In amyotrophic lateral sclerosis (ALS), respiratory decisions rely on serial trends rather than a single value. We evaluated whether early respiratory decline around diagnosis provides prognostic information in a real-world landmark framework. This single-center retrospective cohort screened 94 consecutive patients diagnosed between April 2019 and December 2025. A 6-month landmark was used. Early decline was estimated from %FVC values between - 30 and + 180 days around diagnosis. The primary model included age and early %FVC decline; robustness analyses included time-varying Cox, piecewise Cox, RMST, included-vs-excluded comparison, death-only analysis, and slope-quality filtering. Of 94 screened patients, 62 met baseline eligibility, 56 had calculable early slope, and 45 entered the landmark cohort; 28 post-landmark composite events occurred. In the Cox model, faster early %FVC decline was associated with higher hazard of death or invasive mechanical ventilation via tracheostomy (HR 1.33 per 1%/month faster decline, 95% CI 1.14-1.55, p < 0.001). PH diagnostics suggested non-proportionality (%FVC p = 0.031; NIV p = 0.034 in the expanded model), so this HR was interpreted as an average follow-up association and complemented by PH-robust analyses. The signal was stronger early than late, remained consistent in a death-only analysis, and favored the slower-decline group by RMST at 24 and 36 months. In this selected measurement-capable landmark cohort, early respiratory decline provided a clinically meaningful short-to-medium term prognostic signal for post-landmark adverse outcomes. External validation is required before broader generalization beyond measurement-capable landmark populations.
Dengue transmission in inland Southeast Asia shows strong seasonality and short-term surges that challenge timely public-health response. We assessed whether province-level Google search activity can support short-horizon dengue monitoring in Dong Nai, Vietnam. Monthly reported dengue cases from July 2013 to April 2021 were aligned with the Google Trends index (GTI) for "Sốt xuất huyết". Models were evaluated using leakage-free rolling-origin expanding-window cross-validation with 3-month validation blocks. We compared a negative binomial (NB) autoregressive baseline, NB models incorporating GTI, tree-based machine-learning models using the same covariates, and a simple NB-random-forest ensemble. Predictive performance was assessed using root mean squared error (RMSE), mean absolute error (MAE), R2, and discrimination for 95th-percentile outbreak exceedance. Cross-correlation peaked at lag 0, indicating that GTI functioned primarily as a contemporaneous nowcasting signal rather than a long-lead predictor. NB models incorporating GTI showed competitive calibration, while boosted tree models achieved the lowest point-estimate errors; XGBoost achieved RMSE ≈ 40.95 and R2 ≈ 0.861 compared with RMSE ≈ 45.23 and R2 ≈ 0.823 for NB with GTI. Adding GTI to the autoregressive NB baseline reduced RMSE by 11.77%, but the 95% confidence interval crossed zero, indicating modest and statistically non-significant incremental gain. Search-signal anomaly screening suggested that GTI spikes largely coincided with epidemic peaks and did not clearly inflate out-of-sample errors. Overall, GTI provides operational value for dengue nowcasting and alert triage in inland provinces, while future systems should integrate climate, vector, mobility, and media-monitoring data.
To date, there are limited clinical trials comparing the clinical efficacy between second-generation and third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI)s. The objective of this study was to compare the survival outcomes between afatinib and osimertinib as first-line treatments in patients with advanced EGFR-mutant non-small-cell lung cancer (NSCLC). Between January 2018 and December 2020, we retrospectively enrolled patients with advanced NSCLC harboring an exon 19 deletion or L858R mutation who received afatinib or osimertinib as first-line treatment to analyze the progression-free survival (PFS) and overall survival (OS). A total of 128 patients were included in this study, with 81 in the afatinib group and 47 in the osimertinib group. The median follow-up time was 39.9 months for the afatinib group and 37.0 months for the osimertinib group. The median PFS was 13.5 months in the afatinib group and 18.2 months in the osimertinib group (p = 0.240). The median OS was 40.5 months in the afatinib group and 37.0 months in the osimertinib group (p = 0.980). A total of 63% of patients received osimertinib as sequential therapy following progression on afatinib, with a median OS of 41.7 months. Among these patients, the median OS was 41.7 months for those with a detected T790M mutation, 42.0 months for those without the mutation, and 35.6 months for those with unknown T790M mutation status. Our study demonstrated that both afatinib and osimertinib as first-line treatments offer favorable median OS in patients with advanced EGFR-mutant NSCLC. In addition, we recommend that patients receiving afatinib as first-line therapy undergo sequential osimertinib treatment, regardless of their T790M mutation status.
Cyclophosphamide (CTX) combined with glucocorticoids and rituximab (RTX) are widely used for idiopathic membranous nephropathy (IMN), but clinical data comparing them in newly diagnosed patients with impaired renal function (eGFR < 60 mL/min/1.73 m2) remain scarce. This study aimed to compare their efficacy, safety, and effects on renal function in this specific population. A retrospective study was conducted at the First Affiliated Hospital of Wannan Medical University from November 2019 to July 2024, including 113 newly diagnosed IMN patients (55 in the CTX group, 58 in the RTX group) diagnosed by renal biopsy or positive PLA2R antibodies. All patients were treatment-naive and followed for ≥ 6 months. At 6 months, composite remission rates were 69.09% in the CTX group and 62.07% in the RTX group (P > 0.05). At 12 months, the RTX group showed a numerically higher composite remission rate (83.87% vs. 70.83% in CTX group) without statistical significance (P = 0.186). By 18 months, both groups reached 73.68% composite remission (P = 1.000). In the subgroup with eGFR < 60 mL/min/1.73 m2, RTX significantly improved renal function at 6 months (P = 0.008), while CTX showed no significant improvement (P = 0.113); however, no intergroup difference in eGFR was observed (P = 0.793). The CTX group had a higher incidence of non-serious adverse events, including leukopenia and mild infections (P < 0.05). HypoIgGemia was documented in 5 patients (8.62%) in the RTX group, all mild and asymptomatic. RTX shows comparable efficacy and better safety relative to CTX in this cohort, and may be a preferred option for newly diagnosed untreated IMN, especially in those with early renal impairment. RTX demonstrated comparable efficacy to CTX in newly diagnosed IMN but with superior safety. Notably, RTX showed greater short-term (6-month) renal function improvement in patients with early renal impairment, though long-term effects need further verification in larger-sample prospective studies.
To evaluate the effect of postoperative hydrocortisone dosing on health-related quality of life (HRQoL), metabolic parameters, and hypothalamic-pituitary-adrenal (HPA) axis recovery in cured Cushing's syndrome (CS). This single-centre, randomized, open-label trial included 42 adults with CS and postoperative hypocortisolism randomised to hydrocortisone dose 15 mg/day or 30 mg/day during the first three postoperative months. HRQoL was assessed with e EQ-5D and SF-36 at baseline, at 1 and 3 months, and final follow-up while metabolic parameters were evaluated at baseline and 3 months. Dose effects on metabolic parameters were evaluated using ANCOVA; and HPA axis recovery was assessed using Kaplan-Meier and Cox regression analyses. No significant between-group differences in HRQoL were observed during the three-month period. EQ-5D visual analogue scale scores improved significantly at the final follow-up in both groups, while SF-36 domain scores showed overall improvement over time. At three months, patients receiving 15 mg/day had lower triglycerides, total cholesterol and, HbA1c levels; after adjustment for baseline values, hydrocortisone dose independently affected triglycerides and total cholesterol. No adrenal crises occurred, and there was no excess of acute intercurrent illness or hospitalization in the lower-dose group. HPA axis recovery occurred in 71% of patients and was not associated with hydrocortisone dose. In cured CS, 15 mg/day hydrocortisone does not worsen HRQoL and had better metabolic profile. HRQoL improves over time irrespective of dose suggesting no benefit from supraphysiological hydrocortisone replacement after curative surgery.
Egg allergy is among the most common food allergies in infants. Allergy prevention guidelines have been updated globally based on evidence that earlier egg introduction reduces the risk of egg allergy, and these guidelines have been adopted widely. However, the association of this guideline change with the prevalence of egg allergy is unclear. To estimate the change in population prevalence of egg allergy after a guideline update recommending earlier introduction of egg into the infant diet. This cross-sectional study included infants aged 11 to 15 months in 2 population-based samples, recruited using identical methods when attending their 12-month immunization visit at immunization centers in Melbourne, Australia, before (2007-2011) and after (2018-2019) an update to allergy prevention guidelines. To isolate an association between a change in prevalence of egg allergy and the guideline change, direct regression standardization was used to estimate prevalence in the 2018-2019 sample had the distribution of known risk factors remained the same as in the 2007-2011 sample. Multiple imputation was used to address missing data. Prespecified subgroup analyses were conducted for infants with early eczema and stratified by parent country of birth. Data were analyzed between March 2025 and March 2026. Data on demographics, food allergy risk factors, egg introduction, and reactions were collected via questionnaires. Infants underwent skin prick tests to egg, and those with positive results underwent oral food challenges. A total of 7209 of 9500 eligible infants were included from 2 cohorts: 5276 infants (median [IQR] age, 12.4 [12.2-12.9] months; 50.8% [2665 of 5244] males; response rate, 76% [5276 of 6957]) from the 2007-2011 cohort and 1933 infants (median [IQR] age, 12.5 [12.2-13.0] months; 51.8% [1001 of 1932] males; response rate, 76% [1933 of 2543]) from the 2018-2019 cohort. The median (IQR) age at egg introduction decreased from 8 (6-10) months in 2007-2011 to 6 (6-8) months in 2018-2019. After adjusting for known allergy risk factors, the prevalence of egg allergy decreased from 9.2% in 2007-2011 to 7.6% in 2018-2019 (adjusted absolute difference, -1.6 [95% CI, -3.3 to -0.005] percentage points). In infants with early eczema, egg allergy decreased from 34.6% to 21.9% (adjusted absolute difference, -12.7 [95% CI, -20.0 to -5.4] percentage points). This study provides population-level evidence that updated infant feeding guidelines recommending earlier introduction of egg led to measurable reductions in the population prevalence of egg allergy. The findings suggest that guideline updates informed by randomized trial evidence may be associated with a reduction in food allergy prevalence when implemented effectively.
The present study aimed to estimate the heritability as well as genotypic and phenotypic correlations of body weights at different ages, average daily gain (ADG), and Kleiber ratio (KR) in Magra sheep. A total of 5,469 growth records, spanning 26 years (1998-2023), were obtained from the Arid Region Campus of the ICAR-Central Sheep and Wool Research Institute, Bikaner, Rajasthan. Genetic parameters were estimated using a univariate animal model incorporating fixed effects and random additive genetic effects under the restricted maximum likelihood (REML) framework in WOMBAT software. The estimates of direct heritability were 0.34 ± 0.02, 0.21 ± 0.02, 0.20 ± 0.03, 0.20 ± 0.03, 0.21 ± 0.03, 0.21 ± 0.03, 0.17 ± 0.02, 0.10 ± 0.02, 0.23 ± 0.03, 0.18 ± 0.03 and 0.10 ± 0.02, respectively for birth weight (BWT), weaning weight (3MWT), 6-month weight (6MWT), 9-month weight (9MWT), 12-month weight (12MWT), Average daily gains (ADG) i.e. ADG1 (birth to weaning), ADG2 (weaning to 6 month), ADG3 (6 to 12-month), KR1 (ADG1/3MWT0.75), KR2 (ADG2/6MWT0.75) and KR3 (ADG3/12MWT0.75), respectively. Heritability in present flock was moderate in early growth traits of Magra sheep indicating potential of improvement through selection. The genetic and phenotypic correlations among the studied traits revealed potential for their simultaneous improvement, particularly in association with 3MWT. The findings indicated that early selection based on 3MWT could facilitate substantial genetic progress in the resource population.
Fournier's gangrene (FG) is a rare but life-threatening infectious complication of surgery in the perineum and genital region. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been linked to genital infections in case reports, but the postoperative risk of FG in patients receiving these medications is unclear. We evaluated whether preoperative exposure to SGLT2is increases FG risk following genital or perineal surgery. We conducted a retrospective cohort study using the TriNetX Research Network, including adults who underwent genital or perineal surgery between 2013 and 2025. Exposure was defined as any SGLT2i prescription recorded at least 5 days before surgery. Patients with prior FG or debridement for necrotizing infection were excluded. The primary outcome was FG within 1 month postoperatively; secondary outcomes included risk over 3 months and 1 year. Cohorts were balanced using propensity score matching for demographic factors and comorbidities. Of 510,330 eligible patients, 7575 received SLGT2is and 502,755 did not. After matching, each cohort included 7572 patients. At 1 month, FG occurred in 13 (0.17%) exposed patients and 20 (0.27%) non-exposed patients (RR 0.65, 95% CI 0.32-1.30, p = 0.2). Results were similar at 3 months and 1 year. A subgroup analysis among patients with diabetes yielded results consistent with the primary analysis. Preoperative use of SGLT2is was not associated with increased postoperative FG risk following perineal or genital surgery. If validated, these findings may reassure clinicians and patients that SGLT2i use is safe in surgical patients, though protective medication management practices may contribute to these outcomes.
Finerenone improves cardiovascular and kidney outcomes in patients with type 2 diabetes and chronic kidney disease; however, hyperkalemia remains a safety concern in routine practice. We evaluated the incidence of hyperkalemia, factors associated with its occurrence, and temporal patterns of serum potassium after finerenone initiation. We conducted a single-center retrospective observational cohort study of patients who initiated finerenone between May 2022 and August 2025. The primary outcome was incident hyperkalemia (serum potassium ≥ 5.5 mEq/L). Candidate variables were selected using least absolute shrinkage and selection operator (LASSO)-penalized Cox regression, and associations were estimated using multivariable Cox proportional hazards models. Potassium trajectories were assessed using mixed-effects models over 12 months (6 months before and after finerenone initiation), with subgroup analyses by kidney function and baseline potassium. Among 289 eligible patients, 280 were included (mean age 68 years; 68% male; mean baseline eGFR of 36.8 mL/min/1.73 m2). Hyperkalemia occurred in 38 patients. Incident hyperkalemia was associated with higher baseline potassium and log-transformed C-reactive protein and with use of diuretics and potassium binders. Mean serum potassium increased by approximately 0.10 mEq/L over six months, with the largest rise in the first 1-2 months. Patients with eGFR < 30 mL/min/1.73 m2 or baseline potassium ≥ 4.5 mEq/L had higher potassium levels throughout follow-up. Finerenone was generally well tolerated, with modest potassium increases. In our real-world cohort, hyperkalemia occurred in a notable proportion of patients, underscoring the importance of early monitoring, particularly in those with reduced kidney function or elevated baseline potassium.
Despite free access in France, uptake of HIV pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) remains insufficient, particularly among younger and migrant subpopulations. This study describes a community-based program linking outreach via geosocial/sexual networking applications and community venues to same-day PrEP access at a sexual health center in Paris. MSM and transgender individuals aged ≥ 18 years were recruited and referred to the Le 190/Le SPOT sexual health center. At baseline, they received HIV/STI testing and, depending on results, initiation of PrEP, post-exposure prophylaxis (PEP), or antiretroviral therapy. Sociodemographic, behavioral, and clinical data were collected at baseline and follow-up (months 1, 3, 6). The primary outcome was PrEP uptake among eligible participants (HIV-negative, not on PrEP, without PEP indication); associated factors were assessed using Firth's penalized logistic regression. Between July 2023 and December 2024, 209 individuals were enrolled; 86% were recruited via apps, the median age was 31 years (IQR 26-41), and 47% were born outside France. Participants reported a median of six sexual partners (IQR 3-15) in the past three months; 73% had been tested for HIV/STI in the past year. Fourteen participants (7%) were living with HIV, including five newly diagnosed individuals. Among 164 PrEP-eligible participants, 118 (72%) initiated PrEP at baseline; 82/118 (70%) were retained at month 6. In multivariable analysis, uptake was associated with reporting ≥ 6 partners in the past three months and HIV/STI testing in the past year. These findings indicate high PrEP uptake among individuals presenting to care after community outreach, including younger and foreign-born MSM typically underrepresented in PrEP programs.
To report a case of autoimmune retinopathy (AIR) with multiple systemic involvement RESULTS: A 45-year-old Asian Indian male presented with progressive blurring of vision in the right eye for five years. Initial best-corrected visual acuity (BCVA) was 20/80 in RE and 20/25 in LE. Clinical evaluation was normal except for a few pigmentary alterations in the periphery. Optical coherence tomography (OCT) later revealed ellipsoid zone loss, and fundus fluorescein angiography showed peripheral venular leakage. Uveitis workup was negative except for a positive T-spot TB; Anti-tubercular therapy for nine months didn't improve the symptoms, with BCVA declining to 20/400 in RE. Fundus autofluorescence demonstrated hypo-autofluorescence in the macula surrounded by hyper-autofluorescence. Review of history revealed dermatological features, including alopecia areata and scalp vitiligo, followed by ocular disease and systemic autoimmune abnormalities. The history also indicated onset about two months after COVID-19 vaccination. Antiretinal and other systemic antibodies were positive. The patient was diagnosed with auto immune retinopathy (AIR) and treated with mycophenolate mofetil, escalating to 1.5 g twice daily. At final follow-up 6 months later, BCVA improved to 20/200 in RE and remained stable in LE, with reduced autofluorescence abnormalities. We report a case of multi system autoimmune disease initially presenting with dermatological features, followed by ocular and other systemic features which may have been triggered following COVID-19 vaccination in an otherwise healthy Indian male. We propose it could be a temporal event and are unable to prove a causal factor. A combination of multimodal imaging with multi-disciplinary approach helped us to come to a final diagnosis in this arduous journey for the patient.
The efficacy of self-fixating mesh in laparoscopic inguinal hernia repair remains controversial, and its use is not yet explicitly recommended by international guidelines. The short-term outcomes of patients who underwent trans-abdominal pre-peritoneal (TAPP) repair using Parietex™ Lap.ProGrip™ (Lap.ProGrip) during a 10-year period, were retrospectively analyzed, to evaluate its effectiveness at reducing recurrence and chronic post-operative inguinal pain (CPIP). Data from 965 patients (1,129 hernias), aged ≥ 18 years, who underwent TAPP with Lap.ProGrip between November 2014 and October 2024, were retrieved. The standard post-operative follow-up period was 6 months. The primary endpoint was post-operative recurrence, specifically for large direct hernias (Japan Hernia Society [JHS] M3 type). The secondary endpoint was CPIP, which was defined, based on international guidelines, as pain that persisted for ≥ 3 months, required intervention, and interfered with daily activities. The intra-operative videos of all patients with CPIP were reviewed to identify potential procedural causes. The 6-month follow-up completion rate was 88.4%. Although 478 hernias (42.3%) had a defect size ≥ 3 cm, including 149 hernias (13.2%) of JHS M3 type, no early recurrences occurred. Four patients (0.5%) had CPIP. Intra-operative video review revealed that in three of the four patients, electrocautery for hemostasis within the "trapezoid of disaster" was performed, suggesting nerve injury, and no mesh-related displacement or folding was observed. The self-fixating mesh provides reliable short-term stability, even for large direct hernias. CPIP appears to be more closely associated with intra-operative hemostatic maneuvers than with the mesh.
Physical activity benefits stress and anxiety, yet spiritually motivated walking may confer distinct psychobiological advantages compared with competitive sports. While prior studies have been largely cross-sectional, the longitudinal dynamics of psychological, endocrine, and genetic interactions remain underexplored. We conducted a mixed cross-sectional and longitudinal study including three hundred adults in Iraq (n = 100 athletes, n = 100 spiritual walkers, n = 100 sedentary controls). Subjects were tracked across four waves: baseline (T0), immediate post-activity (T1), 1-month follow-up (T2), and 3-month follow-up (T3). The results revealed perceived stress (PSS-10), state anxiety (STAI-S), salivary cortisol and DHEA-S (ELISA), and genotyping of BDNF Val66Met (rs6265) and 5-HTTLPR. Analyses used ANOVA/ANCOVA, linear mixed models (LMM), and regression models with FDR correction. Across the waves studied, spiritual walkers consistently showed lower levels of stress and anxiety compared to both athletes and control groups (all p ≤ 0.01). Longitudinal linear mixed models corroborated enduring disparities at T3, wherein the spiritual walkers exhibited the most advantageous psychological profile. Endocrine assessments indicated diminished cortisol levels and increased DHEA-S concentrations in walkers, resulting in a persistently favorable cortisol/DHEA-S ratio relative to the other groups. Genetic analyses indicated that BDNF Met/Met and 5-HTTLPR S/S carriers reported heightened distress; however, these effects were less pronounced among walkers. An integrated model elucidated 51.8% of the variance in anxiety, identifying cortisol (β = 0.42) and DHEA-S (β=-0.35) as the most significant predictors. Spiritually motivated walking correlated with persistent decreases in stress and anxiety, along with improved regulation of the HPA-axis and a reduction in genetic vulnerability, effects that persisted for up to 3 months following the intervention. These results underscore the practical applicability of culturally relevant, affordable interventions that incorporate spiritual walking into community mental health initiatives, considering biological factors.
To evaluate the real-world efficacy of chemoimmunotherapy combined with brain radiotherapy and to explore prognostic biomarkers in patients with small cell lung cancer (SCLC) and brain metastases (BM). We retrospectively analyzed 133 consecutive patients with de novo SCLC-BM. Patients were categorized into a chemotherapy-only cohort (n = 54) and a chemoimmunotherapy cohort (n = 79). Survival outcomes were assessed. Exploratory analyses included serum markers (NSE, CEA) and tissue molecular subtypes (SCLC-A/N/P/TN) identified via multiplex immunofluorescence. Chemoimmunotherapy was significantly associated with prolonged median progression-free survival (6.1 vs. 5.1 months, P = 0.034) and overall survival (10.2 vs. 9.0 months, P = 0.019) compared to chemotherapy alone. Time-dependent multivariate analysis confirmed that both chemoimmunotherapy (adjusted HR = 0.65, P = 0.032) and brain radiotherapy (time-dependent HR = 0.63, P = 0.040) were independent protective factors for overall survival. Notably, the longest median overall survival (15.2 months) was observed in patients receiving the combination of chemoimmunotherapy and brain radiotherapy. In exploratory biomarker analyses, high baseline NSE coupled with low CEA levels correlated with poor prognosis (HR = 6.47). Furthermore, distinct molecular heterogeneity was observed; SCLC-N and SCLC-P subtypes were associated with significantly inferior survival compared to SCLC-A and SCLC-TN phenotypes. First-line atezolizumab plus chemotherapy is associated with favorable survival outcomes in patients with SCLC brain metastases, and the longest survival was observed when combined with brain radiotherapy. Additionally, exploratory analyses suggest that high neuroendocrine burden and specific molecular subtypes (SCLC-N/P) may serve as potential prognostic biomarkers, warranting prospective validation.
Effective clinical communication is a core competency in dental education, yet traditional teaching methods often fail to provide authentic, repeatable practice with immediate feedback. Artificial intelligence (AI)-based virtual patients offer a promising alternative, but evidence in dental education remains limited. This study evaluated the effectiveness of an AI virtual patient system for developing clinical communication skills in dental undergraduates. A prospective, single-blind, randomized controlled trial was conducted with 60 fourth-year dental students randomly allocated to an intervention group (n = 30) using an AI virtual patient system for 8 weeks of self-directed inquiry training or a control group (n = 30) receiving traditional peer role-play training. Outcomes included Objective Structured Clinical Examination (OSCE) assessments of inquiry completeness and communication skills, Jefferson Scale of Empathy (JSE) scores, and self-reported learning motivation and clinical confidence. Assessments were conducted at baseline, immediately post-intervention, and at 3-month follow-up. Semi-structured interviews with 12 intervention participants provided qualitative insights into learning experiences. The intervention group demonstrated significantly higher OSCE inquiry completeness (86.4 ± 5.2 vs. 73.8 ± 6.1, p < 0.01), communication skills (89.1 ± 4.8 vs. 76.3 ± 5.9, p < 0.01), and self-reported empathic orientation (JSE scores: 112.4 ± 8.3 vs. 103.7 ± 9.2, p < 0.05) post-intervention, with effects sustained at 3 months. Learning motivation and clinical confidence were also significantly higher in the intervention group (p < 0.05). Qualitative analysis revealed that AI training fostered deliberate practice, reduced communication anxiety, and enhanced reflective learning through immediate feedback. An AI-mediated training package, integrating structured practice with automated feedback, effectively enhances dental students' clinical communication skills, self-reported empathic orientation, and learning motivation, with effects sustained at 3 months. This approach, which integrates established learning theories into a scalable digital format, may help address longstanding challenges in communication training and offers particular value for competency-based curricula and resource-constrained settings.[Box: see text].
Community health workers (CHWs) improve chronic disease management in underserved populations, but scalable integration strategies are limited. To evaluate whether a multidimensional intervention incorporating telementored CHWs and a structured participant-CHW-clinician feedback loop can improve diabetes outcomes. This 12-month randomized clinical trial was conducted at 3 institutionally and geographically diverse community clinics in Texas between September 1, 2023, and April 30, 2025, and included low-income, uninsured White Hispanic adults with type 2 diabetes identified through clinic databases. Data were analyzed between May 1 and July 31, 2025. Individuals were randomized 1:1 to the intervention or control. For the intervention, CHWs delivered (1) group diabetes education, (2) individualized telehealth-based coaching, and (3) a novel participant-CHW-clinician feedback loop to facilitate communication, address participant concerns, and improve care coordination. The control was usual care (quarterly clinician visits and access to multidisciplinary and social services). The primary outcome was baseline to 12-month change in hemoglobin A1c (HbA1c) level. Secondary outcomes included changes in cholesterol levels, American Diabetes Association (ADA) guideline adherence, participant recruitment, intervention fidelity, and feedback loop issue resolution. Of 257 participants included in the intention-to-treat analysis (mean [SD] age 54 [11] years; 166 [64.6%] female), 129 were in the intervention group and 128 were in the control group. The intervention reduced HbA1c (net difference, -1.0 [95% CI, -1.5 to -0.4] percentage points [pp]; P = .001), total cholesterol (net difference, -35.4 mg/dL; 95% CI, -54.6 to -17.2 mg/dL; P = .02), and low-density lipoprotein cholesterol (net difference, -29.7 mg/dL; 95% CI, -44.5 to -14.9 mg/dL; P < .001) levels compared with control. ADA guideline adherence improved for foot examinations (absolute risk [AR], 19.2 [95% CI, 7.4-30.9] pp; relative risk [RR], 1.65 [95% CI, 1.19-2.27]; P = .03) and urine microalbumin screening (AR, 15.8 [95% CI, 5.3-26.3] pp; RR, 1.24 [95% CI, 1.07-1.43]; P = .048). CHWs addressed 490 participant concerns (87.2%) via the feedback loop, including medication refills, glucose management, and access to care. In this randomized clinical trial, the CHW intervention significantly improved diabetes outcomes in low-income settings, potentially by reducing fragmentation through structured feedback. Findings also highlight limitations in usual care, underscoring the need for scalable strategies to strengthen chronic disease management in low-income populations. ClinicalTrials.gov Identifier: NCT04835493.
Heart failure with preserved ejection fraction (HFpEF) remains difficult to manage because conventional therapies often provide limited symptom relief and do not adequately address exercise-related congestion. Right greater splanchnic nerve (GSN) ablation has emerged as a potential therapeutic approach by modulating splanchnic venous capacitance. However, current evidence is limited and includes both uncontrolled and randomized studies. We performed a systematic review and meta-analysis of studies evaluating right GSN ablation in HFpEF. Searches were conducted in PubMed, Scopus, and Embase in December 2024. Randomized and non-randomized studies were included. Continuous outcomes were pooled as mean differences (MDs) with 95% confidence intervals (CIs). Sensitivity analyses excluding the randomized controlled trial (RCT) were performed for selected outcomes. Analyses based on uncontrolled studies and converted median/interquartile range data were considered exploratory. The most consistent findings were observed in functional and exercise-related hemodynamic outcomes. Six-minute walk distance improved at both 6 and 12 months, and KCCQ overall score showed improvement, although with substantial heterogeneity. Provocative hemodynamic measures, including 20 W and peak pulmonary capillary wedge pressure, were reduced at 1 month, whereas resting hemodynamic measures showed no clear pooled benefit. NT-proBNP, renal indices, blood pressure, heart rate, and left ventricular ejection fraction were largely unchanged. Overall, randomized sham-controlled evidence did not demonstrate a clear comparative benefit. Right GSN ablation may improve selected exercise-related hemodynamic, functional, and patient-reported outcomes in HFpEF, but the current evidence base is driven mainly by small uncontrolled studies. Randomized evidence remains neutral, and further sham-controlled trials are required.
The aim of this study is to describe the basic pathoanatomical characteristics of a stable Maisonneuve fracture and mid-term results of its nonoperative treatment. The study included 17 prospectively collected patients with a mean age of 59 years. The postinjury ankle CT had to meet the following criteria: nondisplaced or minimally displaced (up to 1 mm) fracture of medial malleolus, medial clear space less than 3 mm, nondisplaced or minimally displaced (up to 2 mm) fracture of posterior malleolus, anatomical position or minimal malposition of the distal fibula in the fibular notch (widening of the tibiofibular space up to 2 mm or external rotation of the distal fibula up to 10°). The average follow-up period was 34 months, the final follow-up included CT examination and functional evaluation based on AOFAS and FAOS scores. A medial malleolus fracture was recorded in 12% cases, a posterior malleolus fracture in 29% patients and a Tillaux-Chaput tubercle fracture in 18% cases. All fractures of the proximal fibula, medial and posterior malleolus healed within 3 months. The position of the distal fibula in the fibular notch did not change in 11 cases compared to the post-injury CT scan, improved slightly in 5 cases, and worsened slightly in 1 case. The average final AOFAS hindfoot score was 96.9 points and the average final FAOS score was 98.7%. A stable form of the Maisonneuve fracture is characterized by no or minimal displacement on CT scans and can be successfully treated nonoperatively.
Bullying perpetration and victimization are prevalent adolescent peer problems with lasting adverse consequences. Although previous research identifies various parental and family risks for these peer problems, the role of mothers' parental burnout and the underlying longitudinal mechanisms remain underexplored. This three-wave longitudinal study (6-month intervals across 12 months) examined whether higher levels of mothers' parental burnout at T1 predicted higher adolescent bullying perpetration and victimization at T3, and whether adolescents' perceptions of higher psychological control at T2 and lower autonomy support at T2 mediated these associations. The sample included 1,969 adolescents (49.90% boys; Mage = 14.35, SDage = 1.30) and their mothers (Mage = 41.68, SDage = 5.24). After controlling for autoregressive effects and covariates (gender, school, and SES), results showed that higher mothers' parental burnout at T1 predicted higher psychological control at T2 and lower autonomy support at T2, as well as greater bullying perpetration and victimization at T3. Higher psychological control at T2, rather than lower autonomy support at T2, uniquely predicted greater bullying perpetration and victimization at T3 and emerged as the specific significant longitudinal mediator. The indirect effect through psychological control exceeded that through autonomy support for both outcomes (significant at the 90% CI for bullying perpetration and 95% CI for bullying victimization). These findings revealed that psychological control is the specific parenting mechanism through which mothers' parental burnout contributes to adolescents' later bullying perpetration and victimization.
Pseudoprogression is an atypical response pattern observed during treatment with immune checkpoint inhibitors (CPIs) that can complicate clinical decision-making. It is characterized by initial radiologic progression followed by subsequent tumor regression or stabilization, with confirmation requiring repeat imaging. We aimed to characterize the clinical and imaging features of confirmed pseudoprogression in solid tumors treated with CPIs using pooled study data. We systematically searched MEDLINE, Embase, and Web of Science through December 2025. Prospective and retrospective cohort studies and randomized trials reporting confirmed pseudoprogression during CPI therapy were eligible. Two independent reviewers performed study selection and data extraction using predefined criteria. Study quality was assessed using the Joanna Briggs Institute checklist. Pooled analyses were conducted with RevMan and Stata. Outcomes included time to initial radiologic progression, magnitude of tumor burden increase, occurrence of new lesions, changes in nontarget lesions, and subsequent objective response. Thirteen retrospective studies were included; most applied iRECIST criteria. The pooled median time to initial progression was 2.52 months (95% CI, 1.54-3.51). Mean tumor burden increase was 33.0% (95% CI, 22.7-43.3), and new lesions occurred in 35.3% of cases. Tumor burden increases > 100% were rare (3.9%). Despite initial progression, 41.8% subsequently achieved partial response and 6.4% complete response without therapy change. Median time to best response was 2.79 months (95% CI, 0.62-7.20). Pseudoprogression typically occurs early during CPI therapy and is associated with modest tumor growth. Marked tumor increases are uncommon and may help distinguish true progression. Careful clinical and radiologic assessment remains essential.