Effectiveness of the BNT162b2 vaccine in preventing morbidity and mortality associated with COVID-19 in children aged 5 to 11 years: A systematic review and meta-analysis.

A rapid systematic review, based on Cochrane rapid review methodology was conducted to assess the effectiveness of two 10µg doses of BNT162b2 vaccine in preventing morbidity and mortality associated with COVID-19 in children aged 5 to 11 years. We searched the Cochrane Library COVID-19 study register, the COVID-NMA living review database and the McMaster University Living Evidence Synthesis for pre-appraised trials and observational studies up to 7 December 2022. Records were screened independently in duplicate. Where appraisal was not available, these were done in duplicate. Meta-analysis was conducted using RevMan 5.3 presenting risk ratios/odds ratios/inverse vaccine efficacy with 95% confidence intervals (CI). GRADE for assessing the overall certainty of the evidence was done in Gradepro. We screened 403 records and assessed 52 full-text articles for eligibility. One randomised controlled trial (RCT) and 24 observational studies were included. The RCT reported that BNT162b2 was likely safe and 91% efficacious, RR 0.09 (95% CI 0.03 to 0.32) against incident COVID-19 infection (moderate certainty evidence). In absolute terms, this is 19 fewer cases per 1,000 vaccines delivered (ranging from 15 to 21 fewer cases). Observational studies reported vaccine effectiveness (VE) against incident COVID-19 infection of 65% (OR 0.35, 95% CI 0.26 to 0.47) and 76% against hospitalisation (OR 0.24, 95% CI 0.13 to 0.42) (moderate certainty evidence). The absolute effect is 167 fewer cases per 1,000 vaccines given (ranging from 130 fewer to 196 fewer cases) and 4 fewer hospitalisations per 10,000 children (from 3 fewer to 5 fewer hospitalisations). Adverse events following vaccination with BNT162b2 were mild or moderate and transient. The evidence demonstrated a reduction in incident COVID-19 cases and small absolute reduction in hospitalisation if a two-dose BNT162b2 vaccine regimen is offered to children aged 5 to 11 years, compared to placebo. PROSPERO registration: CRD42021286710.

Is South Africa closing the health gaps between districts? Monitoring progress towards universal health service coverage with routine facility data.

BACKGROUND: South Africa is committed to advancing universal health coverage (UHC). The usefulness and potential of using routine health facility data for monitoring progress towards UHC, in the form of the 16-tracer WHO service coverage index (SCI), was assessed. METHODS: Alternative approaches to calculating the WHO SCI from routine data, allowing for disaggregation to district level, were explored. Data extraction, coding, transformation and modelling processes were applied to generate time series for these alternatives. Equity was assessed using socio-economic quintiles by district. RESULTS: The UHC SCI at a national level was 46.1 in 2007-2008 and 56.9 in 2016-2017. Only for the latter period, could the index be calculated for all indicators at a district level. Alternative indicators were formulated for 9 of 16 tracers in the index. Routine or repeated survey data could be used for 14 tracers. Apart from the NCD indicators, a gradient of poorer performance in the most deprived districts was evident in 2016-2017. CONCLUSIONS: It is possible to construct the UHC SCI for South Africa from predominantly routine data sources. Overall, there is evidence from district level data of a trend towards reduced inequity in relation to specific categories (notably RMNCH). Progress towards UHC has the potential to overcome fragmentation and enable harmonisation and interoperability of information systems. Private sector reporting of data into routine information systems should be encouraged.

Improving policies and practices for the extemporaneous compounding of oral liquid dosage forms in Saudi Arabian hospitals.

BACKGROUND: Pharmacists rely heavily on available reference material to guide the extemporaneous compounding of medicines. Extemporaneous compounding for individual patients has traditionally not been closely regulated, but is necessary in every setting. OBJECTIVE: To assess the adequacy of the evidence and recommend changes for the master formulae (MFs) used in the extemporaneous compounding manual at five Ministry of National Guard Health Affairs (MNGHA) tertiary care institutions in Saudi Arabia. METHOD: A descriptive cross-sectional study of all extemporaneous oral liquid dosage forms (n=75) was conducted. Investigators sought to establish if the current list of compounded oral liquid dosage forms were registered commercially, backed by a stability study or followed the Saudi Arabia Food and Drug Administration guidance on assigning beyond-use dates. A literature review of stability studies, tertiary references and package inserts was used to verify the MFs. Findings of each MF were tabulated and compared with available stability studies. RESULTS: It was found that 28 (37.3%) oral liquid dosage forms were registered by a regulatory authority, 8 (10.7%) MFs could not be traced to a stability study, while 3 (4%) MFs used beyond-use dates. The taskforce approved 15 (20%) MFs without changes, while 42 (56%) MFs had to be revised. CONCLUSION: This review found that, although resources on the compounding of oral liquid dosage forms exist, pharmacies need to carefully assess their quality and relevance and update local policies and practices. The majority (80%) of the current MFs used in MNGHA institutions were rejected due to inappropriate compounding practices and inaccuracies.

Candidates for inclusion in a universal antiretroviral regimen: are lamivudine and emtricitabine interchangeable?

PURPOSE OF REVIEW: Lamivudine (3TC) and emtricitabine (FTC) are the most widely used antiretroviral medications worldwide and are considered by the WHO to be interchangeable. This article reviews evidence supporting interchangeability of 3TC and FTC and considerations for future use. RECENT FINDINGS: Three randomized trials have directly compared the safety and efficacy of 3TC and FTC against identical backbone regimens. Each of these trials reported a nonsignificant difference in virological suppression, and when results were pooled the overall difference was nonsignificant (relative risk 1.03, 95% confidence interval 0.96-1.10). These findings of equivalence are further supported by indirect evidence from nine randomized trials comparing 3TC and FTC against a similar backbone regimen of two different nucleoside reverse transcriptase inhibitors (relative risk of virological suppression 0.99, 95% confidence interval 0.96-1.01). Data from observational studies is mixed. Overall, reported differences between 3TC and FTC in observational studies are often associated with differences in the baseline characteristics of the treatment groups, notably with respect to immunological and virological status, comorbidity, substance misuse, and pill burden. SUMMARY: The totality of evidence to date, from pharmacological data to observational studies to direct and indirect comparisons in randomized trials, suggests that 3TC and FTC can be considered to be therapeutically interchangeable and that if there are any differences, these are likely to be very small and not of major clinical importance.

South African HIV self-testing policy and guidance considerations.

The gap in HIV testing remains significant and new modalities such as HIV self-testing (HIVST) have been recommended to reach key and under-tested populations. In December 2016, the World Health Organization (WHO) released the Guidelines on HIV Self-Testing and Partner Notification: A Supplement to the Consolidated Guidelines on HIV Testing Services (HTS) and urged member countries to develop HIVST policy and regulatory frameworks. In South Africa, HIVST was included as a supplementary strategy in the National HIV Testing Services Policy in 2016, and recently, guidelines for HIVST were included in the South African National Strategic Plan for HIV, sexually transmitted infections and tuberculosis 2017-2022. This document serves as an additional guidance for the National HIV Testing Services Policy 2016, with specific focus on HIVST. It is intended for policy advocates, clinical and non-clinical HTS providers, health facility managers and healthcare providers in private and public health facilities, non-governmental, community-based and faith-based organisations involved in HTS and outreach, device manufacturers, workplace programmes and institutes of higher education.

Revision of the International Pharmaceutical Federation's Basel Statements on the future of hospital pharmacy: From Basel to Bangkok.

PURPOSE: The processes used to revise the 2008 Basel Statements on the future of hospital pharmacy are summarized, and the revised statements are presented. METHODS: The process for revising the Basel Statements followed an approach similar to that used during their initial development. The Hospital Pharmacy Section (HPS) of the International Pharmaceutical Federation (FIP) revised the 2008 FIP Basel Statements in four phases, including a survey of hospital pharmacists worldwide, an internal review, online forums, and a face-to-face "World Café" workshop in Bangkok, Thailand. RESULTS: The global survey on the initial Basel Statements included input from 334 respondents from 62 countries. The majority of respondents agreed that most of the initial Basel Statements were acceptable as written and did not require revision. In total, 11 statements were judged by more than 10% of respondents as needing revision or deletion. The FIP HPS executive committee used the survey results to develop 69 initial revised draft statements. After an online discussion with the international hospital pharmacy community, including individuals from 28 countries representing all six World Health Organization regions, a final set of draft statements was prepared for the live discussion involving participants from 20 countries. The final 65 revised Basel Statements were voted on and accepted. CONCLUSION: Systematic revision of the FIP Basel Statements resulted in an updated reflection of aspirational goals for the future of hospital pharmacy practice. While this revision reflects the development of new goals for hospital pharmacy practice, the core principles of the Basel Statements remain an essential foundation for the discipline.

Cost-minimization analysis of imipenem/cilastatin versus meropenem in moderate to severe infections at a tertiary care hospital in Saudi Arabia.

AIM: The aim of this study was to compare the costs of management of moderate to severe infections in patients treated with imipenem/cilastatin (IC) and meropenem (MEM). Pharmacoeconomic studies in Saudi Arabia are scarce. The current hospital formulary contains 2 carbapenems: IC and MEM. These antibiotics share a similar spectrum of activity. There are conflicting reviews with regard to the relative cost-effectiveness of these two agents. METHODS: A retrospective, single-centre cohort study of 88 patients of IC versus MEM in moderate to severe infections was performed, applying cost-minimization analysis (CMA) methods. In accordance with CMA methods, the assumption of equivalent efficacy was first demonstrated by literature retrieved and appraised. Adult patients (⩾18 years old) diagnosed with moderate to severe infections, including skin and skin structure infections (SSIs), sepsis, intra-abdominal infections (IAIs), respiratory tract infections, urinary tract infections (UTIs) and hospital-acquired infections (HAIs), who were prescribed IC 500 mg every six hours intravenously (2 g per day) or MEM 1 g every eight hours (3 g per day), were included in the study. Only direct costs related to the management of the infections were included, in accordance with a payer perspective. RESULTS: Overall there was no difference in the mean total daily costs between IC (SAR 4784.46, 95% CI 4140.68, 5428.24) and MEM (4390.14, 95% CI 3785.82, 4994.45; p = 0.37). A significantly lower medicine acquisition cost per vial of IC was observed when compared to MEM, however there was a significantly higher cost attached to administration sets used in the IC group than the MEM group. Consultation, nursing and physician costs were not significantly different between the groups. No differences were observed in costs associated with adverse drug events (ADEs). CONCLUSION: This study has shown that while acquisition costs of IC at a dose of 500 mg q6 h may be lower than for MEM 1 g q8 h, mean total costs per day were not significantly different between IC and MEM, indicating that medicine costs are only a small element of the overall costs of managing moderate to severe infections.

Are new models needed to optimize the utilization of new medicines to sustain healthcare systems?

Medicines have made an appreciable contribution to improving health. However, even high-income countries are struggling to fund new premium-priced medicines. This will grow necessitating the development of new models to optimize their use. The objective is to review case histories among health authorities to improve the utilization and expenditure on new medicines. Subsequently, use these to develop exemplar models and outline their implications. A number of issues and challenges were identified from the case histories. These included the low number of new medicines seen as innovative alongside increasing requested prices for their reimbursement, especially for oncology, orphan diseases, diabetes and HCV. Proposed models center on the three pillars of pre-, peri- and post-launch including critical drug evaluation, as well as multi-criteria models for valuing medicines for orphan diseases alongside potentially capping pharmaceutical expenditure. In conclusion, the proposed models involving all key stakeholder groups are critical for the sustainability of healthcare systems or enhancing universal access. The models should help stimulate debate as well as restore trust between key stakeholder groups.

The Darwin Awards: sex differences in idiotic behaviour.

Sex differences in risk seeking behaviour, emergency hospital admissions, and mortality are well documented. However, little is known about sex differences in idiotic risk taking behaviour. This paper reviews the data on winners of the Darwin Award over a 20 year period (1995-2014). Winners of the Darwin Award must eliminate themselves from the gene pool in such an idiotic manner that their action ensures one less idiot will survive. This paper reports a marked sex difference in Darwin Award winners: males are significantly more likely to receive the award than females (P<0.0001). We discuss some of the reasons for this difference.

AGREE to disagree: critical appraisal and the publication of practice guidelines.

Treatment guidelines are important in influencing public policy, promoting distributive justice and advocating better healthcare delivery for those in need. With an increased frequency in publication of clinical guidelines in South Africa, there is a heightened responsibility to ensure the application of due process throughout their development and publication. The need for consensus opinion is critical in the application of evidence-based medicine principles, and clinical guidelines contribute fundamentally towards the process of decision making and prioritisation. The SAMJ has recognised these imperatives as well as the important role that guidelines play in setting standards for clinical practice. In fulfilling this obligation, this editorial introduces the journal's readership to the AGREE II instrument as an objective appraisal mechanism against which prospective clinical guidelines will be assessed prior to their publication.

Medicines shortages-unpicking the evidence from a year in South Africa.

Although medicines shortages are a persistent and challenging problem for all health systems, the reasons for such shortages vary considerably between settings. Understanding the range of problems encountered, and the specific reasons for each medicines shortage event, may help to identify the most appropriate systems-wide responses. South Africa's health system is, at this point, still clearly divided between a better-resourced private sector and an overwhelmed public sector. Medicines selection and procurement processes in the two sectors are markedly different. However, in both sectors there is a dearth of publicly accessible information about the incidence and consequences of medicines shortages. This brief report describes the medicines selection and procurement processes currently applied in South Africa's public health sector, and then describes the nature of the medicines shortages that have been experienced in the KwaZulu-Natal provincial health services between July 2012 and June 2013. The degree to which these shortages might have been managed differently, had the recommendations developed by the International Pharmaceutical Federation Summit on Medicines Shortages been implemented, is then explored.

Comparative efficacy of Lamivudine and emtricitabine: a systematic review and meta-analysis of randomized trials.

INTRODUCTION: Lamivudine and emtricitabine are considered equivalent by several guidelines, but evidence of comparable efficacy is conflicting. METHODS: We searched two databases up to June 30 2013 to identify randomized and quasi-randomized trials in which lamivudine and emtricitabine were used as part of combination antiretroviral therapy for treatment-naïve or experienced HIV-positive adult patients. We only included trials where partner drugs in the regimen were identical or could be considered to be comparable. We allowed for comparisons between tenofovir and abacavir provided the study population did not begin treatment with a viral load >100,000 copies/ml. RESULTS: 12 trials contributed 15 different randomized comparisons providing data on 2251 patients receiving lamivudine and 2662 patients receiving emtricitabine. Treatment success was not significantly different in any of the 12 trials. In the three trials that directly compared lamivudine and emtricitabine, the relative risk for achieving treatment success was non-significant (RR 1.03 95%CI 0.96-1.10). For all trials combined, the pooled relative risk for treatment success was not significantly different (RR 1.00, 95%CI 0.97-1.02). No heterogeneity was observed (I (2) = 0). Similarly, there was no difference in the pooled relative risk for treatment failure (RR 1.08, 95%CI 0.94-1.22, I (2) = 3.4%). CONCLUSIONS: The findings of this systematic review suggest that lamivudine and emtricitabine are clinically equivalent.