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A profile of firearm-related fatalities admitted to the Diepkloof Forensic Pathology Service Soweto medico-legal mortuary during the COVID-19 and post COVID-19 periods.

This retrospective descriptive study examined firearm-related fatalities during (April-December 2020; n&#x2009;=&#x2009;241) and after (April-December 2023; n&#x2009;=&#x2009;299) COVID-19 lockdowns using 540 cases from the Diepkloof Forensic Pathology Service, Soweto, South Africa. Data was obtained from autopsy reports, forensic records, police statements, and death scene documentation. Firearm violence affected young adult Black males (22-43&#x2009;years), with only minor demographic shifts post-pandemic. The overall burden and core patterns of violence remained stable, with criminal activity - primarily robbery and interpersonal violence - persisting as the leading contexts, and homicide the dominant manner of death. Post-COVID-19 findings demonstrated contextual shifts, including increased incidents in public and social environments, reflecting greater mobility and resumption of social activity. A significant rise in mean blood alcohol concentration (0.09&#x2009;g/100&#x2009;mL vs 0.14&#x2009;g/100&#x2009;mL; p&#x2009;<&#x2009;0.0001) suggests increased alcohol involvement following easing of restrictions. Unfortunately, persistent information gaps, noted particularly in circumstantial history, incident location, firearm type, highlighting the need for improved data provision and capture systems. While the epidemiology of firearm-related fatalities remained unchanged, the post-COVID-19 period was characterised by increased alcohol involvement, shifts toward public-space violence, and fewer gunshot wounds per victim, suggesting changes in situational and behavioural dynamics rather than underlying drivers of violence.

Humans

Chlorfenapyr-pyrethroid nets for pyrethroid-resistant malaria vectors: efficacy, resistance risks, and policy implications.

The Global Technical Strategy for Malaria 2016-2030 aims to reduce malaria incidence and mortality by 90%, yet widespread pyrethroid resistance among major malaria vectors in sub-Saharan Africa threatens this goal. Thus, the World Health Organization recommends chlorfenapyr-pyrethroid combination nets as a priority intervention where pyrethroid resistance undermines vector control. This systematic review synthesizes evidence on the performance, emerging resistance risks, and policy implications of these next-generation insecticide-treated nets. A structured search of literature from 2010 to 2024 across PubMed, Embase, WHO IRIS, and Google Scholar identified 31 eligible studies from 113 records. Evidence shows that chlorfenapyr-pyrethroid nets consistently outperform pyrethroid-only nets against resistant Anopheles populations, demonstrating a 1.8-fold increase in mosquito mortality (95% CI: 1.5-2.1). Community trials report 40-60% reductions in malaria infection incidence and entomological inoculation rates following deployment. However, early signs of chlorfenapyr resistance have emerged in Anopheles gambiae populations in Central Africa (RR: 2.4, p&#x2009;=&#x2009;0.01), linked to CYP6P4 metabolic overexpression. A significant correlation was also observed between agricultural pesticide use and vector resistance patterns (r&#x2009;=&#x2009;0.62, p&#x2009;<&#x2009;0.05). Although chlorfenapyr-pyrethroid nets provide an important short-term tool for managing pyrethroid resistance, their long-term effectiveness depends on integrated resistance management. Rotational deployment with other insecticide classes, strengthened genetic and phenotypic surveillance, and a coordinated 'One Health' approach involving both public health and agriculture are essential to sustain gains and advance progress toward the 2030 malaria targets.

Pyrethrins

Duration and characteristics of hypoglycemia with once-weekly insulin efsitora alfa versus once-daily basal insulins in adults with type 2 diabetes: Exploratory safety analysis of QWINT 2-4.

AIMS: Efsitora is a novel once-weekly basal insulin. Efsitora demonstrated similar efficacy and safety compared with once-daily basal insulin comparators across four phase 3 clinical trials for type 2 diabetes. This exploratory safety analysis further characterizes hypoglycemia events in the efsitora and once-daily treatment groups in three of these trials (QWINT-2, -3, and -4). METHODS: Median duration of hypoglycemia events was assessed with masked continuous glucose monitoring. Incidence of persistent-recurrent (PR) hypoglycemia was assessed by investigators and by a pre-specified algorithm using SMBG e-diary data. Factors contributing to hypoglycemia, characteristics of hypoglycemia, and treatment methods were reported by participants and assessed across groups. RESULTS: Across the three trials, durations of hypoglycemic events for efsitora vs once-daily basal insulin comparators were: Level 1 and 2 [<70&#xa0;mg/dL]: 40-42.5 vs 40&#xa0;min; Level 2 [<54&#xa0;mg/dL]: 35-39.9 vs 35&#xa0;min. Few incidences of PR hypoglycemia were reported for efsitora or once-daily comparators. No major descriptive differences were observed between hypoglycemia contributing factors, characteristics, or treatment methods in efsitora and once-daily treatment groups. CONCLUSIONS: No clinically relevant differences were observed between the duration or characteristics of hypoglycemic events in efsitora and once-daily treatment groups in the QWINT-2, -3, and -4 trials.

Adult

Ketoacidosis with SGLT2 inhibitors in routine clinical practice of type 2 diabetes: Scandinavian cohort and nested case-control study.

BACKGROUND: SGLT2 inhibitors increase the risk of ketoacidosis, but data from routine clinical practice are scarce. We used nationwide registers with the aim of assessing the incidence, risk factors, and prognosis of ketoacidosis during SGLT2 inhibitor treatment in patients with type 2 diabetes. METHODS: In this cohort and nested case-control study we used data from three Scandinavian countries. In a cohort of SGLT2 inhibitor-treatment episodes among patients with type 2 diabetes aged at least 18 years in Sweden, Denmark, and Norway, we estimated ketoacidosis incidence. Using a nested case-control design (matched on age, sex, region of birth, calendar time, and time since treatment initiation), we assessed risk factors and precipitating or co-occurring events. Changes in diabetes medications were evaluated. FINDINGS: The study period was Jan 1, 2013, to Dec 31, 2021, in Denmark and Sweden, and Jan 1, 2013, to Dec 31, 2022, in Norway. We included 322&#x2008;597 treatment episodes among 282&#x2008;282 patients with type 2 diabetes (mean age 63 years, 116&#x2008;521 [36&#xb7;1%] of 322&#x2008;597 women). During a median (IQR) follow-up of 1&#xb7;3 (0&#xb7;7-2&#xb7;8) years, 1452 ketoacidosis events occurred (incidence 2&#xb7;43 per 1000 person-years). Although highest shortly after initiation, risk persisted throughout follow-up. Strong risk factors included high HbA1c (&#x2265;83 vs &#x2264;52 mmol/mol: odds ratio [OR] 15&#xb7;37 [95% CI 11&#xb7;50-20&#xb7;53]), malnutrition (OR 10&#xb7;54 [7&#xb7;32-15&#xb7;18]), previous ketoacidosis (OR 10&#xb7;40 [7&#xb7;09-15&#xb7;24]), low BMI (<20 kg/m2vs 20 to <25 kg/m2: OR 9&#xb7;98 [5&#xb7;68-17&#xb7;53]), and recent hypoglycaemia (OR 5&#xb7;22 [2&#xb7;60-10&#xb7;49]). Infection was the most common precipitating or co-occurring event (454 [31&#xb7;8%] of 1428 vs 862 [6&#xb7;1%] of 14&#x2008;233 for ketoacidosis cases vs controls; OR 7&#xb7;60 [6&#xb7;62-8&#xb7;71]). The strongest associations were observed for alcohol intoxication, acute renal events, acute abdomen, stroke, and major surgery, although associations for some transient exposures, particularly milder conditions, might have been overestimated because of under-registration among controls. Exploratory analyses suggested that the observed associations were largely general to patients with type 2 diabetes rather than specific to SGLT2 inhibitor use. At 1 year after ketoacidosis, 211 (25&#xb7;1%) of 842 remained on SGLT2 inhibitors and insulin use increased from 269 (31&#xb7;9%) of 842 to 615 (73&#xb7;0%) of 842. INTERPRETATION: Ketoacidosis risk with SGLT2 inhibitors varies greatly by patient characteristics and is not confined to early in treatment. Risk should be assessed throughout treatment, and patients should be instructed to pause treatment during acute illness and stress. FUNDING: Region Stockholm, Swedish Society of Medicine, Karolinska Institutet.

Journal Article

Ultrasound-Guided Microwave Ablation Versus Open Surgery for Benign Breast Disease: Impact on Postoperative Lactation.

BACKGROUND: Benign breast disease (BBD) is common in adult women. While ultrasound-guided microwave ablation (MWA) is an established minimally invasive treatment, its comparative impact on postoperative lactation, particularly mastitis, remains understudied. This study aimed to evaluate mastitis outcomes following MWA versus open surgery for BBD. METHODS: In this retrospective study, 79 patients (105 nodules) treated between January 2018 and August 2023 were included 41 patients (62 nodules) underwent MWA and 38 patients (43 nodules) underwent open surgery. All patients lactated within 5 years post-procedure. The primary outcome was the incidence of lactational mastitis without systemic symptoms (MWoSS) and mastitis with systemic symptoms (MSS). Patient satisfaction was also assessed. RESULTS: The incidence of MWoSS was significantly lower in the MWA group (19.5%) than in the open surgery group (50.0%). Similarly, MSS occurred in 4.9% of the MWA group versus 34.2% of the open surgery group. Multivariate analysis identified open surgery as an independent risk factor, associated with a 4.13-fold increased risk of MWoSS (OR = 4.125, 95% CI: 1.517-11.218) and a 10.14-fold increased risk of MSS (OR = 10.140, 95% CI: 2.107-48.793). Patient satisfaction was significantly higher in the MWA group (9.29 &#xb1; 0.72 vs. 8.15 &#xb1; 1.13, p < 0.001). CONCLUSION: Compared to open surgery, ultrasound-guided MWA for BBD is associated with a significantly lower risk of postoperative mastitis and higher patient satisfaction, supporting its use for women of reproductive age, particularly when future breastfeeding is planned.

Humans

The association of 25-hydroxyvitamin D deficiency with neuroinflammation and prognosis in HIV-negative cryptococcal meningitis.

BACKGROUND: Cryptococcal meningitis (CM) in HIV-negative individuals is increasing, yet the role of vitamin D remains unclear. This study investigates serum 25-hydroxyvitamin D [25(OH)D] levels and their clinical implications in HIV-negative CM patients. METHODS: We conducted a retrospective case-control study of 93 HIV-negative CM patients and 191 healthy controls (HCs). Serum 25(OH)D levels, cerebrospinal fluid (CSF) fungal burden, cytokine profiles, the incidence of postinfectious inflammatory response syndrome (PIIRS), and one-year mortality were assessed. Bivariate logistic regression models identified predictors of mortality. RESULTS: CM patients had significantly lower serum 25(OH)D levels than HCs (18.33 vs. 23.69&#xa0;ng/mL, p&#xa0;<&#xa0;0.001), with a higher rate of deficiency (<20&#xa0;ng/mL) in the CM group (59.14% vs. 34.03%, p&#xa0;<&#xa0;0.001). Lower 25(OH)D levels were associated with elevated CSF levels of IL-6 and IL-8 (p&#xa0;<&#xa0;0.05). Deficiency was linked to increased PIIRS incidence (43.64% vs. 21.05%, p&#xa0;=&#xa0;0.028). Bivariate logistic regression showed a protective trend for 25(OH)D levels (OR 0.939, 95% CI 0.877-1.006, p&#xa0;=&#xa0;0.075), although deficiency was not associated with higher mortality. CONCLUSIONS: Serum 25(OH)D deficiency is prevalent in HIV-negative CM patients and linked to neuroinflammation and increased risk of PIIRS. Serum 25(OH)D levels may serve as a useful prognostic marker, although further research is needed.

Humans

Wildlife forensic DNA evidence links a suspected vehicle to a fatal lowland tapir (Tapirus terrestris) collision in Misiones, Argentina.

Vehicle collisions are recognized as a major driver of biodiversity loss, particularly in road-dense landscapes, exceeding the impact of invasive species and wildlife trafficking. For large-bodied, slow-reproducing, and low-abundance species, such as the lowland tapir (Tapirus terrestris), this threat can have major impacts. Here, we present a wildlife forensic investigation in Misiones, Argentina, involving a tapir, a species afforded the highest level of legal protection as a Provincial Natural Monument. The fatal hit-by-vehicle (HBV) incident occurred in northern Misiones on 31 March 2019 along Provincial Route 19, in a portion that bisects Parque Provincial Urugua-&#xed;, with the driver involved in the collision leaving the scene. The suspect was later located and claimed that the damage to the vehicle resulted from a collision with a horse (Equus caballus) rather than a tapir. To legally resolve the incident, DNA (hair and blood) recovered from the suspected vehicle's bumper (evidence) was compared with tissue samples from the tapir carcass (reference). Genetic confirmation of species identity used a 110-bp region of the mitochondrial cytochrome b gene, and individual identity was assessed using 12 species-specific microsatellite loci. These analyses confirmed that all evidence matched the tapir carcass at both species and individual levels, strongly supporting the association between the suspected vehicle and the HBV tapir, and refuting the alternative explanation proposed by the driver. This case demonstrates the value of using wildlife forensic genetics to reconstruct wildlife-vehicle collisions, supporting environmental law enforcement, and strengthening conservation efforts in the Atlantic Forest of Misiones, Argentina.

Animals

A phase I clinical study of the safety, tolerability, pharmacokinetics and pharmacodynamics of SHR-2106, an anti-CD40 antibody, following single intravenous or subcutaneous administration in healthy participants.

BACKGROUND: SHR-2106 is a humanized IgG1 monoclonal antibody that blocks CD40-CD40L interactions and has demonstrated immunosuppressive activity and graft-prolonging effects in preclinical studies. This first-in-human Phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of single intravenous or subcutaneous doses of SHR-2106 in healthy adults. METHODS: This randomized, double-blind, placebo-controlled Phase I study enrolled healthy participants. Fifty-one participants were enrolled in seven cohorts and received five intravenous doses (50-1200&#x202f;mg) or two subcutaneous doses (300 and 600&#x202f;mg). Safety, serum pharmacokinetics, CD40 occupancy on B cells, and anti-drug antibodies were assessed using standard clinical and bioanalytical methods. RESULTS: SHR-2106 demonstrated a favorable safety and tolerability profile, and most treatment-emergent adverse events were mild to moderate laboratory abnormalities with incidence rates comparable to placebo. SHR-2106 exhibited nonlinear pharmacokinetics consistent with target-mediated drug disposition, with a dose-dependent increase in geometric mean terminal half-life following intravenous administration (1.83-10.7 days). Absolute bioavailability after subcutaneous administration was approximately 60%. CD40 occupancy exceeded 80% within 24&#x202f;h at all doses, with saturation duration increasing from 7 to 70 days across the intravenous dose range and remaining comparable between routes at matched doses. Anti-drug antibody incidence decreased with increasing intravenous dose and did not significantly affect pharmacokinetics or pharmacodynamics. CONCLUSION: SHR-2106 was well tolerated and achieved rapid and sustained CD40 engagement, supporting dose and route selection for Phase II studies.

Humans

Comparison of VCV and PCV-VG modes on diaphragmatic function in diabetic patients undergoing laparoscopic colorectal surgery: a prospective randomized controlled study.

BACKGROUND: Diabetic patients are prone to induce diaphragmatic weakness, which can lead to postoperative pulmonary complications (PPCs). The optimal mechanical ventilation mode may potentially improve postoperative diaphragmatic function. This study evaluates the effects of two ventilation modes under driving pressure-guided ventilation strategy on diaphragmatic function, as assessed by diaphragm thickening fraction (DTF) and diaphragm excursion (DE), in diabetic patients following laparoscopic colorectal surgery. METHODS: Eighty patients diagnosed with Type II diabetes scheduled for elective laparoscopic colorectal surgery, were randomly allocated to either the pressure-controlled volume-guaranteed ventilation (PCV-VG) group (Group P) or the volume-controlled ventilation (VCV) group (Group V) during surgery. The primary outcome was diaphragmatic function assessed during both tidal breathing and maximal inspiratory effort after surgery. Secondary outcomes included intraoperative mechanical power, PPCs, and other complications. RESULTS: A total of eighty patients were included in the final analysis. The averaged area under the curve (AUC) for mechanical power during ventilation was significantly lower in Group P than in Group V (p&#x2009;=&#x2009;0.002). PCV-VG significantly improved both DE and DTF within the first two days post-surgery (AUCDEtidal: p&#x2009;=&#x2009;0.088, AUCDTFtidal: p&#x2009;=&#x2009;0.004, AUCDEmax: p&#x2009;=&#x2009;0.029, AUCDTFmax: p&#x2009;=&#x2009;0.017). Postoperative diaphragmatic weakness was less frequent in Group P than in Group V (p&#x2009;=&#x2009;0.019). However, there was no difference in the incidence of PPCs between the two groups (p&#x2009;=&#x2009;0.155). CONCLUSION: PCV-VG mode can reduce intraoperative mechanical power, better preserve postoperative diaphragmatic function. However, these improvements did not translate into clinical benefits, as evidenced by the lack of reduction in the incidence of PPCs.

Humans

Clinical and genetic features of Ph-negative myeloproliferative neoplasms with dual-driver gene positivity.

OBJECTIVES: To investigate the clinical laboratory characteristics and gene mutation features of dual-driver gene positivity in patients with Philadelphia chromosome-negative myeloproliferative neoplasm (Ph-negative MPN). METHODS: We conducted a retrospective analysis of clinical data and genetic test results from 203 newly diagnosed patients with Ph-negative MPN. Of these, 194 had single-driver gene positivity and 9 had dual-driver gene positivity. High-throughput sequencing was used to detect mutations in JAK2, CALR, and MPL. Clinical characteristics and gene mutation profiles were compared between the two patient groups. RESULTS: The incidence of dual-driver gene positivity was 4.4% (9/203), with the most common combinations being JAK2 with CALR (4 patients) and JAK2 with MPL (4 patients). Compared with the single-driver group, the dual-driver group had a significantly higher risk of bleeding [4.1% (8/194) vs. 33.3% (3/9), P&#x2009;=&#x2009;0.008] and a higher proportion of uncommon mutations [3.6% (7/194) vs. 33.3% (3/9), P&#x2009;=&#x2009;0.006]. No statistically significant differences were observed between the two groups regarding age, thrombosis incidence, splenomegaly, or routine blood test indicators. During follow-up, 1 patient in the dual-driver group died from cerebrovascular disease. No leukaemia transformation or disease-related deaths occurred among the remaining patients. DISCUSSION: The increased bleeding risk in dual-driver patients may be related to a higher proportion of CALR mutations, elevated platelet counts, and higher variant allele frequencies, though these findings require validation in larger cohorts due to the small sample size. The higher prevalence of uncommon mutations suggests a more complex mutational landscape in this subgroup. CONCLUSION: Patients with Ph-negative MPN and dual-driver gene positivity may have a higher risk of bleeding and a more complex gene mutation profile.

Humans

Diabetic macular edema and GLP-1 receptor agonist use: a systematic review and meta-analysis.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for type II diabetes and obesity because of their cardiometabolic benefits. However, concerns regarding potential ocular adverse effects, particularly diabetic macular edema (DME), have prompted the need to clarify their retinal safety. METHODS: A systematic review and meta-analysis study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology statements (PROSPERO registration: CRD420251176164). MEDLINE (Ovid), EMBASE (Ovid), CENTRAL (Ovid), Web of Science, and PubMed were searched from inception to October 24, 2025. Randomized trials and observational cohort or case-control studies, including individuals with diabetes without baseline DME and exposed to GLP-1RAs were eligible. Two reviewers independently screened studies, extracted data, and assessed risk of bias using ROBINS-I. Certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development, and Evaluation. Random-effects models were used to pool incidence proportions and hazard ratios (HRs). RESULTS: Thirteen retrospective cohort studies (2021-2025) using large real-world databases were included. Across 6 studies, the pooled proportion of incident DME among GLP-1RA users was 0.14 (95% CI: 0.07-0.23; I&#xb2;&#x202f;=&#x202f;99.8%). Compared with mixed antihyperglycemic therapies, GLP-1RA use was not associated with increased DME risk (pooled HR: 0.81, 95% CI: 0.52-1.26). GLP-1RAs were associated with a higher relative risk of DME compared with sodium-glucose cotransporter-2 inhibitors (HR: 1.50, 95% CI: 1.17-1.94) but not compared with dipeptidyl peptidase-4 inhibitors (HR: 0.90, 95% CI: 0.69-1.19). Evidence certainty was very low. CONCLUSION: Current low-certainty observational evidence does not support an overall increased risk of DME with GLP-1RA use. Prospective studies are needed to clarify comparative retinal safety.

Humans

Parental son preference in childhood and sex differences in the risk of cardiovascular disease in middle-aged and older adults.

INTRODUCTION: Sex differences in cardiovascular disease (CVD) risk are examined through biological and clinical factors, with less attention to early-life social exposures. This study examined associations of childhood parental son preference with CVD risk, sex differences, and mediation by modifiable risk factors. METHODS: This cohort analysis included China Health and Retirement Longitudinal Study participants aged &#x2265;45 years without baseline CVD. Parental son preference was assessed retrospectively in 2014; incident CVD was self-reported physician-diagnosed heart disease or stroke through 2020. Sampling-weighted, community-clustered Cox models estimated adjusted hazard ratios (aHRs) and 95% CIs. Sex was prespecified as an effect modifier; mediation by 13 risk factors used inverse-odds-ratio weighting. Data were collected from 2011 to 2020 and analyzed from 2025 to 2026. RESULTS: Among 8,079 participants (mean age, 57.5 years; 4,216 women [52.2%]), 1,820 (22.5%) reported parental son preference. Son preference was associated with higher CVD risk overall (aHR 1.23 [95% CI 1.04, 1.46]) and among women (aHR 1.25 [95% CI 1.03, 1.53]); among men, the estimate was 1.16 (95% CI 0.87, 1.56), with limited heterogeneity by sex (ratio of aHRs 1.06 [95% CI 0.72, 1.58]). Among women, risk was concentrated in the highest paternal (aHR 1.47 [95% CI 1.14, 1.90]) and maternal (aHR 1.50 [95% CI 1.12, 1.99]) preference categories. Modifiable risk factors mediated 5.8% (95% CI 1.9%, 9.7%) of the association among women, mainly through socioeconomic and psychosocial factors. CVD risk was highest with both son preference and high risk-factor burden overall (aHR 1.97 [95% CI 1.43, 2.73]) and among women (aHR 2.23 [95% CI 1.61, 3.10]). CONCLUSIONS: Parental son preference was associated with higher incident CVD risk, with the largest estimates in the highest paternal or maternal categories among women. Modifiable risk factors explained a modest proportion, supporting life-course cardiovascular prevention that considers sex-differentiated childhood environments alongside risk-factor modification.

cardiovascular disease

Matching-adjusted indirect comparison of fruquintinib versus ramucirumab in advanced gastric or gastroesophageal junction adenocarcinoma.

Aim: Fruquintinib (Fruq), a selective VEGFR 1/2/3 inhibitor, showed a significant progression-free survival (PFS) benefit in the Phase III FRUTIGA trial for advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma. Ramucirumab (RAM), an anti-VEGFR2 antibody, demonstrated efficacy in the RAINBOW-Asia trial. This anchored matching-adjusted indirect comparison (MAIC) evaluated Fruq plus paclitaxel versus RAM plus paclitaxel as second-line therapy for G/GEJ adenocarcinoma in the absence of head-to-head trials. Materials & methods: Data from individual patients in the FRUTIGA study (N&#xa0;=&#xa0;703) and aggregated data from the RAINBOW-Asia study (N&#xa0;=&#xa0;440) were analyzed. Baseline characteristics were balanced using entropy balancing. The placebo plus paclitaxel (PBO&#xa0;+&#xa0;PTX) groups served as the common comparators. The primary outcome was PFS; secondary outcomes included overall survival, objective response rate (ORR) and disease control rate (DCR). Rates of treatment-emergent adverse events (TEAEs) were also compared as an exploratory outcome using an adjusted indirect risk difference. Sensitivity analyses included restricted mean survival time and simulated treatment comparison. Results: After weighting (effective sample size&#xa0;=&#xa0;564), baseline covariates were balanced. The anchored MAIC demonstrated that Fruq&#xa0;+&#xa0;PTX significantly improved PFS compared with RAM&#xa0;+&#xa0;PTX (HR: 0.70; 95% CI: 0.51-0.96; p&#xa0;=&#xa0;0.0280), corresponding to a 30% reduction in progression risk, with a significant restricted mean survival time benefit of 1.18&#xa0;months at 20&#xa0;months (95% CI: 0.08-2.27; p&#xa0;=&#xa0;0.024). Fruq achieved significantly higher ORR (OR: 1.76, 95% CI: 1.16-2.68; p&#xa0;=&#xa0;0.008) and DCR (OR: 1.94, 95% CI: 1.33-2.83; p&#xa0;<&#xa0;0.001). Overall survival was similar (0.97; 95% CI: 0.73-1.30; p = 0.8640). Subgroup analyses showed PFS benefits with Fruq in patients with ECOG PS 1, peritoneal metastases and two or fewer metastatic sites. In sensitivity analysis, the simulated treatment comparison also suggested a PFS benefit for Fruq&#xa0;+&#xa0;PTX (HR: 0.40, 95% CI: 0.32-0.50; p&#xa0;<&#xa0;0.0001). For any-grade TEAEs, the indirect comparison showed higher adjusted relative incidences of increased bilirubin with Fruq&#xa0;+&#xa0;PTX than with RAM&#xa0;+&#xa0;PTX (RD: 12.3%; 95% CI: 2.3-22.4%, p&#xa0;<&#xa0;0.05) and of hypokalemia (RD: 9.0%; 95% CI: 1.5-16.4%, p&#xa0;<&#xa0;0.05). For grade &#x2265;3 TEAEs, the adjusted relative incidence of decreased body weight was higher with Fruq&#xa0;+&#xa0;PTX than with RAM&#xa0;+&#xa0;PTX (RD: 2.9%; 95% CI: 0.6-5.2%, p&#xa0;<&#xa0;0.05). The adjusted relative incidences of increased AST, ALT and hypocalcemia were numerically lower in the fruquintinib group than in the RAM group. Conclusion: This MAIC indicates that Fruq&#xa0;+&#xa0;PTX may be more effective than RAM&#xa0;+&#xa0;PTX in second-line advanced G/GEJ adenocarcinoma, with potentially improved PFS, ORR and DCR, and similar overall survival. Safety analyses suggested generally comparable safety profiles across the two regimens. Fruq&#xa0;+&#xa0;PTX remains a valuable treatment option, offering important comparative evidence for clinical and health technology assessment decisions. Trial Registration: Clinicaltrials.gov identifiers: NCT07144995.

Adult

The impact of prehabilitation on postoperative outcomes in patients undergoing radical prostatectomy for prostate cancer: a systematic review and meta-analysis.

PURPOSE: Preoperative rehabilitation training can optimize functional reserve before radical prostatectomy (RP), thereby improving postoperative outcomes. However, its effects on urinary incontinence, erectile function, and quality of life (QoL) remain controversial. This study systematically evaluated these outcome measures. METHODS: Data from randomized controlled trials (RCTs) were retrieved from the PubMed, Cochrane Library, Embase, and CINAHL databases. The risk of bias was assessed using the RoB-2 tool, and meta-analysis was performed using Stata 18.0 software. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment. Meta-analyses were conducted using fixed- or random-effects models according to heterogeneity. Outcomes included urinary incontinence incidence, urinary incontinence severity, erectile function, and QoL at different postoperative follow-up time points. RESULTS: 16 randomized controlled trials involving 1,542 participants were included. Prehabilitation significantly reduced the incidence of urinary incontinence at 1&#xa0;month (OR&#x2009;=&#x2009;0.58, 95% CI 0.39-0.84) and 6&#xa0;months (OR&#x2009;=&#x2009;0.52, 95% CI 0.28-0.96) after RP, with a non-significant borderline reduction at 3&#xa0;months, and no significant benefit at 12&#xa0;months. No significant improvement was observed in urinary incontinence severity or erectile function at any follow-up time point. Prehabilitation significantly improved QoL within 3&#xa0;months (SMD&#x2009;=&#x2009;-0.70, 95% CI -1.08 to -0.32) and 6&#xa0;months (SMD&#x2009;=&#x2009;-0.45, 95% CI -0.74 to -0.16) postoperatively. However, within 12&#xa0;months, the effect size attenuated, showing only a marginal trend that did not reach statistical significance (SMD&#x2009;=&#x2009;-0.33, 95% CI -0.66 to 0.00). Risk of bias was generally moderate. CONCLUSION: Prehabilitation reduces early incontinence and improves QoL post-RP, but its effects on severity and erectile function remain unclear. SYSTEMATIC REVIEW REGISTRATION: PROSPERO [CRD420251183407].

Humans

Oil and gas well development and coccidioidomycosis risk in Kern County, CA, USA: a case-crossover study.

BACKGROUND: Coccidioidomycosis is an emerging fungal disease caused by inhaling Coccidioides spp spores. As spores reside in soil, activities that disturb soil and generate dust can aerosolise and transport the pathogen. The oil and gas industry has been extensively developed in some regions that are endemic for Coccidioides spp and has been associated with dust emissions. Although several adverse health outcomes have previously been associated with oil and gas development, its impact on coccidioidomycosis risk has not been investigated. We aimed to estimate the association between exposure to oil and gas well development (ie, wells in preproduction) and risk of coccidioidomycosis among residents living near new wells. METHODS: In this case-crossover study, we obtained information on reported coccidioidomycosis cases and oil and gas well development between 2007 and 2022 in Kern County, CA, USA. We then compared exposure to preproduction wells within 5 km of each individual's place of residence during both hazard (ie, the 49-139 days before case onset) and control periods using conditional logistic regression. FINDINGS: During the study period, 658&#x2009;108&#x2009;(72&#xb7;4%) of 909&#x2009;282 of Kern County residents lived within 5 km of at least one preproduction well, and 116&#x2009;020&#x2009;(12&#xb7;8%) lived within 5 km of 23 or more preproduction wells within a single 90-day period. We estimated that the odds of coccidiomycosis incidence were 12&#xb7;5% (95% CI 5&#xb7;8-19&#xb7;6) higher in the 90 days following exposure to at least one preproduction well within 5 km of an individual's place of residence and that the odds of infection increased by 0&#xb7;7% (0&#xb7;4-0&#xb7;9) for each additional preproduction well developed within this distance. INTERPRETATION: These findings support a previously-unrecognised association between the development of oil and gas wells and transmission of coccidioidomycosis, potentially driven by dust generation. Given the prevalence of oil and gas development in the study region, its impact on coccidioidomycosis incidence might be large. FUNDING: National Institutes of Health, National Science Foundation.

Journal Article

Effectiveness of chlorhexidine gluconate-impregnated dressings in preventing central line-associated bloodstream infection in a paediatric intensive care unit: A randomised controlled trial.

OBJECTIVES: To compare the effectiveness and dermatological safety of chlorhexidine gluconate (CHG)-impregnated dressings versus conventional transparent dressings in preventing central line-associated bloodstream infection (CLABSI) in paediatric patients admitted to a PICU. METHODS: A single-blind, randomised controlled trial with a 1:1 allocation ratio was conducted in a tertiary PICU. A total of 250 paediatric patients with a central venous catheter were included (125 per group). Patient characteristics, catheter-related variables, catheter dwell time and skin alterations were recorded. The primary outcome was CLABSI, defined according to CDC/NHSN criteria. Bivariate analyses and multivariable logistic regression were performed, including clinically relevant covariates related to catheter exposure, dressing type, and vaccination status. The trial was registered at ClinicalTrials.gov (NCT07175116). RESULTS: CLABSI incidence was significantly lower in the CHG group compared with the conventional dressing group (2.4% vs. 18.4%; p&#xa0;<&#xa0;0.001). In multivariable analysis, CHG-impregnated dressings were independently associated with reduced CLABSI risk (OR = 0.15; 95% CI: 0.04-0.58). Longer catheter dwell time (OR = 1.13 per day; 95% CI: 1.04-1.22) and absence of complete vaccination (OR = 8.68; 95% CI: 2.48-30.47) were also associated with increased infection risk. Incomplete vaccination showed a similar trend without reaching statistical significance (OR = 6.48; 95% CI: 0.95-44.20). Skin alterations were more frequent in the CHG group (16.8% vs. 11.2%), predominantly in younger infants. CONCLUSIONS: CHG-impregnated dressings were associated with a significant reduction in CLABSI incidence in critically ill paediatric patients, although their use was linked to a modest increase in mild skin reactions. IMPLICATIONS FOR CLINICAL PRACTICE: CHG-impregnated dressings may be considered as part of a multifaceted infection prevention strategy, alongside appropriate catheter management, minimisation of catheter manipulation and proactive skin monitoring, with cautious and individualised use in infants.

Humans

Intensive glycemic control in adults aged 80&#xa0;years and older: A randomized trial evaluating diabetes complications and competing mortality.

AIMS: To evaluate whether intensive glycemic control reduces microvascular or macrovascular events compared with conservative glycemic targets in independently ambulatory adults aged 80&#xa0;years or older with type 2 diabetes. METHODS: We conducted a prospective, randomized, open-label, single-center trial enrolling independently ambulatory adults aged&#xa0;&#x2265;&#xa0;80&#xa0;years with type 2 diabetes. Participants were assigned (1:1) to an intensive glycemic target (HbA1c&#xa0;<&#xa0;7&#xa0;%) or a conservative target (HbA1c&#xa0;<&#xa0;9&#xa0;%) and followed for 5&#xa0;years. Primary outcomes were composite microvascular and macrovascular events. Analyses were done by intention to treat. Cause-specific Cox models and Fine-Gray subdistribution hazard models were used to account for all-cause mortality as a competing event. This trial is registered with ClinicalTrials.gov, NCT00850798. FINDINGS: 206 participants were randomly assigned to intensive (n&#xa0;=&#xa0;102) or conservative (n&#xa0;=&#xa0;104) treatment. At 5&#xa0;years, mean HbA1c was lower in the intensive group than in the conservative group (7&#xb7;42&#xa0;% vs 8&#xb7;21&#xa0;%; p&#xa0;=&#xa0;0&#xb7;005). Intensive therapy did not reduce microvascular events (hazard ratio [HR] 1&#xb7;24, 95&#xa0;% CI 0&#xb7;76-2&#xb7;04) or macrovascular events (HR 1&#xb7;02, 0&#xb7;36-2&#xb7;92). Competing risk analyses showed no reduction in cumulative incidence of vascular outcomes (subdistribution HR approximately 1&#xb7;0 for both). The cumulative incidence of death exceeded that of vascular events, indicating that many participants died before potential glycemic benefits could be realized. Severe hypoglycemia requiring hospitalization was more frequent with intensive therapy (7 vs 1 event). INTERPRETATION: In adults aged 80&#xa0;years or older with type 2 diabetes, intensive glycaemic control improved glycaemic levels but did not reduce vascular events and increased the risk of severe hypoglycaemia. High competing mortality substantially limits the potential long-term benefit of intensive treatment, supporting conservative and individualized glycemic targets in very old adults. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00850798.

Aged, 80 and over

Comparison of analgesic efficacy of pericapsular group of nerve block versus anterior quadratus lumborum block in adult patients undergoing unilateral hip arthroplasty: A comparative randomized controlled trial.

BACKGROUND: Total hip arthroplasty is a painful surgical procedure; therefore, it is a challenge to manage effective pain control during the perioperative period. STUDY OBJECTIVES: We compared the analgesic efficacy of the pericapsular nerve group block and the anterior quadratus lumborum block in patients undergoing unilateral hip arthroplasty. DESIGN: Randomized controlled trial. SETTINGS: Operating room of a tertiary care center. PATIENTS: 92 adult patients of >18&#xa0;years who underwent elective, unilateral total hip arthroplasty under spinal anesthesia were randomized to either Group P (USG guided PENG block with 30&#xa0;ml 0.25% ropivacaine +4&#xa0;mg dexamethasone) or Group Q (USG guided QL block with 30&#xa0;ml 0.25% ropivacaine +4&#xa0;mg dexamethasone) 20&#xa0;min before surgery. MEASUREMENTS: We compared the total perioperative fentanyl consumption between the two groups in the first 24&#xa0;h as the primary outcome. Other outcomes included time to first rescue analgesia in the postoperative period, NRS scores at rest and on movement at 0, 2, 4, 6, 12, and 24&#xa0;h, incidence of intraoperative hemodynamic changes, and incidence of postoperative PONV. MAIN RESULTS: There was no significant difference in the total fentanyl consumption between the two groups: 237.5 (150-450) &#x3bc;g in the P group and 250 (125-400) &#x3bc;g in the Q group; p&#xa0;=&#xa0;0.617. The time to first rescue analgesia was similar in both groups: the P group (198 [123-268] minutes) and the Q group (241 [180-318] minutes); p&#xa0;=&#xa0;0.120. There was also no difference in pain scores, intraoperative hemodynamic changes, or PONV. CONCLUSION: There was no difference in the perioperative opioid consumption, pain scores, and adverse event rates between the pericapsular nerve group block and anterior quadratus lumborum block in adult patients undergoing unilateral hip arthroplasty. TRIAL REGISTRATION: Clinical Trials Registry of India (CTRI number: CTRI/2023/08/057157).

Humans