The Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised trials in Mozambique, Pakistan, and India: an individual participant-level meta-analysis

To overcome the three delays in triage, transport and treatment that underlie adverse pregnancy outcomes, we aimed to reduce all-cause adverse outcomes with community-level interventions targeting women with pregnancy hypertension in three low-income countries. Methods: In this individual participant-level meta-analysis, we de-identified and pooled data from the Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised controlled trials in Mozambique, Pakistan, and India, which were run in 2014-17. Consenting pregnant women, aged 12-49 years, were recruited in their homes. Clusters, defined by local administrative units, were randomly assigned (1:1) to intervention or control groups. The control groups continued local standard of care. The intervention comprised community engagement and existing community health worker-led mobile health-supported early detection, initial treatment, and hospital referral of women with hypertension. For this meta-analysis, as for the original studies, the primary outcome was a composite of maternal or perinatal outcome (either maternal, fetal, or neonatal death, or severe morbidity for the mother or baby), assessed by unmasked trial surveillance personnel. For this analysis, we included all consenting participants who were followed up with completed pregnancies at trial end. We analysed the outcome data with multilevel modelling and present data with the summary statistic of adjusted odds ratios (ORs) with 95% CIs (fixed effects for maternal age, parity, maternal education, and random effects for country and cluster). This meta-analysis is registered with PROSPERO, CRD42018102564. Findings: Overall, 44 clusters (69 330 pregnant women) were randomly assigned to intervention (22 clusters [36 008 pregnancies]) or control (22 clusters [33 322 pregnancies]) groups. 32 290 (89·7%) pregnancies in the intervention group and 29 698 (89·1%) in the control group were followed up successfully. Median maternal age of included women was 26 years (IQR 22-30). In the intervention clusters, 6990 group and 16 691 home-based community engagement sessions and 138 347 community health worker-led visits to 20 819 (57·8%) of 36 008 women (of whom 11 095 [53·3%] had a visit every 4 weeks) occurred. Blood pressure and dipstick proteinuria were assessed per protocol. Few women were eligible for methyldopa for severe hypertension (181 [1%] of 20 819) or intramuscular magnesium sulfate for pre-eclampsia (198 [1%]), of whom most accepted treatment (162 [89·5%] of 181 for severe hypertension and 133 [67·2%] of 198 for pre-eclampsia). 1255 (6%) were referred to a comprehensive emergency obstetric care facility, of whom 864 (82%) accepted the referral. The primary outcome was similar in the intervention (7871 [24%] of 32 290 pregnancies) and control clusters (6516 [22%] of 29 698; adjusted OR 1·17, 95% CI 0·90-1·51; p=0·24). No intervention-related serious adverse events occurred, and few adverse effects occurred after in-community...

UBC-Nepal expedition: upper and lower limb conduit artery shear stress and flow-mediated dilation on ascent to 5,050 m in lowlanders and Sherpa.

The study of conduit artery endothelial adaptation to hypoxia has been restricted to the brachial artery, and comparisons with highlanders have been confounded by differences in altitude exposure, exercise, and unknown levels of blood viscosity. To address these gaps, we tested the hypothesis that lowlanders, but not Sherpa, would demonstrate decreased mean shear stress and increased retrograde shear stress and subsequently reduced flow-mediated dilation (FMD) in the upper and lower limb conduit arteries on ascent to 5,050 m. Healthy lowlanders (means ± SD, n = 22, 28 ± 6 yr) and Sherpa ( n = 12, 34 ± 11 yr) ascended over 10 days, with measurements taken on nontrekking days at 1,400 m (baseline), 3,440 m ( day 4), 4,371 m ( day 7), and 5,050 m ( day 10). Arterial blood gases, blood viscosity, shear stress, and FMD [duplex ultrasound of the brachial and superficial femoral arteries (BA and SFA, respectively)] were acquired at each time point. Ascent decreased mean and increased retrograde shear stress in the upper and lower limb of lowlanders and Sherpa. Although BA FMD decreased in lowlanders from 7.1 ± 3.9% to 3.8 ± 2.8% at 5,050 versus 1,400 m ( P < 0.001), SFA FMD was preserved. In Sherpa, neither BA nor SFA FMD were changed upon ascent to 5,050 m. In lowlanders, the ascent-related exercise may favorably influence endothelial function in the active limb (SFA); selective impairment in FMD in the BA in lowlanders is likely mediated via the low mean or high oscillatory baseline shear stress. In contrast, Sherpa presented protected endothelial function, suggesting a potential vascular aspect of high-altitude acclimatization/adaptation. NEW & NOTEWORTHY Upper and lower limb arterial shear stress and flow-mediated dilation (FMD) were assessed on matched ascent from 1,400 to 5,050 m in lowlanders and Sherpa. A shear stress pattern associated with vascular dysfunction/risk manifested in both limbs of lowlanders and Sherpa. FMD was impaired only in the upper limb of lowlanders. The findings indicate a limb-specific impact of high-altitude trekking on FMD and a vascular basis to acclimatization wherein endothelial function is protected in Sherpa on ascent.

Mass-gathering Medicine: Risks and Patient Presentations at a 2-Day Electronic Dance Music Event.

INTRODUCTION: Music festivals, including electronic dance music events (EDMEs), increasingly are common in Canada and internationally. Part of a US $4.5 billion industry annually, the target audience is youth and young adults aged 15-25 years. Little is known about the impact of these events on local emergency departments (EDs). METHODS: Drawing on prospective data over a 2-day EDME, the authors of this study employed mixed methods to describe the case mix and prospectively compared patient presentation rate (PPR) and ambulance transfer rate (ATR) between a first aid (FA) only and a higher level of care (HLC) model. RESULTS: There were 20,301 ticketed attendees. Seventy patient encounters were recorded over two days. The average age was 19.1 years. Roughly 69% were female (n=48/70). Forty-six percent of those seen in the main medical area were under the age of 19 years (n=32/70). The average length of stay in the main medical area was 70.8 minutes. The overall PPR was 4.09 per 1,000 attendees. The ATR with FA only would have been 1.98; ATR with HLC model was 0.52. The presence of an on-site HLC team had a significant positive effect on avoiding ambulance transfers. DISCUSSION: Twenty-nine ambulance transfers and ED visits were avoided by the presence of an on-site HLC medical team. Reduction of impact to the public health care system was substantial. CONCLUSIONS: Electronic dance music events have predictable risks and patient presentations, and appropriate on-site health care resources may reduce significantly the impact on the prehospital and emergency health resources in the host community.

Antidiabetic-drug combination treatment for glucose intolerance in adult female rats treated acutely with olanzapine.

Second generation antipsychotic drugs are routinely used as treatment for psychotic disorders. Many of these compounds, including olanzapine, cause metabolic side-effects such as impaired glucose tolerance and insulin resistance. Individual antidiabetic drugs can help control elevated glucose levels in patients treated with antipsychotics, but the effects of combining antidiabetics, which routinely occurs with Type 2 diabetes mellitus patients, have never been studied. Presently, we compared the effects of the three different antidiabetics metformin (500mg/kg, p.o.), rosiglitazone (30mg/kg, p.o.) and glyburide (10mg/kg, p.o.) on metabolic dysregulation in adult female rats treated acutely with olanzapine. In addition, dual combinations of each of these antidiabetics were compared head-to-head against each other and the individual drugs. The animals received two daily treatments with antidiabetics and were then treated acutely with olanzapine (10mg/kg, i.p.). Fasting glucose and insulin levels were measured, followed by a 2h glucose tolerance test. Olanzapine caused a large and highly significant glucose intolerance compared to vehicle treated rats. Rosiglitazone decreased glucose levels non-significantly, while both metformin and glyburide significantly decreased glucose levels compared to olanzapine-only treated animals. For antidiabetic dual-drug combinations, the rosiglitazone-metformin group showed an unexpected increase in glucose levels compared to all of the single antidiabetic drugs. However, both the metformin-glyburide and rosiglitazone-glyburide groups showed significantly greater reductions in glucose levels following olanzapine than with single drug treatment alone for metformin or rosiglitazone, bringing glucose levels down to values equivalent to vehicle-only treated animals. These findings indicate that further study of antidiabetic dual-drug combinations in patients treated with antipsychotic drugs is warranted.

Medical, health-science students bring different perspectives to interdisciplinary ethics course.

The University of British Columbia offers a unique health care ethics course to students in 12 disciplines, including medicine. Organizers say the course addresses the "traditional separatism" in health-sciences teaching that for too long has been characterized by a lack of interdisciplinary collaboration.

Bridging the professions: an integrated and interdisciplinary approach to teaching health care ethics.

In 1993, the authors introduced an interdisciplinary course in health care ethics at the University of British Columbia. They were motivated by two convictions: (1) an interdisciplinary approach to health care decision making is best; and (2) every significant health care decision has an ethical component. They wanted to encourage students from the various health care disciplines to participate in interdisciplinary decision making in their future practices by giving them an opportunity to study health care ethics together during their training. The authors give detailed descriptions of the objectives, format, curriculum, and evaluation of this innovative course in the hope that other educators who may want to develop similar courses can learn from their experience.