Barbara Farrell

Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: A randomised placebo-controlled trial

BACKGROUND Anticonvulsants are used for pre-eclampsia in the belief they prevent eclamptic convulsions, and so improve outcome. Evidence supported magnesium sulphate as the drug to evaluate. METHODS Eligible women (n=10141) had not given birth or were 24 h or less postpartum; blood pressure of 140/90 mm Hg or more, and proteinuria of 1+ (30 mg/dL) or more; and there was clinical uncertainty about magnesium sulphate. Women were randomised in 33 countries to either magnesium sulphate (n=5071) or placebo (n=5070). Primary outcomes were eclampsia and, for women randomised before delivery, death of the baby. Follow up was until discharge from hospital after delivery. Analyses were by intention to treat. FINDINGS Follow-up data were available for 10,110 (99.7%) women, 9992 (99%) of whom received the allocated treatment. 1201 of 4999 (24%) women given magnesium sulphate reported side-effects versus 228 of 4993 (5%) given placebo. Women allocated magnesium sulphate had a 58% lower risk of eclampsia (95% CI 40-71) than those allocated placebo (40, 0.8%, vs 96, 1.9%; 11 fewer women with eclampsia per 1000 women). Maternal mortality was also lower among women allocated magnesium sulphate (relative risk 0.55, 0.26-1.14). For women randomised before delivery, there was no clear difference in the risk of the baby dying (576, 12.7%, vs 558, 12.4%; relative risk 1.02, 99% CI 0.92-1.14). The only notable difference in maternal or neonatal morbidity was for placental abruption (relative risk 0.67, 99% CI 0.45-0.89). INTERPRETATION Magnesium sulphate halves the risk of eclampsia, and probably reduces the risk of maternal death. There do not appear to be substantive harmful effects to mother or baby in the short term.ARTICLES Summary Background Anticonvulsants are used for pre-eclampsia in the belief they prevent eclamptic convulsions, and so improve outcome. Evidence supported magnesium sulphate as the drug to evaluate.

Qualitative Comparison of the Reliability of Health Status Assessments With the EuroQol and SF-36 Questionnaires After Stroke

BACKGROUND AND PURPOSE The reliability of the EuroQol and SF-36 questionnaires after stroke is not known. We therefore aimed to assess and compare the test-retest reliability of both instruments in a group of stroke patients. METHODS A total of 2253 patients with stroke entered by United Kingdom hospitals in the International Stroke Trial were randomized to follow up with either the EuroQol or the SF-36 instruments. For both instruments, we randomly selected one third of respondents and asked them to complete another, identical questionnaire. We assessed test-retest reliability using agreement statistics: unweighted kappa statistics for the categorical domains of the EuroQol and intraclass correlation coefficients for the EuroQol visual analog scale, utility scores, and SF-36. RESULTS For the five categorical domains of the EuroQol, reproducibility was generally good (kappa ranged from 0.63 to 0.80). The reproducibility of the domains of the SF-36 was qualitatively similar for all the domains except mental health (intraclass correlation coefficient=.28). However, the 95% confidence intervals for the difference in scores between test and retest were substantial. For both instruments, reproducibility was better when the patient completed the questionnaires than when a proxy did. CONCLUSIONS Both the EuroQol and SF-36 have acceptable and qualitatively similar test-retest reliability. Therefore, either instrument might function effectively as a discriminatory measure for assessing health-related quality-of-life outcomes in groups of patients after stroke. However, our data do not support the use of either instrument for serial assessments in individual patients unless very large differences over time are expected.

Treatment of Neonatal Sepsis with Intravenous Immune Globulin

BACKGROUND Neonatal sepsis is a major cause of death and complications despite antibiotic treatment. Effective adjunctive treatments are needed. Newborn infants are relatively deficient in endogenous immunoglobulin. Meta-analyses of trials of intravenous immune globulin for suspected or proven neonatal sepsis suggest a reduced rate of death from any cause, but the trials have been small and have varied in quality. METHODS At 113 hospitals in nine countries, we enrolled 3493 infants receiving antibiotics for suspected or proven serious infection and randomly assigned them to receive two infusions of either polyvalent IgG immune globulin (at a dose of 500 mg per kilogram of body weight) or matching placebo 48 hours apart. The primary outcome was death or major disability at the age of 2 years. RESULTS There was no significant between-group difference in the rates of the primary outcome, which occurred in 686 of 1759 infants (39.0%) who received intravenous immune globulin and in 677 of 1734 infants (39.0%) who received placebo (relative risk, 1.00; 95% confidence interval, 0.92 to 1.08). Similarly, there were no significant differences in the rates of secondary outcomes, including the incidence of subsequent sepsis episodes. In follow-up of 2-year-old infants, there were no significant differences in the rates of major or nonmajor disability or of adverse events. CONCLUSIONS Therapy with intravenous immune globulin had no effect on the outcomes of suspected or proven neonatal sepsis.

Improving cardiovascular health at population level: 39 community cluster randomised trial of Cardiovascular Health Awareness Program (CHAP)

Objective To evaluate the effectiveness of the community based Cardiovascular Health Awareness Program (CHAP) on morbidity from cardiovascular disease. Design Community cluster randomised trial. Setting 39 mid-sized communities in Ontario, Canada, stratified by location and population size. Participants Community dwelling residents aged 65 years or over, family physicians, pharmacists, volunteers, community nurses, and local lead organisations. Intervention Communities were randomised to receive CHAP (n=20) or no intervention (n=19). In CHAP communities, residents aged 65 or over were invited to attend volunteer run cardiovascular risk assessment and education sessions held in community based pharmacies over a 10 week period; automated blood pressure readings and self reported risk factor data were collected and shared with participants and their family physicians and pharmacists. Main outcome measure Composite of hospital admissions for acute myocardial infarction, stroke, and congestive heart failure among all community residents aged 65 and over in the year before compared with the year after implementation of CHAP. Results All 20 intervention communities successfully implemented CHAP. A total of 1265 three hour long sessions were held in 129/145 (89%) pharmacies during the 10 week programme. 15 889 unique participants had a total of 27 358 cardiovascular assessments with the assistance of 577 peer volunteers. After adjustment for hospital admission rates in the year before the intervention, CHAP was associated with a 9% relative reduction in the composite end point (rate ratio 0.91, 95% confidence interval 0.86 to 0.97; P=0.002) or 3.02 fewer annual hospital admissions for cardiovascular disease per 1000 people aged 65 and over. Statistically significant reductions favouring the intervention communities were seen in hospital admissions for acute myocardial infarction (rate ratio 0.87, 0.79 to 0.97; P=0.008) and congestive heart failure (0.90, 0.81 to 0.99; P=0.029) but not for stroke (0.99, 0.88 to 1.12; P=0.89). Conclusions A collaborative, multi-pronged, community based health promotion and prevention programme targeted at older adults can reduce cardiovascular morbidity at the population level. Trial registration Current controlled trials ISRCTN50550004.

Integrating Family Medicine and Pharmacy to Advance Primary Care Therapeutics

The prevalence of suboptimal prescribing of medications is well documented. 1 , 2 Patients are often undertreated or not offered therapeutic treatments that are likely to confer benefit. 3 , 4 As a result, drug‐related hospital admissions are common and often preventable. 5 Improvements to the health‐care system are clearly needed in order to maximize the benefits that can be derived from medications. Many countries are changing their primary health‐care systems to improve the quality of health‐care delivery. 6 , 7 One main transformation is the use of multidisciplinary care teams to provide care in a coordinated manner often from the same location or by using the common medical record of the patients. It has been demonstrated that pharmacists can improve prescribing, reduce health‐care utilization and medication costs, and contribute to clinical improvements in many chronic medical conditions, such as cardiovascular disease, diabetes, and psychiatric illness. 8 , 9 , 10 , 11 However, the effect of integrating a pharmacist providing general services into a primary care group has not been extensively studied. The Integrating Family Medicine and Pharmacy to Advance Primary Care Therapeutics (IMPACT) project was designed to provide a real‐world demonstration of the feasibility of integrating the pharmacist into primary care office practice. This article provides a description of the IMPACT project participants; the IMPACT practice model and the concepts incorporated in its development; some initial results from the program evaluation; sustainability of the model; and some reflections on the implementation of the practice model.

What Are Priorities for Deprescribing for Elderly Patients? Capturing the Voice of Practitioners: A Modified Delphi Process

Polypharmacy and inappropriate medication use among older adults contribute to adverse drug reactions, falls, cognitive impairment, noncompliance, hospitalization and mortality. While deprescribing - tapering, reducing or stopping a medication - is feasible and relatively safe, clinicians find it difficult to carry out. Deprescribing guidelines would facilitate this process. The aim of this paper is to identify and prioritize medication classes where evidence-based deprescribing guidelines would be of benefit to clinicians. A modified Delphi approach included a literature review to identify potentially inappropriate medications for the elderly, an expert panel to develop survey content and three survey rounds to seek consensus on priorities. Panel participants included three pharmacists, two family physicians and one social scientist. Sixty-five Canadian geriatrics experts (36 pharmacists, 19 physicians and 10 nurse practitioners) participated in the survey. Twenty-nine drugs/drug classes were included in the first survey with 14 reaching the required (≥ 70%) level of consensus, and 2 new drug classes added from qualitative comments. Fifty-three participants completed round two, and 47 participants completed round three. The final five priorities were benzodiazepines, atypical antipsychotics, statins, tricyclic antidepressants, and proton pump inhibitors; nine other drug classes were also identified as being in need of evidence-based deprescribing guidelines. The Delphi consensus process identified five priority drug classes for which expert clinicians felt guidance is needed for deprescribing. The classes of drugs that emerged strongly from the rankings dealt with mental health, cardiovascular, gastroenterological, and neurological conditions. The results suggest that deprescribing and overtreatment occurs through the full spectrum of primary care, and that evidence-based deprescribing guidelines are a priority in the care of the elderly.

Evaluation of the Ages and Stages Questionnaires in identifying children with neurosensory disability in the Magpie Trial follow-up study

Aim: To evaluate performance of the Ages and Stages Questionnaires (full ASQ), and a shortened version (short ASQ), in detecting children with severe neurosensory disability in the Magpie Trial follow‐up study.

Caesarean section surgical techniques (CORONIS): a fractional, factorial, unmasked, randomised controlled trial

BACKGROUND Variations exist in the surgical techniques used for caesarean section and many have not been rigorously assessed in randomised controlled trials. We aimed to assess whether any surgical techniques were associated with improved outcomes for women and babies. METHODS CORONIS was a pragmatic international 2×2×2×2×2 non-regular fractional, factorial, unmasked, randomised controlled trial that examined five elements of the caesarean section technique in intervention pairs. CORONIS was undertaken at 19 sites in Argentina, Chile, Ghana, India, Kenya, Pakistan, and Sudan. Each site was assigned to three of the five intervention pairs: blunt versus sharp abdominal entry; exteriorisation of the uterus for repair versus intra-abdominal repair; single-layer versus double-layer closure of the uterus; closure versus non-closure of the peritoneum (pelvic and parietal); and chromic catgut versus polyglactin-910 for uterine repair. Pregnant women were eligible if they were to undergo their first or second caesarean section through a planned transverse abdominal incision. Women were randomly assigned by a secure web-based number allocation system to one intervention from each of the three assigned pairs. All investigators, surgeons, and participants were unmasked to treatment allocation. The primary outcome was the composite of death, maternal infectious morbidity, further operative procedures, or blood transfusion (>1 unit) up to the 6-week follow-up visit. Women were analysed in the groups into which they were allocated. The CORONIS Trial is registered with Current Controlled Trials: ISRCTN31089967. FINDINGS Between May 20, 2007, and Dec 31, 2010, 15 935 women were recruited. There were no statistically significant differences within any of the intervention pairs for the primary outcome: blunt versus sharp entry risk ratio 1·03 (95% CI 0·91-1·17), exterior versus intra-abdominal repair 0·96 (0·84-1·08), single-layer versus double-layer closure 0·96 (0·85-1·08), closure versus non-closure 1·06 (0·94-1·20), and chromic catgut versus polyglactin-910 0·90 (0·78-1·04). 144 serious adverse events were reported, of which 26 were possibly related to the intervention. Most of the reported serious adverse events were known complications of surgery or complications of the reasons for the caesarean section. INTERPRETATION These findings suggest that any of these surgical techniques is acceptable. However, longer-term follow-up is needed to assess whether the absence of evidence of short-term effects will translate into an absence of long-term effects. FUNDING UK Medical Research Council and WHO.

Managing clinical trials

Managing clinical trials, of whatever size and complexity, requires efficient trial management. Trials fail because tried and tested systems handed down through apprenticeships have not been documented, evaluated or published to guide new trialists starting out in this important field. For the past three decades, trialists have invented and reinvented the trial management wheel. We suggest that to improve the successful, timely delivery of important clinical trials for patient benefit, it is time to produce standard trial management guidelines and develop robust methods of evaluation.

Four levels of outcomes of information-seeking: A mixed methods study in primary health care

Primary health care practitioners routinely search for information within electronic knowledge resources. We proposed four levels of outcomes of information-seeking: situational relevance, cognitive impact, information use, and patient health outcomes. Our objective was to produce clinical vignettes for describing and testing these levels. We conducted a mixed methods study combining a quantitative longitudinal study and a qualitative multiple case study. Participants were 10 nurses, 10 medical residents, and 10 pharmacists. They had access to an online resource, and did 793 searches for treatment recommendations. Using the Information Assessment Method (IAM), participants rated their searches for each of the four levels. Rated searches were examined in interviews guided by log reports and a think-aloud protocol. Cases were defined as clearly described searches where clinical information was used for a specific patient. For each case, interviewees described the four levels of outcomes. Quantitative and qualitative data were merged into clinical vignettes. We produced 130 clinical vignettes. Specifically, 46 vignettes (35.4%) corresponded to clinical situations where information use was associated with one or more than one type of positive patient health outcome: increased patient knowledge (n = 28), avoidance of unnecessary or inappropriate intervention (n = 25), prevention of disease or health deterioration (n = 9), health improvement (n = 6), and increased patient satisfaction (n = 3). Results suggested information use was associated with perceived benefits for patients. This may encourage clinicians to search for information more often when they feel the need. Results supported the four proposed levels of outcomes, which can be transferable to other information-seeking contexts.