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<\/a>Annals of Internal Medicine<\/b><\/p>\nThe biostatistician backlash\u2014researchers\u2019 inappropriate requests for data analysis<\/u><\/b><\/p>\n
Have you been mis-sold study data by researchers? Even if you critically analysed it, you were likely mis-sold it. You could be entitled to your money back if your claim involves falsifying statistical significance to support a desired result. If you think you were mis-sold study data, act now and we\u2019ll interpret your claim on the basis of expectation, not actual results. Start your claim now you can find out for free if the power calculation was really a priori or post hoc. Don\u2019t miss the claim deadline or we\u2019ll ignore key missing data that could bias the results.<\/span><\/p>\n Wang et al\u2019s survey of 400 statisticians provides<\/a> worrying insight into the mis-selling scandal that is going on in research today and is a must read. The statisticians weren\u2019t asked what they did with the inappropriate requests, but a glance at the state of research reporting might help you extrapolate.<\/span><\/p>\n A confounder conundrum\u2014safety of beta blockers in pregnancy<\/u><\/b><\/p>\n It is a truth universally acknowledged that pregnancy makes treatment of any medical condition anxiety-inducing for patient and clinician alike. Isn\u2019t it lucky then, that this paper is about beta-blockers? I jest\u2014beta-blockers aren\u2019t how I would start to treat anxiety and the reason for treatment in this large cohort study was actually hypertension<\/a>.<\/span><\/p>\n So to the point, Bateman et al focus on beta-blocker use in the first trimester in pregnant women with a diagnosis of hypertension in Denmark, Finland, Iceland, Norway, Sweden, and US. They assessed the risk of congenital malformations and concluded that there was no \u201clarge increase in the risk for overall malformations or cardiac malformations, independent of measured confounders.\u201d<\/span><\/p>\n There will always be a long list of confounders for this type of study design. For example, they note that judging beta blocker exposure by filled prescriptions doesn\u2019t mean the patient actually took the medication. So they re-ran the analysis where they defined exposure as at least two dispensings of the medication as refilling the prescription suggests the patient is taking the medication and they found similar levels of risk.<\/span><\/p>\n They also re-ran the analysis taking into account the potential for pregnancies ending in stillbirth or abortion that their original analyses wouldn\u2019t have captured and again, found similar levels of risk.<\/span><\/p>\n Finally, they only considered women with hypertension to resist the confounding by the indication for needing an anti-hypertensive. However confounding by a hypertensive patient\u2019s blood pressure being high enough to require treatment means there will be unmeasured differences between the exposed and unexposed groups that could influence the results. Still, in practice, decisions must be made and this is the best available evidence at the moment.<\/span><\/p>\n JAMA<\/b><\/p>\n The Roux-en-Y reassessment\u2014which measure of weight regain is useful<\/u><\/b><\/p>\n Look to this study<\/a>, not for how it will affect you or your practice (it won\u2019t unless you are a patient or researcher of bariatric surgery), but to admire the authors\u2019 concern for which outcome of weight regain after bariatric surgery is associated with outcomes that are important for patients. King et al conclude that their findings \u201cmay inform standardizing the measurement of weight regain in studies of bariatric surgery\u201d\u2014a laudable aim given how many different ways of measuring weight regain there are. <\/span><\/p>\n There\u2019s weight, BMI, weight regain as a percentage of presurgery weight, weight regain as a percentage of nadir weight and thresholds of these such as greater than 10kg, greater than 5 BMI points, 10% of presurgery weight and so on. They compared 13 different measures of weight regain for association with progression of diabetes, hyperlipidaemia, and hypertension and declines in physical and mental health-related quality of life and satisfaction with surgery. Weight regain quantified as percentage of maximum weight lost came out top. This may disappoint some readers as it requires more than one step of calculation.<\/span><\/p>\n Lancet<\/b><\/p>\n The machine manages\u2014CT head analysis by deep learning algorithms<\/u><\/b><\/p>\n The time is ripe for deep learning for diagnosis. Chilamkurthy et al<\/a> designed algorithms for nine \u201ccritical findings\u201d on the extremely ubiquitous test, non-contrast CT head. They base the \u201cgold standard\u201d on reporting by three independent radiologists. The authors validated their algorithm on scans from two different datasets\u2014one at another centre, but the algorithm did not perform as well there. The authors proposed two slightly tenuous reasons for the poorer performance\u2014first that the radiologists of the other centre\u2019s dataset had access to the clinical history and second that the majority decision of three radiologists used for their primary validation dataset is a \u201cbetter gold standard.\u201d This begs a few questions. Would the algorithm have performed better if it learned from more radiologists? Can a gold standard truly be defined without seeing what happened to the patients? The authors conclude that the algorithms could be used for triage which presumably means a radiologist would still report the scan. Their algorithms probably meet the bar for this application.<\/span><\/p>\n It is also worth mentioning that the study was funded by a company called qure.ai that employs almost all the authors, but I suppose that\u2019s who does this work. I suspect there will be several more bridges to cross before this can be implemented in clinical practice. A lot of this will be about trust and credibility. Which a Lancet<\/em> paper can bring. But independent validation and expert scrutiny would help, and ideally before the inevitable randomised controlled trials, to avoid exposing patients to unwarranted risk. Will there be a regulatory body for this soon?<\/span><\/p>\n An unambiguous undoing\u2014clindamycin for bacterial vaginosis in pregnancy<\/u><\/b><\/p>\n The French government-funded PREMEVA trial<\/a> is a breath of fresh air. This large double-blind randomised controlled trial found no evidence of reduced risk of late miscarriage or spontaneous very preterm birth with screening for and subsequent treatment of bacterial vaginosis. The treatment was clindamycin and those who received it had significantly more diarrhoea and abdominal pain than those randomised to placebo. Cancelling out an indication for antibiotics\u2014great. Filtering this into clinical practice\u2014priceless.<\/span><\/p>\n JAMA Internal Medicine<\/b><\/p>\n The hip-hop high\u2014tobacco and marijuana products in music videos<\/u><\/b><\/p>\n There are two types of journal readers\u2014homies, who think \u201cI must read this\u201d when they see hip-hop music videos in the title, and not-at-homies, who don\u2019t. After reading the title, I anticipated something quite light-hearted. But Knutzen et al found that 40-50% of videos<\/a> (analysed from 2013 to 2017) contained combustible or electronic tobacco or marijuana use with the more popular songs (by number of views) having a higher prevalence of use. Apparently, this corresponds to over 39 billion views. No one can quantify the impact this level of visibility has on public health but it must be enormous. There was a particularly dramatic rise in the appearance of branded electronic products from 2013 to 2017. The discussion was interesting. The authors discuss the introduction of warning statements mandated by the US Food and Drug Administration (FDA). However, more ethical music producers may want to ban this type of product placement altogether.<\/span><\/p>\n A daring decision\u2014attitudes of over 65s to deprescribing<\/u><\/b><\/p>\n Many clinicians observe some patients who resist deprescribing and this may be discouraging them from deprescribing for other patients to avoid conflict. That is why this paper<\/a> on the attitudes of older Americans is so important. It shows that the majority are willing to have medication deprescribed if their physician said it was possible and that more than two thirds want to reduce the number of medicines they are taking. I sincerely hope this research encourages open discussion between clinicians and their patients to reach a decision that is patient-centred.<\/span><\/p>\n NEJM<\/b><\/p>\n Immunotherapy for advanced breast cancer<\/u><\/b><\/p>\n In this double-blind randomised controlled trial<\/a>, the pharmaceutical company \u201ccollaborated\u201d with the academic steering committee on the trial design, data collection, analysis, and interpretation. Trials are hard to run without sponsorship, but if conflicts of interest were DEFCON levels this trial would probably be at 1 i.e. can\u2019t get more conflicted than this.<\/span><\/p>\n No surprise then that the trial is painted positively and referred to in the press release as \u201ca massive step forward\u201d when all it showed was an improvement in progression free survival (hazard ratio 0.8 with p=0.002) but not overall survival (hazard ratio 0.84 but p=0.08) and more adverse events with the new treatment (atezolizumab). The press release says \u201cwe are able to significantly extend lives.\u201d Whose interpretation was this? Progression free survival is when the disease on the scan doesn\u2019t worsen and the patient doesn\u2019t die. The press release comment seems to refer to actual survival which was not statistically significant in this trial. The survival did look better in the subgroup positive for the receptor that the drug is supposed to bind to (PD-L1 positive).<\/span><\/p>\n Presenting these results as more than they are can give false hope to patients, clinicians, and researchers.<\/span><\/p>\n The other one\u2014cyclin dependent kinase inhibitor for Advanced Breast Cancer<\/u><\/b><\/p>\n This double-blind randomised controlled trial<\/a> has a different drug, different breast cancer type, and a different pharmaceutical company, but again the sponsor was a part of the steering committee and was involved in critical aspects including collection and interpretation of data. Again there was no statistically significant difference in overall survival, but a positive interpretation of the subgroup who were sensitive to previous endocrine therapy that did have better survival. What happened to progression-free survival you might ask? Well, that was presented in a previous paper and was positive, but this alone has no meaning for patients. Again the press release declares that this treatment should be the standard of care.\u00a0<\/span><\/p>\n BMJ<\/b><\/p>\n Pre-eclampsia and vascular dementia<\/u><\/b><\/p>\n Pre-eclampsia is a fascinating, but also very serious condition manifesting as hypertension and organ dysfunction in pregnancy. Basit et al conducted a large prospective cohort study<\/a> with long follow-up to look at the association of pre-eclampsia with later dementia in Denmark. They found women with a history of pre-eclampsia had more than three times the risk of vascular dementia. This is a lot higher than I would have guessed even though vascular dysfunction is well known to underlie pre-eclampsia. And the association persisted despite adjustment for comorbidities such as cardiovascular disease, diabetes, and hypertension.\u201d<\/span><\/p>\n