PLoS Medicine最新文献

Background: Estimating the proportion of individuals currently infected with Mycobacterium tuberculosis (Mtb) is key for informing global health policies. Although a substantial portion of the global population exhibit tuberculous immunoreactivity, not all have a viable Mtb infection. Moreover, individuals with recent infections are at a higher risk of developing tuberculosis (TB). Here, we present estimates of the global burden of viable Mtb infection, using new insights into the natural history of TB.

Methods and findings: We constructed country-specific trends in annual risk of infection considering estimates of TB burden, immunoreactivity reversion, and age-specific mixing. We applied these trends to a deterministic mathematical model incorporating reinfection and self-clearance to estimate recent (within 2 years) and total viable Mtb infections. Empirical data on self-clearance are limited, so rates were informed by modelling estimates. In 2022, we estimated that 133.7 million people (95% uncertainty interval [UI]: 104.0, 171.1) had a recent Mtb infection, representing 1.7% (95% UI: 1.3, 2.2) of the global population. In total, 288.9 million people (95% UI: 242.2, 342.7)-or 3.7% (95% UI: 3.1, 4.3) globally-were estimated to harbour a viable Mtb infection. Among those recently infected, 12.0% (95% UI: 11.4, 12.7) were children under 15 years of age. Most recent infections were found in the World Health Organization regions of South-East Asia (49.0%; 95% UI: 37.2, 62.4), the Western Pacific (19.7%; 95% UI: 12.6, 30.5), and Africa (17.9%; 95% UI: 12.9, 24.1). India, Indonesia, and China had the highest burden, with 39.1 million (95% UI: 18.0, 73.6), 12.0 million (95% UI: 5.8, 22.9), and 11.2 million (95% UI: 5.0, 25.5) people, respectively, recently infected with Mtb. Sensitivity analyses of varying self-clearance scenarios showed significant changes in global estimates of viable Mtb infection, particularly in total burden, with lower self-clearance rates. Overall uncertainty in the estimates was considerable, reflecting limitations in the underlying data informing key model parameters.

Conclusions: Our findings offer global burden estimates of viable Mtb infection and reveal a sizable population recently infected with Mtb and at high risk of progression to disease. New diagnostic tools that can detect individuals with viable Mtb-particularly those who would benefit from TB preventive therapy-are urgently needed.

While global interest in mpox may be waning, outbreaks, illness, and death continue across Africa and the world. Ending transmission requires a sustained global response that moves beyond reactive measures.

Background: Reducing health inequalities is of national importance. Total hip replacement (THR) is a commonly used elective surgical procedure. Few studies have examined area-level inequalities for a wide range of outcomes following THR. The aim of this study is to compare area-level socioeconomic differences in outcomes following primary THR surgery for osteoarthritis in England.

Methods and findings: This is a population-based prospective cohort study of the National Joint Registry (NJR). Data from the NJR were linked to national mortality, Hospital Episode Statistics and Patient Reported Outcome Measures (PROMs) databases for England from 2007 to 2017 with follow-up to 2023 for outcomes, for patients aged 50 years and over with osteoarthritis. Outcomes of 90-day mortality; 5-year revision rate; 6-month health complications; 1-year rehospitalisation and reoperation for orthopaedic indications; and patient-reported Oxford Hip Score (OHS), post-THR surgery were examined by area-level Index of Multiple Deprivation quintiles. Modified Poisson regression was adjusted for patient age, sex, body mass index, pre-operative physical state and comorbidity. Among 448,184 patients with primary THR, mean age was 70 years (standard deviation: 9 years) and 61% were women. Patients from the most deprived group were more likely to die within 90 days of the operation compared to the least deprived group (adjusted rate ratio, RR: 1.25 (95% confidence interval (CI) [1.07, 1.46]); adjusted risk difference, RD: 9 (95% CI [2, 16]) per 10,000. Similarly, those from the most deprived group were more likely to experience complications (RR: 1.26 (95% CI [1.21, 1.32]); RD: 1.14% (95% CI [0.92, 1.36])); be rehospitalised (RR: 1.16 (95% CI [1.14, 1.19]; RD: 2.78% (95% CI [2.39, 3.17])) or reoperated (RR: 1.23 (95% CI [1.13, 1.33]); RD: 0.31% (95% CI [0.19, 0.44])) and report poorer OHS (adjusted score: -2.97 (95% CI [-3.10, -2.84]) N = 200,522). There was no variation by deprivation level for THR revision rates at 5 years (RR: 1.02 (95% CI [0.94, 1.10]); RD: 0.02% (95% CI [-0.10, 0.15])). The main study limitations are the lack of complete PROMs data, and the exclusion of self-funded patients or those with private insurance for THR procedures in independent hospitals.

Conclusions: Inequalities in several outcomes after THR are present in England by area-level deprivation. These findings are useful to inform shared decision-making for patients deciding whether to undergo hip replacement and to benchmark the effectiveness of policies which aim to reduce health inequalities following THR.

Antibody-drug conjugates are redefining treatment options in advanced breast cancer, demonstrating efficacy across all breast cancer subtypes. However, their rapid clinical expansion has resulted in several unresolved challenges, including the need for rational sequencing strategies, appropriate and ethical trial design, drug tolerability, and the limitation of mono-national development programs.

Background: Sex hormones have been implicated in leukemogenesis, but evidence regarding hormonal contraceptive use and leukemia risk remains limited and primarily based on older formulations. Given the widespread use of contemporary hormonal contraceptives, clarification of this potential association is needed. This study examines the association between contemporary hormonal contraceptives and leukemia risk.

Methods and findings: In a nationwide cohort design, we assessed associations between the use of contemporary hormonal contraceptives and the risk of leukemia based on a cohort of all women aged 15-49 years residing in Denmark from 1995 to 2021 with no previous cancer, hysterectomy, oophorectomy, or sterilization. Information on hormonal contraception use, leukemia diagnoses, and potential confounders (age, calendar year, education) was obtained from nationwide registries. Adjusted incidence rate ratios (IRRs) and 95% confidence intervals [CIs] were estimated for any leukemia, and specific types of leukemia, associated with any hormonal contraceptive use, current and recent use, and previous use, type of product used, duration, and time since last use. Among 1,957,490 pre-menopausal women followed for 24.5 million person-years (median 12.5 years, interquartile range: 5.9,20.5), 671 were diagnosed with leukemia. The incidence rate for leukemia among current and recent users was similar to that among women who had never used hormonal contraception: IRR 0.95 (95% CI [0.78,1.16]; p = 0.62). No association with different durations of use was found: 0-5 years; IRR 0.93 (95% CI [0.75,1.14]; p = 0.48), >5-10 years; IRR 1.16 (95% CI [0.84,1.61]; p = 0.37), >10 years; IRR 0.67 (95% CI [0.33,1.37]; p = 0.27); nor for time since last use: 0-5 years; IRR 1.01 (95% CI [0.78,1.29]; p = 0.96), >5-10 years; IRR 1.05 (95% CI [0.76,1.45]; p = 0.75), >10 years; IRR 0.88 (95% CI [0.60,1.29]; p = 0.52). Also, the IRRs for leukemia with use of different hormonal contraceptive types (e.g., combined products; IRR 0.91 (95% CI [0.73,1.14]; p = 0.42) and progestin-only products; IRR 1.05 (95% CI [0.78,1.40]; p = 0.75)), as well as for product-specific durations of use, were for the majority close to 1. The IRRs were similar for different types of leukemia. Main study limitations include small case numbers in some analyses; therefore, additional large-scale studies are warranted to reliably exclude weak associations.

Conclusions: Contemporary hormonal contraceptives were not associated with leukemia, independent of product used, duration of use, time since last use, and type of leukemia. While estimates were imprecise for some subgroups, the overall findings do not support an association.

Climate change is accelerating the frequency and severity of extreme weather events and increasingly threatening human health and life, particularly in low- and middle-income countries. Research on the effectiveness of climate adaptation interventions for human health, as well as their desirability, implementation, and financial viability, are urgently required.