823 e-Letters

  • Survey to perfection

    This cross-sectional survey was a very good starting point for further detailed study between alcohol uses and other clinical implications e.g. behavioral disorder, mood disorder or psychiatric disorder besides emotional effect in different countries and sociodemographic backgrounds.
    Overall the survey showed clear-cut connection between various positive and negative feelings with level of risk of alcohol use classified using AUDIT scores. However, selection bias existing in this study, either the under-coverage of the representative populations as the survey was only confined to people who had internet connection and also the small sample of people who did not attend high school. Response bias could probably be involved and must be also taken into consideration in setting up the survey. And individual co-morbidities must be included to further reduce the biases.

  • Hashimoto’s thyroiditis and cholelithiasis Inherited Real Risks are different in nature.

    According to Constitution-Dependent, Inherited Real Risks (1), Hashimoto’s thyroiditis depends on Autoimmune Constitution (2). On the contrary, exclusively individuals involved by Lithiasis Constitution can suffer from Cholelithiasis (3, 4). Importantly, as all other Inherited Real Risks, also those mentioned above, bedside diagnosed since birth with a common stethoscope, are removed by inexpensive Reconstructing Mitochondrial Quantum Therapy (5).

    1) Stagnaro Sergio. Reale Rischio Semeiotico Biofisico. I Dispositivi Endoarteriolari di Blocco neoformati, patologici, tipo I, sottotipo a) oncologico, e b) aspecifico. Ediz. Travel Factory, www.travelfactory.it, Roma, 2009.
    2) Stagnaro S., Sindrome percusso-ascoltatoria autoimmune. Gazz. Med. It. 142, 555, 1983.
    3) Simone Caramel and Sergio Stagnaro (2012). Vascular calcification and Inherited Real Risk of lithiasis. Front. In Encocrin. 3:119. doi: 10.3389/fendo.2012.00119 http://www.frontiersin.org/Bone_Research/10.3389/fendo.2012.00119/full [MEDLINE]
    4) Stagnaro S., Stagnaro-Neri M., Diagnosi percusso-ascoltatoria dei calcoli biliari silenti. 6° Incontro Segusino di Medicina e Chirurgia. Susa 19 Maggio, 1990. Atti, pg. 79. Ed. Minerva Medica
    5) Caramel S., Marchionni M., Stagnaro S. Morinda citrifolia Plays a Central Role in the Primary Prevention...

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  • Gout and hearing impairment

    One retrospective cohort study conducted by Singh and colleagues reported that gout is associated with a 1.4-fold increased risk of hearing impairment in older adults (hazard ratio 1.44, 95% CI 1.40-1.49).1 Some caveats should be discussed. Gout is a form of arthritis due to the deposition of monosodium urate crystals within joints, which is associated with persistently high levels of uric acid in the blood.2 Clinically, it is not feasible to check the uric acid levels every day. So we cannot be sure the onset date of hyperuricemia. Because hearing impairment is an insidious condition without a well-defined onset date, we can only approximate the onset date by applying the claims-based definition of ICD-9-CM 389. When a cohort study examines the relationship between hyperuricemia and hearing impairment, we cannot definitely determine which condition comes first because of the onset date not clear. Gout is characterized by recurrent acute attacks of joint inflammation.3 When an acute attack subsides, the joint inflammation is also relieved. Thus, how can we make a reasonable link between the remission state of gout and hearing impairment? That is, how does the remission state of gout have an impact on the insidious course of hearing impairment? Similarly Parkinson’s disease is an insidious condition, but no association is detected between gout and Parkinson’s disease in older adults in Taiwan.4
    Perhaps there could be an association between gout and hearing impairment....

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  • Further response from a reviewer: Are large randomised controlled trials in severe sepsis and septic shock statistically disadvantaged by repeated inadvertent underestimates of required sample size?

    In their manuscript, Wong et al. discuss an important aspect of randomized control trial (RCT) design: sample size determination. Although their focus is on RCTs for sepsis with the primary outcome of mortality, their review is generalizable to RCTs with binary primary outcomes (i.e. the presence or absence of an event of interest) and thus, may influence the design of RCTs in many patient populations. Therefore, it is important to address one of the primary conclusions of the manuscript.

    Wong et al. reviewed the sample size calculations for 13 RCTs for sepsis where the average treatment effect was defined as the absolute difference in the mortality rate comparing the control arm to the intervention arm. We will subsequently refer to this average treatment effect as AD. To determine the required sample size needed per arm for the RCT, it is required to specify both the anticipated mortality rate in the control arm and the AD. For the 13 RCTs, Wong et al. extracted and compared, via meta-analysis, the anticipated mortality rate in the control arm and AD used in the sample size calculation to the respective values obtained from the completed RCTs. They found that for both the control arm mortality rate and the AD, the anticipated values were, on average, greater than the values from the completed RCTs. The third paragraph of their discussion states “The consistent overestimation of control arm event rate (or lower than anticipated actual control arm event rate...

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  • Thiazolidinedione therapy and the risk of Parkinson Disease

    The effect of Thiazolidinedione therapy on the risk of Parkinson’s disease is controversial. One article by Wu and colleagues in Taiwan reported that pioglitazone use was not associated with the risk of Parkinson’s disease in people with diabetes mellitus (hazard ratio 0.90, 95% CI 0.68-1.18).1 To the contrary, another article by Lin and colleagues in Taiwan reported that thiazolidinedione use was associated with a 60% reduced risk of Parkinson’s disease in people with diabetes mellitus.2 Similarly, conflicting results were also found in Western countries.3,4 There was no measure of the hemoglobin A1c in the above studies. We cannot determine whether the risk of Parkinson’s disease is associated with good glycemic control or poor control among people on thiazolidinedione therapy. Therefore, any study exploring the association between anti-diabetic medications and Parkinson’s disease should estimate the hemoglobin A1c levels.
    Theoretically, a study should be designed to compare people on thiazolidinedione therapy only with those people not taking any medication. However, according to the recommendation of the American Diabetes Association, metformin is the first-line therapy for type 2 diabetes mellitus.5 People with diabetes mellitus usually take metformin alone or use combined therapy with other anti-diabetic medications. Thiazolidinedione is usually recommended as combined therapy with metformin for type 2 diabetes mellitus. So it is difficult to identify peo...

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  • Moncada's Manoeuvre is useful and reliable also in urological disorders.

    The Moncada's Manoeuvre, among a lot of other clinical manoeuvres and signs, allows doctors to bedside differentiate easily and quickly benigne from, even initally, malignant disorders (1-3).
    For instance, the differential diagnosis between urinary tract hemorrhage benign or malignant in nature is often difficult ayt the bedside. In addition, Moncada 'Manoeuvre proved to be very useful in the differential diagnosis between prostate adenoma and prostate cancer, even initial, as Oncological Terrain-Dependent, Inherited Real Risk..
    1)Sergio Stagnaro (2018).Manovra di Moncada*: Diagnosi Differenziale tra Lesione Benigna e Maligna in 15 secondi. in pdf http://www.sisbq.org/uploads/5/6/8/7/5687930/manovradimoncada.pdf
    2) Sergio Stagnaro. Massucco’s Sign in the war against to Prostate Cancer. Letter to FDA; www.melatonina.it ; 2 May, 2010, http://www.melatonina.it/articoli/247-2010-05-02.html
    3) Sergio Stagnaro. Bedside Detecting Inherited Real Risk of Prostate Cancer, and overt Cancer: Massucco’s Sign. European Urology. 27 April, 2011, http://www.europeanurology.com/article/S0302-2838%2810%2900944-9/fulltex...

  • Editor's Note

    The Editor of BMJ Open has received the comments from Albert Donnay on this paper. The authors of the paper have been contacted and have been asked to provide a response.

  • The Value of Reporting PPI

    Thank you for your response...The first step to change is raising awareness I think a powerful next motivator might be sufficient funding to get the work done well! The value of reporting PPI is to increase good methods and reproducibility. It is a challenge to learn any new form of reporting for research. When RCTs, statistics and epidemiology were first introduced they were not well reported or funding, it does take time. You touch on an interesting point in terms of funding. We could ask if researchers are granted sufficient dedicated PPI funding to deliver training and impact.

    "If user involvement remains an international policy imperative with little if any support at the vital stage of bid development, policy‐makers, service user organizations, researchers, health service providers and commissioners will need to recognize the limited nature of involvement that may result and the impact this would have on the evidence base. Researchers will need to recognize the resource implications of involvement at this point, and user groups will need to decide whether to participate when there is the greatest chance of influencing research but little or no funding (p. 175)"

    This was a quote from 2007 and the question is still open!

    Staniszewska S, Jones N, Newburn M, Marshall S. User involvement in the development of research bid: barriers, enablers and impacts. Health Expectations, 2007; 10: 173–183. [PubMed]

  • In response to: Association between QTc prolongation and mortality in patients with suspected poisoning in the emergency department: a transnational propensity score matched cohort study.

    To the editor:

    We read with interest the paper by Hansen et al1 and commend the authors on their work, however we would like to point out some significant limitations of the study
    First, it is unclear whether the reported deaths are related to arrhythmic events resulting from QT prolongation or any other cause. While it is intuitive to that patients with abnormal heart tracings or underlying channelopathies are at a higher risk of death compared to healthy individuals, the association demonstrated in this study is far from causation. Additionally, the authors do not report pertinent clinical information such as electrolyte imbalances or the use of medications know to prolong the QT interval. Such preventable and reversible causes of QT prolongation theoretically should not affect 30-day mortality if adequately addressed. Finally, despite the use of the term “transnational” in title of the paper, patients included are from four different hospitals located in close geographical area and are likely more genetically homogenous than patients in single urban teaching hospital in a major US city. Thus the absence of demographic data severely limits the applicability of their findings to a global environment.

    In conclusion, while this topic is of significant interest, methodological and analytical flaws limit the validity and applicability of the authors’ conclusions.

    1-Schade Hansen C, Pottegård A, Ekelund U, et al. Association between QTc prolongati...

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  • Unpublished methods and results in "Screening for carbon monoxide exposure..."

    In “Screening for carbon monoxide poisoning…in England: a prospective observational study,”(1) Clarke et al mischaracterize Masimo's Rad57 pulse CO-oximeter as a measure of venous carboxyhaemoglobin. As noted in one of their references(2) and the Rad57 Operator’s Manual,(3) Masimo’s trademarked “SpCO” measures arterial carboxyhaemoglobin. Based on this misunderstanding, the authors checked their [arterial] Rad57 ([a]Rad57) results against [venous] carboxyhaemoglobin ([v]COHb) measured by unspecified “point-of-care blood analyzers.”(4)

    Instead of publishing these results separately, however, the authors simply combined them—by which 76 of 1758 patients were “positive” for CO poisoning (COp).(1) Only in an unpublished report to their funder did they disclose the R2 correlation among 608 paired [a]Rad57 and [v]COHb measurements was just 0.03.(4) Without any other testing, they assumed [v]COHb was more accurate and used this whenever available, even when [a]Rad57 was higher. By this method, they classified 293 with high [a]Rad57 but normal [v]COHb as false positives—and discharged them without the COp treatment and home inspection given 60 cases confirmed by high [v]COHb.(4)

    Also disclosed only to the funder: the authors’ original protocol was “non-invasive” with a nested case-control design.(4) Blood CO-oximetry was only added after the controls—three per case—were dropped because “a number [unspecified] had high COHb readings [unspecified] on the...

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