Adverse events profile of PrePex a non-surgical device for adult male circumcision in a Ugandan urban setting

Background: Safe Male Circumcision is a proven approach for partial HIV prevention. Several sub Saharan African countries have plans to reach a prevalence of 80% of their adult males circumcised by 2015. These targets require out of ordinary organization, demand creation, timely execution and perhaps the use of SMC devices. Objective: To profile Adverse Events rate and acceptance of PrePex, a non surgical device for adult male circumcision. Methods: A prospective study, conducted at International Hospital Kampala, Uganda, between August and October 2012. Ethical approval was obtained from Uganda National Council of Science and Technology. Results: Of 1,040 men received to undergo SMC, 678 opted for PrePex, 36 were excluded at an initial physical examination screening. 642 were enrolled and consented, and another 17 were excluded before device placement. 625 underwent the procedure. Average age was 24 years (67). Twelve moderate AEs occurred among 10 participants 12/625, (1.9%). These were all reversible. Five had device displacement, one had an everted foreskin; five had bleeding after the device was removed and one had voiding difficulties. The majority (279 out of 300) of men interviewed complained of some pain within the week of placement. Mean pain score at device placement (using visual analogue scale) was 0.5, at device removal 4.5 and within 2 min of removal the pain score was 1.4. Over 70% of the devices were placed and removed by non-physician clinicians. Presented with a choice, 60% of men chose PrePex over surgical SMC. Close to 90% would recommend the device to their friends. Odour from the necrotic skin was a concern. Removals done 1–2 days earlier than day 7 were beneficial and conferred no extra risk. Conclusion: AEs of a moderate or severe nature associated with PrePex were low and reversible. PrePex is feasible for mass safe male circumcision scaling up

Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial

Background: The safety, effectiveness, and cost-effectiveness of molnupiravir, an oral antiviral medication for SARS-CoV-2, has not been established in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. We aimed to establish whether the addition of molnupiravir to usual care reduced hospital admissions and deaths associated with COVID-19 in this population. Methods: PANORAMIC was a UK-based, national, multicentre, open-label, multigroup, prospective, platform adaptive randomised controlled trial. Eligible participants were aged 50 years or older—or aged 18 years or older with relevant comorbidities—and had been unwell with confirmed COVID-19 for 5 days or fewer in the community. Participants were randomly assigned (1:1) to receive 800 mg molnupiravir twice daily for 5 days plus usual care or usual care only. A secure, web-based system (Spinnaker) was used for randomisation, which was stratified by age (<50 years vs ≥50 years) and vaccination status (yes vs no). COVID-19 outcomes were tracked via a self-completed online daily diary for 28 days after randomisation. The primary outcome was all-cause hospitalisation or death within 28 days of randomisation, which was analysed using Bayesian models in all eligible participants who were randomly assigned. This trial is registered with ISRCTN, number 30448031. Findings: Between Dec 8, 2021, and April 27, 2022, 26 411 participants were randomly assigned, 12 821 to molnupiravir plus usual care, 12 962 to usual care alone, and 628 to other treatment groups (which will be reported separately). 12 529 participants from the molnupiravir plus usual care group, and 12 525 from the usual care group were included in the primary analysis population. The mean age of the population was 56·6 years (SD 12·6), and 24 290 (94%) of 25 708 participants had had at least three doses of a SARS-CoV-2 vaccine. Hospitalisations or deaths were recorded in 105 (1%) of 12 529 participants in the molnupiravir plus usual care group versus 98 (1%) of 12 525 in the usual care group (adjusted odds ratio 1·06 [95% Bayesian credible interval 0·81–1·41]; probability of superiority 0·33). There was no evidence of treatment interaction between subgroups. Serious adverse events were recorded for 50 (0·4%) of 12 774 participants in the molnupiravir plus usual care group and for 45 (0·3%) of 12 934 in the usual care group. None of these events were judged to be related to molnupiravir. Interpretation: Molnupiravir did not reduce the frequency of COVID-19-associated hospitalisations or death among high-risk vaccinated adults in the community

Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial

BackgroundThe safety, effectiveness, and cost-effectiveness of molnupiravir, an oral antiviral medication for SARS-CoV-2, has not been established in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. We aimed to establish whether the addition of molnupiravir to usual care reduced hospital admissions and deaths associated with COVID-19 in this population.MethodsPANORAMIC was a UK-based, national, multicentre, open-label, multigroup, prospective, platform adaptive randomised controlled trial. Eligible participants were aged 50 years or older—or aged 18 years or older with relevant comorbidities—and had been unwell with confirmed COVID-19 for 5 days or fewer in the community. Participants were randomly assigned (1:1) to receive 800 mg molnupiravir twice daily for 5 days plus usual care or usual care only. A secure, web-based system (Spinnaker) was used for randomisation, which was stratified by age (<50 years vs ≥50 years) and vaccination status (yes vs no). COVID-19 outcomes were tracked via a self-completed online daily diary for 28 days after randomisation. The primary outcome was all-cause hospitalisation or death within 28 days of randomisation, which was analysed using Bayesian models in all eligible participants who were randomly assigned. This trial is registered with ISRCTN, number 30448031.FindingsBetween Dec 8, 2021, and April 27, 2022, 26 411 participants were randomly assigned, 12 821 to molnupiravir plus usual care, 12 962 to usual care alone, and 628 to other treatment groups (which will be reported separately). 12 529 participants from the molnupiravir plus usual care group, and 12 525 from the usual care group were included in the primary analysis population. The mean age of the population was 56·6 years (SD 12·6), and 24 290 (94%) of 25 708 participants had had at least three doses of a SARS-CoV-2 vaccine. Hospitalisations or deaths were recorded in 105 (1%) of 12 529 participants in the molnupiravir plus usual care group versus 98 (1%) of 12 525 in the usual care group (adjusted odds ratio 1·06 [95% Bayesian credible interval 0·81–1·41]; probability of superiority 0·33). There was no evidence of treatment interaction between subgroups. Serious adverse events were recorded for 50 (0·4%) of 12 774 participants in the molnupiravir plus usual care group and for 45 (0·3%) of 12 934 in the usual care group. None of these events were judged to be related to molnupiravir.InterpretationMolnupiravir did not reduce the frequency of COVID-19-associated hospitalisations or death among high-risk vaccinated adults in the community

Home and Online Management and Evaluation of Blood Pressure (HOME BP) using a digital intervention in poorly controlled hypertension: randomised controlled trial

Objective: The HOME BP (Home and Online Management and Evaluation of Blood Pressure) trial aimed to test a digital intervention for hypertension management in primary care by combining self-monitoring of blood pressure with guided self-management. Design: Unmasked randomised controlled trial with automated ascertainment of primary endpoint. Setting: 76 general practices in the United Kingdom. Participants: 622 people with treated but poorly controlled hypertension (&gt;140/90 mm Hg) and access to the internet. Interventions: Participants were randomised by using a minimisation algorithm to self-monitoring of blood pressure with a digital intervention (305 participants) or usual care (routine hypertension care, with appointments and drug changes made at the discretion of the general practitioner; 317 participants). The digital intervention provided feedback of blood pressure results to patients and professionals with optional lifestyle advice and motivational support. Target blood pressure for hypertension, diabetes, and people aged 80 or older followed UK national guidelines. Main outcome measures: The primary outcome was the difference in systolic blood pressure (mean of second and third readings) after one year, adjusted for baseline blood pressure, blood pressure target, age, and practice, with multiple imputation for missing values. Results: After one year, data were available from 552 participants (88.6%) with imputation for the remaining 70 participants (11.4%). Mean blood pressure dropped from 151.7/86.4 to 138.4/80.2 mm Hg in the intervention group and from 151.6/85.3 to 141.8/79.8 mm Hg in the usual care group, giving a mean difference in systolic blood pressure of −3.4 mm Hg (95% confidence interval −6.1 to −0.8 mm Hg) and a mean difference in diastolic blood pressure of −0.5 mm Hg (−1.9 to 0.9 mm Hg). Results were comparable in the complete case analysis and adverse effects were similar between groups. Within trial costs showed an incremental cost effectiveness ratio of £11 ($15, €12; 95% confidence interval £6 to £29) per mm Hg reduction. Conclusions: The HOME BP digital intervention for the management of hypertension by using self-monitored blood pressure led to better control of systolic blood pressure after one year than usual care, with low incremental costs. Implementation in primary care will require integration into clinical workflows and consideration of people who are digitally excluded. Trial registration: ISRCTN13790648

Primary Healthcare in East Africa: For How Long Shall Countries Run After Diseases?

Primary Health Care (PHC) is a pivotal discipline in disease prevention, promotion of community-oriented primary care and implementation of evidence-based strategies to improve the health status of the people. This textbook focuses on PHC in the African context in comparison to the rest of the world. It provides fundamental concepts in health such as the current epidemiological trend in East Africa, comprehensive versus selective PHC, emerging and re-emerging diseases, social health insurance and a critical analysis of whether health for all has been achieved

Skills Training of Health Workers in the Use of a Non Surgical Device (PrePex) for Adult Safe Male Circumcision

<div><p>Background</p><p>Safe Male Circumcision (SMC) is a proven approach for partial protection of men from acquisition of HIV infection. Several sub-Saharan African countries have a target to circumcise 80% of males aged 15 to 49. The use of devices such as PrePex would aid scaling up of SMC. Since most health workers would have no prior experience with use of devices, skills training is needed. This paper explores a skills transfer model at an urban site in Uganda.</p><p>Objective</p><p>To assess the practicability and feasibility of rapid short duration training for safe PrePex device use.</p><p>Methods</p><p>A prospective study, conducted over 8 weeks (August–October 2012) at International Hospital Kampala, an urban Kampala hospital, examining the performance of various health worker cadres after training in the use of a non-surgical device (PrePex). The prospective study obtained approval from the Makerere School of Medicine Research and Ethics Committee and the Uganda National Council of Science and Technology. If eligible, and after the subject signed the informed consent form, they were enrolled into the study.</p><p>Results</p><p>Ten health workers were successfully trained in use of PrePex during a 3 day non-residential on-the-job training course. After the first three days of training, the trained health workers performed 561 placements and 529 device removals successfully. Over all adverse events (AE) rates were below ≤2%; however, there were some differences in AE rates across the cadres trained but not significant (p>0.25 for moderate AEs).</p><p>Conclusion</p><p>Rapid training for safe use of the PrePex device is feasible for the range of health workers available for SMC in resource limited settings, but among those with past SMC experience.</p></div

An economic model for the use of yoghurt in type 2 diabetes risk reduction in the UK

BACKGROUND: In the UK, diabetes accounts for approximately 10% of the total UK National Health Service (NHS) resource expenditure, a figure that has been predicted to increase to 17% by 2035/2036. Meta-analysis of association studies indicate that yogurt consumption is potentially protective against type 2 diabetes (T2D). The purpose of this study was to explore the potential economic benefit to the UK NHS of a population increase in yoghurt consumption as a preventative measure against development of T2D. METHODS: A patient simulation model was constructed for adults in the UK over the age of 25 years old using incidence rates for developing T2D with both current and increased yoghurt consumption. The reduction in risk in developing T2D associated with higher yoghurt consumption was taken from a meta-analysis of studies of dairy consumption on T2D risk. In each annual cycle of the model a patient could develop complications and comorbidities that are known to be more common in patients with T2D. Incidence rates for these conditions for diabetics and non-diabetics were taken from published studies. The model had a 25 year time horizon. RESULTS: The model predicts that increasing average yoghurt consumption by adults over 25 years of age in the UK by 100g daily could result in 388,000 fewer people developing T2D over 25 years. This could save the UK NHS £2.3bn in direct T2D treatment costs and the costs of treating T2D associated complications. In addition, 267,000 QALYs would be generated. If the NHS values a QALY valued at £20,000, this would mean that the NHS should be prepared to pay £5.5bn for an intervention that generated the same number of QALYs. CONCLUSIONS: Increasing yoghurt consumption in the adult population of the UK by 100g per day could generate substantial cost savings to the NHS as well as significant patient benefit through reductions in the incidence of T2D

Specific PrePex device placement maneuvers at Kampala IHK site, Uganda 2013.

<p>*Maneuver can be performed by either.</p

Comparative HR needs in the SMC programme, Uganda PrePex study 2012.

<p>Comparative HR needs in the SMC programme, Uganda PrePex study 2012.</p