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Meta-analysis and pharmacoeconomic study of rasagiline versus selegiline in the treatment of Parkinson's disease.

OBJECTIVE: Given the persistent absence of direct head-to-head trials, this study aimed to evaluate the comparative efficacy, safety, and cost-effectiveness of rasagiline versus selegiline as early-stage monotherapy for Parkinson's disease (PD), informing clinical selection and healthcare policies in China. METHODS: A systematic search of PubMed, Embase, and the Cochrane Library identified randomized controlled trials (RCTs) up to April 2026. Focusing on short-term outcomes (10-16 weeks), an adjusted indirect treatment comparison (ITC) using placebo as a common anchor evaluated symptom improvement (UPDRS total scores) and adverse event (AE) incidence. For economic evaluation, a 2-year Markov model was constructed from a Chinese healthcare-system perspective. The incremental cost-effectiveness ratio (ICER) was calculated alongside robust sensitivity analyses. RESULTS: Ten RCTs (rasagiline: 6; selegiline: 4) were included. The ITC revealed no statistically significant differences between rasagiline and selegiline in short-term symptomatic relief (Mean Difference = -0.82, 95% CI [-2.08, 0.44], p = 0.203) or AE risk (Odds Ratio = 0.83, 95% CI [0.50, 1.38], p = 0.475). The overall evidence certainty was rated as moderate. Economically, the base-case simulation indicated rasagiline yielded a marginal benefit of 0.0088 QALYs over selegiline but incurred an additional 17,111.10 Yuan. This resulted in an ICER of 1,951,505.55 Yuan/QALY, substantially exceeding the conventional willingness-to-pay threshold. CONCLUSION: Supported by moderate-certainty evidence, rasagiline and selegiline provide comparable short-term efficacy and safety for early-stage PD monotherapy. However, at its current pricing, rasagiline is not cost-effective. Significant price reductions or definitive proof of long-term superiority are required to justify its economic value.

Humans

Cannabis and cannabinoids for the treatment of mental and substance use disorders and symptoms: A systematic review and meta-analysis of experimental and observational studies.

BACKGROUND: Interest in cannabinoids for mental and substance use disorders is increasing. We examined experimental and observational evidence for treating these disorders and their symptoms. METHODS: Systematic review and meta-analysis (PROSPERO CRD42023467536). We searched CENTRAL, MEDLINE, Embase and PsycINFO to May 2025 for studies of cannabinoids in adults (≥18 years) with ADHD, anxiety, depression, PTSD, psychosis or Tourette syndrome, or alcohol, cannabis, opioid or tobacco use disorders. Two reviewers screened, extracted and assessed quality using a risk-of-bias tool and GRADE. RESULTS: We included 82 experimental and 118 observational studies. In RCTs, cannabinoids reduced anxiety symptoms (SMD=-0.40; 95% CI: -0.57, -0.23; I²=90%) and, in one small trial, PTSD symptoms (SMD=-2.60; 95% CI: -4.58, -0.62; n=20), with trivial-to-no effect on depression (SMD=-0.20; 95% CI: -0.43, 0.04; I²=91.6%), ADHD, psychosis and Tourette syndrome. Much anxiety and depression evidence came from symptoms measured as secondary outcomes in other primary conditions. Cannabinoids worsened cannabis use disorder severity in one RCT (SMD=2.35; 95% CI: 1.49, 3.21), with no effect on craving or withdrawal; evidence for alcohol, opioid and tobacco use disorders was very limited. Observational studies suggested improvements but had high risk of bias. The only significant safety finding was increased withdrawals due to adverse events with THC (OR=2.78; 95% CI: 1.66, 4.65). Certainty was predominantly very low. DISCUSSION: The evidence base shows very low certainty, high heterogeneity and methodological limitations, and is insufficient to support cannabinoids as first-line treatment. Signals for anxiety and PTSD are limited by indirectness and low certainty; no benefit was evident for depression; THC-related safety signals warrant careful consideration.

Humans

Treatment of Established Groin Lymphatic Complications After Arterial Surgery: A Systematic Review.

BACKGROUND: To systematically review the effectiveness and safety of interventions for established groin lymphatic complications after arterial vascular surgery. METHODS: PubMed, Embase, and Cochrane CENTRAL were searched from inception to May 28, 2025. This review was registered in PROSPERO (CRD420251061708) and conducted according to PRISMA, PRISMA-S, and Synthesis Without Meta-analysis (SWiM) guidance. Eligible studies included adults with established groin lymphorrhea/lymphocutaneous fistula or seroma/lymphocele after arterial exposure in the common femoral or iliofemoral region. Prophylactic studies were excluded. Two reviewers independently screened studies and assessed full texts. Prespecified outcomes were resolution, time to resolution, length of stay, surgical site infection, wound complications, reintervention, and recurrence. Owing to substantial heterogeneity, meta-analysis was not performed. RESULTS: Eighteen retrospective single-center studies were included; no randomized trials were identified. Reported strategy-family totals were operative control (n = 240, including 55 dye-assisted cases), intranodal lymphangiography with glue embolization (n = 39), intracavitary or chemical instillation (n = 52), negative-pressure wound therapy (n = 20), radiotherapy (n = 206), and drainage or aspiration alone (n = 7). One additional cohort compared nonsurgical with surgical management. Definitions, follow-up windows, and statistical reporting were inconsistent, and arm-level denominators were frequently incomplete. Risk of bias was serious to critical across the evidence base, mainly because of retrospective design, confounding by indication, treatment-selection bias, inconsistent outcome definitions, and incomplete reporting. Using GRADE principles, certainty of evidence was very low across strategies and phenotypes. Across study arms, conduit-directed approaches for external leak and cavity-directed approaches for encapsulated collections often achieved control, but valid comparative inference was not possible. CONCLUSION: Evidence is limited to small retrospective series with heterogeneous definitions, serious to critical risk of bias, and very low certainty. Reliable comparisons between interventions cannot currently be made. Standardized phenotype-specific definitions and outcome reporting are needed to support prospective studies and future trials.

Humans

Efficacy and Safety of Rivaroxaban in Patients with Peripheral Artery Disease: A GRADE-assessed Systematic Review and Meta-Analysis.

BACKGROUND: Peripheral artery disease (PAD) is a common atherosclerotic disorder characterized by progressive arterial narrowing in the limbs. This study aims to determine the efficacy and safety of rivaroxaban, focusing on major cardiovascular events, limb outcomes, and bleeding risks. METHODS: PubMed, Cochrane, and EMBASE were searched for randomized controlled trials (RCTs) and nonrandomized comparative studies that compared rivaroxaban, either alone or in combination with aspirin, to placebo or standard care such as antiplatelet therapy. Risk ratios and hazard ratios with 95% confidence intervals were pooled using R v4.5.1 with an appropriate random-effects model applied. Subgroup analyses were performed according to rivaroxaban plus aspirin versus rivaroxaban alone. RESULTS: A total of 39,991 participants across 6 studies were included. Compared with control, use of rivaroxaban was linked to a significant reduction in composite efficacy outcomes (relative risk [RR] = 0.84, 95% confidence interval [CI] 0.78-0.91, P < 0.001), risk of acute limb ischemia (RR = 0.65, 95% CI 0.55-0.78, P < 0.001), and thromboembolism (RR = 0.60, 95% CI 0.38-0.97, P = 0.037). Although rivaroxaban plus aspirin failed to show a significant reduction in the risk of amputation, rivaroxaban alone reported a significant risk reduction (RR = 0.50, 95% CI 0.30-0.85, P = 0.003). However, its use was associated with a significantly higher risk of major bleeding (hazard ratio [HR] = 1.54, 95% CI 1.38-1.72, P < 0.001) and International Society on Thrombosis and Hemostasis-defined bleeding (RR = 1.45, 95% CI 1.19-1.76, P < 0.001). No significant differences were observed for stroke, myocardial infarction, major adverse limb events, fatal bleeding, mortality, or cardiovascular mortality. CONCLUSION: Rivaroxaban-based therapy reduced the trial-defined composite efficacy outcome, acute limb ischemia, and thromboembolism in patients with PAD, but increased the risk of major bleeding. These findings support individualized use of rivaroxaban-based therapy in carefully selected patients, balancing ischemic and limb-protective benefits against bleeding risk.

Humans

Qualitative evidence of service user experiences and perspectives on long-acting injectable buprenorphine for opioid treatment - a scoping review.

BACKGROUND: There is substantial literature on opioid treatment program (OTP) formulations and how they relate to the pharmacotherapy service user experience. As a newer formulation, less is known about service user experiences of long-acting injectable buprenorphine (LAIB). The aim of this scoping review is to map the qualitative evidence and gaps in the literature on service user experiences and perspectives of LAIB. METHODS: Our search strategy included Medline, Embase, PsycINFO, CINAHL, Scopus and Web Science, and citation chaining, from January 2016 to June 2025. Studies were included if reporting qualitative descriptions of LAIB service user experiences of treatment for opioid dependence, inclusive of qualitative, mixed methods (description of qualitative data only), case reports and English language. Articles were screened by two reviewers. A living experience first author led the analysis using inductive coding and thematic analysis, to produce a descriptive summary of synthesised findings alongside key study characteristics and quality appraisal, adhering to the Systematic reviews and Meta-Analysis for Scoping Reviews (PRISMA-ScR) checklist. RESULTS: After screening 838 titles/abstracts and reviewing 150 full texts, 40 studies met the eligibility criteria. All were conducted in high income countries, principally the US (n=12); Australia (n=10); and England and Wales (n=9). We identified five themes: Navigating LAIB treatment; Embodied and relational effects of LAIB; Impact and role of the service provider; Narratives of harm reduction and recovery; Stigma and criminalisation. LAIB was commonly experienced as increasing convenience, stability and freedom from daily supervised dosing, enabling improved work, travel, privacy and social participation. Reduced clinic/dosing contact often lessened enacted stigma and treatment burden. However, experiences were heterogenous. Some participants described injection-site discomfort, uncertainty about dose adequacy, reduced flexibility once injected, and ambivalence about LAIB effects. There was inconsistency in LAIB service user reports on service connection, isolation and psychosocial support. Treatment experiences were strongly shaped by provider practices. CONCLUSIONS: Findings underscore the need for integrated, flexible, harm-reduction oriented and person-centred LAIB treatment models that prioritise choice, autonomy and therapeutic relationships to maximise benefit for service users. However, evidence of LAIB service user experiences is concentrated in high-income countries, and the absence of perspectives from low- and middle-income country settings represents a substantial gap in the evidence base.

LAIB

Effects of digital health-based exercise interventions on older adults with sarcopenia: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Sarcopenia, the progressive loss of muscle mass and function, impairs independence in older adults. Digital health exercise interventions are scalable solutions for older adults with sarcopenia. This systematic review and meta-analysis aimed to synthesize the evidence on their efficacy in populations with clinically diagnosed sarcopenia and identify influential intervention characteristics associated with treatment outcomes. METHODS: We systematically searched PubMed, EMBASE, Web of Science, Cochrane Library, CINAHL, CNKI, and Wanfang on May 20, 2026, with no date restrictions. We included randomized controlled trials involving adults aged &#x2265;60 with sarcopenia receiving digital exercise interventions. Two reviewers independently screened studies, extracted data, and assessed risk of bias; analyses were performed using R and Review Manager. RESULTS: Fourteen trials (n&#xa0;=&#xa0;927) were included. Digital interventions showed potential improvements in muscle mass (MD&#xa0;=&#xa0;0.25, 95%CI:0.03-0.46, 95% PI:-0.36 to 0.85), muscle strength (MD&#xa0;=&#xa0;2.14, 95% CI:1.18-3.11, P&#xa0;<&#xa0;0.001), balance ability (SMD&#xa0;=&#xa0;0.31, 95% CI:0.12-0.51, P&#xa0;=&#xa0;0.001), walking performance (SMD&#xa0;=&#xa0;0.55, 95% CI:0.21-0.89, 95% PI:-0.70 to 1.79), and physical function (SMD&#xa0;=&#xa0;0.89, 95% CI:0.08-1.71, 95% PI:-2.33 to 4.12), but not quality of life (SMD&#xa0;=&#xa0;0.08, 95% CI:-0.19 to 0.35, P&#xa0;=&#xa0;0.53). Exploratory subgroup analyses suggested that factors such as supervision, program duration, and measurement tools may influence outcomes; however, formal tests for subgroup differences were generally non-significant, and consistent patterns across all metrics were not observed. CONCLUSION: Digital exercise interventions show potential for managing sarcopenia in older adults, though the very low to moderate certainty of evidence indicates that true effects may differ substantially from observed estimates. This review explores potential roles of intervention design, supervision, and multimodal delivery. Future research should adopt rigorous designs and longer follow-up to validate results and enhance clinical application. TRIAL REGISTRATION: PROSPERO CRD420251135174.

Humans

ALID score for treatment-effect heterogeneity of adjunctive low-voltage area ablation in persistent atrial fibrillation: A post hoc analysis of SUPPRESS-AF.

BACKGROUND: In persistent atrial fibrillation (AF), the incremental benefit of adjunctive low-voltage area (LVA) ablation beyond pulmonary vein isolation (PVI) remains inconsistent. OBJECTIVE: To examine whether a simple clinical score characterizes treatment-effect heterogeneity of adjunctive LVA ablation among patients with mapped LVA&#xa0;>&#xa0;5&#xa0;cm2 and to perform an exploratory supportive analysis in an independent randomized cohort. METHODS: In this post-hoc analysis of SUPPRESS-AF, which included patients with persistent AF and mapped LVA&#xa0;>&#xa0;5&#xa0;cm2 after PVI, four variables-age&#xa0;&#x2265;&#xa0;75&#xa0;years, left atrial diameter&#xa0;>&#xa0;44&#xa0;mm, estimated glomerular filtration rate&#xa0;<&#xa0;60&#xa0;mL/min/1.73&#xa0;m2, and absence of diabetes-were combined into the ALID score (0-4). Patients were stratified into low (0-1), intermediate (2), and high (3-4) score groups. Because EARNEST-PVI did not use LVA-guided ablation or select patients based on mapped LVA, it was analyzed as an exploratory supportive cohort rather than as an external validation cohort. RESULTS: In SUPPRESS-AF (n&#xa0;=&#xa0;336), a significant treatment-by-score interaction was observed (P&#xa0;<&#xa0;0.001). Adjunctive LVA ablation was associated with increased recurrence in the low-score stratum (HR 3.92; 95% CI 1.50-10.20) and reduced recurrence in the high-score stratum (HR 0.48; 95% CI 0.26-0.86). In EARNEST-PVI (n&#xa0;=&#xa0;494), a qualitatively similar interaction pattern was observed for additional ablation beyond PVI (interaction P&#xa0;=&#xa0;0.029), although the ablation strategy differed from LVA-guided ablation. CONCLUSIONS: Among patients with persistent AF and mapped LVA >5&#xa0;cm2, the ALID score identified heterogeneity in response to adjunctive LVA ablation. These hypothesis-generating findings require prospective validation before clinical implementation.

Humans

Predictors of Efficacy Maintenance After Vunakizumab Discontinuation in Patients With Moderate-to-Severe Plaque Psoriasis: A Post Hoc Analysis of a Randomized Controlled Trial.

BACKGROUND: Efficacy cannot be maintained in some psoriasis patients after biological discontinuation. This study aimed to explore predictors of efficacy maintenance after vunakizumab discontinuation in patients with moderate-to-severe plaque psoriasis. METHODS: This post hoc analysis used data from a phase III trial (NCT04839016); 291 patients with moderate-to-severe plaque psoriasis who achieved 100% improvement in Psoriasis Area and Severity Index (PASI) score at Week 52 were enrolled. Efficacy maintenance was defined as patients who maintained PASI 90 or PASI 100 after 20&#x2009;weeks of vunakizumab discontinuation. RESULTS: There were 44.7% and 72.5% of patients with PASI 100 and PASI 90 maintenance, respectively. In the multivariate logistic regression model, body mass index (BMI) (odds ratio [OR]&#x2009;=&#x2009;0.922, p&#x2009;=&#x2009;0.024) and treatment interruption (OR&#x2009;=&#x2009;0.550, p&#x2009;=&#x2009;0.020) were independently associated with a lower possibility of PASI 100 maintenance; however, the association of family history of psoriasis and the first time of PASI 100 achievement with PASI 100 maintenance did not achieve statistical significance. Duration of psoriasis (OR&#x2009;=&#x2009;0.972, p&#x2009;=&#x2009;0.049) and treatment interruption (OR&#x2009;=&#x2009;0.257, p&#x2009;<&#x2009;0.001) were independently associated with a lower possibility of PASI 90 maintenance. Two nomograms for predicting PASI 90 and PASI 100 maintenance were constructed based on the multivariate models, which disclosed good calibration performance. CONCLUSIONS: PASI 90 and PASI 100 maintenance rates are 72.5% and 44.7% after 20&#x2009;weeks of vunakizumab discontinuation in patients with moderate-to-severe plaque psoriasis. BMI, treatment interruption, and duration of psoriasis predict a lower possibility of efficacy maintenance after vunakizumab discontinuation.

Humans

Efficacy of CagriSema for Reaching Anthropometric Treatment Targets and Cardiometabolic Outcomes: A Secondary, Post hoc Analysis of REDEFINE 1.

AIMS: To assess the added value of absolute anthropometric targets alongside percentage weight loss in the clinical management of obesity. MATERIALS AND METHODS: The phase 3a, 68-week REDEFINE 1 trial randomised adults without diabetes with BMI &#x2265;&#x2009;30&#x2009;kg/m2, or&#x2009;&#x2265;&#x2009;27&#x2009;kg/m2 with &#x2265;&#x2009;1 obesity-related complication, to once-weekly CagriSema 2.4&#x2009;mg/2.4&#x2009;mg, semaglutide 2.4&#x2009;mg, cagrilintide 2.4&#x2009;mg, or placebo, plus lifestyle intervention. This secondary, post hoc analysis assessed the proportions of participants achieving BMI <&#x2009;27&#x2009;kg/m2 and/or WHtR <&#x2009;0.53 targets, and percentage weight loss by anthropometric target. The association between the proportion of participants maintaining or achieving normalisation of four cardiometabolic outcomes: normoglycemia (glycated haemoglobin <&#x2009;5.7% and fasting plasma glucose <&#x2009;5.6&#x2009;mmol/L); blood pressure (<&#x2009;130/80&#x2009;mmHg); triglycerides (<&#x2009;1.7&#x2009;mmol/L); lipids (high-density lipoprotein cholesterol &#x2265;&#x2009;1.3&#x2009;mmol/L [female] or &#x2265;&#x2009;1.0&#x2009;mmol/L [male]) and reaching anthropometric targets or change in body weight (%) was also assessed. RESULTS: The proportion of participants achieving both BMI <&#x2009;27&#x2009;kg/m2 and WHtR <&#x2009;0.53 targets at week 68 was 30.3%, 19.1%, 9.0%, and 3.3% in participants who received CagriSema, semaglutide, cagrilintide, or placebo respectively. Both BMI and WHtR performed similarly as indicators for all four cardiometabolic outcomes. At more stringent cut-off values, anthropometric targets were better measures than percentage weight loss. CONCLUSIONS: The proportion of participants achieving anthropometric targets was greater with CagriSema Versus other treatments. These findings support further validation of BMI and WHtR anthropometric treatment targets and indicate a potential for indicating amelioration of clinical outcomes in obesity and a greater emphasis on target-based treatment strategies.

Humans

Efficacy of afoxolaner (NexGard&#xae;) for the treatment of myiasis caused by the zoonotic tumbu fly, Cordylobia anthropophaga, in domestic dogs under field conditions.

Cordylobia anthropophaga is a major cause of furuncular myiasis in dogs and humans in sub-Saharan Africa, yet evidence for pharmacological control remains limited. Current management relies mainly on mechanical larval removal, and no controlled studies have assessed the efficacy of modern antiparasitic agents. This study evaluated the curative and preventive efficacy of a single dose of afoxolaner (NexGard&#xae;) in dogs with naturally acquired C. anthropophaga infestation under field conditions and explored a possible indirect protective effect in puppies after maternal treatment. A randomized, blinded, negative-controlled field study was conducted in Samburu County, Kenya, and included 104 naturally infested dogs allocated to a treated group (n&#x202f;=&#x202f;53) or an untreated control group (n&#x202f;=&#x202f;51). Clinical evaluations were performed on Days 0, 15 (&#xb1;2), 30 (&#xb1;2), and 45 (&#xb1;2). Efficacy was assessed based on the presence of active nodules and clinical scores. Additional observational data were collected from puppies born to or nursing from treated bitches. Compared to the control group, parasiticide efficacy was 94% on Day 15 and 100% on Day 30. The number of parasite-free dogs reached 86.3% on Day 15, 100% on Day 30, and 95.3% on Day 45. Treated dogs showed a significant clinical improvement from the first post-treatment assessment, whereas infestation persisted in controls (nodules: OR = 0.003, 95% CI 0.001-0.017; skin lesions: OR = 0.010, 95% CI 0.002-0.051; lymph node: OR = 0.013, 95% CI 0.002-0.074; body condition: OR = 0.073, 95% CI 0.027-0.195; all p&#x202f;<&#x202f;.001), with large effect sizes at the final visit for all outcomes (r&#x202f;=&#x202f;0.521-0.793). No C. anthropophaga infestations were detected in examined puppies from treated dams, including puppies exposed during pregnancy or lactation, up to 4 weeks after birth and up to 11 weeks of age, respectively. Afoxolaner appears effective to control canine cordylobiosis and may offer indirect protection to puppies, warranting further investigation.

Animals

Hip Arthroscopy During Female Menstruation: A Retrospective Analysis of Safety and Clinical Outcomes With 24-Month Follow-Up.

OBJECTIVES: To investigate the safety and clinical outcomes of hip arthroscopy performed during menstruation in reproductive-age female patients, and to determine whether surgery during menstruation increases intraoperative risks or adversely affects postoperative recovery. Currently, clear clinical guidelines regarding the timing of elective orthopedic surgeries relative to the menstrual cycle are lacking, often leading to unnecessary surgical rescheduling. Therefore, this study aimed to provide evidence-based guidance for perioperative management and optimal surgical scheduling, thereby addressing a critical clinical need. METHODS: This retrospective cohort study included reproductive-age female patients who underwent hip arthroscopy at the First Medical Center of Chinese PLA General Hospital, the Fourth Medical Center of Chinese PLA General Hospital, and the Department of Sports Medicine at the Second Hospital of Shandong University from December 2018 to September 2023. Patients were categorized into the menstruation group (MP) and the non-menstruation group (NMP) based on whether they were menstruating on the day of surgery. The NMP group consisted of equally sized ovulatory (OP) and luteal (LP) phases. Perioperative outcomes included: intraoperative blood loss, anesthetic dosage, operative time, hemoglobin (Hb) change (within 24&#x2009;h postoperatively), prothrombin time (PT), and activated partial thromboplastin time (APTT). Postoperative outcomes included analgesic consumption, duration of analgesic use, time to first unassisted weight-bearing ambulation, complications, and urinary tract infections. Functional outcomes were assessed at 24-month follow-up using the Visual Analog Scale (VAS), Modified Harris Hip Score (mHHS), International Hip Outcome Tool-12 (iHOT-12), Hip Outcome Score-Activities of Daily Living (HOS-ADL), and Hip Outcome Score-Sports Specific Subscale (HOS-SSS). RESULTS: Of 884 eligible patients, 28 were included in the MP group and 56 matched patients in the NMP group. Operative time, anesthetic use, Hb change, PT, and APTT were comparable between the two groups (all p&#x2009;>&#x2009;0.05). No serious complications or urinary tract infections occurred in either group. At the 24-month follow-up, both groups demonstrated significant improvements in VAS, mHHS, iHOT-12, HOS-ADL, and HOS-SSS (all p&#x2009;<&#x2009;0.001), with no statistically significant differences observed between the groups. CONCLUSIONS: Hip arthroscopy during menstruation does not increase intraoperative bleeding, impair coagulation, or delay functional recovery for female patients. Menstruation should not be considered a contraindication when appropriate perioperative management is applied.

Humans

Implementation of a Face-To-Face Vs Virtual Peer-Integrated Collaborative Care Intervention for Mental Health Treatment of Physical Trauma Survivors: A Qualitative Study of Lessons from the COVID-19 Pandemic.

OBJECTIVE: We assessed the impact of the COVID-19 pandemic on the implementation of a peer-integrated enhancement of integrated clinical care intervention to address the mental health needs of 450 patients undergoing treatment for a physical injury. METHODS: Qualitative data were collected by 7 clinician investigators of a randomized controlled trial acting as participant observers in a trauma care setting of a major U.S. metropolitan hospital and analyzed in collaboration with an external mixed methods specialist. RESULTS: The pandemic created or exacerbated several implementation barriers, including increased risk of infection, homelessness, hospitalizations and comorbid conditions such as fentanyl overdoses that increased demand on emergency department and Trauma Center services, imposition of safety measures to reduce risk of infection in clinical settings, transition from face-to-face to virtual interactions with study patients, shortages of specialty mental health providers, suspension of recruitment of patients into the study, scheduling calls with patients, and an increased workload for the study clinical interventionists. Peer specialists perceived the transition to virtual interactions with patients reduced their effectiveness; however, this was not reflected in assessments of patient satisfaction with services received and may have inadvertently increased adoption by Trauma Center staff. Reduction in reach of the intervention to target population was temporary. CONCLUSIONS: The COVID-19 pandemic exacerbated existing barriers and created new barriers to successfully implementing evidence-based practices in trauma care settings, resulting in an attenuation of their effectiveness. However, the shift from face-to-face to virtual services delivery may have actually led to improved implementation outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03569878. Registered June 15, 2018.

Humans

A systematic review of international/national guidelines for the management of nasopharyngeal carcinoma: Convergence and divergence of recommendations.

Increasing numbers of clinical practice guidelines have been published by international/national groups for nasopharyngeal carcinoma (NPC), providing valuable references for clinicians in making evidence-based decisions on treatment. However, there are substantial discrepancies in various recommendations, leading to uncertainties in choosing the optimal strategies. The authors systematically searched databases and organizational websites for NPC guidelines published between January 2000 and November 2025. All identified guidelines underwent quality appraisal; in total, 26 clinical practice guidelines rated recommended for use were included. The recommendations covering all management aspects (diagnosis, staging, radiotherapy, systemic therapy, follow-up surveillance, biomarkers, and salvage of recurrent/metastatic diseases) were summarized and comparatively analyzed for consistency and disparities. Strong consensus exists for diagnostic workup, staging systems, and induction chemotherapy plus concurrent chemoradiotherapy for advanced disease, whereas marked disparities exist on radiotherapy details, particularly target volume delineation, elective coverage extent, and dose specifications. Although systemic therapy strategies for different stage groups were mostly consistent, substantial disparities exist in alternative options and treatment details. This first comprehensive systematic synthesis of international NPC guidelines provides a practical reference for clinicians to understand all recommendations and select optimal options based on local resources and expertise while identifying current controversies that demand future research for further standardization and harmonization.

Humans

Molecular targeted therapy in combination with chemotherapy for the treatment of platinum-resistant/refractory ovarian cancer (PROC): a systematic review and network meta-analysis.

BACKGROUND: Although single-agent chemotherapy is the most common approach for treating platinum-resistant or refractory ovarian cancer (PROC), there is growing evidence that combining molecular targeted agents with chemotherapy is beneficial, especially for certain patient groups. However, the most effective combination regimen remains elusive. OBJECTIVES: This Bayesian network meta-analysis (NMA) aims to identify the best combination therapy for PROC. METHODS: Relevant studies were searched in PubMed, EMBASE, Web of Science and the Cochrane Central Register of Controlled Trials from their inception until October 2024. The primary outcomes were overall survival (OS), progression-free survival (PFS) and adverse events (AEs). Statistical analyses were performed using the GEMTC package (1.0-2) and R 4.2.0. This review was registered in PROSPERO (CRD42023428414). RESULTS: Our analysis of 22 randomized controlled trials (RCTs) (n&#xa0;=&#xa0;3408) demonstrated that chemotherapy combinations with bevacizumab (hazard ratio (HR)&#xa0;=&#xa0;0.52-0.65), sorafenib (HR = 0.65, 95% confidence interval (CI): 0.45-0.93) or adavosertib (HR = 0.56, 95%CI: 0.35-0.90) significantly improved OS and PFS versus chemotherapy alone. Notably, adavosertib&#xa0;+&#xa0;gemcitabine was associated with an increased risk of grade 3-4 AEs (relative risk (RR)&#xa0;=&#xa0;1.8, 95%CI: 1.3-2.7), but these were generally manageable. CONCLUSIONS: Bevacizumab-based combinations demonstrate consistent benefits across multiple regimens for PROC. Paclitaxel&#xa0;+&#xa0;bevacizumab emerges as the optimal balance of efficacy and safety. Topotecan&#xa0;+&#xa0;sorafenib could be an alternative for patients who are ineligible for anti-angiogenic therapy.

Humans

RENOIR phase 3 rituximab-lenalidomide vs rituximab as maintenance treatment in relapsed/refractory follicular lymphoma.

Maintenance treatment in older patients with relapsed or refractory (R/R) follicular lymphoma (FL) remains an area of investigation. RENOIR was a multicenter, phase 3, open-label randomized trial conducted by the Fondazione Italiana Linfomi (FIL) in older patients with R/R FL after 1 or 2 previous therapies. Patients achieving partial response or complete response (CR) after 4 to 6 cycles of standard rituximab (R)-based chemotherapy were randomized 1:1 to maintenance with R alone (standard arm) or R plus lenalidomide (R2; experimental arm). The primary end point was 2-year progression-free survival (PFS) from randomization, with an expected hazard ratio (HR) of 0.5. A total of 152 patients (median age, 71 years) were enrolled. After induction, 129 (85%) achieved an overall response (CR, 58%) and were randomized to R (n = 65) or R2 (n = 64). At a median follow-up of 68 months, the 2-year PFS was 73% in the R2 arm and 64% in the R arm. An unplanned hypothesis-generating subgroup analysis showed a greater 2-year PFS benefit with R2 in patients aged <70 years: R2, 96% vs R, 69%. Two-year overall survival rates were similar (R2, 80% vs R, 89%). Grade 3/4 adverse events were more frequent in R2, mainly neutropenia and gastrointestinal disorders. In conclusion, the primary end point of the study was not met, and R2 maintenance did not significantly improve 2-year PFS in older patients with R/R FL, although a numerical benefit was observed. R2 showed a more favorable benefit-risk profile in patients aged <70 years, whereas in older patients careful consideration of individual tolerability is warranted. This trial was registered at www.clinicaltrials.gov as NCT02390869.

Humans

Influence of microplastics on microalgal performance during wastewater polishing.

Microplastics (MPs) are emerging contaminants that are increasingly accumulating in aquatic ecosystems due to excessive anthropogenic activity and insufficient mitigation strategies, posing serious environmental and public health risks. Their impact on wastewater (WW) treatment processes remains poorly understood. This study evaluated the effects of five MPs commonly found in WW - polypropylene, polystyrene, polyamide, low-density polyethylene, and high-density polyethylene - on the physiology and bioremediation performance of the microalga Chlorella vulgaris in synthetic WW (SWW). Metabolic responses were assessed via esterase activity and intracellular reactive oxygen species (ROS), while nitrogen (N), phosphorus (P), and glucose removal were monitored to evaluate bioremediation efficiency. MPs inhibited esterase activity and elevated ROS levels, indicating oxidative stress. Nevertheless, C. vulgaris maintained a high bioremediation capacity (> 75 % N, > 60 % P, and > 70 % for glucose). Environmental conditions modulated microalga response to MPs exposure. Under N-limited conditions, C. vulgaris exhibited enhanced nutrient uptake and biomass production, but a 12 h/12 h light/dark photoperiod reduced N removal but stimulated glucose consumption via heterotrophic metabolism. In contrast, C-limited conditions exacerbated oxidative stress and compromised nutrient removal, resulting in residual concentrations exceeding legal limits. These findings highlight that environmental factors can either mitigate or exacerbate the physiological stress induced by MPs, ultimately affecting WW polishing. This work provides a comprehensive insight into the cellular and metabolic effects of MPs on microalgae and supports C. vulgaris as a resilient and sustainable approach for nutrient and carbon removal in MP-contaminated WW systems.

Microalgae

Sensor-based measures of knee brace adherence have low agreement with self-report methods: A multi-measure study among knee osteoarthritis patients.

OBJECTIVE: To explore agreement between self-report and objectively measured adherence to brace wearing by patients with knee osteoarthritis. METHOD: A single-arm observational analysis nested within the PROP OA randomised controlled trial (ISRCTN28555470). Of 237 adults with symptomatic knee osteoarthritis randomised to brace treatment, 60 were included in this sub-study investigating three different methods of assessing knee brace wear time over 26 weeks: 1. Self-report questionnaires (SRQ) at 12 weeks and 26 weeks; 2. Short message service (SMS) questions (days worn in past week, typical hours per day when worn) administered from week 1 to week 24; 3. A skin temperature sensor embedded in the brace, sampling every 10&#x202f;min for 26 weeks. The presence and reason for the sensor were concealed from participants. The estimated proportion of participants meeting "minimum brace use", defined a priori as &#x2265;1&#x202f;h on &#x2265;2 days in past week, was described for each measurement method, overall and by brace type (unloader, neutral). For temperature sensor measurements, time spent above 24&#xb0;C and time spent above 25&#xb0;C were used. Agreement between the measures was summarised by percentage agreement and kappa (&#x138;). RESULTS: The estimated proportions of participants meeting "minimum brace use" at 12 weeks were 83% (SRQ), 83% (SMS), 60% and 58% (temperature sensor, 24&#xb0;C and 25&#xb0;C thresholds, respectively). At 26 weeks, the corresponding estimates reduced to 72%, 71% (SMS at 24 weeks), 43% and 37%. Sensor data suggested the sharpest decline in brace use occurred within the first 12 weeks. Agreement between self-report measures was higher than between self-report measures and sensor (SRQ vs SMS at 12 weeks: 92% agreement, &#x138;=0.67 (95%CI: 0.34, 1.00); SRQ vs Sensor at 12 weeks: 74%, 0.35 (0.10, 0.60); SMS vs Sens at 12 weeks: 76%, 0.36 (0.05, 0.66). Agreement between all measurement methods reduced at 26 weeks. CONCLUSIONS: This novel use of a temperature sensor to monitor brace adherence in knee osteoarthritis indicates that self-report adherence substantially overestimates knee brace wearing time, with implications for clinical trials and practice.

Humans

Comparative Effectiveness of Exercise Interventions for Hamstring Injury Prevention in Football Players: A Systematic Review and Network Meta-analysis.

BACKGROUND: Hamstring strain injury is a leading time-loss injury in football, yet trials have evaluated diverse exercise-based prevention programs with limited direct head-to-head evidence. This systematic review and network meta-analysis aimed to compare the effectiveness of exercise-based interventions for preventing hamstring injuries in football players using exposure-adjusted incidence rate ratios. METHODS: We conducted a PRISMA-aligned systematic review and random-effects network meta-analysis of randomized controlled trials in football players comparing exercise-based interventions to prevent hamstring injuries. Searches covered PubMed, Cochrane Library, Embase and Web of Science from inception to January 5, 2026. Interventions were modeled as separate nodes (Nordic hamstring exercise [NHE], FIFA 11, FIFA 11&#x2009;+&#x2009;, FIFA 11&#x2009;+&#x2009;Kids, bounding exercise program [BEP], usual training). The primary effect measure was incidence rate ratio (IRR) versus usual training, with ranking by P-scores; exploratory subgroup analyses were conducted by sex-restricted male-only evidence and age group. RESULTS: Eleven randomized controlled trials involving 9,282 participants were included. The network was connected but largely star-shaped, with most evidence comparing active interventions against usual training and no direct active-active comparisons. FIFA 11&#x2009;+&#x2009;showed the most consistent exposure-adjusted association with reduced hamstring injury incidence versus usual training (IRR&#x2009;=&#x2009;0.55, 95% CI 0.31-0.98; P-score&#x2009;=&#x2009;0.84). FIFA 11&#x2009;+&#x2009;Kids showed a favorable but imprecise estimate, whereas NHE showed a modest non-significant reduction and FIFA 11 and BEP showed no clear benefit. Male-only findings were broadly consistent with the primary analysis. Age-stratified analyses suggested that the apparent hierarchy was not fully identical across age strata, but subgroup networks were sparse and exploratory. RoB 2 judged three studies as high risk and eight as having some concerns; no trial was judged as overall low risk. Between-study heterogeneity was substantial, and treatment rankings were, therefore, interpreted cautiously. CONCLUSIONS: In this IRR-based network meta-analysis, FIFA 11&#x2009;+&#x2009;showed the most consistent exposure-adjusted association with reduced hamstring injury incidence compared with usual training. However, certainty across the primary comparisons ranged from low to very low because of clinical and methodological heterogeneity, sparse direct evidence for several nodes, reliance on indirect active-active comparisons, substantial between-study heterogeneity, and moderate-to-high risk of bias across the included studies. The treatment hierarchy should, therefore, be interpreted as a low-to-very-low-certainty, population-level summary rather than as a basis for firm recommendations. Further well-reported, age- and population-specific head-to-head trials with consistent exposure, injury-definition, adherence, and intervention-dose reporting are needed. Registration Systematic review registration PROSPERO (CRD420251243576).

FIFA 11&#x2009;+&#x2009;