Since the inception of World AIDS Day in 1988, advances with antiretroviral drugs have revolutionized the landscape of HIV/AIDS treatment and prevention. In 2025, we reflect on progress made, highlight promising therapeutic developments, and look ahead to what is needed to end the AIDS epidemic.
The Global Burden of Disease 2023 represents the most comprehensive iteration of its kind since first reported in 1993. Despite improved health monitoring, data acquisition, and analytical methods, its expansion creates new challenges and opportunities for improving its accuracy, completeness, external validity, and policy relevance.
Background: Implant revision is an operation with exchange of implants, and is used as a standard outcome after total hip replacement (THR), but may not fully represent the patient experience after a THR. Major reoperation (hereafter referred to as 'reoperation') without revision of implants can also lead to increased patient morbidity and mortality, and most commonly occurs when the femur fractures around an implant (postoperative periprosthetic femoral fractures; POPFF) and is treated with fixation and the implant is left in place. Reliance on revision metrics that do not capture these reoperations has led to large-scale underreporting of reoperations in THR, and is likely to have affected implant performance estimates, which have guided national policy and implant selection. It is important to include these additional reoperations when estimating treatment success to guide innovation and clinical practice. We aimed to estimate the incidence of reoperation following primary THR.
Methods and findings: We performed a large national cohort study on a mandatory, prospective database, the National Joint Registry, linked to Hospital Episode Statistics. All linkable primary THRs using recently available implants, with highest safety ratings between 01/01/2010 and 31/12/2020, were included. Major reoperation was defined as the first revision for any cause or fixation of POPFF and was identified using a combination of procedural and diagnosis codes. We identified 372,967 THRs representing 2,127,464 prostheses years at risk with a median follow-up time of 5.39 years (range 0 to 12.1 years). A total of 8,043 reoperations were identified that had been surgically treated by revision for any cause or fixation of POPFF. The incidence of reoperation was 3.78% (95% confidence interval [CI 3.70%, 3.86%]) per 1,000 prostheses years in comparison to 3.00% (95% CI [2.93%, 3.07%]) per 1,000 prostheses years when using conventional revision only outcomes. Cumulative incidence of major reoperation at 10 years was 3.1% (95% CI [3.0%, 3.1%]). Cumulative reoperation estimates were stratified by age and sex. In men aged 68 years and older, collared cementless stems performed better than cemented stems and in women aged 75 years and older, the relationship was reversed. Residual differences in patient characteristics may affect the accuracy of the estimates.
Conclusions: Treatment failure after THR has been underrepresented by revision-only estimates. Major reoperation rates in older men were lowest with cementless collared stems, and in older women, reoperation rates were lowest with cemented polished taper stems made of stainless steel. These results prompt a review of the current implant guidance for hip replacements in older patients.
Level of evidence: III (Retrospective cohort study).
The discovery of insulin transformed type 1 diabetes from an acutely lethal illness to a chronic disease that is managed with insulin dependence. Now, exciting developments in preventive treatments and stem cell-based therapies bring the prospects of arresting the disease and achieving insulin independence for type 1 diabetics closer to reality.
Background: Major fetal anomalies are an important cause of perinatal morbidity and mortality. While routine second-trimester ultrasound screening around 20 weeks is the current standard, advances in imaging have enabled earlier anatomical assessment in the first trimester. Despite increasing practice of early screening in England, there is no national policy recommending first-trimester anatomical evaluation, and little is known about its impact on detection rates at population level. Our aim was to examine if different policies of fetal anatomical ultrasound practice have an impact on earlier diagnosis of major fetal anomalies.
Methods and findings: We conducted a nationwide, population-based study linking data from a national survey of first-trimester ultrasound protocols in all NHS maternity units in England with congenital anomaly registration data from the National Congenital Anomaly and Rare Disease Registration Service (NCARDRS) for pregnancies between April 2017 and March 2019. NHS trusts were classified into four protocol groups: no anatomical assessment, basic, advanced, and extended anatomical protocols. We evaluated the proportion of 14 predefined major congenital anomalies detected prior to 16 weeks' gestation across these groups. A total of 1,030,224 pregnancies were included from 110 NHS trusts (84% response rate), with 5,895 fetuses affected by one of the anomalies of interest. First-trimester anatomical assessment was routinely conducted in 75% of trusts, though the scope varied. Overall, 32.7% (95% CI 31.5-33.9) of anomalies were detected before 16 weeks, with detection rates increasing stepwise by protocol detail: 27.7% (95% CI 25.4-30.0) in trusts with no protocol to 40.4% (95% CI 37.3-43.4) in those with extended protocols (p < 0.0001 for trend). Conditions such as acrania, exomphalos, and gastroschisis were commonly detected early regardless of protocol, whereas for anomalies such as spina bifida, limb reduction defects, and major cardiac malformations, detection was significantly higher in centers employing detailed first-trimester anatomical protocols. Due to data access restrictions and confidentiality considerations, analyses were conducted at the level of protocol group rather than individual hospitals. Hospital-level characteristics, including sonographer expertise and patient population risk, could not be adjusted for and may act as confounders.
Conclusions: More detailed first-trimester anatomical screening protocols are associated with significantly higher early detection rates of major fetal anomalies. While current practices vary considerably across England, this study provides population-level evidence suggesting that systematic first-trimester screening could improve the timeliness of anomaly detection. These findings support the consideration of standardized national guidance to reduce inequity and enhance prenatal care.
Just as tuberculosis services were recovering after the COVID-19 pandemic disruptions, abrupt funding cuts by G7 nations are putting progress at risk. These trends, while perilous, also reveal a turning point toward a more equitable, resilient, and self-reliant TB response, led by high-burden countries.
Background: There is growing evidence that access to joint replacement surgery is being restricted based on body mass index (BMI) despite any formal recommendations. Our aim was to investigate the association between BMI and patient outcomes after elective primary shoulder replacement surgery to inform future commissioning and national guidance.
Methods and findings: In this population-based cohort study, patients aged 18-100 years having elective primary shoulder replacement surgery were identified using linked national joint registry and hospital data from public and private hospitals in the United Kingdom (2018-22) and Denmark (2006-21). The main outcome measure was mortality within 365 days of surgery. Secondary outcome measures included mortality within 90 days, serious adverse events within 90 days, and revision surgery within 4.5 years of surgery. The association between BMI and patient outcomes was assessed using flexible parametric survival models and logistic regression models, adjusting for age, sex, deprivation, main surgical indication and American Society of Anaesthesiologists (ASA) score. 15,320 and 5,446 shoulder replacement procedures from within the United Kingdom and Denmark, respectively, met the inclusion criteria. In the United Kingdom, the average age was 72.2 years, 68.3% were female and the average BMI was 29.4 kg/m2. In Denmark, the average age was 70.5 years, 65.3% were female and the average BMI was 28.0 kg/m2. There was a decreased risk of 365-day mortality in obese (BMI 40 kg/m2) patients (hazard ratio (HR) 0.40 [95%CI 0.21, 0.73]) and an increased risk in underweight (BMI < 18.5 kg/m2) patients (HR 1.18 [95%CI 1.06, 1.32]), compared to patients with BMI 21.75 kg/m2. Underweight patients had an increased risk of 90-day mortality (HR 1.69 [95%CI 1.14, 2.52]), 90-day serious adverse events (odds ratio 1.36 [95%CI 1.05, 1.77]) and revision surgery (HR 1.70 [95%CI 1.25, 2.33]). Increasing BMI was not associated with a significantly increased risk of any secondary outcome. The main limitation of this study was the high proportion of missing BMI data and the small case numbers for the underweight study population (n = 131[UK], 70[Denmark]).
Conclusions: Increasing BMI was associated with lower 365-day mortality, and no poorer outcomes after elective primary shoulder replacement surgery. This surgery is safe and effective in obese patients and access to shoulder replacements should not be restricted based on BMI alone. Clinicians and hospitals should be aware that underweight patients appear more at risk of mortality, serious adverse events and revision surgery after shoulder replacement.
Background: Assisted dying and euthanasia (ADE) for patients with psychiatric disorders or dementia have increased in jurisdictions where the practice is legal. In this study, we examine trends in euthanasia cases involving patients with these conditions in Belgium, where the law makes a distinction based on whether a patient's death is not expected in the foreseeable future (>12 months)-a common situation in cases of dementia or psychiatric disorders.
Methods and findings: We use data on all cases of euthanasia reported to the Federal Commission for the Control and Evaluation of Euthanasia from 2002 (when the legislation was introduced) to 2023 (N = 33,592). Psychiatric disorders and dementia represent 1.27% and 0.92% of all cases, respectively. Using time-series zero-inflated negative binomial regression, we model trends by first examining interactions between euthanasia reasons and year, then extending to three-way interactions with patients' characteristics. The model calculates change in count and is replicated with an offset to account for demographic changes and generate rates. Our results show that euthanasia for psychiatric disorders and dementia showed distinct trends over time. Although slightly increasing, euthanasia for psychiatric disorders followed trends similar to the other types of euthanasia (count = 1.00 [95%CI: 0.98; 1.03]-rate = 1.02 [95%CI: 0.99; 1.04]), while euthanasia cases for dementia increased faster than other types of euthanasia (count = 1.03 [95%CI: 1.00; 1.06]-rate = 1.04 [95%CI: 1.01;1.07]). Trends in euthanasia for dementia and psychiatric disorders coincide with demographic changes. While euthanasia rates for psychiatric disorders were initially higher among women, the rate among men has been increasing over time. Regional trends show higher overall euthanasia rates in the Dutch-speaking population, but with faster increases in the French-speaking population. A key limitation of this study is the lack of information on patients' socio-economic profiles.
Conclusions: In Belgium, between 2002 and 2023, there are distinct trends for euthanasia for non-terminal illnesses. Euthanasia for psychiatric disorders followed similar trends as euthanasia for terminal illnesses, whereas euthanasia cases involving cognitive conditions increased at a faster rate. Furthermore, there were gender and regional differences, which diminished over time.
Background: Uncertainties persist regarding the precise shape of the smoking-outcome curves across various cardiovascular and mortality endpoints. This study aims to elucidate the relationships among smoking burden, intensity, and cessation duration across multiple cardiovascular outcomes.
Methods and findings: Cox proportional hazard models were constructed to evaluate the association between pack-years, cigarettes per day (CPD), and years since cessation with cardiovascular outcomes in participants from 22 prospective cohort studies within the Cross-Cohort Collaboration Tobacco Working Group. We evaluated myocardial infarction (MI), stroke, coronary heart disease (CHD; MI, coronary revascularization, or coronary death), cardiovascular disease (CVD; stroke or cardiovascular death), heart failure (HF), atrial fibrillation (AFib), CHD mortality, CVD mortality, and all-cause mortality. Median follow-up varied across outcomes, with 14.4 years for MI (17,570 events), 19.3 years for CHD (30,625 events), 18.6 years for CVD (54,078 events), and approximately 19.4-19.9 years for mortality outcomes (CHD mortality: 17,429 events; CVD mortality: 33,120 events; all-cause mortality: 125,044 events). Spline terms were used to investigate the nonlinear association of continuous smoking/cessation measures with the examined outcomes. Models were adjusted for demographic, socioeconomic, and other cardiovascular risk factors. The study included 323,826 adults (148,635 non-mortality and 176,396 mortality outcomes with 25 and 16 million person-years at risk, respectively). Compared to never-smokers, current smokers had significantly increased risks for CVD (hazard ratio (HR) 1.74, 95% confidence intervals (CIs) [1.66,1.83] in men; HR 2.07, 95% CI [2.00,2.14] in women) and all-cause mortality (HR 2.17, 95% CI [2.09,2.25] in men; HR 2.43, 95% CI [2.38,2.48] in women; all p < 0.001). Compared with never-smokers, participants with 2-5 CPD demonstrated substantially elevated cardiovascular risks, with HR ranging from 1.26 (95% CI [1.09,1.45], p = 0.002) for AFib to 1.57 (95% CI [1.39,1.78], p < 0.001) for HF. Smoking 2-5 CPD was associated with increased CVD mortality (HR 1.57, 95% CI [1.41,1.75]), and all-cause mortality (HR 1.60, 95% CI [1.52,1.69]; both p < 0.001). Smoking 11-15 CPD conferred a higher risk of CVD (HR 1.87, 95% CI [1.69,2.06]) and all-cause mortality (HR 2.30, 95% CI [2.14,2.47]; both p < 0.001). The increased risk associated with the evaluated outcomes was steeper for the initial 20 pack-years and 20 CPD, respectively, compared to further smoking exposure. The most substantial reduction in risk across all outcomes was observed within the first 10 years after smoking cessation. However, the progressive risk reduction continues over extended time periods, with former smokers demonstrating over 80% lower relative risk than those of current smokers within 20 years of cessation. Limitations include potential exposu
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