EClinicalMedicine最新文献

Background: Reducing risk of cardiovascular disease is crucial in managing type 2 diabetes (T2D). This study assessed the comparative cardiovascular effectiveness of newer glucose-lowering drugs in real-world elderly individuals with T2D, and examined how age modified these effects.

Methods: We conducted a cohort study using Danish nationwide registries to emulate a three-arm randomized clinical trial. Participants aged ≥70 years were new users of glucagon-like peptide 1 receptor agonists (GLP1-RAs), sodium-glucose cotransporter 2 inhibitors (SGLT-2is), or dipeptidyl peptidase 4 inhibitors (DPP-4is), between 2012 and 2020. We estimated the overall and age-specific incidence rate ratios (IRR) of 3-point major adverse cardiovascular events (3P-MACE) and hospitalization for heart failure (HHF) using Poisson regression models. Summarized weights were used to balance baseline characteristics and treatment adherence.

Findings: The study included 35,679 participants (DPP-4is: 21,848 (62%), GLP1-RAs: 5702 (16%), SGLT-2is: 8129 (23%)). In the as-treated analysis, GLP1-RAs and SGLT-2is were associated with significantly reduced rates of 3P-MACE and HHF compared to DPP-4is. The overall IRR for 3P-MACE was 0.68 (95% CI 0.65-0.71) (GLP1-RAs vs. DPP4is) and 0.65 (95% CI 0.63-0.68) (SGLT-2is vs. DPP4is), while for HHF the IRR was 0.81 (95% CI 0.74-0.88) (GLP1-RAs vs. DPP4is) and 0.60 (95% CI 0.55-0.66) (SGLT-2is vs. DPP4is). These effects were predominantly independent of age. No significant difference was observed between SGLT-2is and GLP1-RAs on 3P-MACE, however, SGLT-2is were associated with a significant reduction of HHF, compared to GLP1-RAs, with an overall IRR of 0.75 (95% CI 0.67-0.83), and with age-dependent variations for both outcomes.

Interpretation: In the elderly, use of GLP1-RAs and SGLT-2is was associated with reduced rates of 3P-MACE and HHF compared to DPP-4is, independent of age. SGLT-2is were also associated with reduced rates of HHF compared to GLP1-RAs, largely independent of age, in this population of individuals aged 70 years and above. This provides real-world evidence on the comparative cardiovascular effectiveness of the three most recent glucose-lowering medications and may help strengthen implementation of guidelines into clinical practice.

Funding: None.

Background: A pooled data analysis by Quinten et al. (2009) found three European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) health-related quality of life (HRQoL) scales to be prognostic for survival: physical functioning, pain and appetite loss. This study aims to replicate these findings in an independent data set comprising a broader cancer population.

Methods: Data were obtained from 46 clinical trials across three cancer research networks conducted between 1996 and 2013 that assessed HRQoL using the EORTC QLQ-C30. A stratified Cox proportional hazards model was employed to assess the prognostic significance of baseline QLQ-C30 scale scores on overall survival, adjusting for socio-demographic and clinical variables. Stepwise model selection was done at 5% significance level. Model stability and prognostic accuracy were evaluated via bootstrapping and the C index respectively.

Findings: Data from 16,210 patients reporting HRQoL at baseline, spanning 17 cancer types, was used. The stratified multivariable model confirmed that better physical functioning (hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.93-0.96), lower pain (HR, 1.02; 95% CI, 1.01-1.03), and appetite loss (HR, 1.04; 95% CI, 1.03-1.05) were significantly associated with survival. Additionally, global health status/QoL, dyspnoea, emotional and cognitive functioning were found to be prognostic for survival. This final model, encompassing sociodemographic, clinical, and HRQoL variables, achieved a corrected C index of 0.74, marking a 48% enhancement in discriminatory ability. Bootstrap evaluation indicated no major instability issues.

Interpretation: These results support previous findings that baseline physical functioning, pain, and appetite loss scores, along with four other scales from the EORTC QLQ-C30, predict survival in cancer patients.

Funding: EORTC Quality of Life Group.

Background: Person-centered maternity care (PCMC) refers to respectful, responsive, and compassionate childbirth care. The PCMC scale enables quantitative measurement of PCMC. Despite the widespread use of the PCMC scale, no global synthesis exists. We, therefore, conducted a global systematic review of studies using the PCMC scale to quantitatively assess women's childbirth experiences, evaluate the scale's psychometric properties, and identify predictors of PCMC.

Methods: We searched PubMed, Web of Science, and Embase from inception to September 3, 2024. Included studies used the PCMC scale by Afulani et al. to examine the facility-based childbirth experiences of women in any setting, with no time or language restrictions. Three reviewers independently assessed titles, abstracts, and full texts. We assessed study quality using Joanna Briggs Institute critical appraisal tools. We utilized a standardized extraction template to extract full PCMC and sub-scale scores (standardizing scores to a 0-100 range for easier comparison), predictors, and psychometric properties. The primary outcome is the mean PCMC score.

Findings: Our initial search yielded 415 articles, of which 41 publications from 32 independent samples were included. Most studies were conducted in Africa (63%). Mean PCMC scores were generally lower in studies from Africa (under 75), moderate in Asia (60 to over 90), and higher in North America (over 80). The lowest score reported was 38.2/100 (SD = 15.8) in an observational study conducted in Sierra Leone, while the highest was 97.1/100 (SD = 2.9) following an intervention in India. The lowest scoring domain across countries was communication and autonomy, with the lowest score at 18.1/100 in a study in Ethiopia. Positive predictors of PCMC included higher wealth, education, early antenatal care, and birth in lower-level and private health facilities. Inconsistent predictors included age, marital status, and obstetric complications.

Interpretation: PCMC is sub-optimal globally, particularly in the domain of communication and autonomy. There are also inequities in PCMC driven by various sociodemographic and health systems-related factors. Interventions to improve women's experiences and to address the inequities are therefore needed.

Funding: None.

[This corrects the article DOI: 10.1016/j.eclinm.2024.102655.].

Background: Adverse events during tuberculosis treatment are common and are a major challenge for patients and front-line care providers. We did a systematic review of treatment guidelines for rifampicin-susceptible tuberculosis to evaluate the adequacy of recommendations for adverse event management.

Methods: We searched websites, guideline registries, PubMed, and mobile health Apps to identify treatment guidelines published from October 2004 to October 2024. We recorded the presence and evidence base for specific recommendations for management of nausea/vomiting, hepatotoxicity, skin reactions, neuropathy, visual changes, drug fever, and arthralgias.

Findings: We included 47 guidelines: 25 from high-burden countries, 12 international and prominent national guidelines, and 10 non-governmental guidelines. 37 guidelines (79%) included recommendations for managing adverse events: 24 (96%) of guidelines from high-burden countries, eight (80%) of those from non-governmental organizations, and four (33%) of international and prominent national guidelines. Four recommendations had formal ratings of supporting evidence.

Interpretation: International and prominent national guidelines frequently lack recommendations for adverse event management or had non-specific recommendations. Research on prevention and management of common and serious adverse events should be a priority for improving the patient's experience and the outcomes of tuberculosis treatment.

Funding: This research was supported by Wellcome Trust Clinical Grants.

Background: In the phase I Epi-RCHOP study (NCT02889523), we reported that R-CHOP-tazemetostat was well tolerated with the recommended phase II dose, consistent with monotherapy.

Methods: Phase II included newly diagnosed diffuse large B cell lymphoma patients aged 60-80 years who received six cycles of rituximab-CHOP (R-CHOP) with continuous tazemetostat (800 mg BID), plus two cycles of tazemetostat and rituximab (cycles 7 and 8), from July 31, 2020 to July 18, 2022. Primary endpoint was positron emission tomography complete metabolic response (CMR). Sample size was calculated with H0 of 70% and H1 assumption of 80%.

Findings: The trial enrolled 122 patients: median age 70 (60-80), 90.2% with stage III-IV, and 73.8% with International Prognostic Index 3-5. Overall, 100 patients (82%) received eight cycles, while 22 had premature treatment discontinuation (PTD), including 12 during the first two cycles. Reasons for PTD were consent withdrawal (N = 10), adverse events (N = 6), death (N = 2), protocol deviation (N = 2), progressive disease (N = 1), and physician decision (N = 1). The median percentage of relative dose intensity of tazemetostat and R-CHOP exceeded 90%, but required a protocol amendment and reduction in vincristine dosage at 1 mg full dose. At the end of treatment or PTD, 92/122 patients (75.4%) achieved CMR, eight (6.6%) partial metabolic response, five (4.1%) progressive disease, two (1.6%) died (septic shock), and 15 (12.3%) were not evaluated. Sensitivity analysis, excluding ten non-evaluated patients who withdrew consent, showed CMR in 82.1%. After a median follow-up of 18.5 months (IQR: 15.4-21), estimated progression-free and overall survival at 18 months were 77.7% (95% CI: 67.5-85.1%) and 88.8% (95% CI: 79.9-93.9%), respectively.

Interpretation: R-CHOP plus tazemetostat is feasible with a promising CMR in elderly DLBCL patients. Complementary biomarker studies are needed for a more personalized approach.

Funding: This study was sponsored under a grant from Ipsen.

Background: Tuberculosis (TB) mortality remains persistently high, despite global TB control efforts. The aim of this study was to assess if a quality improvement (QI) intervention reduced deaths in TB patients accessing primary healthcare (PHC) services.

Methods: In this pre specified secondary analysis of a cluster-randomized controlled study conducted in 2016-2018 in South Africa (Clinicaltrials.gov, NCT02654613), we compared 18-month case-fatality rates among newly diagnosed TB patients irrespective of HIV status randomized to clinics receiving the QI intervention and standard of care (SOC) [(eight clusters and 20 clinics per arm)]. Statistical inferences used a t-test from a two-stage approach recommended for cluster-randomized trials with fewer than 15 clusters per arm.

Findings: Among the 5817 newly diagnosed TB patients enrolled (intervention = 3473; control = 2344), 562 died by 18-months [case-fatality rate (CFR) = 9·7%]. Ninety percent of the deaths (506/562) occurred within six months of TB treatment initiation. Quality improvement intervention arm clinics compared to control arm clinics did not demonstrate a significant difference in TB CFR. Case-fatality rates were 9·5% [95% Confidence Interval (CI): 6·9-12·9] and 11·3% (95% CI: 8·7-14·7) [adjusted rate ratio (aRR), 0·9 (95% CI: 0·6-1·2)] in the intervention and control arms, respectively. In people living with HIV/AIDS (PLWHA) CFR in the intervention and control arms: were 10·8% (95% CI: 7·8-14·7) and 14·4% (95% CI: 9·3-22·4) in those on antiretroviral therapy (ART) and 18·6 (95% CI: 9·1-38·0) and 33·0 (95% CI: 16·2-67·3), in those with no ART data respectively. In the intervention and control arms CFR in HIV-TB coinfected patients was 6·5 (95% CI: 3·6-11·6) and 11·5 (95% CI: 6·5-20·0) in those on ART with viral loads <200 copies/ml and 22·4 (95% CI: 16·7-30·2) and 19·7 (95% CI: 11·3-34·5) in those with no viral load data as they commenced ART within 12 months before initiating TB treatment, respectively.

Interpretation: The quality improvement intervention did not significantly reduce mortality. We observed that TB CFR was higher among PLWHA not on ART and HIV-TB coinfected patients.

Funding: Research reported in this publication was supported by South African Medical Research Council (SAMRC), and UK Government's Newton Fund through United Kingdom Medical Research Council (UKMRC).

Background: Women experiencing co-occurring forms of intimate partner violence (IPV; ie, physical, sexual, and/or psychological) often face more severe psychological and health consequences than those experiencing a single form. However, research on IPV co-occurrence in low- and middle-income countries (LMICs) remains limited. This study examines the prevalence of IPV co-occurrence in LMICs and its education-based inequalities.

Methods: Data from the most recent Demographic and Health Surveys in 49 LMICs (2011-2023) were used. Our primary outcome was IPV co-occurrence, defined as a woman aged 15-49 ever experiencing any two or three forms of physical, sexual, or psychological IPV from her partner within the past year. We categorised IPV co-occurrence into four subtypes: co-occurrence of (1) physical and sexual IPV, (2) physical and psychological IPV, (3) sexual and psychological IPV, and (4) all three forms of IPV. We analysed the prevalence of IPV co-occurrence and its subtypes by women's education levels, calculating odds ratios to assess inequalities. Nonparametric restricted cubic splines were used to explore nonlinear relationships between education and IPV.

Findings: The study included a total of 344,661 women. The weighted prevalence of IPV co-occurrence varied widely across countries-from 2.4% in Armenia to 38.9% in Papua New Guinea. Overall, women with no education were most at risk, experiencing an adjusted prevalence of 14.3% (95% CI: 13.3-15.2), compared to 11.8% (95% CI: 10.8-12.9) among those with primary education, 9.9% (95% CI: 9.3-10.6) for secondary education, and 5.3% (95% CI: 4.5-6.2) for higher education. The prevalence of IPV co-occurrence involving sexual IPV was highest among women with primary education, with 4.1% (95% CI: 3.4-4.8) reporting concurrent physical and sexual violence, compared to 1.5% (95% CI: 1.1-1.9) to 3.7% (95% CI: 3.2-4.1) among other education levels.

Interpretation: IPV co-occurrence remains high, particularly among women with little or no education. Education-focused interventions are urgently needed to reduce IPV risk and its severe impact. However, the findings may be influenced by potential reporting biases and cross-country variability in IPV measurement methodologies, which may limit generalizability.

Funding: The China National Natural Science Foundation (Grant numbers 72203119) and The Research Fund, Vanke School of Public Health, Tsinghua University.