() presents significant clinical challenges. This study evaluated the synergistic effects of a β-lactam and β-lactamase inhibitor combination against and explored the underlying mechanisms. Synergy was assessed through MIC tests and time-kill studies, and binding affinities of nine β-lactams and BLIs to eight target receptors (L,D-transpeptidases [LDT] 1-5, D,D-carboxypeptidase, penicillin-binding protein [PBP] B, and PBP-lipo) were assessed using mass spectrometry and kinetic studies. Thermal stability and morphological changes were determined. Imipenem demonstrated high binding affinity to LDTs and PBPs, with extremely low inhibition constants (; ≤0.002 mg/L for LDT1-2, ≤0.6 mg/L for PBPs), while cephalosporins, sulopenem, tebipenem, and amoxicillin exhibited moderate to low binding affinity. Durlobactam inactivated Bla and LDT/PBPs more potently than avibactam. The s of durlobactam for PBP B, PBP-lipo, and LDT2 were below clinically achievable unbound concentrations, while avibactam’s for LDT/PBPs exceeded the clinical concentrations. Single β-lactam treatments resulted in minimal killing (~1 log reduction). Although avibactam yielded no effect, combinations with avibactam showed a significant reduction (~4 log CFU/mL). Durlobactam alone showed ~2 log reduction, and when combined with imipenem or two β-lactams, durlobactam achieved near-eradication of , surpassing the current therapy (amikacin + clarithromycin + imipenem/cefoxitin). Inactivation of PBP-lipo by sulopenem, imipenem, durlobactam, and amoxicillin (with avibactam) led to morphological changes, showing filaments. This study demonstrates the mechanistic basis of combinations therapy, particularly imipenem + durlobactam, in overcoming β-lactam resistance in .

There is a dearth of evidence regarding the global economic burden of ischaemic heart diseases (IHDs). This systematic review aims to synthesise national-level studies worldwide quantifying the economic burden of IHDs from a provider’s perspective.

Stand-alone HIV clinics in sub-Saharan Africa (SSA) have effectively expanded antiretroviral therapy since the 2000s, transforming HIV from a deadly infection into a chronic condition. However, over the past decade, there has been a significant rise in the prevalence of non-communicable diseases (NCDs) globally and in SSA. People living with HIV are at higher risk for some NCDs, including hypertension, diabetes and different cancers. The region’s current healthcare infrastructure is not equipped to address this growing burden. Integrating health services for HIV and NCDs (ie, combining services for HIV with services for hypertension, diabetes, depression and mental health, substance use disorder or cancer) could be one strategy for responding to these challenges. In this scoping review, we aim to identify randomised controlled trials on HIV-NCD integration, assess implemented integration models and measured outcomes and highlight evidence gaps.

Maternal mortality remains a large challenge in global health. Learning from the experience of similar countries can help to accelerate progress. In this analysis we develop a typology of country groupings for maternal health and provide guidance on how policy implications vary by country typology. We used estimates from the Global Maternal Health (GMatH) microsimulation model, which was empirically calibrated to a range of fertility, process, and mortality indicators and provides estimates for 200 countries and territories. We used the 2022 estimates of the maternal mortality ratio (MMR) and lifetime risk of maternal death (LTR) and used a k-means clustering algorithm to define groups of countries based on these indicators. We estimated the means of other maternal indicators for each group, as well as the mean impact of different policy interventions. We identified 7 groups (A-G) of country typologies with different salient features. High burden countries (A-B) generally have MMRs above 500 and LTRs above 2%, and account for nearly 25% of global maternal deaths. Countries in these groups are estimated to benefit most from improving access to family planning and increasing facility births. Middle burden countries (C-E) generally have MMRs between 100-500 and LTRs between 0.5%-3%. Countries in these groups account for 55% of global maternal deaths and would benefit most from increasing facility births and improving quality of care. Low burden countries (F-G) generally have MMRs below 100 and LTRs below 0.5%, account for 20% of global maternal deaths, and would benefit most from improving access to family planning and community-based interventions and linkages to care. Indicators vary widely across groups, but also within groups, highlighting the importance of considering multiple indicators when assessing progress in maternal health. Policy impacts also differ by country typology, providing policymakers with information to help prioritize interventions.

It remains unclear if and how body mass index (BMI) levels have changed over time in HIV endemic regions. We described trends in mean BMI and prevalence of overweight between 2003-2019 in 10 countries in Africa including people living with (PLWH) and without (PLWoH) HIV. We pooled Demographic and Health Surveys (DHS) from countries where ≥2 surveys >4 years apart were available with height/weight measurements and HIV tests. HIV status was ascertained with a finger-prick dried blood spot (DBS) specimen tested in a laboratory. The DBS is taken as part of the regular DHS procedures. We summarized age and socioeconomic status standardized sex-specific mean BMI (kg/m2) and prevalence of overweight (BMI ≥25 kg/m2) by HIV status. We fitted country-level meta-regressions to ascertain if changes in ART coverage were correlated with changes in BMI. Before 2011, women LWH (22.9 [95% CI: 22.2-23.6]) and LWoH (22.6 [95% CI: 22.3-22.8]) had similar mean BMI. Over time, mean BMI increased more in women LWH (+0.8 [95% CI: 0.7-0.8] BMI units) than LWoH (+0.2 [95% CI: 0.2-0.3]). Before 2013, the mean BMI was similar between men LWH (21.1 (95% CI: 20.3-21.9)) and LWoH (20.8 (95% CI: 20.6-21.1)). Over time, mean BMI increased more in men LWoH (+0.3 [95% CI: 0.3-0.3]) than LWH (+0.1 [95% CI: 0.1-0.1]). The same profile was observed for prevalence of overweight. ART coverage was not strongly associated with BMI changes. Mean BMI and prevalence of overweight were similar in PLWH and PLWoH, yet in some cases the estimates for PWLH were on track to catch up with those for PLWoH. BMI monitoring programs are warranted in PLWH to address the rising BMI trends.

The medical literature has demonstrated that macro-variables and social factors can influence suicide rates. Additionally, social science literature has shown that women in prominent political positions (such as mayors) can influence the behavior of other women. The purpose of our work is to demonstrate that women in such positions reduce suicide rates within a group affected by gender inequality: married women.

Observational studies are critical tools in clinical research and public health response, but challenges arise in ensuring the data produced by these studies are scientifically robust and socially valuable. Resolving these challenges requires careful attention to prioritising the most valuable research questions, ensuring robust study design, strong data management practices, expansive community engagement, and access and benefit sharing of results and research materials. This paper opens with a discussion of how well-designed observational studies contribute to biomedical evidence and provides examples from across the clinical literature of how these methods generate hypotheses for future research and uncover otherwise unattainable insights by providing examples from across the clinical literature. Then, we present obstacles that remain in ensuring observational studies are optimally designed, conducted and communicated.