Many low- and middle-income countries (LMIC) are moving towards enforcing prescription-only access to antibiotics. This systematic literature review aims to assess the interventions used to enforce existing legislation prohibiting over-the-counter (OTC) sales of antibiotics in LMICs, their impact and examine the methods chosen for impact measurement including their strengths and weaknesses. Both PubMed and Embase were systematically searched for studies reporting on impact measurement in moving towards prescription only access to antibiotics in LMICs. The PRISMA methodological review framework was used to ensure systematic data collection and analysis of literature. Narrative data synthesis was used due to heterogeneity of study designs. In total, 15 studies were included that assessed policy impact in 10 different countries. Strategies employed to enforce regulations prohibiting OTC sales of systemic antibiotics included retention of prescriptions for antibiotics by pharmacies, government inspections, engaging pharmacists in the design of interventions, media campaigns for the general public and educational activities for health care workers. A variety of outcomes was used to assess the policy impact; changes in antimicrobial resistance rates, changes in levels of antibiotic use, changes in trends of antibiotic use, changes in OTC supply of antibiotics, and changes in reported practices and knowledge of pharmacists, medicine sellers and the general public. Differences in methodological approaches and outcome assessment made it difficult to compare the effectiveness of law enforcement activities. Most effective appeared to be multifaceted approaches that involved all stakeholders. Monitoring of the impact on total sales of antibiotics by means of an interrupted time series (ITS) analysis and analysis of pharmacies selling antibiotics OTC using mystery clients were the methodologically strongest designs used. The published literature describing activities to enforce prescription-only access to antibiotics in LMICs is sparse and offers limited guidance. Most likely to be effective are comprehensive multifaceted interventions targeting all stakeholders with regular reinforcement of messages. Policy evaluation should be planned as part of implementation to assess the impact and effectiveness of intervention strategies and to identify targets for further activities. Robust study designs such as ITS analyses and mystery client surveys should be used to monitor policy impact.

Aims: To assess the association between concurrent use of potential pharmacokinetic or pharmacodynamic interacting drugs and major bleeding among direct oral anticoagulant (DOAC) users.Methods: We performed a case–control study nested in a cohort of new users of DOACs (dabigatran etexilate, apixaban or rivaroxaban). Data were obtained from the UK Clinical Practice Research Datalink linked to Hospital Episode Statistics (2008–2015). Cases were patients hospitalized having a primary diagnosis of major bleeding. Up to 4 controls were matched on age, sex, index date and region. Odds ratios (ORs) for the risk of major bleeding were assessed by conditional logistic regression analysis and adjusted for well‐known covariates for the risk of bleeding.Results: We identified 393 patients with a major bleeding from a total of 23 492 new users of DOACs and 1494 matched controls. Most subjects were users of rivaroxaban (58.8%) on the index date. The concurrent use of pharmacodynamic interacting drugs was associated with an increased risk of major bleeding (21.6% of cases vs 13.5% of controls, adjusted odds ratio [aOR] 1.92; 95% confidence interval [CI], 1.40–2.66). For the antiplatelet drugs the aOR was 2.01 (95% CI, 1.29–3.11) and for the selective serotonin reuptake inhibitors the aOR was 1.68 (95% CI, 1.10–2.59). We found no increased risk of major bleeding for concurrent use of pharmacokinetic interacting drugs vs DOACs alone (45.0 vs 51.2%; aOR: 0.77; 95% CI: 0.53–1.10).Conclusion: Among patients taking DOACs the concurrent use of antiplatelet drugs or selective serotonin reuptake inhibitors was associated with increased risk of major bleeding, while pharmacokinetic interacting drugs do not increase this risk.

Snakebites continue to be a public health concern in sub-Saharan Africa, where availability of appropriate medical treatment is rare, even though death and disability can be prevented with timely intervention. A challenge is the lack of sociopolitical studies to inform health policies. This study aimed to identify snakebite patient profiles, healthcare workers’ (HCWs) knowledge of snakebite, and facilities’ snakebite treatment capacity in Kenya, Uganda, and Zambia to inform interventions to improve access to appropriate treatment. The research comprised a cross-sectional key informant survey among HCWs from health facilities in Kenya (n = 145), Uganda (n = 144), and Zambia (n = 108). Data were collected between March 2018 and November 2019. Most of the HCWs suggested that the number of snakebite incidents was similar between the genders, that most patients were aged 21–30 years, and most people were bitten when farming or walking. Overall, only 12% of HCWs had received formal training in snakebite management. Only about 20% of HCWs in each country said their health facility had the medicines needed to treat snakebites, with antivenom available in 0–34% of facilities across the sectors and countries, and snakebites were not systematically recorded. This research shows that an integrative approach through policies to increase resource allocation for health system strengthening, including community education, HCW training, and improved access to snakebite treatment, is needed. Part of this approach should include regulations that ensure antivenoms available in health facilities meet quality control standards and that snakebites are accommodated into routine reporting systems to assess progress.

Objective: To establish the risk of major bleeding in direct oral anticoagulant (DOAC) users (overall and by class) versus vitamin K antagonist (VKA) users, using health care databases from four European countries and six provinces in Canada.Methods: A retrospective cohort study was performed according to a similar protocol. First‐users of VKAs or DOACs with a diagnosis of non‐valvular atrial fibrillation (NVAF) were included. The main outcome of interest was major bleeding and secondary outcomes included gastrointestinal (GI) bleeding and intracranial haemorrhage (ICH). Incidence rates of events per 1000 person years were calculated. Hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated using a Cox proportional hazard regression model. Exposure and confounders were measured and analysed in a time‐dependant way. Risk estimates were pooled using a random effect model.Results: 421 523 patients were included. The risk of major bleeding for the group of DOACs compared to VKAs showed a pooled HR of 0.94 (95% CI: 0.87–1.02). Rivaroxaban showed a modestly increased risk (HR 1.11, 95% CI: 1.06–1.16). Apixaban and dabigatran showed a decreased risk of respectively HR 0.76 (95% CI: 0.69–0.84) and HR 0.85 (95% CI: 0.75–0.96).Conclusions: This study confirms that the risk of major bleeding of DOACs compared to VKAs is not increased when combining all DOACs. However, we observed a modest higher risk of major bleeding for rivaroxaban, whereas for apixaban and dabigatran lower risks of major bleeding were observed compared to VKAs.

Aims: The introduction of direct oral anticoagulants (DOACs) has broadened the treatment arsenal for nonvalvular atrial fibrillation, but observational studies on the benefit–risk balance of DOACs compared to vitamin K antagonists (VKAs) are needed. The aim of this study was to characterize the risk of major bleeding in DOAC users using longitudinal data collected from electronic health care databases from 4 different EU‐countries analysed with a common study protocol.Methods: A cohort study was conducted among new users (≥18 years) of DOACs or VKAs with nonvalvular atrial fibrillation using data from the UK, Spain, Germany and Denmark. The incidence of major bleeding events (overall and by bleeding site) was compared between current use of DOACs and VKAs. Cox regression analysis was used to calculate hazard ratios and 95% confidence intervals (CI) and adjust for confounders.Results/Conclusion: Overall, 251 719 patients were included across the 4 study cohorts (mean age ~75 years, % females between 41.3 and 54.3%), with overall hazard ratios of major bleeding risk for DOACs vs VKAs ranging between 0.84 (95% CI: 0.79–0.90) in Denmark and 1.13 (95% CI 1.02–1.25) in the UK. When stratifying according to the bleeding site, risk of gastrointestinal bleeding was increased by 48–67% in dabigatran users and 30–50% for rivaroxaban users compared to VKA users in all data sources except Denmark. Compared to VKAs, apixaban was not associated with an increased risk of gastrointestinal bleeding in all data sources and seemed to be associated with the lowest risk of major bleeding events compared to dabigatran and rivaroxaban.

• Research on policies promoting price transparency is scarce and (partially) inconclusive. • Public disclosure of medicine prices could be effective in reducing prices. • More robust evidence is needed to confirm the effects of these policies. • Future research should also focus on unintended effects of these policies.