Tag: BMJ

Sodium Valproate Review : Who knew What and When ?

Cumulative meta-analysis gives extra insights

2018 Abstract

Sodium valproate is licensed in the EU for treating generalised, partial or other forms of epilepsy. It has also been used to treat bipolar disorder and to prevent migraine. In February of this year, the European Medicines Agency recommended that sodium valproate should not be used during pregnancy unless no other effective treatment is available, and that it must not be used in women able to have children, unless the conditions of a pregnancy prevention programme are met. These measures to protect women and their children are welcome, but we argue that they should have been instituted several years ago, as the evidence was clear as far back as 1990 that there were risks of congenital malformations in women exposed to valproate.

Our analysis shows the value of cumulative meta-analysis, which, in our view, should be performed as standard in systematic reviews when any concerns about harms arise during the use of medications. …

…, we consider that drug companies, journal editors, prescribers and systematic reviewers have all acted too late. We, therefore, consider that from 1990 individuals should have been offered the opportunity to switch to treatments with lower risks, where they existed, and given minimum effective doses of valproate if alternative treatments were not available or advisable. In the intervening years, many women’s children will have been harmed. Manufacturers and regulators should be responsible for ensuring that cumulative analyses are carried out as part of postmarketing risk management plans.

Air pollution exposed children with mental health problems

Association between neighbourhood air pollution concentrations and dispensed medication for psychiatric disorders in a large longitudinal cohort of Swedish children and adolescents

Abstract

Objective
To investigate associations between exposure to air pollution and child and adolescent mental health.

Design
Observational study.

Setting
Swedish National Register data on dispensed medications for a broad range of psychiatric disorders, including sedative medications, sleeping pills and antipsychotic medications, together with socioeconomic and demographic data and a national land use regression model for air pollution concentrations for NO2, PM10 and PM2.5.

Participants
The entire population under 18 years of age in 4 major counties. We excluded cohort members whose parents had dispensed a medication in the same medication group since the start date of the register. The cohort size was 552 221.

Main outcome measures
Cox proportional hazards models to estimate HRs and their 95% CIs for the outcomes, adjusted for individual-level and group-level characteristics.

Results
The average length of follow-up was 3.5 years, with an average number of events per 1000 cohort members of ∼21. The mean annual level of NO2 was 9.8 µg/m3. Children and adolescents living in areas with higher air pollution concentrations were more likely to have a dispensed medication for a psychiatric disorder during follow-up (HR=1.09, 95% CI 1.06 to 1.12, associated with a 10 µg/m3 increase in NO2). The association with NO2 was clearly present in 3 out of 4 counties in the study area; however, no statistically significant heterogeneity was detected.

Conclusion
There may be a link between exposure to air pollution and dispensed medications for certain psychiatric disorders in children and adolescents even at the relatively low levels of air pollution in the study regions. The findings should be corroborated by others.

Reference.

The Guardian press releases : here, here, here, here, here, here.

Identifying research evidence relevant to clinical practice

Identifying the evidence that matters, keeping up to date and applying evidence in practice is a significant challenge for busy clinicians

When the BMJ Evidence-Based Medicine Journal was launched, about 10,500 randomised trials were indexed on PubMed. Identifying the trials that affect practice has become harder: 20 years later, over 30,000 trials are published annually. If we focused purely on systematic reviews, we would face similar problems: over 19,000 systematic reviews were indexed on PubMed in 2017.

As a result, the BMJ EBM Journal has set out to identify, and focus on, the research evidence that provides definitive conclusions and research that confirms, refutes or improves current practice.

The EBM Journal has focused on two questions:

  1. does this research apply to the patients we see in practice?
  2. and what difference could this evidence make to my patient?

In doing so, the BMJ EBM Journal can remove a substantial amount of research that does not matter.

Read Introducing the EBM Verdict: research evidence relevant to clinical practice, bestpractice.bmj, 2019.

Evidence-based medicine : what’s best ?

What is the best research evidence and how to find it

Evidence-based medicine (EBM) refers to the application of the best available research to clinical care, which requires the integration of evidence with clinical expertise and patient values.

Overview

  • Why is research evidence better than expert opinion alone?
  • What studies are more reliable?
  • Why we shouldn’t read studies
  • Why we should read systematic reviewsThree reasons why we shouldn’t read (most) systematic reviews
  • Three alternatives to access the best evidence?
    1. Pick the best systematic review
    2. Read trustworthy guidelines
    3. Use point-of-care tools
  • The future

Read What is the best evidence and how to find it, bestpractice.bmj, 2019.

Cochrane HPV vaccine review not found to be ‘Trusted Evidence’

The Cochrane HPV vaccine review was incomplete and ignored important evidence of bias

In May 2018, the Cochrane Collaboration published its review of the human papillomavirus (HPV) vaccines. The review primarily assessed the vaccines’ effect on precursors to cervical cancer. Cochrane has high standards for its reviews; however, there were important limitations in its HPV vaccine review, which we address in this paper.

Key findings

  • The Cochrane human papillomavirus (HPV) vaccine review missed nearly half of the eligible trials
  • No included trial in the Cochrane review used a placebo comparator
  • The included HPV vaccine trials used composite surrogate outcomes for cervical cancer
  • The Cochrane review incompletely assessed serious and systemic adverse events
  • The Cochrane review did not assess HPV vaccine-related safety signals
  • Industry trial funding and other conflicts of interest
  • Cochrane’s public relations of the review were uncritical

Conclusion

Part of the Cochrane Collaboration’s motto is ‘Trusted evidence’. We do not find the Cochrane HPV vaccine review to be ‘Trusted evidence’, as it was influenced by reporting bias and biased trial designs. We believe that the Cochrane review does not meet the standards for Cochrane reviews or the needs of the citizens or healthcare providers that consult Cochrane reviews to make ‘Informed decisions’, which also is part of Cochrane’s motto. We recommend that authors of Cochrane reviews make every effort to identify all trials and their limitations and conduct reviews accordingly.

Read the author’s full paper on The BMJ.

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Lessons learnt on transparency, scientific process and publication ethics

The short story of a long journey to get into the public domain unpublished data, methodological flaws and bias of the Cochrane HPV vaccines review

Abstract

Cochrane meta-analyses are considered the gold standard to assess public health interventions’ benefits and risks. Cochrane reviews shall apply evidence-based medicine (EBM) methodology on the best available evidence; they shall adhere to strict ethical guidelines as authors of Cochrane reviews are supposed to not have bias, nor conflicts of interest. Our 6 years’ documented case on the Cochrane human papillomavirus (HPV) vaccines review demonstrates that Cochrane guidelines can fail. According to EBM standards, such relevant methodological and ethical flaws void Cochrane positive conclusions on HPV vaccines efficacy.

Cochrane published a review of the human papillomavirus (HPV) vaccines on 9 May 2018. On 4 June, we submitted a detailed analysis of this review as a comment via the Cochrane website.

Our comment highlights serious methodological flaws in the review:

  • (A) studies’ quality not properly assessed;

  • (B) post hoc subgroup analyses presented as randomised controlled trial results;

  • (C) reporting bias not acknowledged;

  • (D) selective reporting not taken into consideration;

  • (E) biased trial designs;

  • (F) unpublished data not included;

  • (G) conflict of interests (COI) in the authors’ group;

  • (H) n=7 studies on Gardasil included, n=18 for Cervarix—the latter not being marketed in the USA anymore.

… continue reading on The BMJ, by Catherine Riva, December 2018.

visit re-check ref hpv-vaccination.

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Will Brexit harm the NHS ?

Patients lack answers to too many questions about their healthcare after Brexit

Predictions of a smaller UK economy, at least in the short term, and fewer EU healthcare staff present challenges for the NHS after 29 March 2019, argues Anand Menon.

But Graham Gudgin is unconvinced by what he believes are biased estimates promoted by a government pushing for a soft Brexit.

Read Could Brexit harm the NHS? on The BMJ, 26 September 2018.

Air pollution may increase dementia risk by 40 percent, London study finds

Are noise and air pollution related to the incidence of dementia ?
A cohort study in London, England, 2018

Air pollution may increase the chance of developing dementia, a study has suggested, in fresh evidence that the health of people of all ages is at risk from breathing dirty air, TheGuardian reports.

Abstract

Objective
To investigate whether the incidence of dementia is related to residential levels of air and noise pollution in London.

bmDesign
Retrospective cohort study using primary care data.

Setting
75 Greater London practices.

Participants
130 978 adults aged 50–79 years registered with their general practices on 1 January 2005, with no recorded history of dementia or care home residence.

Primary and secondary outcome measures
A first recorded diagnosis of dementia and, where specified, subgroups of Alzheimer’s disease and vascular dementia during 2005–2013. The average annual concentrations during 2004 of nitrogen dioxide (NO2), particulate matter with a median aerodynamic diameter ≤2.5 µm (PM2.5) and ozone (O3) were estimated at 20×20 m resolution from dispersion models. Traffic intensity, distance from major road and night-time noise levels (Lnight) were estimated at the postcode level. All exposure measures were linked anonymously to clinical data via residential postcode. HRs from Cox models were adjusted for age, sex, ethnicity, smoking and body mass index, with further adjustments explored for area deprivation and comorbidity.

Results
2181 subjects (1.7%) received an incident diagnosis of dementia (39% mentioning Alzheimer’s disease, 29% vascular dementia). There was a positive exposure response relationship between dementia and all measures of air pollution except O3, which was not readily explained by further adjustment. Adults living in areas with the highest fifth of NO2 concentration (>41.5 µg/m3) versus the lowest fifth (<31.9 µg/m3) were at a higher risk of dementia (HR=1.40, 95% CI 1.12 to 1.74). Increases in dementia risk were also observed with PM2.5, PM2.5 specifically from primary traffic sources only and Lnight, but only NO2 and PM2.5 remained statistically significant in multipollutant models. Associations were more consistent for Alzheimer’s disease than vascular dementia.

Conclusions
We have found evidence of a positive association between residential levels of air pollution across London and being diagnosed with dementia, which is unexplained by known confounding factors.

Is cancer fundraising fuelling quackery ?

Are crowdfunding sites promoting quack treatments for cancer ?

Figures published by The BMJ show how crowdfunding for alternative therapies for patients with terminal cancer has soared in recent years. But there are fears that huge sums are being raised for treatments that are not backed by evidence and which, in some cases, may even do then harm, MedicalXpress reports.

JustGiving’s own figures show more than 2300 UK cancer related appeals were set up on its site in 2016, a sevenfold rise on the number for 2015.

The phenomenon has allowed less well-off patients to access expensive, experimental treatments that are not funded by the NHS but have some evidence of benefit. But many fear it has also opened up a new and lucrative revenue stream for cranks, charlatans, and conmen who prey on the vulnerable.

“We are concerned that so many UK patients are raising huge sums for treatments which are not evidence based and which in some cases may even do them harm.”

The society’s project director, Michael Marshall, said.

Melanie Newman, freelance journalist, London, UK, examines calls to help ensure patients and their donors are not being exploited.

Featured image credit @bmj_company.

89% of clinical trials run by European universities violate EU regulations, study shows

Compliance with requirement to report results on the EU Clinical Trials Register: cohort study and web resource

Data released today via the BMJ show that thousands of clinical trials conducted in Europe violate EU rules that require results to be published within 12 months. Failure to publish trial results endangers patients, contributes to exploding drug costs, and slows down the discovery of new treatments and cures, transparimed reports.

Abstract

Objectives
To ascertain compliance rates with the European Commission’s requirement that all trials on the EU Clinical Trials Register (EUCTR) post results to the registry within 12 months of completion (final compliance date 21 December 2016); to identify features associated with non-compliance; to rank sponsors by compliance; and to build a tool for live ongoing audit of compliance.

Design
Retrospective cohort study.

Setting
EUCTR.

Participants
7274 of 11 531 trials listed as completed on EUCTR and where results could be established as due.

Main outcome measure
Publication of results on EUCTR.

Results
Of 7274 trials where results were due, 49.5% (95% confidence interval 48.4% to 50.7%) reported results. Trials with a commercial sponsor were substantially more likely to post results than those with a non-commercial sponsor (68.1% v 11.0%, adjusted odds ratio 23.2, 95% confidence interval 19.2 to 28.2); as were trials by a sponsor who conducted a large number of trials (77.9% v 18.4%, adjusted odds ratio 18.4, 15.3 to 22.1). More recent trials were more likely to report results (per year odds ratio 1.05, 95% confidence interval 1.03 to 1.07). Extensive evidence was found of errors, omissions, and contradictory entries in EUCTR data that prevented ascertainment of compliance for some trials.

Conclusions
Compliance with the European Commission requirement for all trials to post results on to the EUCTR within 12 months of completion has been poor, with half of all trials non-compliant. EU registry data commonly contain inconsistencies that might prevent even regulators assessing compliance. Accessible and timely information on the compliance status of each individual trial and sponsor may help to improve reporting rates.