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PubMed2026

Effectiveness of Yoga and Combined Exercise in Female With Rheumatoid Arthritis: Randomized Controlled Trial.

BACKGROUND: Although exercise is beneficial for Rheumatoid Arthritis (RA), the comparative efficacy of different modalities for patients in clinical remission remains unclear. This study compared the short- and long-term effects of yoga versus a combined exercise programme on pain, balance, mobility, fatigue, depression, and quality of life in females with RA in remission. METHODS: In this single-blind, randomized controlled trial, 74 female participants were allocated to yoga (n = 25), combined exercise (n = 25), or a usual care control group (n = 24). The intervention groups underwent an 8-week supervised programme. Clinical assessments, including the Visual Analogue Scale (pain), Berg Balance Scale, Timed Up and Go Test, Beck Depression Inventory, Fatigue Severity Scale, and Short Form-36, were conducted at baseline, post-intervention (8 weeks), and follow-up (20 weeks). RESULTS: Both intervention groups demonstrated significant improvements in all outcome measures compared with the control group at post-treatment and follow-up (p < 0.05). Notably, the yoga group exhibited superior outcomes compared to the combined exercise group in reducing pain intensity (median reduction of 4.00 vs. 2.00 points; p < 0.001, η2 = 0.724), as well as in physical function, balance, fatigue, depression, and quality of life at the 20-week follow-up. These benefits may be partly attributed to the incorporation of breathing and relaxation techniques inherent to yoga practice. CONCLUSIONS: Both 8-week yoga and combined exercise programs are effective in managing residual symptoms in females with RA in clinical remission. However, yoga appears to provide superior benefits in pain management and psychosocial well-being, supporting its integration into multidisciplinary RA management protocols, particularly for addressing psychosocial burden in patients achieving remission. TRIAL REGISTRATION: This study was retrospectively registered at NCT07072754 (clinicaltrials.gov).

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PubMed2026

Symptoms and treatment response to florensocatib and inhaled tobramycin in bronchiectasis: Post hoc analysis of two randomized trials.

Inhaled antibiotics and DPP-1 inhibitors improve clinical outcomes in bronchiectasis, but whether baseline symptom burden predicts differential treatment responses remains unclear. In this post hoc analysis of two multicenter randomized trials (SAVE-BE, n = 224; TORNASOL, n = 357), we evaluate the association between baseline Quality of Life-Bronchiectasis Respiratory Symptom Scale (QoL-B-RSS) and treatment effects of florensocatib and inhaled tobramycin. In SAVE-BE, florensocatib reduces exacerbation rates versus placebo (relative risk [RR], 0.47; 95% confidence interval [CI], 0.33-0.67; p < 0.0001), with RRs of 0.53 and 0.40 observed in patients with high and low symptom burdens, respectively, but no significant symptomatic improvement. In TORNASOL, tobramycin produces clinically meaningful QoL-B-RSS improvements (exceeding the 8-point cutoff in high-symptom patients) and ameliorates bronchitic symptoms, with greater benefits in those with higher baseline symptom burden. These hypothesis-generating findings suggest that baseline symptom burden may identify differential responses to anti-inflammatory versus anti-infective therapies in bronchiectasis and support its potential as a simple, practical stratification tool to guide personalized treatment.

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PubMed2026

Metabolic ketosis attenuates NLRP3 inflammasome activation and is associated with improvements in hepatic steatosis and liver stiffness in MASLD: a pilot randomized controlled trial.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a systemic metabolic-inflammatory disorder in which metabolic stress and innate immune activation, particularly through the NLRP3 inflammasome, contribute to disease progression. Metabolic ketosis, characterized by increased levels of circulating ketone bodies, especially β-hydroxybutyrate, has emerged as a promising strategy to modulate substrate utilization, inflammatory signaling, and hepatic injury. However, clinical evidence integrating molecular, metabolic, and hepatic outcomes remains limited. METHODS: In this pilot randomized controlled trial, 20 participants with newly diagnosed MASLD were randomly assigned to either a 3-month intervention with a daily C8-enriched medium-chain fatty acid formulation (m-CAP; meta-Capridin, providing approximately 20 g/day of C8) or a standardized low-carbohydrate dietary protocol. Metabolic indices, inflammatory mediators, adipokines, and hepatic enzymes were assessed. The expression of key inflammasome components (NLRP3, caspase-1, and ASC) was evaluated in peripheral blood mononuclear cells, and hepatic steatosis and liver stiffness were measured via transient elastography. RESULTS: The C8-enriched intervention was associated with increased circulating β-hydroxybutyrate levels, indicating the achievement of nutritional ketosis. Changes over time were observed in metabolic parameters, including fasting serum glucose (p < 0.05), HOMA-IR (p < 0.05), body fat percentage (p < 0.05), and BMI (p < 0.05). Alterations in inflammatory mediators and adipokine-related outcomes were also observed following the intervention. At the molecular level, changes in inflammasome-related markers were detected, including caspase-1 mRNA expression (p < 0.05) and NLRP3 expression at the transcriptional (p < 0.05) and protein levels (p < 0.01), whereas ASC expression remained unchanged. Changes in hepatic steatosis (p < 0.01) and liver stiffness measurements were observed following the intervention. Given the absence of significant Group × Time interactions for several secondary outcomes, these findings should be interpreted as exploratory and hypothesis-generating. CONCLUSIONS: Induction of metabolic ketosis was associated with changes in metabolic, inflammatory, and hepatic parameters in patients with MASLD. The observed associations between ketosis, inflammasome-related markers, and noninvasive liver outcomes warrant further investigation of ketosis-based interventions as adjunctive approaches in MASLD. Larger and longer-term clinical trials are needed to confirm these findings and to determine whether short-term changes in liver stiffness reflect sustained alterations in hepatic status rather than structural fibrosis regression. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT); Unique identifier: IRCT20170315033086N12; Registration date: 19 September 2024; Registry URL: https://www.irct.ir. IRCT is a primary registry in the WHO Registry Network (https://www.who.int/tools/clinical-trials-registry-platform/network/primary-registries).

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PubMed2026

Bioabsorbable vs. titanium screws in first metatarsophalangeal joint arthrodesis: a pilot randomized controlled trial with 2-year follow-up.

INTRODUCTION: To assess the feasibility and preliminary clinical outcomes of bioabsorbable screw fixation in first metatarsophalangeal joint arthrodesis compared to conventional titanium screw fixation. METHODS: In this prospective pilot randomized controlled trial, 30 patients were allocated 1:1 to bioabsorbable or titanium cannulated lag screw fixation. Arthrodesis was performed using a cup-and-cone technique at two Finnish hospitals. Full weight-bearing in an orthopaedic shoe was allowed after six weeks. Outcomes included AOFAS and VA-FAS FA-VAS scores, union rates, and complications assessed at 3, 6, 12, and 24 months. RESULTS: Both groups showed significant functional improvement with no between-group differences. At 24 months, mean AOFAS scores were 89.1 (SD 2.7) in the titanium group and 90.0 (SD 0.0) in the bioabsorbable group (p = 0.23). Mean FA-VAS total scores (sum of pain, function, and complaints subscales) were 1948 (SE 59.4) in the titanium group and 1914 (SE 61.4) in the bioabsorbable group (p = 0.655). Union rate was 90% overall; nonunion occurred in one titanium and two bioabsorbable patients, all requiring revision. No implant-related complications or hardware removal surgeries were recorded. Degradation of bioabsorbable screws caused no adverse clinical or radiographic reactions. CONCLUSIONS: Bioabsorbable screws appear safe and feasible in first metatarsophalangeal joint arthrodesis, with preliminary outcomes comparable to titanium fixation. These findings support the conduct of a larger confirmatory trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03133039, registered 28 April 2017. https://clinicaltrials.gov/ct2/show/NCT03133039.

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PubMed2026

Hypertension in a Randomized Trial of Dolutegravir- Versus Efavirenz-Based Antiretroviral Therapy in Pregnant and Postpartum Women with HIV.

INTRODUCTION: We performed an analysis of incident hypertension in a randomized trial comparing dolutegravir (DTG) + emtricitabine (F)/tenofovir alafenamide (TAF) versus DTG + F/tenofovir disoproxil fumarate (TDF) versus efavirenz (EFV)/F/TDF in pregnant and postpartum women with HIV. METHODS: Women were randomized at 14-28 weeks gestational age (GA) to start DTG + F/TAF, DTG + F/TDF, or EFV/F/TDF and followed through 50 weeks postpartum. The composite incident hypertension outcome was defined as initiation of antihypertensive medication or ≥2 elevated blood pressures categorized as elevated (130-139 and/or 80-89 mmHg), mild (140-159 and/or 90-99 mmHg), moderate (≥160-179 and/or ≥100-109 mmHg), and severe (≥180 and/or ≥110 mmHg). Incident gestational hypertension was defined by initiation of antihypertensive medication or ≥2 blood pressures ≥ 140 and/or ≥90 mmHg at ≥20 weeks GA with resolution by 12 weeks postpartum. Cox proportional hazard models were used for by-arm comparisons of the composite outcome and to look for the effect of weight change within arm. RESULTS: Of 626 women without baseline hypertension (median age 26.6 years), the composite incident outcome occurred in 49% (n = 308), predominantly due to the incident elevated category of elevated blood pressure, with no significant differences by arm, although hypertension was numerically more likely in the DTG arms. Each additional 5 kg of weight was associated with an 8%-17% higher hazard of the composite hypertension outcome. Twenty-seven participants (4.3%) had gestational hypertension with no apparent differences between arms. CONCLUSIONS: Our data contribute information regarding the safety of DTG-based ART and TAF in pregnant and postpartum women and highlight the importance of monitoring weight and performing hypertension screening as part of maternal health care for young women with HIV.

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PubMed2026

Effects of testosterone-augmented multimodal exercise intervention in spinal cord injury: a randomized controlled trial.

CONTEXT: Spinal cord injury (SCI) leads to profound muscle atrophy, aerobic deconditioning, and metabolic dysfunction. Exercise-based interventions alone produce modest benefits. Whether testosterone can augment physiologic responses to exercise in this population remains untested. OBJECTIVE: To evaluate efficacy and safety of home-based intervention combining functional electrical stimulation-assisted leg cycling (FES-LC), arm ergometry (AE), and testosterone compared with FES-LC, AE plus placebo in adults with SCI. METHODS: This randomized, placebo-controlled, double-blind trial enrolled 84 adults (76 males and 8 females) aged 19-70 years with SCI (neurologic levels C4-T12; AIS grades A-D). Participants were randomized to multimodality intervention (home-based FES-LC, AE and intramuscular testosterone undecanoate) (n = 38) or control intervention (FES-LC, AE plus placebo) (n = 46) for 16 weeks. The primary outcome was change in aerobic capacity (peak VO2) during AE cardiopulmonary exercise testing. Secondary outcomes included lean mass, hemoglobin, cardiometabolic markers, and safety. RESULTS: Mean (SD) age was 44 (13) years and time since injury was 13.9 (13) years). Between-group changes in peak VO2 were not statistically significant. Within-group improvements were larger in multimodality (∼19% increase; 0.10 L/min; 95% CI, 0.02-0.18 L/min) compared to controls (∼6% increase; 0.06 L/min; 95% CI, -0.01-0.13). The multimodality group gained significantly more lean mass (whole-body:1.84 kg, 95% CI: 0.52-3.16, P = .007; lower extremity 0.92 kg, 95% CI: 0.38-1.45, P = .001), and anemia was corrected in a greater proportion of participants. Adverse event rates were similar between groups. CONCLUSION: A home-based multimodality intervention combining FES-LC, AE, and testosterone was safe and associated with greater improvements in lean mass and hemoglobin. Although between-group differences in aerobic capacity were not statistically significant, greater within-group increases were observed in the multimodality group. These findings may inform future studies of testosterone-augmented exercise interventions for individuals living with SCI.

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PubMed2026

Predictors of Treatment Failure in Children With HIV Starting First-line Antiretroviral Therapy in the ODYSSEY Trial.

BACKGROUND: Data on predictors of treatment failure in children starting antiretroviral therapy (ART) are limited, particularly on dolutegravir-based regimens (DTG). METHODS: ODYSSEY demonstrated superior efficacy of DTG versus standard-of-care (SOC). We assessed predictors at ART initiation of treatment failure by 96 weeks. RESULTS: Three hundred and eighty-one children started first-line ART (82% African). At ART-initiation, median age was 10.5 years (IQR: 6.5, 14.0, 67 < 3 years), CD4% 20% (IQR: 12, 28), BMI-for-age Z-score -.58 (IQR:-1.48, +.25). One hundred and eighty-nine children started DTG, 192 started SOC (91% ≥3 years started efavirenz; 79% <3 years started lopinavir). Seventy-five children experienced treatment failure (24 DTG, 51 SOC). Failure risk was lower on DTG than SOC (hazard ratio [HR] = 0.47, 95% CI: 0.29-0.77, P = .002). Lower BMI-for-age Z-score (HR = 0.82 for each unit gain, 95% CI: 0.70-0.96, P = .01) and being at an African site (HR = 2.09, 95% CI: 0.82-5.31, P = .09) were associated with higher failure risk. Risk was also higher at younger ages with the steepest increase in the youngest children and increased at lower CD4%, with a stronger CD4% effect at younger ages. At CD4% = 20, HRs relative to age 10 years were 2.40 (95% CI: 1.58-3.65) at age 1 year, 1.30 (95% CI: 1.15-1.48) at age 5 years, and 0.80 (95% CI: 0.72-0.89) at age 18 years. At age 1 year, HRs relative to CD4% = 20 were 1.39 (95% CI: 1.16-1.66) at CD4% = 15, and 0.52 (95% CI: 0.36-0.75) at CD4% = 30; at age 10, corresponding estimates were 1.07 (95% CI: 0.94-1.20) at CD4% = 15, and 0.88 (95% CI: 0.69-1.13) at CD4% = 30. CONCLUSIONS: Young age, low BMI-for-age, and low CD4% at ART initiation predicted higher risk of treatment failure and can guide targeted support.

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PubMed2026

The effect of monetary versus point-based rewards on effort-cost decision making in individuals at clinical high risk for psychosis.

OBJECTIVE: The dissemination of inexpensive computerized behavioral tasks indexing amotivation may enhance the assessment of clinical high risk (CHR) across settings. However, the impact of varying reward value in such tasks is unclear. If point-based rewards engage participants, this could improve the scalability of computerized assessments. We tested how point-based rewards versus money impacted effort-cost decision-making in CHR individuals. We further assessed how negative symptom severity and household income interacted with reward-type to impact behavior. METHODS: Participants completed the Effort Expenditure for Reward Task (EEfRT). Participants were randomly assigned to receive either money or points for their performance during the EEfRT. Data from a large sample of CHR (N = 233) individuals and healthy controls (HC; N = 157) were collected. RESULTS: Across diagnostic groups, we observed heightened effort expenditure when money was used as a reward (b = 0.13, p = 0.018). We did not find an interaction of CHR status (b = 0.07, p = 0.845) or negative symptoms (b = 0.01, p = 0.429) with reward-type. Within CHR individuals, heightened negative symptom severity was associated with reduced expended effort (b = -0.03, p = 0.016), regardless of reward type. In an exploratory analysis, we found that individuals in the money condition with relatively high household income expended less effort during high reward, high probability trials (b = -0.24, p = 0.046). CONCLUSIONS: Across CHR and HC individuals, individuals pursuing money expended greater effort. While we did not find a group by reward type interaction, CHR individuals with heightened negative symptom severity expended less effort across trials, replicating prior work. Present findings support further study of point-based rewards in tasks indexing amotivation.

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PubMed2026

MIS-TLIF Versus Open TLIF in Combined Lumbar Stenosis and Low-Grade Spondylolisthesis : Of Discharge Timing and Treatment Pricing.

STUDY DESIGN: An open-label, randomized, noninferiority clinical trial. OBJECTIVE: To determine the effectiveness of the MIS-TLIF over the O-TLIF in patients with symptomatic lumbar stenosis combined with low-grade spondylolisthesis by comparing the clinical efficacy and safety. SUMMARY OF BACKGROUND DATA: In patients with combined lumbar spinal stenosis and spondylolisthesis, it remains uncertain whether minimally invasive fusion surgery is noninferior to the open approach. MATERIALS AND METHODS: We conducted an open-label, noninferiority trial involving patients with symptomatic lumbar stenosis combined with low-grade spondylolisthesis. Patients were randomly assigned in a 1:1 ratio to undergo either MIS-TLIF or open TLIF surgery. The primary endpoint was the reduction in the Oswestry disability index (ODI) score from baseline to three months postsurgery, with a noninferiority margin of 12 points. Secondary outcomes included three-month changes from baseline in back and leg pain, neuropathic pain, satisfaction with treatment, intraoperative data, and cost-effectiveness. RESULTS: In the modified intention-to-treat population, the mean difference was 0.4, with the corresponding 90% CI of -5.7 to 6.5, having a lower bound below the noninferiority margin of 12. Similar results were obtained by analysis of the per-protocol population. 82.8% of patients achieved the MCID for the ODI. Results for secondary outcomes (clinical scales, complications) showed no significant differences between the treatment groups (all P >0.05). Although the open TLIF group had a hospital stay that was 1.5 days longer ( P =0.005) and required additional analgesia more frequently ( P =0.026), direct costs were 10.5% higher in the MIS-TLIF group ( P <0.001). CONCLUSIONS: This is the first high-quality study comparing open TLIF and MIS-TLIF with a validated primary endpoint. Among patients with combined lumbar degenerative stenosis and degenerative spondylolisthesis, MIS-TLIF resulted in clinical outcomes at three months that were noninferior to those with open TLIF.

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PubMed2025

Application of Perioperative Real-Time Fluorescence Imaging to Achieve High-Quality Debridement: A Randomized Control Trial.

OBJECTIVE: To investigate the effectiveness of real-time fluorescence imaging (RTFI)-assisted debridement in managing chronic wounds compared with standard surgical debridement. APPROACH: This study was a patient-blinded, randomized clinical trial conducted from February 17, 2021, to July 30, 2021, on patients with chronic wounds. Patients were randomized to an RTFI group (M group) or conventional group (C group). The primary outcomes were as follows: percentage of residual bacterial area (preoperative and postoperative), number of debridements, high-quality debridement ratio, operation duration, and wound healing duration. RESULTS: A total of 100 patients were enrolled in both groups. No significant difference in the percentage of preoperative residual bacterial area or high-quality debridement ratio was seen. The M group underwent debridement an average of 2.6 times and had a significantly longer duration of operation (33.5 ± 12.7 min) than the C group (29.9 ± 10.4 min; p = 0.031). The postoperative residual bacterial area was significantly lower in the M than in the C group (6.83% ± 1.39% vs. 30.0% ± 12.37%, respectively; p < 0.001). The M group required significantly fewer wound healing days (49.2 ± 25.3 vs. 63.0 ± 27.9, p < 0.001). Secondary outcomes also demonstrated statistically significant differences in total hospitalized days (17.5 ± 9.3 vs. 21.5 ± 12.5, p < 0.01), days of antibiotic use (15.5 ± 8.7 vs. 18.7 ± 6.7, p < 0.01), and reinfection rates (4 of 100 vs. 22 of 100, p < 0.001). INNOVATION: RTFI can detect signals from normal skin components and bacterial metabolites. Therefore, interpretation of RTFI results should be correlated with the clinical condition. RTFI is associated with high-quality debridement. This technique can also be applied in targeted biopsy and in training young staff to mature debridement procedures. CONCLUSION: RTFI in debridement is associated with favorable clinical outcomes and may have a positive influence on chronic wound healing.

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PubMed2026

Near and distance vergence facility provides complementary clinical information in concussion-related convergence insufficiency.

PURPOSE: To compare near and distance vergence facility testing in adolescents and young adults with concussion-related convergence insufficiency and evaluate changes following office-based vergence/accommodative therapy (OBVAM). METHODS: This secondary analysis of the CONCUSS randomized clinical trial evaluated vergence facility at near (40 cm) and distance (4 m) using a 12Δ base out/3Δ base in prism flipper. Participants aged 11-25 years with concussion-related convergence insufficiency were randomized to immediate or 6 weeks delayed OBVAM. Vergence facility was assessed at baseline, outcome time 1 assessment (after 12 therapy sessions for the immediate group and 6 weeks of watchful waiting for the delayed group), and outcome time 2 assessment (after both groups completed 16 therapy sessions). Agreement between near and distance vergence facility classifications was evaluated, and treatment-related changes were compared between groups. RESULTS: Of the 106 enrolled participants, 102 completed all study visits. At baseline, the near and distance vergence facility classifications demonstrated substantial discordance. Among 101 participants with both measures available, 49 demonstrated reduced distance vergence facility despite normal near vergence facility, whereas only two showed the opposite pattern (Cohen's κ = 0.12; p < 0.0001). Vergence facility improved following therapy in both treatment groups, with larger early improvements in the immediate-treatment group. CONCLUSIONS: Near and distance vergence facility testing provided complementary rather than interchangeable clinical information in adolescents and young adults with concussion-related convergence insufficiency. Both measures improved following vergence/accommodative therapy, supporting consideration of both testing distances in clinical assessment.

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PubMed2026

Acute Haemodynamic and Perceptual Responses to Graded Intradialytic Exercise in Patients on Maintenance Haemodialysis: A Randomised Crossover Trial.

BACKGROUND: Acute responses to graded intradialytic exercise in people receiving haemodialysis remain incompletely characterised. OBJECTIVES: To examine acute haemodynamic and perceptual responses to graded intradialytic resistance exercise compared with a non-exercise control condition. DESIGN: Randomised crossover trial. PARTICIPANTS: Forty-eight clinically stable adults receiving maintenance haemodialysis. MEASUREMENTS: Participants completed seated control and graded lower-limb resistance exercise targeting Borg category-ratio 10 ratings of 3, 5 and 7. Systolic and diastolic blood pressure, mean arterial pressure, heart rate, peripheral oxygen saturation, rating of perceived exertion and acute fatigue were measured before, immediately after and 30 min after each condition. RESULTS: Responses increased progressively with perceived intensity. Compared with control, higher perceived intensity increased systolic blood pressure by 14.9 mmHg (95% confidence interval = 12.7-17.0), diastolic blood pressure by 8.4 mmHg (6.8-10.0), mean arterial pressure by 10.6 mmHg (9.2-12.0) and heart rate by 15.5 beats per minute (12.9-18.1). Rating of perceived exertion increased by 6.7 points (95% confidence interval = 6.3-7.1). Mean peripheral oxygen saturation remained between 95.1% and 97.5%, with no value below 90%. Recorded symptoms occurred in 13 out of 48 higher perceived-intensity sessions; no serious adverse events occurred. CONCLUSIONS: Graded, rating-guided intradialytic resistance exercise produced clear acute dose-response haemodynamic and perceptual changes. These findings support supervised individualisation of acute exercise dose but do not establish long-term safety or superiority of higher perceived-intensity training. TRIAL REGISTRATION: Pan African Clinical Trial Registry: PACTR202606476360900.

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PubMed2026

Comparing Clinical and Cytokine Profiling of Genital Inflammation as Predictors of HIV Acquisition in Women.

BACKGROUND: Inflammation in the female genital tract is a key risk factor for HIV acquisition, but it remains unclear whether clinical or immunological measures best predict risk. We aimed to compare HIV acquisition among women with clinically and/or immunologically defined inflammation. SETTING: HIV-uninfected women enrolled in the CAPRISA 004 tenofovir gel randomized controlled trial in South Africa were followed for up to 34 months. METHODS: We analyzed data from 889 women, with cytokine measurements available for 774 participants. Clinical genital abnormalities were assessed at scheduled visits, and 9 cytokines were measured in cervicovaginal lavage samples. HIV incidence was compared across categories of clinical and immunological inflammation using time varying Cox proportional hazards models, adjusting for relevant covariates. RESULTS: Immunological inflammation, defined as ≥9 elevated cytokines, was present in 18% (140/774) of women. Among specific clinical signs, abnormal genital discharge (adjusted hazard ratio: 2.67, 95% confidence interval [CI]: 1.14 to 6.23, P = 0.024) and cervicitis (adjusted hazard ratio: 10.34, 95% CI: 2.46 to 43.65, P = 0.001) were significantly associated with increased HIV acquisition. Women with both clinical and immunological inflammation had the highest risk of HIV acquisition, with adjusted hazard ratios of 2.08 (95% CI: 1.10 to 3.91, P = 0.022) and 2.46 (95% CI: 1.21 to 5.03, P = 0.013), respectively. CONCLUSIONS: Clinical and immunological definitions of inflammation were each independently associated with increased HIV acquisition risk and combined, they reflected greater susceptibility. These findings highlight the important role of genital inflammation in women's HIV susceptibility, suggesting that clinical signs may provide practical early indicators of risk even as cytokine profiles provide more sensitive measures of underlying inflammation.

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PubMed2026

Spironolactone, early acute eGFR changes, and clinical outcomes in patients with heart failure with preserved ejection fraction: insights from TOPCAT Americas.

AIMS: Early acute changes in estimated glomerular filtration rate (eGFR) have been well described with renin-angiotensin system inhibitors and sodium-glucose cotransporter-2 inhibitors, but less is known about the frequency, prognostic relevance, and implications of these changes after mineralocorticoid receptor antagonist (MRA) initiation in patients with heart failure with preserved ejection fraction (HFpEF). METHODS: We performed a post-hoc analysis of 1648 patients enrolled in the TOPCAT trial (Americas regional subgroup), defining an early eGFR dip as a ≥15% decrease in eGFR between baseline and week 4. Landmark analyses assessed the association of eGFR changes, treatment, and the primary composite endpoint (cardiovascular death, HF hospitalization, or aborted cardiac arrest). RESULTS: Within 4 weeks of treatment initiation, 431 (26%) patients experienced acute eGFR decrease with a higher proportion of patients assigned to spironolactone [269 (33%)] compared with placebo [162 (20%)] (odds ratio 1.97; 95% confidence interval 1.58-2.47). An acute eGFR decrease was independently associated with higher risk of subsequent cardiovascular outcomes, irrespective of treatment arm. However, treatment with spironolactone appeared beneficial in reducing the primary cardiovascular outcome irrespective of the presence [hazard ratio 0.75 (0.53-1.08)] or absence [0.80 (0.64-1.00)] of early eGFR decrease (Pinteraction = .81). At any given magnitude of eGFR decline, risk of the primary endpoint was consistently lower with spironolactone compared with placebo (Pinteraction = .64). CONCLUSIONS: Early acute eGFR changes were common and adversely prognostic in patients with HFpEF. Spironolactone treatment was beneficial in improving cardiovascular outcomes, despite a modest increase in the likelihood of acute eGFR decrease. An acute eGFR decrease early after MRA initiation should not automatically prompt treatment discontinuation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00094302.

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PubMed2026

Direct Initiation of Long-Acting Cabotegravir Plus Rilpivirine in People with HIV and Suboptimal Virologic Suppression: A Randomized Trial.

BACKGROUND: Long-acting injectable cabotegravir plus rilpivirine (LA CAB+RPV) is approved for virally suppressed people with human immunodeficiency virus (HIV), but evidence for its use in those with persistent viremia and adherence challenges remains limited. METHODS: We conducted a multicenter, open-label, randomized study involving oral antiretroviral therapy (ART)-experienced people with HIV who had been diagnosed with HIV for at least 12 months and a most recent HIV-1 RNA level of at least 200 copies per milliliter. Participants with resistance-associated mutations to CAB or RPV were excluded. Eligible participants were randomly assigned in a 1:1 ratio to receive immediate LA CAB+RPV or to continue standard oral therapy until Week 24 (delayed switch group). The primary endpoint was the proportion of participants with an HIV-1 RNA level of less than 200 copies per milliliter at Week 24. RESULTS: Of 61 randomized participants, 45 met eligibility criteria and were included in the analysis; 91% were male, and the median baseline HIV-1 RNA was 35,000 copies/mL. At Week 24, viral suppression was achieved in 88.0% (22/25) in the immediate LA group versus 55.0% (11/20) in the delayed switch group (relative risk for failure to achieve viral suppression, 0.27; 95% CI, 0.08-0.86; p = 0.026). The effect of LA CAB+RPV was sustained through Week 52. CONCLUSIONS: Among people with HIV and viremia associated with adherence challenges, immediate initiation of LA CAB+RPV resulted in higher rates of viral suppression than continued oral ART, supporting its use beyond populations with stable suppression.

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PubMed2026

Long-term motor outcomes after parent-administered early physiotherapy in children born very preterm.

OBJECTIVE: This observational follow-up study investigated whether early parent-administered physiotherapy during the neonatal period was associated with motor outcomes in childhood, and compared these outcomes between two preterm groups and a term-born control group. STUDY DESIGN: This is a follow-up of a pragmatic randomised controlled trial that initially included 153 infants born very preterm (≤32 weeks' gestation), randomised to either early parent-administered physiotherapy or standard care, between 34 and 37 weeks' gestation. At 7-10 years, motor outcomes were assessed in 92 children (intervention, n = 43; standard care, n = 49) and in 83 term-born controls. The primary outcome was the Movement Assessment Battery for Children-Second Edition (MABC-2). Group differences were analysed using linear mixed models adjusted for age, sex, and parental education. Odds ratios (ORs) were calculated for scores ≤5th and ≤ 15th percentiles to estimate the likelihood of having or being at risk for movement difficulties. RESULTS: Mean MABC-2 total score was 9.0 (SD3.0) in the intervention group, 9.6 (SD3.0) in the standard care group, and 10.8 (SD2.9) in the control group. Adjusted mean difference between the intervention and the standard care groups did not differ but both the intervention and standard care groups had lower scores than the control group (-1.2; 95% CI: -2.3 to -0.2 and -0.6; 95% CI: -1.6 to 0.3, respectively). Adjusted ORs for scoring ≤5th or ≤15th percentile did not differ in either preterm group compared with the control group. CONCLUSION: At 7-10 years, motor outcomes did not differ between children born very preterm who received three-week parent-administered physiotherapy and those who received standard care during the neonatal period. However, both preterm groups had lower motor scores than term-born peers.

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PubMed2026

Effect of a PROtein-enriched MEDiterranean diet and EXercise (PROMED-EX) on nutritional status and cognitive performance in older adults at risk of undernutrition and cognitive decline: the PROMED-EX randomized controlled trial.

BACKGROUND: Undernutrition in older adults is associated with adverse health outcomes including cognitive decline, yet evidence for effective preventive strategies is limited. OBJECTIVES: The objective of this study was to investigate effects of a protein-enriched Mediterranean diet, with and without exercise, on nutritional status and cognitive performance in "at risk" community-dwelling older adults. METHODS: A total of 105 participants (69% female; aged 67.7 ± 6.1 y) at risk of undernutrition and cognitive decline were randomized to 1 of 3 groups: 1) PROMED-EX (personalized dietary counseling plus home-based exercise); 2) PROMED (personalized dietary counseling only); or 3) CON (healthy eating leaflet). The primary outcome was change in nutritional status at 6 mo, measured by the Mini Nutritional Assessment (MNA; 0-30 points). Secondary outcomes included neurocognitive test battery (NTB) z-score, PROMED diet quality score (0-14), physical performance, and health-related quality of life. Analyses followed an intention-to-treat approach using linear regression to assess between-group differences in 6-mo outcomes. RESULTS: At baseline, the mean MNA score was 22.5 ± 2.3. After 6 mo, nutritional status improved significantly in both intervention groups compared with CON: mean differences in MNA were 2.7 [95% confidence interval (CI): 1.3, 4.2] for PROMED and 2.9 (95% CI: 1.5, 4.3) for PROMED-EX (both P < 0.001). Cognitive function also improved, with NTB z-score differences of 0.3 (95% CI: 0.1, 0.5; P = 0.01) in PROMED and 0.2 (95% CI: 0.0, 0.4; P = 0.02) in PROMED-EX compared with CON. Diet quality scores significantly increased with mean differences of 4.0 (95% CI: 2.9, 5.0) for PROMED and 3.9 (95% CI: 2.8, 4.9) for PROMED-EX compared with CON (both P < 0.001). Despite low adherence to exercise, additional benefits were observed for physical performance and quality of life. CONCLUSIONS: Dietary intervention improved nutritional status in community-dwelling older adults at risk of undernutrition. Correcting undernutrition could help to slow cognitive decline and promote physical health and quality of life during aging. This study was registered at clinicaltrials.gov as NCT05166564.

Humans↗

PubMed2026

Comparison of opioid-free versus opioid-based total intravenous anaesthesia in elderly patients undergoing short-duration surgery: a randomized controlled trial.

INTRODUCTION: Older adults who undergo short-duration surgery are vulnerable to opioid-related complications. It is uncertain whether an opioid-free total intravenous anaesthesia (OFA) can reduce these events. We aimed to determine whether OFA reduces the incidence of major postoperative adverse events compared with standard opioid-based total intravenous anaesthesia (OBA). PATIENTS AND METHODS: This single-center randomized clinical trial was conducted in China. From May to August 2025, 400 patients aged ≥60 years undergoing elective, short-duration surgery (anticipated duration of less than 90 min) were randomized 1:1 to receive either OFA (n = 200) or OBA (n = 200). The primary outcome was a composite of postoperative hypoxemia, delirium, or nausea and vomiting (PONV) within 48 h. RESULTS: A total of 400 randomized patients (mean [SD] age, 69.5 [7.0] years; 125 [31.3%] women). The primary composite outcome occurred in 50 patients (25.0%) in the OFA group and 87 patients (43.5%) in the OBA group (adjusted odds ratio, 0.40; 95% CI, 0.25 to 0.62; p < .001). Among the OFA group had a lower incidence of hypoxemia (15.0% vs 32.0%) and PONV (8.0% vs 16.0%). Intraoperative hemodynamic stability was greater in the OFA group. However, the OFA group had a higher incidence of intraoperative bradycardia (10.0% vs 3.0%; p = .005) and longer extubation times (mean, 9.5 vs 7.2 min; p < .001). CONCLUSION: These findings suggest that OFA is a viable alternative to opioid-based anesthesia for improving postoperative outcomes by reducing the incidence of hypoxemia and PONV in this population, while warranting careful management of its associated side effects. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2500102550.

Humans↗