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The increasing number of bacterial infections globally that do not respond to any available antibiotics indicates a need to invest in—and ensure access to—new antibiotics, vaccines, and diagnostics. The traditional model of drug development, which depends on substantial revenues to motivate investment, is no longer economically viable without push and pull incentives. Moreover, drugs developed through these mechanisms are unlikely to be affordable for all patients in need, particularly in low-income and middle-income countries. New, publicly funded models based on public–private partnerships could support investment in antibiotics and novel alternatives, and lower patients' out-of-pocket costs, making drugs more accessible. Cost reductions can be achieved with public goods, such as clinical trial networks and platform-based quality assurance, manufacturing, and product development support. Preserving antibiotic effectiveness relies on accurate and timely diagnosis; however scaling up diagnostics faces technological, economic, and behavioural challenges. New technologies appeared during the COVID-19 pandemic, but there is a need for a deeper understanding of market, physician, and consumer behaviour to improve the use of diagnostics in patient management. Ensuring sustainable access to antibiotics also requires infection prevention. Vaccines offer the potential to prevent infections from drug-resistant pathogens, but funding for vaccine development has been scarce in this context. The High-Level Meeting of the UN General Assembly in 2024 offers an opportunity to rethink how research and development can be reoriented to serve disease management, prevention, patient access, and antibiotic stewardship.

Hypertension remains the leading cause of cardiovascular disease worldwide and disproportionately impacts patients living in low- and middle-income countries (LMICs). Telemedicine offers a potential solution for improving access to health care for vulnerable patients in LMICs. The purpose of this scoping review was to summarize the evidence for telemedicine interventions for blood pressure management in LMICs and assess the relationships between the telemedicine intervention characteristics and clinical outcomes. Published studies were identified from the following databases (from their inception to May 2020): PubMed, Scopus, and Embase. Search terms related to \"Low and Middle Income Countries,\" \"Telemedicine,\" and \"Hypertension\" were used, and clinical outcomes were extracted from the screened articles. Our search resulted in 530 unique articles, and 14 studies were included in this review. Five studies assessed telemedicine interventions for patient-provider behavioral counseling, four assessed patient-provider medical management, and five assessed provider-provider consultation technologies. Out of fourteen individual studies, eleven demonstrated a significant improvement in systolic or diastolic blood pressure in the intervention group. Of the eight studies that reported difference-in-differences changes in systolic blood pressure, between-arm differences ranged from 13.2 mmHg to 0.4 mmHg. The majority of the studies in this review demonstrated a significant reduction in blood pressure with use of the telemedicine intervention, though the magnitude of benefit was not consistently large. Limitations of the studies included small sample sizes, short duration, and intervention heterogeneity. Current evidence suggests that telemedicine may provide a promising approach to increase access to care and improve outcomes for hypertension in LMICs, especially during events that limit access to in-person care, such as the COVID-19 pandemic. However, high-quality clinical trials of sufficient size and duration are needed to establish the impact and role of telemedicine in hypertension care. The protocol for this review was not registered.

Carbapenem-resistant Gram-negative (CRGN) bacterial infections are an urgent health threat, especially in low-income and middle-income countries (LMICs), where they are rarely detected and might not be treated appropriately given inadequate health system capacity. To understand this treatment gap, we estimated the total number of CRGN bacterial infections requiring an active agent and the number of individuals potentially initiated on appropriate treatment in eight large LMICs. For eight selected countries (Bangladesh, Brazil, Egypt, India, Kenya, Mexico, Pakistan, and South Africa), we estimated deaths associated with CRGN bacterial infections (that were not susceptible to other antibiotics) in 2019 using data from the Global Burden of Disease 2021 study on antimicrobial resistance. We used estimates from the literature to establish infection type-specific case fatality rates and an overall case fatality rate for CRGN bacterial infections. The total number of CRGN bacterial infections requiring an active agent could then be calculated by dividing the total number of CRGN bacterial infection-related deaths by the overall case fatality rate. We estimated the treatment gap (ie, the number of individuals with CRGN bacterial infections who were not appropriately treated) by subtracting from the total number of infections the number of individuals who initiated appropriate treatment, which was estimated using 2019 IQVIA sales data for six antibiotics active against CRGN bacteria, corrected to account for IQVIA's partial data coverage for each country and dose-adjusted by age. In 2019, in the eight selected countries, we estimated that there were 1 496 219 CRGN bacterial infections (95% CI 1 365 392–1 627 047) but that only 103 647 treatment courses were procured. The resulting treatment gap (1 392 572 cases [95% CI 1 261 745–1 523 400]) meant that only 6·9% of patients were treated appropriately. The treatment gap persisted even when we used more restrictive assumptions. The most-procured antibiotic was tigecycline (intravenous; 47 531 [45·9%] of 103 647 courses). India procured most of the treatment courses (83 468 [80·5%] courses), with 7·8% of infections treated appropriately (treatment gap 982 848 cases [95% CI 909 291–1 056 405]). The rates of appropriate treatment coverage were highest in Mexico (5634 [5·4%] courses procured; treatment gap 32 141 cases [30 416–33 867]) and Egypt (7572 [7·3%] courses procured; treatment gap 43 258 cases [38 742–47 774]), both with 14·9% of infections treated appropriately. Infections caused by CRGN bacteria are likely to be significantly undertreated in LMICs. To close this treatment gap, improved access to diagnostics and antibiotics, strengthening of health systems, and research to identify gaps in the treatment pathway are needed. Global Antibiotic Research and Development Partnership, supported by the Governments of Canada, Germany, Japan, Monaco, the Netherlands, Switzerland, and the UK, and by the Canton of Geneva, the EU, the Bill & Melinda Gates Foundation, Global Health EDCTP3, GSK, the RIGHT Foundation, the South African Medical Research Council, and Wellcome.

Securing access to effective antimicrobials is one of the greatest challenges today. Until now, efforts to address this issue have been isolated and uncoordinated, with little focus on sustainable and international solutions. Global collective action is necessary to improve access to life-saving antimicrobials, conserving them, and ensuring continued innovation. Access, conservation, and innovation are beneficial when achieved independently, but much more effective and sustainable if implemented in concert within and across countries. WHO alone will not be able to drive these actions. It will require a multisector response (including the health, agriculture, and veterinary sectors), global coordination, and financing mechanisms with sufficient mandates, authority, resources, and power. Fortunately, securing access to effective antimicrobials has finally gained a place on the global political agenda, and we call on policy makers to develop, endorse, and finance new global institutional arrangements that can ensure robust implementation and bold collective action.

Background The detection and quantification of hepatitis B (HBV) DNA and hepatitis C (HCV) RNA in whole blood collected on dried blood spots (DBS) may facilitate access to diagnosis and treatment of HBV and HCV infection in resource-poor settings. We evaluated the diagnostic performance of DBS compared to venous blood samples for detection and quantification of HBV-DNA and HCV-RNA in two systematic reviews and meta-analyses on the diagnostic accuracy of HBV DNA and HCV RNA from DBS compared to venous blood samples. Methods We searched MEDLINE, Embase, Global Health, Web of Science, LILAC and Cochrane library for studies that assessed diagnostic accuracy with DBS. Heterogeneity was assessed and where appropriate pooled estimates of sensitivity and specificity were generated using bivariate analyses with maximum likelihood estimates and 95% confidence intervals. We also conducted a narrative review on the impact of varying storage conditions or different cut-offs for detection from studies that undertook this in a subset of samples. The QUADAS-2 tool was used to assess risk of bias. Results In the quantitative synthesis for diagnostic accuracy of HBV-DNA using DBS, 521 citations were identified, and 12 studies met the inclusion criteria. Overall quality of studies was rated as low. The pooled estimate of sensitivity and specificity for HBV-DNA was 95% (95% CI: 83–99) and 99% (95% CI: 53–100), respectively. In the two studies that reported on cut-offs and limit of detection (LoD) – one reported a sensitivity of 98% for a cut-off of ≥2000 IU/ml and another reported a LoD of 914 IU/ml using a commercial assay. Varying storage conditions for individual samples did not result in a significant variation of results. In the synthesis for diagnostic accuracy of HCV-RNA using DBS, 15 studies met the inclusion criteria, and this included six additional studies to a previously published review. The pooled sensitivity and specificity was 98% (95% CI:95–99) and 98% (95% CI:95–99.0), respectively. Varying storage conditions resulted in a decrease in accuracy for quantification but not for reported positivity. Conclusions These findings show a high level of diagnostic performance for the use of DBS for HBV-DNA and HCV-RNA detection. However, this was based on a limited number and quality of studies. There is a need for development of standardized protocols by manufacturers on the use of DBS with their assays, as well as for larger studies on use of DBS conducted in different settings and with varying storage conditions.

Background Dried blood spots (DBS) are a convenient tool to enable diagnostic testing for viral diseases due to transport, handling and logistical advantages over conventional venous blood sampling. A better understanding of the performance of serological testing for hepatitis C (HCV) and hepatitis B virus (HBV) from DBS is important to enable more widespread use of this sampling approach in resource limited settings, and to inform the 2017 World Health Organization (WHO) guidance on testing for HBV/HCV. Methods We conducted two systematic reviews and meta-analyses on the diagnostic accuracy of HCV antibody (HCV-Ab) and HBV surface antigen (HBsAg) from DBS samples compared to venous blood samples. MEDLINE, EMBASE, Global Health and Cochrane library were searched for studies that assessed diagnostic accuracy with DBS and agreement between DBS and venous sampling. Heterogeneity of results was assessed and where possible a pooled analysis of sensitivity and specificity was performed using a bivariate analysis with maximum likelihood estimate and 95% confidence intervals (95%CI). We conducted a narrative review on the impact of varying storage conditions or limits of detection in subsets of samples. The QUADAS-2 tool was used to assess risk of bias. Results For the diagnostic accuracy of HBsAg from DBS compared to venous blood, 19 studies were included in a quantitative meta-analysis, and 23 in a narrative review. Pooled sensitivity and specificity were 98% (95%CI:95%–99%) and 100% (95%CI:99–100%), respectively. For the diagnostic accuracy of HCV-Ab from DBS, 19 studies were included in a pooled quantitative meta-analysis, and 23 studies were included in a narrative review. Pooled estimates of sensitivity and specificity were 98% (CI95%:95–99) and 99% (CI95%:98–100), respectively. Overall quality of studies and heterogeneity were rated as moderate in both systematic reviews. Conclusion HCV-Ab and HBsAg testing using DBS compared to venous blood sampling was associated with excellent diagnostic accuracy. However, generalizability is limited as no uniform protocol was applied and most studies did not use fresh samples. Future studies on diagnostic accuracy should include an assessment of impact of environmental conditions common in low resource field settings. Manufacturers also need to formally validate their assays for DBS for use with their commercial assays.

Hypertension is the most important risk factor for cardiovascular diseases (CVDs), which are the leading global cause of death. Hypertension is under-diagnosed and under-treated in most low- and middle-income countries (LMICs). Current algorithms for hypertension treatment are complex for the healthcare worker, limit decentralization, complicate procurement and often translate to a large pill burden for the person with hypertension. We summarize evidence supporting implementation of simple, algorithmic, accessible, non-toxic and effective (SAANE) algorithms to provide a feasible way to access and maintain quality care for hypertension. Implementation of these algorithms will enable task shifting to less specialised health care workers and lay cadres, provision of fixed dose combinations, consolidation of the market while retaining generic competition, simplification of laboratory requirements, and lowering costs for health systems and people who incur out of pocket expenses.

Over 1 million children aged 0 to 14 years were estimated to develop tuberculosis in 2021, resulting in over 200,000 deaths. Practical interventions are urgently needed to improve diagnosis and antituberculosis treatment (ATT) initiation in children aged 0 to 14 years and to increase coverage of tuberculosis preventive therapy (TPT) in children at high risk of developing tuberculosis disease. The multicountry CaP-TB intervention scaled up facility-based intensified case finding and strengthened household contact management and TPT provision at HIV clinics. To add to the limited health-economic evidence on interventions to improve ATT and TPT in children, we evaluated the cost-effectiveness of the CaP-TB intervention. We analysed clinic-level pre/post data to quantify the impact of the CaP-TB intervention on ATT and TPT initiation across 9 sub-Saharan African countries. Data on tuberculosis diagnosis and ATT/TPT initiation counts with corresponding follow-up time were available for 146 sites across the 9 countries prior to and post project implementation, stratified by 0 to 4 and 5 to 14 year age-groups. Preintervention data were retrospectively collected from facility registers for a 12-month period, and intervention data were prospectively collected from December 2018 to June 2021 using project-specific forms. Bayesian generalised linear mixed-effects models were used to estimate country-level rate ratios for tuberculosis diagnosis and ATT/TPT initiation. We analysed project expenditure and cascade data to determine unit costs of intervention components and used mathematical modelling to project health impact, health system costs, and cost-effectiveness. Overall, ATT and TPT initiation increased, with country-level incidence rate ratios varying between 0.8 (95% uncertainty interval [UI], 0.7 to 1.0) and 2.9 (95% UI, 2.3 to 3.6) for ATT and between 1.6 (95% UI, 1.5 to 1.8) and 9.8 (95% UI, 8.1 to 11.8) for TPT. We projected that for every 100 children starting either ATT or TPT at baseline, the intervention package translated to between 1 (95% UI, -1 to 3) and 38 (95% UI, 24 to 58) deaths averted, with a median incremental cost-effectiveness ratio (ICER) of US$634 per disability-adjusted life year (DALY) averted. ICERs ranged between US$135/DALY averted in Democratic of the Congo and US$6,804/DALY averted in Cameroon. The main limitation of our study is that the impact is based on pre/post comparisons, which could be confounded. In most countries, the CaP-TB intervention package improved tuberculosis treatment and prevention services for children aged under 15 years, but large variation in estimated impact and ICERs highlights the importance of local context. This evaluation is part of the TIPPI study, registered with ClinicalTrials.gov (NCT03948698).

Maternal complete heart block can pose significant challenges for the anesthesiologist in the antepartum, peripartum, and postpartum periods. Some patients may present for the first time in the puerperium with dizziness, weakness, syncope, or congestive heart failure as a result of the additional hemodynamic burden that accompanies pregnancy. Although there is an increase in permanent pacemaker placement in young symptomatic patients before pregnancy, prophylactic placement of pacemakers in asymptomatic parturients is not always indicated. The need for temporary or permanent pacemakers in asymptomatic women should be assessed on a case-by-case basis; many of these patients may be safely managed during labor and delivery without pacing. The parturient with complete heart block must be followed vigilantly during pregnancy and post delivery, as the need for pacemaker insertion can also arise in the postpartum period. We present a case of third-degree heart block in a 26-year-old parturient. •Complete heart block may present for the first time in pregnancy.•Placement of pacemakers in these patients is controversial.•It is essential to maintain hemodynamic stability in the peripartum period.