Greg Irving

Pharmacological agents for the prevention of vestibular migraine

BACKGROUNDnVestibular migraine is a common cause of episodic vertigo. Many preventive treatments have been proposed for this condition, including calcium antagonists, beta-blockers, antidepressants, anticonvulsants, selective 5-HT1 agonists, serotonin antagonists and non-steroidal anti-inflammatory drugs (NSAIDs).nnnOBJECTIVESnTo assess the effects of pharmacological agents for the prevention of vestibular migraine.nnnSEARCH METHODSnThe Cochrane Ear, Nose and Throat Disorders Group (CENTDG) Trials Search Co-ordinator searched the CENTDG Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 5); PubMed; EMBASE; CINAHL; Web of Science; Clinicaltrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 5 June 2015.nnnSELECTION CRITERIAnRandomised controlled trials (RCTs) in adults (over 18 years) with a diagnosis of vestibular migraine orprobable vestibular migraine according to the Bárány Society/International Headache Society (IHS) criteria, treated in any setting, comparing pharmacological treatments used in the prevention of vestibular migraine, including beta-blockers, calcium antagonists, anticonvulsants, antidepressants, serotonin antagonists and non-steroidal anti-inflammatory drugs (NSAIDs) against placebo or no treatment.nnnDATA COLLECTION AND ANALYSISnWe used the standard methodological procedures expected by The Cochrane Collaboration.nnnMAIN RESULTSnOur literature search identified 558 reports, however only 11 were sufficiently relevant for further assessment. We excluded two studies because they did not use the IHS diagnostic criteria for vestibular migraine. We excluded a further eight studies for various reasons related to their design (e.g. lack of placebo or no treatment comparator), aim (e.g. treatment of vestibular migraine rather than prevention) or conduct (e.g. early termination). We identified one ongoing study comparing metoprolol to placebo. The results of this study are awaited; recruitment of the last patient is expected by the end of 2016.nnnAUTHORS CONCLUSIONSnWe found no evidence from RCTs to answer the question set out in the review objectives. This review has identified the need for well-designed randomised controlled trials to answer questions about the efficacy of current and new treatments.

International variations in primary care physician consultation time: a systematic review of 67 countries

Objective To describe the average primary care physician consultation length in economically developed and low-income/middle-income countries, and to examine the relationship between consultation length and organisational-level economic, and health outcomes. Design and outcome measures This is a systematic review of published and grey literature in English, Chinese, Japanese, Spanish, Portuguese and Russian languages from 1946 to 2016, for articles reporting on primary care physician consultation lengths. Data were extracted and analysed for quality, and linear regression models were constructed to examine the relationship between consultation length and health service outcomes. Results One hundred and seventy nine studies were identified from 111 publications covering 28 570 712 consultations in 67 countries. Average consultation length differed across the world, ranging from 48u2009s in Bangladesh to 22.5u2009min in Sweden. We found that 18 countries representing about 50% of the global population spend 5u2009min or less with their primary care physicians. We also found significant associations between consultation length and healthcare spending per capita, admissions to hospital with ambulatory sensitive conditions such as diabetes, primary care physician density, physician efficiency and physician satisfaction. Conclusion There are international variations in consultation length, and it is concerning that a large proportion of the global population have only a few minutes with their primary care physicians. Such a short consultation length is likely to adversely affect patient healthcare and physician workload and stress.

How blockchain-timestamped protocols could improve the trustworthiness of medical science

Trust in scientific research is diminished by evidence that data are being manipulated. Outcome switching, data dredging and selective publication are some of the problems that undermine the integrity of published research. Methods for using blockchain to provide proof of pre-specified endpoints in clinical trial protocols were first reported by Carlisle.xa0We wished to empirically test such an approach using a clinical trial protocol where outcome switching has previously been reported. Here we confirm the use of blockchain as a low cost, independently verifiable method to audit and confirm the reliability of scientific studies.

Which cuff should I use? Indirect blood pressure measurement for the diagnosis of hypertension in patients with obesity: a diagnostic accuracy review

Objective To determine the diagnostic accuracy of different methods of blood pressure (BP) measurement compared with reference standards for the diagnosis of hypertension in patients with obesity with a large arm circumference. Design Systematic review with meta-analysis with hierarchical summary receiver operating characteristic models. Bland-Altman analyses where individual patient data were available. Methodological quality appraised using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS2) criteria. Data sources MEDLINE, EMBASE, Cochrane, DARE, Medion and Trip databases were searched. Eligibility criteria Cross-sectional, randomised and cohort studies of diagnostic test accuracy that compared any non-invasive BP tests (upper arm, forearm, wrist, finger) with an appropriate reference standard (invasive BP, correctly fitting upper arm cuff, ambulatory BP monitoring) in primary care were included. Results 4037 potentially relevant papers were identified. 20 studies involving 26 different comparisons met the inclusion criteria. Individual patient data were available from 4 studies. No studies satisfied all QUADAS2 criteria. Compared with the reference test of invasive BP, a correctly fitting upper arm BP cuff had a sensitivity of 0.87 (0.79 to 0.93) and a specificity of 0.85 (0.64 to 0.95); insufficient evidence was available for other comparisons to invasive BP. Compared with the reference test of a correctly fitting upper arm cuff, BP measurement at the wrist had a sensitivity of 0.92 (0.64 to 0.99) and a specificity of 0.92 (0.85 to 0.87). Measurement with an incorrectly fitting standard cuff had a sensitivity of 0.73 (0.67 to 0.78) and a specificity of 0.76 (0.69 to 0.82). Measurement at the forearm had a sensitivity of 0.84 (0.71 to 0.92) and a specificity 0.75 of (0.66 to 0.83). Bland-Altman analysis of individual patient data from 3 studies comparing wrist and upper arm BP showed a mean difference of 0.46u2005mmu2005Hg for systolic BP measurement and 2.2u2005mmu2005Hg for diastolic BP measurement. Conclusions BP measurement with a correctly fitting upper arm cuff is sufficiently sensitive and specific to diagnose hypertension in patients with obesity with a large upper arm circumference. If a correctly fitting upper arm cuff cannot be applied, an incorrectly fitting standard size cuff should not be used and BP measurement at the wrist should be considered.

Interventions to increase or decrease the length of primary care physicians' consultation.

BACKGROUNDnObservational studies have shown differences in process and outcome between the consultations of primary care physicians whose average consultation lengths differ. These differences may be due to self selection. This is the first update of the original review.nnnOBJECTIVESnTo assess the effects of interventions to alter the length of primary care physicians consultations.nnnSEARCH METHODSnWe searched the following electronic databases until 4 January 2016: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP).nnnSELECTION CRITERIAnRandomised controlled trials and non-randomised controlled trials of interventions to alter the length of primary care physicians consultations.nnnDATA COLLECTION AND ANALYSISnTwo review authors independently extracted data and assessed the risk of bias of included studies using agreed criteria and resolved disagreements by discussion. We attempted to contact authors of primary studies with missing data. Given the heterogeneity of studies, we did not conduct a meta-analysis. We assessed the certainty of the evidence for the most important outcomes using the GRADE approach and have presented the results in a narrative summary.nnnMAIN RESULTSnFive studies met the inclusion criteria. All were conducted in the UK, and tested short-term changes in the consultation time allocated to each patient. Overall, our confidence in the results was very low; most studies had a high risk of bias, particularly due to non-random allocation of participants and the absence of data on participants characteristics and small sample sizes. We are uncertain whether altering appointment length increases primary care consultation length, number of referrals and investigations, prescriptions, or patient satisfaction based on very low-certainty evidence. None of the studies reported on the effects of altering the length of consultation on resources used.nnnAUTHORS CONCLUSIONSnWe did not find sufficient evidence to support or refute a policy of altering the lengths of primary care physicians consultations. It is possible that these findings may change if high-quality trials are reported in the future. Further trials are needed that focus on health outcomes and cost-effectiveness.

Should we screen for atrial fibrillation

No country has yet established a national screening programme (NSP) for atrial fibrillation (AF), including the UK. However, there is an increasing body of evidence suggesting screening may be beneficial, prompting recommendations from prominent expert bodies to screen for AF.1 Despite these data, the UK National Screening Committee (NSC) has not recommended systematic population screening. The review in 2014 concluded ‘… it is not clear that those identified as at risk through screening would benefit from early diagnosis’.2 The NSC also identified a need to improve clinical management and standardise the treatment services currently available to those with diagnosed AF. The British Cardiovascular Society issued a subsequent statement in response to the decision questioning the interpretation of the evidence and suggesting that it would be in the public interest to reconsider their decision.3 A further review by the UK NSC is scheduled for 2017/2018.nnAF is the most common cardiac arrhythmia, present in around 1% of the population and 5% of those aged ≥65 years.4 Approximately 1 million people are …

The ecology of medical care on an isolated island in Okinawa, Japan: a retrospective open cohort study

BackgroundWe aimed to describe the ecology of medical care on an isolated island with limited access to secondary care, and to evaluate the gatekeeping function of the island’s primary care clinic through comparison with a previous nationwide survey.MethodsWe conducted this retrospective, open cohort study on Iheya, an isolated island in Okinawa Prefecture that has one primary care clinic. We considered Iheya as unique location in which to examine the role of primary care in Japan. Participants were patients who visited the island’s clinic between February 1, 2013 and January 31, 2014. We calculated the number of visits to the clinic and referrals to off-island medical facilities using electronic medical records. We also compared data for Iheya with a nationwide survey conducted in 2003.ResultsIheya had 1314 inhabitants in 2013. Of the 5682 visits to the clinic in the 1-year study period, 290 people were referred to off-island medical institutions. There were 64 referrals to emergency departments; of these, 57 people were admitted to hospital. The rate of visits to the clinic per month per 1000 inhabitants was 360.4 visits (95% confidence interval: 351.0–369.7). Of these, 18.4 (16.3–20.5) were referred off-island, with 4.1 (3.1–5.1) referrals to emergency departments and 3.6 (2.6–4.6) hospitalizations. Despite the high incidence of visits to the primary care clinic, the rates of hospital-based outpatient clinic visits, emergency department visits, and hospitalizations were lower than rates reported in a previous Japanese study.ConclusionsThis suggests that several dimensions of primary care, its gatekeeping function in particular, are likely to play important roles in this geographical setting.

The AGREE Reporting Checklist is useful for assessing the quality of clinical practice guideline development.

At least two systematic reviews of national and international clinical practice guidelines have used the AGREE tools (I and II).1 2 3 Both found that no guideline was perfect and highlighted the same key problems—a lack of applicability and stakeholder involvement. These domains relate to …

Metformin in non-diabetic hyperglycaemia: the GLINT feasibility RCT

BACKGROUNDnThe treatment of people with diabetes with metformin can reduce cardiovascular disease (CVD) and may reduce the risk of cancer. However, it is unknown whether or not metformin can reduce the risk of these outcomes in people with elevated blood glucose levels below the threshold for diabetes [i.e. non-diabetic hyperglycaemia (NDH)].nnnOBJECTIVEnTo assess the feasibility of the Glucose Lowering In Non-diabetic hyperglycaemia Trial (GLINT) and to estimate the key parameters to inform the design of the full trial. These parameters include the recruitment strategy, randomisation, electronic data capture, postal drug distribution, retention, study medication adherence, safety monitoring and remote collection of outcome data.nnnDESIGNnA multicentre, individually randomised, double-blind, parallel-group, pragmatic, primary prevention trial. Participants were individually randomised on a 1u2009:u20091 basis, blocked within each site.nnnSETTINGnGeneral practices and clinical research facilities in Cambridgeshire, Norfolk and Leicestershire.nnnPARTICIPANTSnMales and females aged ≥u200940 years with NDH who had a high risk of CVD.nnnINTERVENTIONSnProlonged-release metformin (500u2009mg) (Glucophage® SR, Merck KGaA, Bedfont Cross, Middlesex, UK) or the matched placebo, up to three tablets per day, distributed by post.nnnMAIN OUTCOME MEASURESnRecruitment rates; adherence to study medication; laboratory results at baseline and 3 and 6 months; reliability and acceptability of study drug delivery; questionnaire return rates; and quality of life.nnnRESULTSnWe sent 5251 invitations, with 511 individuals consenting to participate. Of these, 249 were eligible and were randomised between March and November 2015 (125 to the metformin group and 124 to the placebo group). Participants were followed up for 0.99 years [standard deviation (SD) 0.30 years]. The use of electronic medical records to identify potentially eligible individuals in individual practices was resource intensive. Participants were generally elderly [mean age 70 years (SD 6.7 years)], overweight [mean body mass index 30.1u2009kg/m2 (SD 4.5u2009kg/m2)] and male (88%), and the mean modelled 10-year CVD risk was 28.8% (SD 8.5%). Randomisation, postal delivery of the study drug and outcome assessment using registers/medical records were feasible and acceptable to participants. Most participants were able to take three tablets per day, but premature discontinuation of the study drug was common (≈30% of participants by 6 months), although there were no differences between the groups. All randomised participants returned questionnaires at baseline and 67% of participants returned questionnaires by the end of the study. There was no between-group difference in Short Form questionnaire-8 items or EuroQol-5 Dimensions scores. Compared with placebo, metformin was associated with small improvements in the mean glycated haemoglobin level [-0.82u2009mmol/mol, 95% confidence interval (CI) -1.39 to -0.24u2009mmol/mol], mean estimated glomerular filtration rate (2.31u2009ml/minute/1.73u2009m2, 95% CI -0.2 to 4.81u2009ml/minute/1.73u2009m2) and mean low-density lipoprotein cholesterol level (-0.11u2009mmol/l, 95% CI -0.25 to 0.02u2009mmol/l) and a reduction in mean plasma vitamin B12 level (-16.4u2009ng/l, 95% CI -32.9 to -0.01u2009ng/l). There were 35 serious adverse events (13 in the placebo group, 22 in the metformin group), with none deemed to be treatment related.nnnLIMITATIONSnChanges to sponsorship reduced the study duration, the limited availability of information in medical records reduced recruitment efficiency and discontinuation of study medication exceeded forecasts.nnnCONCLUSIONSnA large, pragmatic trial comparing the effects of prolonged-release metformin and placebo on the risk of CVD events is potentially feasible. However, changes to the study design and conduct are recommended to enable an efficient scaling up of the trial. Recommendations include changing the inclusion criteria to recruit people with pre-existing CVD to increase the recruitment and event rates, using large primary/secondary care databases to increase recruitment rates, conducting follow-up remotely to improve efficiency and including a run-in period prior to randomisation to optimise trial adherence.nnnTRIAL REGISTRATIONnCurrent Controlled Trials ISRCTN34875079.nnnFUNDINGnThe project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 18. See the NIHR Journals Library website for further project information. Merck KGaA provided metformin and matching placebo.

Cardiovascular disease and cancer compete for the outcome of death

Life is a game of multiple competing risks, and problems arise when we forget that death is a single, non-repetitive event usually attributable to one cause.1 Doctors often consider issues of competing risks when caring for patients with multimorbid chronic disease. For example, it’s not uncommon for a GP to ask, “Will my …