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Early Analgesia for the Management of Acute Pancreatitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: We aimed to evaluate the efficacy and safety of early analgesic interventions, particularly NSAIDs versus opioids, in reducing pain and improving clinical outcomes among adults with AP. METHODS: A systematic literature search was conducted across PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, and ClinicalTrials.gov from database/registry inception to December 2025 to obtain relevant data. Randomized controlled trials involving adults aged 18 years or older diagnosed with AP, irrespective of the etiology and severity, who were administered analgesics (opioids, nonsteroidal anti-inflammatory drugs, cyclooxygenase-2 inhibitors, epidural anesthesia, local anesthesia, and paracetamol) and compared with placebo, conventional treatment, or another analgesic modality were included in this review. The primary outcome assessed was pain reduction. The secondary outcomes assessed were the need for rescue analgesia, length of hospital stay, complications (local and/or systemic), mortality, and adverse drug effects. Risk of bias was assessed using the Cochrane Risk of Bias tool 2.0. Effect estimates were pooled using a random-effects meta-analysis (DerSimonian-Laird approach), while nonpooled outcomes were summarized narratively. RESULTS: A total of 13 studies were included in the analysis. NSAIDs provided pain relief comparable to opioids, with a lower incidence of local complications (RR: 0.59, 95% CI: 0.37-0.94). No significant differences in the need for rescue analgesia (OR: 0.88, 95% CI: 0.33-2.35), length of hospital stay (MD: -2.68 d, 95% CI: -6.27 to 0.91), mortality (RR: 0.76, 95% CI: 0.19-3.05), and adverse drug effects (RR: 0.55, 95% CI: 0.17-1.76) were observed. However, the findings are limited by study bias and heterogeneity. CONCLUSION: Early analgesia with NSAIDs has efficacy and safety comparable to opioids in adults with AP, with the advantage of reducing local complications.

Humans

Characterization of local tolerability of TV-46000, a long-acting subcutaneous formulation of risperidone for the treatment of schizophrenia.

TV-46000 is a long-acting injectable antipsychotic (LAI) approved for the treatment of adults with schizophrenia and bipolar I disorder. LAIs like TV-46000 can improve adherence and reduce relapse in patients with schizophrenia; however, injection site reactions (ISRs) can contribute to LAI discontinuation. ISRs with TV-46000 treatment were characterized using data from two phase 3 trials of patients with schizophrenia (RISE [NCT03503318], SHINE [NCT03893825]) and a phase 1 study of patients with schizophrenia or schizoaffective disorder. Patients in the pooled safety population (aged 16-67 years) from RISE and SHINE (n = 525 TV-46000, n = 179 placebo) received 4554 TV-46000 injections and 2721 placebo injections. ISRs were reported in 19 % (n = 102) of patients who received TV-46000, corresponding to an exposure-adjusted event rate (EAER)/100 patient-years of 48.67. ISRs led to 9 (1.7 %) treatment discontinuations of TV-46000. The most frequently reported ISR adverse events were injection site pain (EAER, 15.38, n = 36 [7 %]) and injection site nodule (EAER, 12.01, n = 35 [7 %]). ISR frequency and pain and nodule adverse event frequency decreased after the first injection. In the phase 1 study (n = 99), mean injection site pain scores were highest immediately after injection, showed a notable decrease within 10 min of injection, and further decreased within 1 h after injection. In conclusion, for >4500 injections evaluated, ISR rates with TV-46000 were modest. Most ISRs were mild or moderate and rarely led to treatment discontinuation. Results support the favorable tolerability of TV-46000 as a treatment for schizophrenia in adults.

Humans

Esketamine vs. sufentanil for quality of recovery after outpatient gynecological surgery: a randomized clinical trial.

BACKGROUND: Perioperative administration of esketamine has been reported to improve early quality of recovery (QoR). However, data on its effects in outpatient surgery are limited. This study aimed to assess the impact of esketamine on QoR in patients undergoing outpatient gynecological procedures. METHODS: In this investigator-initiated, double-blind, randomized clinical trial, patients aged 18-65&#x2009;years scheduled for outpatient gynecological surgery under sedation were allocated to receive esketamine (0.2&#x2009;mg/kg) or sufentanil (0.1&#x2009;&#x3bc;g/kg) combined with propofol (1.5-3&#x2009;mg/kg). The primary outcome was quality of recovery on postoperative day (POD) 1. Secondary outcomes included quality of recovery on POD2, sedation success rate, length of post-anesthesia care unit (PACU) stay, injection pain, postoperative pain, nausea and vomiting, fatigue, patient and clinician satisfaction, sleep quality, and anxiety and depression. RESULTS: A total of 126 patients were randomized, with 63 assigned to the esketamine group and 63 to the sufentanil group. Of these, 125 patients were included in the final analysis (62 in the esketamine group and 63 in the sufentanil group), as one patient lacked follow-up data. The mean (SD) QoR-15 score on POD1 was 137.9 (14.5) in the esketamine group and 137.8 (10.7) in the sufentanil group, with no significant difference between groups (absolute difference, 0.2; 95% CI, -4.2 to 4.6; p&#x2009;=&#x2009;0.93). For secondary outcomes, the esketamine group had a longer PACU stay (median, 28.0 vs. 23.0&#x2009;min; p&#x2009;<&#x2009;0.001), a lower incidence of severe injection pain (22.6% vs. 50.8%; p&#x2009;=&#x2009;0.002), a higher proportion of patients with pain scores &#x2265; 4 at 30&#x2009;min postoperatively (30.6% vs. 6.3%; p&#x2009;=&#x2009;0.001), and higher fatigue scores (median, 3.0 vs. 2.0; p&#x2009;=&#x2009;0.01). Other secondary outcomes did not differ significantly between groups. CONCLUSION: Among patients undergoing sedation for outpatient gynecological procedures, esketamine did not significantly improve quality of recovery on POD1 compared to sufentanil. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2500098466.

Humans

The effect of compression dressing on postoperative outcomes after upper eyelid blepharoplasty: a randomized, controlled, observer-blinded evaluation study.

PURPOSE: This study aimed to evaluate the impact of a compression dressing on postoperative pain, ocular surface changes, edema, ecchymosis, and aesthetic outcomes following upper eyelid blepharoplasty. METHODS: This observer-blinded, randomized, controlled trial included 112 eyelids from 56 patients who underwent bilateral upper eyelid blepharoplasty between June and August 2025. After surgery, one eyelid received a compression dressing (CD), while the other eyelid received no dressing (ND). Edema and ecchymosis were graded by masked observers on postoperative days 1, 7, 30, and 90. Aesthetic outcomes were evaluated using the Global Aesthetic Improvement Score. Pain was evaluated using a visual analog scale, and patient comfort was assessed by side preference. RESULTS: On postoperative day 1, ecchymosis scores were significantly lower in the CD group than in the ND group (unadjusted p = 0.002; Holm-adjusted p = 0.012). Edema scores were also lower on the CD side (unadjusted p = 0.012) and aesthetic scores were higher (unadjusted p = 0.046); however, neither difference remained statistically significant after Holm-Bonferroni correction for multiple comparisons (adjusted p = 0.060 and p = 0.138, respectively). No significant differences were observed in any parameter on postoperative days 7, 30, or 90 (all adjusted p > 0.05). Corneal staining scores were comparable between groups at all follow-ups, and no corneal erosions were observed. Pain scores on day 1 were similar (p = 0.977). CONCLUSIONS: Compression dressing after upper eyelid blepharoplasty was associated with a significant reduction in early postoperative ecchymosis, an effect that persisted after correction for multiple comparisons. Reductions in edema and improvements in aesthetic scores were observed on postoperative day 1 but did not remain statistically significant after adjustment. Overall, the benefits of compression dressing were limited in magnitude and transient, and routine use may not be necessary; its application should be individualized according to patient needs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT07701265 (retrospectively registered on July 8, 2026).

Humans

Comparative effects of 12-week resistance training on unstable and stable surfaces on muscle stiffness, muscle co-activation, and balance in older patients with knee osteoarthritis.

OBJECTIVE: This randomized trial compared the effects of unstable resistance training (URT), involving resistance exercises on unstable surfaces, and stable resistance training (SRT), performed on stable surfaces, on muscle stiffness, co-activation, and balance in older adults with knee osteoarthritis (KOA). We hypothesized that URT would yield greater improvements by enhancing neuromuscular adaptability. METHODS: Fifty patients with KOA were randomly assigned to the URT group (n&#x202f;=&#x202f;25) or the SRT group (n&#x202f;=&#x202f;25). After attrition, 46 participants (URT: n&#x202f;=&#x202f;23; SRT: n&#x202f;=&#x202f;23) completed the intervention and were included in the final analysis. Both groups completed a 12-week supervised lower-limb resistance training program (3 sessions/week) consisting of 10 exercises performed under either unstable or stable support conditions. RESULTS: After 12 weeks of intervention, both groups showed significant reductions in pain intensity (p&#x202f;<&#x202f;0.001). However, compared with the SRT group, the URT group demonstrated significantly greater reductions in quadriceps stiffness (p&#x202f;<&#x202f;0.05), selected hamstring stiffness outcomes (p&#x202f;<&#x202f;0.05), and quadriceps-hamstring co-activation (p&#x202f;<&#x202f;0.001), alongside superior improvements in both dynamic balance and static balance (all p&#x202f;<&#x202f;0.05). CONCLUSION: While both training modalities are effective for pain relief, URT elicited greater improvements in balance-related performance and neuromuscular-mechanical outcomes than SRT in older adults with KOA. These findings suggest that incorporating unstable support conditions into resistance training may provide additional rehabilitation benefits for this population.

Humans

IMPROVE kidney care: perspectives from marginalised people with CKD and risk factors for CKD on access to, and experience of, kidney care services: a cross-sector collaborative exploration, employing qualitative approaches.

BACKGROUND: Access to, and experience of, chronic kidney disease (CKD) care is inequitable-with barriers to accessing quality care for marginalised groups. We conducted an exploratory study employing qualitative approaches to understand the factors that influence access to, and experience of, healthcare services for marginalised people with CKD and at risk of CKD. METHODS: An exploratory study employing qualitative approaches was conducted as a cross-sector collaboration between kidney care services and an activist, antiracist community-based research and social justice organisation (Mabadiliko Community Interest Company (CIC)). Two groups were recruited: 1) those with risk factors for CKD or early-stage CKD, and 2) people who presented late to kidney care services. Semi-structured interviews were co-designed with people with lived experience and conducted by Mabadiliko CIC. Thematic analysis was undertaken, with themes refined by participants. RESULTS: Twenty interviews were undertaken with a diverse cohort of participants. Knowledge and awareness of CKD was limited, and compounded by a lack of delivery of accessible, culturally congruent information. Significant barriers to accessing kidney care exist for marginalised people, including people who are from global majority ethnic backgrounds, Disabled people, and/or people experiencing material hardship. These barriers are compounded by interpersonal discrimination and paternalistic power dynamics within healthcare interactions. CONCLUSION: This study captures the experiences of marginalised people at different stages of their journey with CKD, in accessing and engaging with kidney care services. Participants faced a complex array of challenges, highlighting opportunities for multi-level intervention. We outline recommendations to address these issues, co-developed with participants.

chronic kidney disease

Single-slice Functional Lung MRI During Metronome-Paced Tachypnea Detects Changes in Regional Ventilation Dynamics After a Single Dose of Dual Bronchodilator Treatment in COPD.

Dual long-acting bronchodilators are a standard treatment in chronic obstructive pulmonary disease (COPD), aimed at alleviating dyspnea, improving exercise tolerance, and preventing exacerbations. Metronome-paced tachypnea (MPT) offers a feasible alternative to exercise testing for the evaluation of dynamic hyperinflation (DH) in COPD. Because MPT can be performed during MRI, its combination with single-slice phase-resolved functional lung (PREFUL) MRI provides a promising approach to investigate changes in regional ventilation dynamics induced by DH. This approach was evaluated in a randomized, investigator-blinded, placebo-controlled, single-dose (SD) crossover trial with a two-week extension of once daily dual bronchodilator medication, in which patients with stable COPD underwent PREFUL MRI during resting tidal breathing (RTB) and during MPT. During RTB, no significant improvements in MRI-derived parameters were observed after SD treatment compared with placebo. During MPT, however, regional ventilation, flow-volume loop correlation, its defect percentage, and end-expiratory lung area improved significantly after SD treatment compared to the placebo scan (all p&#x2009;<&#x2009;0.02). After multi-dose treatment, five out of six measured parameters improved during MPT, when compared to the baseline scan without bronchodilator treatment (all p&#x2009;<&#x2009;0.03). In contrast to RTB, PREFUL MRI during MPT was able to detect changes in COPD patients already after SD treatment. The combination of MPT and PREFUL MRI represents a promising method to evaluate the effects of dual bronchodilators on regional ventilation dynamics and hyperinflation.

Humans

Effect of an oral complementary medicine combination for symptomatic knee osteoarthritis: A double-blind, randomized, placebo-controlled trial.

OBJECTIVE: Many individuals use complementary medicine therapies for osteoarthritis, despite limited scientific supporting evidence. These therapies have demonstrated anti-inflammatory, antioxidative, and chondroprotective effects via different molecular pathways, suggesting potential therapeutic benefits. This trial aimed to evaluate the efficacy and safety of a novel oral complementary medicine combination in adults with symptomatic knee osteoarthritis at 12 weeks. DESIGN: The 12-week, double-blind, randomized, placebo-controlled ATLAS trial was conducted in Australia from July 2024 to April 2025 (ACTRN12623000380695). Eligible participants were aged &#x2265;40 years with symptomatic knee osteoarthritis and radiographic Kellgren-Lawrence grade &#x2265;2. Participants were randomized 1:1 to receive the complementary medicine combination, comprising a total daily dose of Boswellia serrata extract 250&#x202f;mg, pine bark extract 100&#x202f;mg, methylsulfonylmethane 1500&#x202f;mg, curcumin 500&#x202f;mg, and piperine 5&#x202f;mg, or placebo. The primary outcome was the 12-week change in knee pain (0-100&#x202f;mm visual analogue scale (VAS)). A 95% confidence interval excluding differences >18&#x202f;mm between groups was interpreted as the absence of a clinically meaningful difference. Harms were monitored weekly. RESULTS: Eighty-four participants were recruited (mean [SD], age 63.7 [8.0] years, BMI 29.0 [5.5] kg/m2), and 57% were female. At 12-weeks, both groups (intention-to-treat population: complementary medicine, n=42; placebo, n=41) showed a decrease in VAS pain (least squares means: complementary medicine 20.1&#x202f;mm vs placebo 20.3&#x202f;mm), however with no difference between groups: 0.16&#x202f;mm (95% CI -6.81 to 7.12). The safety profile of experiencing any AE was similar between groups (risk difference, -3.4% [95% CI -24.8-17.9%]); and most adverse events were mild or moderate. Four participants experienced serious adverse events, unrelated to the treatment. CONCLUSIONS: The complementary medicine combination was not superior to placebo for improving pain over 12 weeks, and the evidence does not support the use of this combination to treat people with symptomatic knee osteoarthritis.

Humans

Improving Patient Comfort of Vibratory Anesthetic Devices With a Dampener: A Pilot Study.

BACKGROUND: Vibratory anesthetic devices (VADs) reduce dermatologic injection pain, but their vibration can feel harsh at sensitive anatomical sites. Simple modifications improving patient comfort may enhance VAD adoption. OBJECTIVE: The authors evaluated whether dampening VAD vibration with a cotton buffer improves patient comfort and characterized tactile features influencing preferences. MATERIALS AND METHODS: In a single-site, participant-blinded pilot study (N = 53), adults received a dampened VAD (D-VAD) and standard VAD (S-VAD) at 5 sites-lateral nasal wall, submalar cheek, ear helix, lateral neck, and dorsal forearm-in randomized, contralateral application. Site-specific preference was analyzed with binomial and Cochran Q tests; demographic associations with univariate analyses. Word2vec and hierarchical clustering analyzed qualitative reasons behind patient preference. RESULTS: D-VAD was preferred at all sites across demographics-lateral nasal wall (88.7%), submalar cheek (84.9%), ear helix (88.7%), lateral neck (77.4%), and dorsal forearm (75.5%) (all p < .001), with strongest preference at face and head/neck (p = .018). Computational semantics analysis of qualitative responses identified 6 themes driving preference: Smoothness, Gentleness, Controlled, Low Frequency, Low Intensity, and Less Bothersome. CONCLUSION: Dampening VAD vibration with a cotton buffer enhances comfort across sensitive sites, with reduced harshness and smoother sensation underlying preference. This simple modification may improve patient experience, encouraging broader VAD adoption.

Humans

Barriers to physical activity in patients with systemic lupus erythematosus in the UK.

INTRODUCTION: Physical activity (PA) may play an important role as a non-pharmacological addition to the management of SLE for disease control and reduction of cardiovascular risk factors. Those with SLE have been reported to engage in PA less than the general population. OBJECTIVE: To describe PA patterns and patient-reported barriers to PA for people with SLE in the UK. METHODS: An online survey was conducted of adults aged&#x2009;&#x2265;&#x2009;18 years. Participants were recruited from posters in outpatient clinics, newsletters and Lupus UK social media platforms. Survey questions included demographic information, perception of disease activity, the International Physical Activity Questionnaire (IPAQ) and specific leisure time questions. RESULTS: Two hundred sixty-eight patients participated, with a median (IQR) age of 51 (39-59) years and SLE disease duration of 10 (4-20) years&#xa0;were included. SLE-diagnosis was collected by self-report. In those with complete IPAQ data, 178/228 (79.1%) were in a moderate/high activity group. Participants in this group were more likely to be in employment and had lower levels of fatigue and pain. Fatigue was the most reported barrier to PA, irrespective of activity levels. Participants in the low PA group were more likely to have SLE-specific barriers such as higher disease activity and higher pain scores. CONCLUSIONS: Perceptions and preferences in relation to PA differ greatly between individuals with SLE. The most common self-reported barrier to PA was fatigue. Exploration of individual perceptions of PA should form part of consultations, to address perceived barriers. Key Points &#x2022; Some patients with self-reported SLE can meet WHO physical activity targets, especially those who remain in work. &#x2022; Fatigue is the most frequently reported barrier to physical activity for patients, irrespective of their activity levels. &#x2022; People are less likely to engage in PA if they believe it will negatively affect their SLE.

Humans

Impact of oliceridine versus sufentanil on postoperative nausea and vomiting in patients undergoing thyroid surgery: a prospective, double-blind, randomized controlled trial.

PURPOSE: Postoperative nausea and vomiting (PONV) is a common complication following thyroid surgery, often exacerbated by opioid use. Oliceridine, a novel G protein-biased &#x3bc;-opioid receptor agonist, may reduce opioid-related adverse events. This study aimed to compare the impact of oliceridine versus sufentanil on the incidence and severity of PONV in patients undergoing thyroid surgery. PATIENTS AND METHODS: In this prospective, double-blind, randomised controlled trial conducted between May 2025 and February 2026, 232 patients scheduled for thyroid surgery were randomly assigned to receive either oliceridine or sufentanil for intraoperative analgesia. The primary outcome was the incidence of PONV during the first 48&#x2009;h postoperatively. Secondary outcomes included PONV severity, need for rescue anti-emetics, postoperative pain scores, recovery quality, and other adverse events. RESULTS: The incidence of PONV within 48&#x2009;h postoperatively was significantly lower in the oliceridine group [13/107 (12%)] compared with the sufentanil group [31/110 (28%)] (OR = 0.35, 95% CI: 0.17-0.72, p&#x2009;=&#x2009;0.006). Postoperative pain scores, rescue analgesia requirements, and Quality of Recovery-15 scores were comparable between the two groups (p&#x2009;>&#x2009;0.05). Besides, exploratory unadjusted analyses revealed fewer rescue anti-emetics: O group 8/107 (8%) vs S group 25/110 (23%) (OR = 0.27, 95% CI: 0.12-0.64, p&#x2009;=&#x2009;0.002); and less abdominal distension: O group 4/107 (4%) vs S group 19/110 (17%) (OR = 0.19, 95% CI: 0.06-0.57, p&#x2009;=&#x2009;0.001). CONCLUSION: For young ASA I-II patients undergoing thyroid surgery, oliceridine yields adequate postoperative analgesia and lower PONV rates versus sufentanil. Additional trials involving high-intensity surgical procedures are needed to confirm consistent equivalence.

Humans

Outcomes of stereotactic radiosurgery for spine multiple myeloma-a systematic review.

Spinal involvement in multiple myeloma (MM) commonly results in pain, vertebral instability, epidural spinal cord compression, and neurological deficits. Although conventional external beam radiation therapy (EBRT) remains the standard radiation modality because of the radiosensitive nature of MM, stereotactic radiosurgery (SRS) has emerged as a highly conformal treatment option capable of delivering focal high-dose radiation while sparing adjacent spinal cord structures and uninvolved bone marrow. This systematic review evaluated the clinical outcomes and safety profile of SRS for spinal MM.&#xa0;A systematic review of the literature was performed to identify studies evaluating SRS for spinal MM. Extracted variables included patient demographics, tumor characteristics, treatment parameters, radiographic outcomes, pain response, neurological outcomes, local control, overall survival, and adverse events.&#xa0;Three retrospective studies comprising 133 patients and 181 treated spinal lesions met the inclusion criteria. Median patient age ranged from 59 to 65 years, with a slight male predominance across studies. Thoracic spine lesions represented the most treated region (55.5-67.7%). Median prescribed SRS dose was 14-16&#xa0;Gy, predominantly delivered in a single fraction. Median follow-up ranged from 11.2 to 27.8 months. Local control rates ranged from 89.4 to 100%, with 6- and 12-month local control rates of 94% and 91%, respectively, in one study. Pain improvement was reported in 41-88% of treated patients/sites, with a median time to pain relief of 1.6 months in one cohort. Neurological improvement occurred in 56-71.4% of patients with preexisting deficits. Reported adverse events included vertebral compression fractures, fracture progression, pain flare, and tracheoesophageal fistula. De novo vertebral fractures ranged from 3.6 to 7%, while fracture progression ranged from 14 to 18%.&#xa0;SRS appears to provide excellent local control and meaningful pain and neurological improvement in patients with spinal MM, with acceptable toxicity profiles. The highly conformal nature of SRS may preserve uninvolved bone marrow and facilitate continuation of systemic therapy. However, the current evidence is limited to small retrospective studies with heterogeneous reporting, and further prospective comparative studies are needed to better define the role of SRS relative to conventional EBRT in spinal MM.

Humans

Anatomy and Biomechanics of the Deltoid Ligament Complex in Healthy Ankles: Protocol for a Systematic Review and Meta-Analysis.

INTRODUCTION: Up to one in two individuals who have a history of an ankle injury will develop chronic ankle instability, which subsequently increases the risk of osteoarthritis development. Although lateral ankle ligament injuries are the most common, recent research shows that concomitant injuries to the deltoid (medial collateral) ligament complex may be more prevalent than previously recognised. However, the anatomy and biomechanics of the deltoid ligament complex are reported inconsistently in the literature. This systematic review will summarise current evidence on the anatomy and biomechanics of the deltoid ligament complex in healthy adult ankles. METHODS: Searches will be conducted in Scopus, MEDLINE, Embase, CINAHL and SPORTDiscus. Our search strategy will cover terms associated with 'deltoid ligament', 'anatomy' and 'biomechanics'. We will only include dissection and imaging studies published in English that report any of the listed clinically relevant properties of the deltoid ligament in healthy adult human ankles. Two reviewers will independently perform screening and assess study quality using the anatomical quality assessment (AQUA) tool. One reviewer will extract relevant data, which will be independently verified by co-authors. Primary outcomes include band prevalence, length, width, cross-sectional area, maximum and/or failure load and elastic modulus. If three or more studies report a primary outcome, we will conduct a meta-analysis and report findings as pooled means with 95% confidence intervals. If a meta-analysis is not feasible, outcomes will be summarised as a narrative analysis. Measures will be taken during data synthesis to address anticipated methodological heterogeneity across included studies, and pooled estimates will be interpreted with caution. DISCUSSION: This protocol details a systematic review that aims to summarise the anatomy and biomechanics of the deltoid ligament complex. Our findings will inform computational modelling, clinical management and biomechanics for ankle pathologies, as well as identifying research gaps and directions for future research. TRIAL REGISTRATION: PROSPERO: CRD420251142867.

Humans

A polygenic risk score for peripheral artery disease and major adverse limb events.

BACKGROUND AND AIMS: Large-scale genome-wide association studies have identified common genetic variants that predict the risk of peripheral artery disease (PAD). This study assessed whether a polygenic risk score (PRS) is associated with PAD and the incidence of major adverse limb events (MALE) independent of clinical risk factors in patients with established cardiometabolic disease. METHODS: A genetic analysis was performed, pooling individual patient-level data from six TIMI trials. The association of a recently validated PAD PRS with prevalent PAD and the incidence of MALE (acute limb ischaemia, chronic limb-threatening ischaemia, major amputation, or peripheral revascularization) was assessed. RESULTS: A total of 68 816 patients were included in this analysis, with a median follow-up of 2.6 years. Of these, 5986 (8.7%) had known PAD at baseline. After adjusting for clinical risk factors, a higher PAD PRS was independently associated with a 15% greater odds of prevalent PAD (adjusted odds ratio per 1-SD: 1.15 [95% confidence interval 1.12-1.18], P < .0001), a magnitude of risk as strong as established clinical risk factors. A total of 577 patients experienced MALE during follow-up. A higher PAD PRS was associated with a 30% increased risk of MALE (adjusted hazard ratio per 1-SD: 1.30 [1.19-1.42], P < .0001). Adding the PAD PRS to clinical risk factors resulted in a statistically significant but modest improvement in discrimination (area under the curve went from 0.651 to 0.662 P < .0001). CONCLUSIONS: In a broad spectrum of patients with cardiometabolic disease, the PAD PRS is associated with an increased risk of PAD and the incidence of MALE beyond clinical risk factors; however, the improvement in discrimination was statistically significant but clinically modest.

Humans

Vaginal Hysterectomy Versus Vaginal Assisted Natural Orifice Transluminal Endoscopic Surgery Hysterectomy; Results of a Randomised Controlled Trial.

OBJECTIVE: To compare Vaginal Hysterectomy (VH) with Vaginal Assisted Natural Orifice Transluminal Endoscopic Surgery (NOTES) hysterectomy (VANH) as a day-care procedure. DESIGN: Single-blind, multicentre randomised controlled trial. SETTING: Two Dutch non-academic teaching hospitals. POPULATION: Women aged &#x2265;&#x2009;18&#x2009;years undergoing hysterectomy for benign indications. METHODS: Women were randomised 1:2 (VH or VANH). Primary outcome was SDD. Secondary outcomes included operative time, rate of elective salpingectomies, intraoperative blood loss, complications (Clavien-Dindo), pain scores (NRS) and analgesic use, post-operative recovery (RI-10), and quality of life (EQ-5D-5L). Analyses were performed on an intention-to-treat basis. RESULTS: A total of 113 patients were included in the analyses (n&#x2009;=&#x2009;42 VH, and n&#x2009;=&#x2009;71 VANH). SDD occurred significantly more frequently in the VANH group (87.3%) than VH group (71.4%; OR 2.76, 95% CI 1.04-7.25; p&#x2009;=&#x2009;0.04). VANH was associated with a significantly shorter operative time (median 55&#x2009;min versus 65&#x2009;min; p&#x2009;=&#x2009;0.005), less blood loss (median 50&#x2009;mL vs. 150&#x2009;mL; p&#x2009;<&#x2009;0.001) and more often elective opportunistic salpingectomy compared to VH (100% vs. 77.4%; p&#x2009;=&#x2009;0.008). NRS were significantly lower in the VANH group the first hour post-operative (3 vs. 1, p&#x2009;<&#x2009;0.001). Post-operative complications (VH 9.5% vs. VANH 15.5%; p&#x2009;=&#x2009;0.34), readmission (VH 4.8% vs. VANH 8.5%; p&#x2009;=&#x2009;0.47), analgesic use, recovery, and quality of life were not statistically significant. CONCLUSIONS: VANH is a safe and effective alternative to VH, offering a higher likelihood of SDD, shorter operative time, reduced blood loss, and more often an elective salpingectomy, without increased complications or differences in pain, recovery, or quality of life.

Humans

Second Primary Malignancies in Patients With B-Cell Lymphomas Treated With Bruton's Tyrosine Kinase Inhibitors: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the overall second primary malignancy (SPM) burden in patients with B-cell lymphomas treated with Bruton's tyrosine kinase (BTK) inhibitors and compare SPM risk versus non-BTK inhibitor or placebo controls. METHODS: We searched major databases from inception to September 30, 2025. The primary outcome was SPM incidence. Consistent treatment backgrounds were defined as comparable baseline clinical and treatment characteristics, with BTK inhibitor exposure as the main between-arm difference. RESULTS: Fifty-two studies involving 9337 patients were included, mainly CLL/SLL; MCL was the largest non-CLL/SLL subtype. Pooled SPM incidence was 8% (95% CI: 6%-11%) with a median follow-up of 31.5&#x2009;months. Multivariable meta-regression identified follow-up duration as the only independent predictor, whereas disease subtype, inhibitor generation, prior therapy lines, study design, and age were not significant. Furthermore, SPM patterns were comparable between CLL/SLL and non-CLL/SLL cohorts. Compared with controls, BTK inhibitors did not significantly increase SPM risk (RR&#x2009;=&#x2009;1.30, 95% CI: 0.95-1.78), a finding confirmed in analyses with consistent treatment backgrounds (RR&#x2009;=&#x2009;1.03, 95% CI: 0.85-1.25). CONCLUSIONS: SPMs occur across disease backgrounds and are mainly influenced by follow-up duration. Current evidence does not establish a direct carcinogenic effect of BTK inhibitors.

Humans

Efficacy of esketamine in reducing nausea and vomiting after anesthesia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Postoperative nausea and vomiting (PONV) are significant perioperative challenges. This study evaluated the efficacy of perioperative esketamine in preventing PONV. MATERIALS AND METHODS: We systematically searched Embase, PubMed, Web of Science, and the Cochrane Library from inception to August 2025 for randomized controlled trials investigating the effect of perioperative esketamine on PONV. The primary outcome was PONV incidence. Secondary outcomes included time to first flatus, postoperative pain degree, anxiety scores, agitation, anesthesia recovery time, and post-anesthesia care unit (PACU) stay duration. Data were analyzed using RevMan 5.4 and STATA 15.0 software. Sensitivity and subgroup analyses were performed to assess result stability and explore potential sources of heterogeneity. RESULTS: Thirty-eight randomized trials (3,425 patients) were included. Esketamine reduced the risk of nausea (RR=0.69, 95% CI: 0.53-0.90) and vomiting (RR=0.75, 95% CI: 0.57-0.98), shortened time to first flatus (SMD=-0.81, 95% CI: -1.48 to -0.15), and decreased rescue analgesic needs within 2 days (SMD=0.32, 95% CI: 0.2-0.5). However, it prolonged anesthesia recovery time (SMD=0.97, 95% CI: 0.28-1.67) and PACU stay (SMD=0.76, 95% CI: 0.27-1.26). CONCLUSIONS: Perioperative esketamine may reduce PONV and aid gastrointestinal recovery, but its potential to delay anesthesia recovery and PACU discharge requires consideration. Further studies are needed to clarify its risk-benefit profile. DATE OF FIRST SUBMISSION TO PROSPERO: 10 March 2024. DATE OF THE START OF STUDY SCREENING AGAINST ELIGIBILITY CRITERIA: 21 March 2024.

Humans

Effectiveness of a blended care intervention in physiotherapy with exercise and education for patients with hip or knee osteoarthritis (SmArt-E): A multicentre pragmatic randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of a twelve-month smartphone-assisted physiotherapy (SmArt-E) intervention versus usual care in hip and/or knee osteoarthritis (OA), and to assess usability and patient satisfaction with the digital support. METHOD: We conducted a multicentre, pragmatic, parallel-group randomized controlled trial in 27 physiotherapy practices in Germany. Patients with physician-diagnosed hip and/or knee OA aged &#x2265;50 (hip) or &#x2265;38 years (knee) were randomly allocated to SmArt-E (IG; n=166) or usual care (CG; n=164). The twelve-month intervention combined supervised and smartphone-assisted training and education (blended care). Primary outcomes were pain (NRS, 0-10) and physical function (HOOS/KOOS-ADL, 0-100) at twelve months. Secondary outcomes followed OARSI domains; usability and patient satisfaction were also assessed. RESULTS: Among 330 participants (mean age 64&#xb1;8 years), baseline NRS was 3.2&#xb1;2.3 in the CG and 3.5&#xb1;2.4 in the IG; HOOS/KOOS-ADL was 71.6&#xb1;17.7 and 69.4&#xb1;17.5, respectively. No significant between-group differences were found for pain (-0.36; 95% CI: -0.84 to 0.12; p=0.14) or physical function (2.66; 95% CI: -0.46 to 5.77; p=0.09). Among 13 secondary outcomes, significant differences favouring the IG emerged at three and twelve months for several domains; however, effect sizes were small and unlikely to be clinically meaningful. CONCLUSION: SmArt-E did not demonstrate superior effectiveness over usual care in mild hip and/or knee OA. Both groups improved over time, with slightly more favourable but clinically inconclusive outcomes in the IG. Findings highlight the need to refine the intervention, better identify eligible patients, and optimize digital and in-person components.

Humans