Large trials have shown that sodium glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of adverse kidney and cardiovascular outcomes in patients with heart failure or chronic kidney disease, or with type 2 diabetes and high risk of atherosclerotic cardiovascular disease. None of the trials recruiting patients with and without diabetes were designed to assess outcomes separately in patients without diabetes.

Timely diagnosis and treatment of HIV is crucial in HIV-exposed infants to prevent the high rates of mortality seen during the first 2 years of life if HIV is untreated. However, challenges with sample transportation, testing, and result delivery to caregivers have led to long delays in treatment initiation. We aimed to compare the clinical effect of point-of-care HIV testing versus laboratory-based testing (standard of care) in HIV-exposed infants.

Behavioural, cognitive, and pharmacological interventions can all be effective for insomnia. However, because of inadequate resources, medications are more frequently used worldwide. We aimed to estimate the comparative effectiveness of pharmacological treatments for the acute and long-term treatment of adults with insomnia disorder.

Estimates of the effectiveness of water, sanitation, and hygiene (WASH) interventions that provide high levels of service on childhood diarrhoea are scarce. We aimed to provide up-to-date estimates on the burden of disease attributable to WASH and on the effects of different types of WASH interventions on childhood diarrhoea in low-income and middle-income countries (LMICs).

Global road mortality is a leading cause of death in many low-income and middle-income countries. Data to support priority setting under current resource constraints are urgently needed to achieve Sustainable Development Goal (SDG) 3.6. This Series paper estimates the potential number of lives saved if each country implemented interventions to address risk factors for road injuries. We did a systematic review of all available evidence-based, preventive interventions for mortality reduction that targeted the four main risk factors for road injuries (ie, speeding, drink driving, helmet use, and use of seatbelt or child restraint). We used literature review variables and considered three key country-level variables (gross domestic product per capita, population density, and government effectiveness) to generate country-specific estimates on the potential annual attributable number of lives that would be saved by interventions focusing on these four risk factors in 185 countries. Our results suggest that the implementation of evidence-based road safety interventions that target the four main road safety risk factors could prevent between 25% and 40% of all fatal road injuries worldwide. Interventions addressing speed could save about 347 258 lives globally per year, and at least 16 304 lives would be saved through drink driving interventions. The implementation of seatbelt interventions could save about 121 083 lives, and 51 698 lives could be saved by helmet interventions. We identify country-specific estimates of the potential number of lives saved that would be attributable to these interventions. Our results show the potential effectiveness of the implementation and scaling of these interventions. This paper presents key evidence for priority setting on road safety interventions and shows a path for reaching SDG 3.6.

Excessive opioid prescribing after surgery has contributed to the current opioid crisis; however, the value of prescribing opioids at surgical discharge remains uncertain. We aimed to estimate the extent to which opioid prescribing after discharge affects self-reported pain intensity and adverse events in comparison with an opioid-free analgesic regimen.

Over the past two decades, global health diplomacy, foreign policy for health, and global health policy have changed substantially. Diplomacy is a constitutive part of the system of global health governance. COVID-19 hit the world when multilateral cooperation was subject to major challenges, and global health has since become integral to geopolitics. The importance of global health diplomacy, especially at WHO, in keeping countries jointly committed to improving health for everyone, has once again been shown. Through a systematic review, this Series paper explores how international relations concepts and theories have been applied to better understand the role of power in shaping positions, negotiations, and outcomes in global health diplomacy. We apply an international relations perspective to reflect on the effect that those concepts and theories have had on global health diplomacy over the past two decades. This Series paper argues that a more central role of international relations concepts and theories in analysing global health diplomacy would help develop a more nuanced understanding of global health policy making. However, the world has changed to an extent that was not envisioned in academic discourse. This shift calls for new international relations concepts and theories to inform global health diplomacy.

Schizophrenia is a common, severe, and usually chronic disorder. Maintenance treatment with antipsychotic drugs can prevent relapse but also causes side-effects. We aimed to compare the efficacy and tolerability of antipsychotics as maintenance treatment for non-treatment resistant patients with schizophrenia.

Knowing whether COVID-19 vaccine effectiveness wanes is crucial for informing vaccine policy, such as the need for and timing of booster doses. We aimed to systematically review the evidence for the duration of protection of COVID-19 vaccines against various clinical outcomes, and to assess changes in the rates of breakthrough infection caused by the delta variant with increasing time since vaccination.

Antimicrobial resistance (AMR) poses a major threat to human health around the world. Previous publications have estimated the effect of AMR on incidence, deaths, hospital length of stay, and health-care costs for specific pathogen-drug combinations in select locations. To our knowledge, this study presents the most comprehensive estimates of AMR burden to date.

Pharmacotherapy provides an option for adults with overweight and obesity to reduce their bodyweight if lifestyle modifications fail. We summarised the latest evidence for the benefits and harms of weight-lowering drugs.

Trials examining the benefit of thrombectomy in anterior circulation proximal large vessel occlusion stroke have enrolled patients considered to have salvageable brain tissue, who were randomly assigned beyond 6 h and (depending on study protocol) up to 24 h from time last seen well. We aimed to estimate the benefit of thrombectomy overall and in prespecified subgroups through individual patient data meta-analysis.

Understanding the spread of SARS-CoV-2, how and when evidence emerged, and the timing of local, national, regional, and global responses is essential to establish how an outbreak became a pandemic and to prepare for future health threats. With that aim, the Independent Panel for Pandemic Preparedness and Response has developed a chronology of events, actions, and recommendations, from December, 2019, when the first cases of COVID-19 were identified in China, to the end of March, 2020, by which time the outbreak had spread extensively worldwide and had been characterised as a pandemic. Datapoints are based on two literature reviews, WHO documents and correspondence, submissions to the Panel, and an expert verification process. The retrospective analysis of the chronology shows a dedicated initial response by WHO and some national governments, but also aspects of the response that could have been quicker, including outbreak notifications under the International Health Regulations (IHR), presumption and confirmation of human-to-human transmission of SARS-CoV-2, declaration of a Public Health Emergency of International Concern, and, most importantly, the public health response of many national governments. The chronology also shows that some countries, largely those with previous experience with similar outbreaks, reacted quickly, even ahead of WHO alerts, and were more successful in initially containing the virus. Mapping actions against IHR obligations, the chronology shows where efficiency and accountability could be improved at local, national, and international levels to more quickly alert and contain health threats in the future. In particular, these improvements include necessary reforms to international law and governance for pandemic preparedness and response, including the IHR and a potential framework convention on pandemic preparedness and response.

Before 2020, mental disorders were leading causes of the global health-related burden, with depressive and anxiety disorders being leading contributors to this burden. The emergence of the COVID-19 pandemic has created an environment where many determinants of poor mental health are exacerbated. The need for up-to-date information on the mental health impacts of COVID-19 in a way that informs health system responses is imperative. In this study, we aimed to quantify the impact of the COVID-19 pandemic on the prevalence and burden of major depressive disorder and anxiety disorders globally in 2020.

Mortality remains unacceptably high in patients with heart failure and reduced left ventricular ejection fraction (LVEF) despite advances in therapeutics. We hypothesised that a novel artificial intelligence approach could better assess multiple and higher-dimension interactions of comorbidities, and define clusters of β-blocker efficacy in patients with sinus rhythm and atrial fibrillation.

The educational attainment of parents, particularly mothers, has been associated with lower levels of child mortality, yet there is no consensus on the magnitude of this relationship globally. We aimed to estimate the total reductions in under-5 mortality that are associated with increased maternal and paternal education, during distinct age intervals.

Whether guided selection of antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI) is effective in improving outcomes compared with standard antiplatelet therapy remains controversial. We assessed the safety and efficacy of guided versus standard selection of antiplatelet therapy in patients undergoing PCI.

Preterm birth is a global health priority. Using a progestogen during high-risk pregnancy could reduce preterm birth and adverse neonatal outcomes.

Hearing loss affects access to spoken language, which can affect cognition and development, and can negatively affect social wellbeing. We present updated estimates from the Global Burden of Disease (GBD) study on the prevalence of hearing loss in 2019, as well as the condition's associated disability.

The clinical benefit of LDL cholesterol lowering treatment in older patients remains debated. We aimed to summarise the evidence of LDL cholesterol lowering therapies in older patients.