten Luftaustausch von Angesicht zu Angesicht während des Spiels erfolgt und dass die kontaminierte Luft nicht unbedingt vor dem Luftaustausch zwischen Kindern durch den Filter strömt. Die Verwendung von HEPA-Filtern kann auch zu einem Sicherheitsgefühl führen, was zu einem verringerten vorbeugenden Verhalten führt."

    Die Studie enthält keine Untersuchung über den Verhaltensvergleich in den Kindergärten der zwei Kohorten (Mit/Ohne Filter).

    Insofern vermisse ich in der Schlußfolgerung diese Aussage als eine Vermutung kenntlich zu machen.
    Ich finde, daß "Ergebnis" und "Schlußfolgerung" zwei verschiedene Themen sind. Die Schlußfolgerung müßte meines Erachtens lauten: HEPA Filter bringen keinen Vorteil.

    Ich finde die Schlußfolgerung eher in Brosa formuliert und somit abweichend vom vorhergehenden Text der Studie. Für mich macht dies die Qualität der Studie zunichte wenn Vermutungen angestellt werden welche nicht Umfang der Studie waren. Mithin viele Studien nur nach Abstrakt, Ergebnis & Schlußfolgerung lesen.
    Wenn die Studienverfasser einen Beweis nahelegen, dann muß das Verhalten der Kinder in den Kohorten überprüft und nachgewiesen werden.

  • Limitation of the study

    there are several limitations that should be considered:

    Sampling Bias: The study relies on blood samples collected for unrelated tests, which may introduce a sampling bias. Patients who undergo routine testing may differ from those who do not, potentially affecting the generalizability of the findings to the broader population.

    Cross-Sectional Design: The study design is cross-sectional, meaning it captures data at a single point in time. This limits the ability to establish causation or assess changes over time. Longitudinal studies would provide more robust evidence of the effectiveness of opportunistic screening.

    Exclusion Criteria: The study excludes samples from patients with a previous diagnosis of diabetes or those who underwent diabetes screening in the past 12 months. However, the accuracy of this exclusion depends on the completeness and accuracy of medical records, which might not capture all instances of diabetes diagnoses.

    Age Discrepancies: The study finds age-related differences in HbA1c levels but adjusts for these differences. However, age alone may not capture the complexity of diabetes risk factors. Other factors such as lifestyle, family history, and comorbidities could contribute to variations in HbA1c levels.

    Limited Generalizability: The study is conducted in a specific Australian setting, and the findings may not be directly applicable to other regions with different demographics, healthcare systems, or diabetes p...

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  • IV iron before surgery

    We read with interest the proposal for the FORGE trial. We are concerned that the authors are repeating work that has already been undertaken, without learning from previous trials. The authors criticise the PREVENTT trial, but fail to elaborate their reasons and then proceed to essentially duplicate the very same protocol.

    In summary, the PREVENTT RCT (1) was the largest multicentre RCT to assess the role of IV iron compared to placebo in patients before major abdominal surgery. Included were 138 patients undergoing gynaecological surgery and most common operation was a Wertheim’s hysterectomy, a debulking procedure in gynaecological oncology. Of note about two thirds had Tsats < 20% (table 10), essentially representing the same PICO (and size) as proposed in the FORGE trial. There are a couple of key aspects of relevance to FORGE aside from the key question of why they need to repeat the data powered for change in haemoglobin?

    A. A key limitation in recruitment was the ‘2-week rule’ whereby patients listed for cancer surgery are mandated to have their operation within 2 weeks (Chapter 4 of the NIHR report (1)). How do the authors propose to overcome this hurdle in FORGE?

    B. The benefit of modern IV iron is the ability to give a full treatment dose, normally 20mg/kg, why are the authors proposing a lower dose?

    We applaud the authors undertaking a randomised controlled trial but urge them to learn from existing studies to avoid future mist...

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  • Sample size amendment

    I am writing to you regarding an amendment to the sample size section of the following 2021 published protocol paper: Mylrea-Foley B et al. TRUFFLE 2 Collaborators List. Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol. BMJ Open. 2022 Apr 15;12(4):e055543. doi: 10.1136/bmjopen-2021-055543. PMID: 35428631; PMCID: PMC9014041.

    In light of a higher-than-expected overall rate of the primary outcome and based on advice from both the TRUFFLE 2 Independent Data Monitoring and the Trial Steering Committees, we have had to amend our sample size for the TRUFFLE 2 randomised trial. It is important for transparency, that the new section is published, and can be found below.

    Yours sincerely,

    Dr Rebecca Cannings-John, on behalf of the TRUFFLE 2 Trial Management Group

    Statistics and data analysis

    Sample size

    The trial is powered to detect if immediate delivery following cerebral redistribution is superior to expectant management following cerebral redistribution on this outcome. The original sample size was based on a difference in the proportion with the primary outcome from 15% in the delayed delivery to 9% in the immediate delivery (based on the TRUFFLE 2 feasibility study) and demonstrated an odds ratio (OR) of 0.56. At two-sided 5% significance with 95% power, 780 participants per arm were required, giving 1560 in total.

    In light of a higher than expected overa...

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  • Barriers that exist for the approach of asthmatic children.

    Dear editor
    The treatment of asthma is based on four fundamental pillars: patient education, dealergenization or environmental control measures aimed at avoiding the allergen, symptomatic pharmacological treatment and allergen-specific immunotherapy.
    In each country there must be political will from the state, which does not exist in underdeveloped countries, to successfully control asthma and avoid the numerous crises of the disease that deteriorate the quality of life of patients.
    Adequate health education is necessary, establishing simplified treatment plans and promoting shared decision-making with asthmatics themselves and their family, in addition to the necessary knowledge on the part of the professionals who attend consultations in primary care to improve the control of these patients.
    It is very important to emphasize the use of inhaled corticosteroids, essential medications for controlling the disease, as well as explaining and showing their proper handling because when this fails it leads to non-control of asthma. It is also very important to take into account the ages of the patients and their characteristics, collected in their medical history to personalize each of the behaviors to be taken and improve the quality of life of each patient.
    Regarding immunotherapy, it has been shown in numerous studies that it is the only way capable of modifying the course of the disease, controlling it. There are several allergenic extracts in Cu...

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  • The R21/Matrix-M vaccine is a new 2nd malaria vaccine recommended by the World Health Organization (WHO) for the prevention of plasmodium falciparum malaria in children

    Dear Editor
    The R21/Matrix-M vaccine is a new vaccine recommended by the World Health Organization (WHO) for the prevention of malaria in children below age 5 years , in pregnant women, in travellers and individuals with HIV and AIDS (1) . It is the second malaria vaccine recommended by WHO, following the first RTS,S/AS01 vaccine, which received a WHO recommendation in 2021 (1) . The R21 vaccine is shown to be safe and effective in preventing malaria in children and, when implemented broadly, is expected to have high public health impact (1) in the rainy season.
    The R21/Matrix-M vaccine was developed by the University of Oxford and is a low-dose vaccine that can be manufactured at mass scale and modest cost, enabling as many as hundreds of millions of doses to be supplied to African countries which are suffering a significant malaria burden (3) . The vaccine targets the first form of the malaria parasite (the plasmodium sporozoite) to enter the body after a person is bitten by an infected mosquito (2)
    The updated WHO malaria vaccine recommendation is informed by evidence from an ongoing R21 vaccine clinical trial and other studies, which showed high efficacy when given just before the high transmission season. In areas with highly seasonal malaria transmission (where malaria transmission is largely limited to 4 or 5 months per year as it is in Ghana and Nigeria), the R21 vaccine was shown to reduce symptomatic cases of malaria by 75%-77% during the 12...

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