rss

Recent eLetters

Displaying 11-19 letters out of 299 published

  1. Trial protocol must explain how possible adverse effects will be looked for and managed

    Grigg and colleagues have published their design for the first-ever randomised controlled in Plasmodium knowlesi malaria, to be carried out over a 2-year period in Sabah [1]. We are concerned because one arm of the trial involves a fixed combination of mefloquine + artesunate.

    The authors of the study protocol rightly acknowledge that mefloquine is associated with neuropsychiatric adverse events (AEs), but go on to state that these are 'self-limiting'. This claim by Grigg et al is incompatible with published reports of neuropsychiatric AEs from mefloquine that have persisted for months, or years [2] [3] [4]. Last year the US Food and Drug Administration strengthened its warning on the neurological and psychiatric adverse effects of mefloquine to its highest level (i.e. a 'black box' warning); the change was prompted by the recognition that the adverse effects of mefloquine can be prolonged and even, in some patients, permanent [5].

    We recommend that the protocol for this trial should include details of how possible adverse effects of mefloquine will be looked for at and after the end of the study, and how the authors propose to manage neuropsychiatric or other AEs that prove to be prolonged, or permanent.

    Andrew Herxheimer

    Ashley Croft

    UK Cochrane Centre, Summertown Pavilion, 18-24 Middle Way, Oxford OX2 7LG, UK

    Conflict of Interest:

    None declared

    Read all letters published for this article

    Submit response
  2. Correction: Ambulatory blood pressure adds little to Framingham Risk Score for the primary prevention of cardiovascular disease in older men: secondary analysis of observational study data

    The correct affiliation for Andrew Hayen is: School of Public Health and Community Medicine, The University of New South Wales, Sydney, New South Wales, Australia

    Conflict of Interest:

    None declared

    Read all letters published for this article

    Submit response
  3. Correction for the reference 28

    The 28th reference cited in this article should be corrected as:

    28. Xie Y, Ho SC. Prenotification had no additional effect on the response rate and survey quality: a randomized trial. J Clin Epidemiol 2013;66:1422-6.

    Conflict of Interest:

    None declared

    Read all letters published for this article

    Submit response
  4. Stillbirth data seem incorrect

    "The registry is considered complete through the period" Hedegaard et al state in their registry study (1) without a supporting reference. However, there seem to be an issue with the quality of the data as the number of stillbirths deviate from the published official statistics. The authors in their online supplement report 539 stillbirths in 2009-10 decreasing to 489 in 2011-12. But according to the published official statistics the number of stillbirths were 260+255=515 in 2009-10 (2) decreasing to 274+236=510 in 2011-12 (3). Thus the seemingly dramatic decrease between the two time periods is reduced from 50 (=539-489) in the paper to 5 (=515-510) according to the official statistics. Even though we all hope for miracles, all too often they evaporate into thin air on closer inspection. I cannot see any other solutions to this conundrum than either the authors thoroughly document the validity of their data or they retract their paper.

    1) Hedegaard M, Lidegaard O, Skovlund CW, Morch LS, Hedegaard M. Reduction in stillbirths at term after new birth induction paradigm: results of a national intervention. BMJ Open. 2014 Aug 14;4(8)

    2) Sundhedsstyrelsen. Fodselsstatistikken 2011. Copenhagen, Sundhedsstyrelsen, 2012.

    3) Statens Serum Institut. Fodselsstatistikken - tal og analyser, 2012. Available at http://www.ssi.dk/~/media/Indhold/DK%20- %20dansk/Sundhedsdata%20og%20it/NSF/Registre/Fodselsregisteret/f%C3%B8dselsstatistikken2012_vers%204.ashx. Accessed September 8th.

    Conflict of Interest:

    None declared

    Read all letters published for this article

    Submit response
  5. Response: Assessing the effect of an interactive decision-aid smartphone smoking cessation application (app) on quit rates: a double-blind automated randomised control trial protocol

    Author have come out with an interesting concept of using smart phone app in medical research. Smart phones are rapidly becoming omnipresent with greater processing power and memory and now are commonly used as first device to access information from or off internet. Thousands of medical apps are available for layman to get information regarding diseases. Also, several apps are available to physicians to quickly asses information from guidelines, algorithms and medical formulas making pocket books redundant. Increasingly new app are being developed to provide diagnostics at nominal cost.

    I think this is the first serious attempt to use phone app in medical research, Authors have meticulously prepared protocol and though some provision like locking the device to one particular group may have got frown from some ethical committee members but I think that was essential to have valid randomization.

    In my personal view this is well planned study on a very important socio-medical problem. I shall be very eagerly waiting for the study results and how this concept per se is taken by medical fraternity.

    Dr. Sandeep Tak

    Conflict of Interest:

    None declared

    Read all letters published for this article

    Submit response
  6. Does CAM training for GPs really reduce healthcare costs?

    I read with interest the recent contribution from Baars and Kooreman [1]. The present study is a replication of a previous study, using a different data set, as described by the authors in their introduction. The 2012 study by Kooreman and Baars [2] garnered criticism from me and others [3-5]. Furthermore, the new study was also presented in an earlier form [6], and this also faced criticism [7,8]. Baars and Kooreman provided response to both of these at the time [9,10].

    The authors have heeded some, if not all, of the criticisms directed at their previous work. In particular, the authors' reporting of their results is somewhat more measured and the limitations of the analysis are more thoroughly presented. It is likely that selection into the two groups at least partially (perhaps fully) explains the observed differences in costs, and the authors are right to identify this as a limitation. The new analysis of mortality data is a welcome improvement.

    In addition to the limitations already outlined by critics of the previous publication - and by the authors themselves - it is unfortunate that the new analysis did not account for the hierarchical structure of the data, with patients clustered by GP practice. It appears that the authors were able to identify this source of clustering in their data, so it is disappointing that a multilevel model was not used to account for this potential source of bias (which might also explain part of the observed difference). It is also regrettable that the results of the log-linear regression of costs appear to have been misreported in Table 4 (Appendix 2).

    Baars and Kooreman's statement that they intend to carry out further analyses on this or similar data with more appropriate estimation strategies is encouraging. Such analyses are crucial due to the limitations of this study. The implementation of better estimation strategies, such as propensity score matching or (as the authors suggest) use of instrumental variables, will be an important part of this. I look forward to reading these potentially enlightening studies once completed.

    References

    [1] Baars EW, Kooreman P. A 6-year comparative economic evaluation of healthcare costs and mortality rates of Dutch patients from conventional and CAM GPs. BMJ Open 2014;4:e005332. doi: 10.1136/bmjopen-2014-005332

    [2] Kooreman P, Baars EW Patients whose GP knows complementary medicine tend to have lower costs and live longer. European Journal of Health Economics 2012;13(6):769-76. doi: 10.1007/s10198-011-0330-2

    [3] Sampson CJ, Whitehurst DGT, Street A. Do patients registered with CAM-trained GPs really use fewer health care resources and live longer? A response to Kooreman and Baars. Eur J Health Econ (2012). 13:769-776. European Journal of Health Economics 2013;14(4):703-5. doi: 10.1007/s10198-013-0466-3

    [4] van Erp P. Alternatieve huisartsen werken 15 procent goedkoper? Een verzinsel!. [Blog] Kloptdatwel? 2013. Available at: http://kloptdatwel.nl/2013/05/10/alternatieve-huisartsen-werken-15-procent-goedkoper-een-verzinsel [Accessed 3 Sep. 2014].

    [5] Sampson CJ, Whitehurst DGT, Street A. Bad science in health economics: complementary medicine, costs and mortality. [Blog] The Academic Health Economists' Blog 2013. Available at: http://aheblog.com/2013/06/05/bad-science-in-health-economics-complementary-medicine-costs-and-mortality [Accessed 3 Sep. 2014].

    [6] Kooreman P, Baars EW. Complementair werkende huisartsen en de kosten van zorg. Economisch Statistische Berichten 2014;99(4678):90-2.

    [7] Pomp, M. Reactie op: Complementair werkende huisartsen en de kosten van zorg. Economisch Statistische Berichten 2014;99(4679):125.

    [8] van Erp P. Verzekerde zorgkosten van pati?nten bij alternatieve huisarts. [Blog] Kloptdatwel? 2014. Available at: http://kloptdatwel.nl/2014/03/05/verzekerde-zorgkosten-van-patienten-bij-alternatieve-huisarts. [Accessed 3 Sep. 2014].

    [9] Kooreman P, Baars EW. Do patients registered with CAM-trained GPs really use fewer health care resources and live longer? A reply to Christopher James Sampson. European Journal of Health Economics 2013;14(4):707-8. doi: 10.1007/s10198-013-0475-2

    [10] Kooreman P, Baars EW. Reactie op: Complementair werkende huisartsen en de kosten van zorg (Naschrift). Economisch Statistische Berichten 2014;99(4679):125.

    Conflict of Interest:

    None declared

    Read all letters published for this article

    Submit response
  7. Re: Herbal medicine (Gan Mai Da Zao decoction) for depression: a systematic review protocol

    This is a very interesting research proposal to evaluate a formula originated from Chinese traditional medicine, Gan Mai Da Zao (GMDZ) decoction. The protocol for a systematic review is generally well written; however, there are several points that need to be addressed from the standpoint of Japanese traditional Kampo medicine, which incorporated the Gan Mai Da Zao decoction as kambakutaisoto.

    Kampo medicine originated from ancient Chinese traditional medicine, but developed distinctively [1]. Kampo medicine was the orthodox medicine in Japan until the 19th century when modern Western medicine took over. Nevertheless, some Kampo formulae are still officially registered in the Japanese Pharmacopoeia [2]. Since 1967, Kampo formulae have been covered by National Health Insurance, and currently 148 Kampo formulae are approved for ethical use [3]. Although Kampo extracts are crude drugs derived from plants, animals, and minerals, their quality is strictly controlled in accordance with the Japanese Pharmacopoeia by quantitative analysis of marker components using high-performance liquid chromatography.

    Unlike China and Korea, traditional medicine in Japan is used in a Western-style medical system, and is prescribed by medical doctors, educated in Western medicine [3], who are required to have a basic knowledge of Kampo formulae. Reflecting the needs for establishing evidence-based medicine in Kampo, the Japan Society for Oriental Medicine has run a project from 2001 to gather comprehensive data on the randomized controlled trials (RCTs) of Kampo formulae in Japan, and to compile structured abstracts with critical appraisal. This report is published annually as Evidence Reports of Kampo Treatment (EKAT) in Japanese and English.[4] In the current version EKAT 2013, 402 RCTs of Kampo formulae are included.

    The first point to be addressed is that the systematic review protocol developed by Dr. Jun et al. lacks searches of articles written in Japanese; thus, it may result in a biased review. The authors are encouraged to search in Japanese database, Ichushi [5], although no RCTs of kambakutaisoto (Japanese name for GMDZ decoction) seem to be reported in EKAT 2013. Secondary, the authors mention that they include forms of GMDZ such as extracts, tablets, capsules, pills, powders or injections. However, unlike Japanese Kampo extracts, the quality and ingredients of the formulae such as tablets, capsules, or crude powders are not strictly controlled, especially in the older articles, which may result in a bias. Thirdly, although the authors are planning to search the Kampo formula by kambakutaisoto or kam baku tai soto, older articles seem to use the word kanbaku-taiso-to to express the formula, and this word should be included in the search. The structured notation of kambakutaisoto is not quite correct; it should be Kambaku-taiso-To.

    1. Matsumoto M, Inoue K, Kajii E. Integrating traditional medicine in Japan: the case of Kampo medicines. Complement Ther Med 1999;7(4):254-5 2. Kawashima N, Deveaux TE, Yoshida N, et al. Choreito, a formula from Japanese traditional medicine (Kampo medicine), for massive hemorrhagic cystitis and clot retention in a pediatric patient with refractory acute lymphoblastic leukemia. Phytomedicine 2012;19(12):1143-6. 3. Motoo Y, Arai I, Tsutani K. Use of Kampo diagnosis in randomized controlled trials of kampo products in Japan: a systematic review. PLoS One 2014;9(8):e104422. 4. Task Force for Evidence Reports/Clinical Practice Guidelines (ER/CPG- TF) Special Committee for Evidence-based Medicine (EBM), The Japan Society for Oriental Medicine (JSOM). Evidence Reports of Kampo Treatment (EKAT) Appendix 2012. Retrieved September 4, 2014, from http://www.jsom.or.jp/medical/ebm/ere/pdf/EKATE_Appendix_2012.pdf. 5. Tomizawa Y. Ichushi, Japanese medical bibliography. Kyobu Geka 2010;63(7):585-9, in Japanese

    Conflict of Interest:

    None declared

    Read all letters published for this article

    Submit response
  8. Reply to Clausen and Rydahl.

    Thanks to Jette Clausen (JC) and Eva Rydahl (ER) for their considerations on our study on stillbirths.

    JC and ER suggest our interpretation being "overly optimistic" due to our observational design. But again, observational studies have identified a long list of causes of diseases, be it lung cancer among smokers, venous thrombosis among users of hormonal contraception, greenhouse gas emissions as a cause of global warming, etc. Not only do we identify and quantify causes by observations, we also act according to the knowledge they bring. By combining different observational strategies we may actually achieve evidence of causation, amounting almost to certainty.

    So a well confounder controlled study may actually bring new knowledge, which should - of course - be confirmed by other independent studies, but which in the end may bring progress in our clinical practice. So much in general on interpreting observational studies.

    And no, we have examined a long list of fetal and neonatal outcomes. Our first publication, however, focused on stillbirths. We have submitted the next paper assessing the frequency of asphyxia, cerebral palsy, neonatal deaths, Apgar score, referral to neonatal intensive care units, shoulder dystocia, and peripheral nerve injuries with the more proactive induction practice, and look forward to continue the discussion with these new data.

    The stochastic year-to-year variations in stillbirth rates don't change the convincing and substantial declining trend in stillbirth rates by time, a decline which was steeper after 2009 than before 2009.

    And no, we did not restrict the study window to the period 2009 to 2012 but to the 13-year period 2000-2012, and we acknowledged that several factors in addition to the more proactive induction contributed to the fall in stillbirths. About preeclampsia and intrauterine growth restriction, please see our reply to Carbillon, Hosseraye & Mekinian.

    We have as JC and ER also noticed a still very low stillbirth rate in 2013, actually the next lowest ever measured. Isn't that reassuring?

    Conflict of Interest:

    See original paper.

    Read all letters published for this article

    Submit response
  9. Re:Foetal growth restriction, induction of labour and reduced still birth rate at term

    Thanks to Lionel Carbillon, Claire de la Hosseraye & Arsene Mekinian for their interest in and comments to our paper on stillbirth reduction in Denmark with a more proactive induction practice.

    No doubt, that the improved ultrasound monitoring of pregnancies at term is expected to have decreased the stillbirth rates all over the industrialised world. It is also true, that the stillbirth rates may be higher in women with preeclampsia and intrauterine growth restriction.

    The number of deaths after 37 weeks associated with IUGR was around 6 per year without any consistent trend during the study period. The adjusted hazard ratio of stillbirth among women with IUGR was 1.85 (1.4- 2.5). And the mean gestational age at delivery among women with IUGR was stable during the study period (39 weeks +/- 1 day). Thus, IUGR had a relatively little share of the total number of fetal deaths from 37 weeks, and did not play any confounding role on the influence of inductions.

    The number of women with preeclampsia (or more correctly with a diagnosis of preeclampsia) increased through the study period, but stillbirths in women with preeclampsia were slightly decreasing from 6 to 4 deaths per year. The HR of stillbirths among women with preeclampsia was not significantly elevated. The average gestational age at delivery among women with preeclampsia was (surprisingly) stable through the study period; 39 + 1-2. The confounding influence from preeclampsia on the influence of induction was not significant.

    Our point was and still is that the more intensive surveillance of women with IUGR or preeclampsia did not differ from our neighbour countries. While the stillbirth rates have been rather stable in these countries, our stillbirth rates were substantially reduced. Therefore, we don't think that these two conditions or the handling of them, can explain the substantial reduction in stillbirths in Denmark, especially not the decrease after 40 weeks, at which time the majority of women with these two conditions have delivered. Earlier induction in women having passed 40 weeks is certainly not the only contributing factor for the decrease in stillbirths in Denmark. We already had a low rate 10 years ago, but have experienced a further substantial reduction with the new induction practice, a reduction not seen in other countries. Thus, we still think that the more proactive induction practice has the main responsibility for this recent decrease.

    Conflict of Interest:

    See original paper.

    Read all letters published for this article

    Submit response

Don't forget to sign up for content alerts to receive selected information relevant to your specialty interests and be the first to know when the latest research is published.