eLetters

4 e-Letters

published between 2018 and 2021

  • Advice on how to navigate the MODREC process for junior researchers in the Defence Medical Services

    Dear Sir,

    The paper by Dr Schmidt details the history of the first independent Research Ethics Committee (REC) at Porton Down in the 1960’s. This REC was created to address ethical and legal concerns about research on human subjects. Since the 1960’s the emphasis has rightly shifted from “the doctor/scientist is always right” to “the participants must be protected from any unnecessary harms”. This has led to an expansion of the ethics review process and level of scrutiny, which has left many junior researchers feeling frustrated when their plans are criticised or delayed.

    This letter will list some advice for junior researchers in the Defence Medical Services on how to navigate the process and improve the quality of their research and the chance of a successful ethical approval for research involving human participants:
    1. First, use the NHS Health Research Authority tool to confirm that your study design is research and that it requires ethical approval.
    2. Read JSP 536 Pt 1 (48 pages) and 2 (64 pages).
    3. Be familiar with the main tenets of medical ethics - respect for autonomy, beneficence, non-maleficence, justice and equipoise.
    4. Involve patients and other stakeholders in the design of the study.
    5. Do not underestimate the time required, it may take six to 12 months.
    6. Be resilient and ensure you have support. It will be stressful.
    7. The REC process is a combination of prestigious journal submission and viv...

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  • Statistical problems in the vitamin C and common cold trial with South Korean army recruits

    The report on vitamin C for preventing the common cold in the Republic of South Korea army recruits by Kim et al. [1] has several statistical problems.

    First, Kim et al. did not follow the intention-to-treat [ITT] approach. Figure 1 shows that 49 participants were excluded because they “stopped intake of vitamin C”, and 84 participants were excluded because they “stopped intake of placebo” [1]. The CONSORT recommendation for ITT analysis states as follows [2, Box 6]: “participants who … did not take all the intended treatment ... exclusion of any participants for such reasons is incompatible with intention-to-treat analysis”.

    Second, Altman et al. pointed out that “The odds ratio should not be interpreted as an approximate relative risk [RR] unless the events are rare in both groups (say, less than 20-30%)”[3]. The common cold is not rare. Over 50% of the participants in the Kim et al. trial had the common cold during the trial period which greatly exceeds the 20-30% limit. Furthermore, there is no need to use the OR as the approximation for RR, because the RR can be calculated from the trial data in Table 1, RR = 0.916 (= 0.538/0.587) [1].

    Third, in their abstract, Kim et al. wrote “the vitamin C group had a 0.80-fold lower risk of getting a common cold” implying that vitamin C decreased the incidence of colds by 20%. However, the correct effect estimate is given by the RR above, which indicates only 8.4% lower risk of colds in the vitamin C group....

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  • Hyperbaric oxygen treatment can be an early adjunctive therapy in sudden deafness

    We read with interest the article by Bayoumy et al. concerning the effects of hyperbaric oxygen therapy (HBOT) associated with corticosteroid therapy in military personnel with acute acoustic trauma1. This paper helps to discuss about the most appropriate treatment of sudden deafness (SD). As recently stated, a spontaneous recovery, in the general population, is less than 40%. The precise role of HBOT has not yet been clearly established2. Our clinical experience during the last 15 years in a second referral hyperbaric center indicates the need of clear guide-lines, for the treatment of this acute disease. Nowadays there are two main therapeutic approaches to SD of different origin, the corticosteroid medication and HBOT.
    Clearly, at first, it has to be ascertained the nature of a deafness excluding, cerebral diseases, vascular, traumatic and neoplastic. A subsequent otolaryngology evaluation enables to ascertain possible associated vestibular diseases, and to measure Pure Tone Average. Medical contraindications to HBOT and corticosteroids medication have to be excluded. An early treatment, not beyond the first 48 hours after the acute event is recommended 1. Today the HBOT standardized protocol, consists in a daily oxygen 100% at 2.2-2.5 atmosphere for 90 minutes, for a minimum of 10 sessions in case of satisfying functional recovery. On the contrary, in case of absolutely negative results, the treatment should be interrupted. Otherwise, HBOT can be prolonged to a...

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  • Penthrox for the military: Possilbly, but you need to understand what you are using

    The article by Cohen and Wolstenholme provides a useful overview of Penthrox but is unfortunately incomplete.

    Compared with modern anaesthetic agents, Penthrox is an unclean drug and would not get a product license if invented today. The high fat solubility means a tissue reservoir persists for ≈1 week. About 70% is biotransformed, and this continues after administration until the tissue reservoir is empty. Nephrotoxicity was not just “a concern” but actually happened; ≈20 people died [1].

    It has only been possible to use Penthrox 5 million times safely because of essential pre-use checks to ensure no contraindications. It is worth remembering that methoxyflurane was used 10-12 million times before the nephrotoxic potential was established [1].

    Penthrox produces nephrotoxic metabolites at all doses, but this only becomes clinically significant above a certain level. The claim that Penthrox use is not nephrotoxic is technically correct, however, the presence of other factors that can also induce renal injury will reduce the Penthrox safety net. Of relevance to military use, this includes crush injury, hypovolaemic shock and patients subsequently requiring nephrotoxic antibiotics. Other potential issues for military use: (1) Limit to ≈50min administration (two bottles); (2) Activated charcoal adsorber is only effective IF the patient exhales through it. The patient will continue to exhale small amounts of drug for hours after administration; (3) There i...

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