Introduction: There are positive aspects regarding the prescribing of fixed dose combinations (FDCs) versus prescribing the medicines separately. However, these have to be balanced against concerns including increased costs and their irrationality in some cases. Consequently, there is a need to review their value among lower- and middle-income countries (LMICs) which have the greatest prevalence of both infectious and noninfectious diseases and issues of affordability. Areas covered: Review of potential advantages, disadvantages, cost-effectiveness, and availability of FDCs in high priority disease areas in LMICs and possible initiatives to enhance the prescribing of valued FDCs and limit their use where there are concerns with their value. Expert commentary: FDCs are valued across LMICs. Advantages include potentially improved response rates, reduced adverse reactions, increased adherence rates, and reduced costs. Concerns include increased chances of drug:drug interactions, reduced effectiveness, potential for imprecise diagnoses and higher unjustified prices. Overall certain FDCs including those for malaria, tuberculosis, and hypertension are valued and listed in the country’s essential medicine lists, with initiatives needed to enhance their prescribing where currently low prescribing rates. Proposed initiatives include robust clinical and economic data to address the current paucity of pharmacoeconomic data. Irrational FDCs persists in some countries which are being addressed.

The effectiveness of ketamine as adjunctive or monotherapy for post-intubation sedation in adults with trauma on mechanical ventilation is unclear. A rapid review of systematic reviews of randomized controlled trials, then randomized controlled trials or observational studies was conducted searching three electronic databases (PubMed, Embase, Cochrane Library) and one clinical trial registry on June 1, 2022. We used a prespecified protocol following Cochrane rapid review methods. We identified eight systematic reviews of randomized controlled trials and observational studies. Among the included reviews, only the most relevant, up to date, highest quality-assessed reviews and reviews that reported on critical outcomes were considered. Adjunctive ketamine showed a morphine sparing effect (MD −13.19 µmg kg^–1 h^–1, 95 % CI −22.10 to −4.28, moderate certainty of evidence, 6 RCTs), but no to little effect on midazolam sparing effect (MD 0.75 µmg kg^–1 h^–1, 95 % CI −1.11 to 2.61, low certainty of evidence, 6 RCTs) or duration of mechanical ventilation in days (MD −0.17 days, 95 % CI −3.03 to 2.69, moderate certainty of evidence, 3 RCTs). Adjunctive ketamine therapy may reduce mortality (OR 0.88, 95 % CI 0.54 to 1.43, P = 0.60, very low certainty of evidence, 5 RCTs, n = 3076 patients) resulting in 30 fewer deaths per 1000, ranging from 132 fewer to 87 more, but the evidence is very uncertain. Ketamine results in little to no difference in length of ICU stay (MD 0.04 days, 95 % CI −0.12 to 0.20, high certainty of evidence, 5 RCTs n = 390 patients) or length of hospital stay (MD −0.53 days, 95 % CI −1.36 to 0.30, high certainty of evidence, 5 RCTs, n = 277 patients). Monotherapy may have a positive effect on respiratory and haemodynamic outcomes, however the evidence is very uncertain. Adjunctive ketamine for post-intubation analgosedation results in a moderate meaningful net benefit but there is uncertainty for benefit and harms as monotherapy.

Introduction: Academic–government partnerships are important to advance timely, responsive and relevant evidence for decision-making (policy, guideline, law and regulation) deliberations. Deliberate and strategic integrated knowledge translation (KT) approaches within such partnerships have been shown to facilitate evidence-informed decision-making (EIDM). We used Cochrane’s KT Framework to map and analyse COVID-19 response activities instituted by a strategic academic-government partnership to support EIDM during the COVID-19 pandemic in South Africa. Methods: We used Cochrane’s KT Framework to map and analyse COVID-19 response activities instituted by a strategic academic–government partnership to support EIDM during the COVID-19 pandemic in South Africa. The COVID-19 response activities included coproducing rapid therapeutics reviews, engaging stakeholders with review evidence, packaging and disseminating review products, facilitating access to rapid reviews for evidence users and adapting partnership processes for rapid review production. Results: This paper highlights the importance of (a) authentic partnerships between evidence producers and users (motivated by context-specific goals, trust and relationships); (b) intentional and systematic stakeholder engagement to promote the rapid exchange of information; (c) using tailored, responsive and relevant KT to promote the uptake of evidence and (d) monitoring and evaluating the implementation of KT to identify lessons learnt and adaptation of KT approaches. Conclusion: In responding to future emergencies, a comprehensive KT strategy, including the expertise of KT practitioners and science communicators to make evidence and guideline recommendations accessible, should be embedded. Additionally, streamlining bureaucratic processes for approving and communicating information; identifying and addressing decision-maker capacity needs; engaging a range of stakeholders and integrating KT in usual decision-making processes, is recommended. Adequate investment by governments is needed for sustaining KT approaches that can enhance EIDM for improving public health outcomes.

Background: South Africa has a high HIV incidence and oral pre-exposure prophylaxis (PrEP) is available as public-sector standard of care. Access to alternative prevention methods for women may further reduce HIV acquisition. Setting: South African public sector. Methods: We performed a systematic search for high-quality up-to-date guidelines recommending dapivirine rings as PrEP using the Grading of Recommendations Assessment, Development, and Evaluation-Adolopment process. We appraised the systematic review and randomized controlled trial (RCT) evidence underpinning the selected guideline's recommendations and conducted a cost-effectiveness analysis. The Grading of Recommendations Assessment, Development, and Evaluation evidence-to-decision framework guided the adaptation of source guideline recommendations, according to our local context. Results: We identified the 2021 World Health Organization PrEP Guidelines, informed by 2 placebo-controlled RCTs, which were included in a contemporaneous systematic review. There were 23 fewer HIV acquisitions per 1000 clients with dapivirine ring vs placebo (95% confidence interval: 10 to 34), with no increase in adverse events (moderate certainty evidence). We found no RCTs comparing dapivirine to oral PrEP or among adolescent/pregnant/breastfeeding clients. Dapivirine is less cost-effective than oral PrEP at $14.59/ring, at the current price. Conclusions: The source guideline recommendation was adapted for the local context. Dapivirine ring seems to be less efficacious than oral PrEP, although comparative studies are lacking. Data on adolescents and pregnancy are also lacking, currently limiting the use of dapivirine as an alternative for women unable to take oral PrEP. At the current price, dapivirine is not cost-effective and unaffordable for inclusion in the South African Essential Medicines List.

Medicines have been re-purposed as therapeutics for COVID-19 and it is with great interest that we read the publication entitled, “Effects of Vitamin D Supplementation on COVID-19 Related Outcomes: A Systematic Review and Meta-Analysis”

Background. Bipolar disorder (BD) is a severe mental illness associated with multimorbidity, psychosocial disability and significant public health issues. However, guideline heterogeneity clouds therapeutic decisions, particularly in relapse prevention. Polypharmacy and poor health outcomes are common. For low- and middle-income countries, deciding which medicines to procure and how to treat BD in an integrated manner remains elusive. Although South Africa (SA) is committed to universal health coverage, the estimated treatment gap for mental disorders in the public health sector is 91%. An Essential Medicines List (EML) enables equitable access to medicines, while Standard Treatment Guidelines (STGs) facilitate rational prescribing and quality care. Objectives. To describe the medicine selection process for the treatment of BD in the SA public health sector, and the treatment algorithms developed to guide integrated care. Methods. Evidence-based medicine principles, stakeholder consultation and consensus decision-making were used. The existing (2015) BD guideline and stakeholder comments were reviewed by a ministerially appointed expert review committee, following which a research question with eligibility criteria was formed, and rapid systematic evidence synthesis conducted. PubMed and Cochrane databases were searched for systematic reviews of randomised controlled trials and observational studies of acute and maintenance treatment in BD, with an additional PubMed search for primary research. Quality of the systematic reviews was appraised using the 11-item assessment of multiple systematic reviews. After costing to ensure affordability, final recommendations were made to the National EML Committee (NEMLC) using the strength of recommendation taxonomy classification. Following approval by the NEMLC, proposed medicines were incorporated into the 2019 National Department of Health Adult Hospital STGs. As the STGs are updated every 3 years, stakeholder input was sought in 2021 and 2023, with no changes to the medicine selection. Results. Seven systematic reviews and one observational study were included in the evidence synthesis. Six medicines were selected as essential for maintenance treatment: lithium, valproate, lamotrigine, olanzapine, quetiapine and clozapine. While risperidone and benzodiazepines were retained for acute mania, carbamazepine and fluoxetine were removed from acute depression. Treatment algorithms for predominantly manic and depressive courses of illness were constructed to encourage person-centred care, aiming for euthymia, individual functioning and relapse prevention. Conclusion. Evidence-based medicine principles enabled the NEMLC to select a range of essential medicines for the management of BD in a middle-income country. Local monitoring and evaluation are needed to inform future editions of the STGs and EML.