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Comparative effects of pharmacological interventions in the prophylactic treatment of tension-type headache: systematic review and network meta-analysis.

BACKGROUND: Tension-type headache (TTH) is the most common neurological disorder. The comparative effect of pharmacological interventions for TTH prophylaxis remains unclear. We aimed to assess the comparative effects of pharmacological interventions in the prophylactic treatment of TTH. METHODS: Ovid Medline, Embase, and Cochrane were searched from inception to 12 December, 2025. Randomized controlled trials (RCTs) of medications compared to placebo or another medication for preventing TTH were included. The primary outcome was headache days per month. A Bayesian random-effect model was employed as the primary analysis of chronic TTH. RESULTS: Thirty-five RCTs were included, 33 (88.6%) RCTs involved chronic TTH patients, and 24 RCTs provided available data for meta-analysis. Amitriptyline 100 mg presented more reduction of monthly headache days than placebo at 4 and 8 weeks (4 weeks: MD -6.59, 95% CrI -11.22 to -0.64; 8 weeks: MD -6.14, 95% CrI -10.27 to -0.87). BTX-A 100 U can reduce monthly headache days (MD -3.79, 95% CrI -7.16 to -0.33). Amitriptyline 100 mg was the highest-ranked treatment for monthly headache days at 4 (SUCRA 0.85), 8 (SUCRA 0.85), and 24 (SUCRA 0.87) weeks; 12 weeks was lidocaine 25 ml (SUCRA 0.75). Amitriptyline 100 mg and BTX-A 500 U showed a higher adverse event rate than placebo. CONCLUSION: Amitriptyline 100 mg and BTX-A 100 U may be options to reduce monthly headache days in patients with chronic TTH. Given the low to very low certainty of evidence, high risk of bias, and high heterogeneity, more studies are needed. TRIAL REGISTRATION: PROSPERO (CRD42025639586).

Humans

Comparative Effectiveness of Pharmacogenomics for Treatment of Depression.

PURPOSE/BACKGROUND: Pharmacogenomics (PGx), or the use of genetic information to assess drug-gene interactions, is an important step toward precision medicine. It is unclear if clinician use of PGx yields better outcomes for their patients. This study compared the effectiveness of combinatorial PGx-guided plus guideline-informed treatment (PGx+GIT) with guideline-informed treatment (GIT) alone to improve well-being in individuals with major depressive disorder. METHODS/PROCEDURES: Eligible participants (N=201) were randomized to PGx+GIT or GIT alone. PGx was measured with the proprietary GeneSight combinatorial test. PGx+GIT participant clinicians received test results within 2 business days to inform decisions about medication changes. Participants completed the World Health Organization Well-Being Index (WHO-5), Patient Health Questionnaire (PHQ-9), and PROMIS Profile physical functioning and social roles and activity domains every 2 weeks for 2 months and then every 2 months for the remaining 10 months. Monthly medication changes operationalized as necessary clinical adjustments were tracked with the medication recommendation tracking form. FINDINGS/RESULTS: Both groups improved average well-being over the 12-month study period (model-based change in WHO-5 per log (week) [95% CI]: 4.1 [3.3, 5.0] PGx+GIT and 4.8 [4.0, 5.5] GIT). PGx+GIT did not result in superior improvement in well-being (model-based difference [95% CI]: -0.6 [-1.8, 0.5], P =0.270), or any secondary outcomes. The effect of randomized treatment on well-being was not moderated by depression severity, number of previous failed medications for major depressive disorder, or presence of a comorbid condition. IMPLICATIONS/CONCLUSIONS: These data suggest PGx+GIT was not superior to GIT alone, possibly due to a ceiling effect of GIT, or PGx did not yield better results.

Humans

Effectiveness of psychologically informed physical therapy, tendon-specific exercise program and routine physical therapy in prolonged unilateral shoulder pain and symptom correlations with imaging: a single-center, randomized, parallel-group, three-arm study (RESPECT).

BACKGROUND: Shoulder complaints are one of the most common musculoskeletal ailments. Patient-specific characteristics such as obesity, depression and physical labor are established risk factors, whereas imaging findings are common and associations between specific imaging findings and symptomatology is limited. General exercises are considered useful in treatment whereas evidence for specific tendon exercises is lacking. Biopsychosocial model is also recommended, but has not been extensively studied concerning shoulder symptoms. This article describes the study protocol designed to evaluate the effectiveness and the cost-effectiveness of routine and specific physical therapy (PT) interventions. Imaging is performed for descriptive, longitudinal and imaging-symptom correlation studies. METHODS: The Rehabilitation of Shoulder Pain: Evaluation and Clinical Trial (RESPECT) is a randomized three-arm parallel-group study involving 300 participants aged 20 to 60 years with prolonged unilateral shoulder pain. Participants will receive either routine PT, physiotherapist-guided tendon-specific exercise program or psychologically informed PT. Bilateral shoulder radiographs, ultrasound and magnetic resonance imaging will be done at the baseline and at 12 and 36 months. Electronic surveys will be completed at the baseline and at 3, 6, 12 and 36 months. The primary outcome will be patient-specific functional scale (PSFS) at 12 months, analyzed using analysis of covariance (ANCOVA), adjusted for baseline PSFS. DISCUSSION: RESPECT will provide systematic and controlled data regarding different PT interventions in prolonged shoulder symptoms, which is currently limited. Being one of the most common sources of musculoskeletal pain, improved management could reduce symptom-related burden and prolonged functional impairment at individual and population level. CLINICALTRIALS: gov; Registration number NCT07235969; Registered November 18th, 2025; Version: 1.0.

Humans

Impact of early nurse-led implementation of an intensive care unit diary following major trauma on quality of life: The QUALITRAU randomized controlled trial.

BACKGROUND: Survivors of major trauma often experience long-term impairments in health-related quality of life (HRQoL) and post-traumatic stress disorder (PTSD). Intensive care unit (ICU) diaries have been proposed to reduce psychological sequelae, but evidence remains conflicting and not specific to trauma patients. OBJECTIVE: To assess whether, in patients with major trauma, a nurse-led ICU diary implemented within the first 48 h after trauma improves HRQoL at 1 year vs. usual care. METHODS: The QUALITRAU randomized controlled trial was conducted in three ICUs of a French tertiary hospital. Adult patients with major trauma (Injury Severity Score > 15) were randomized within 48 h of admission to receive either an ICU diary combined with usual care or usual care alone. The primary outcome was HRQoL at 12 months, assessed with the 4 domains of the WHOQOL-BREF questionnaire. Secondary outcomes included PTSD severity measured with the Impact of Event Scale (IES). Analyses were performed on an intention-to-treat basis. RESULTS: Between November 2014 and November 2016, 208 patients were randomized (101 intervention, 107 control), with primary outcome available for 121 (53 intervention, 68 control). Median age was 35 years [IQR 25-51], 81% were men, and 63% had severe traumatic brain injury. At 12 months, there were no differences between intervention and control groups in the WHOQOL-BREF domains (physical: 5.7 [IQR 4.6-11.4] vs 9.1 [IQR 4.6-13.1],P = 0.16; psychological: 8.0 [IQR 6.7-13.3] vs 11.3 [IQR 6.7-13.3],P = 0.08; social: 5.3 [IQR 4.0-14.7] vs 12.0 [IQR 4.0-14.7],P = 0.10; environment: 8.0 [IQR 5.5-14.5] vs 12.0 [IQR 5.5-15.5], P = 0.05). IES scores were also not different. CONCLUSIONS: Early implementation of nurse-led ICU diaries was not associated with improved long-term HRQoL or reduced PTSD symptoms in patients with major trauma. IMPLICATION FOR CLINICAL PRACTICE: These findings suggest that ICU diaries may need to be integrated into broader, multimodal rehabilitation strategies and may depend on factors such as timing, content, or patient characteristics.

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

Efficacy and safety of postoperative chewing gum for gastrointestinal recovery in children undergoing surgery: an updated systematic review and meta-analysis.

Chewing gum may stimulate gut motility through a "sham feeding" mechanism, but evidence in children is limited. We performed an updated systematic review and meta-analysis of randomized controlled trials comparing chewing gum plus usual care versus usual care alone in patients younger than 18 years undergoing any surgery. We searched five databases through June 2025. Primary outcomes were the time to first flatus, time to first defecation, and postoperative length of stay (LOS). Certainty was assessed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Ten studies (n = 649) were included: abdominal surgery (5), spinal fusion (3), and tonsillectomy (2). Chewing gum may result in little to no difference in the time to first flatus (MD - 3.58 h, 95% CI - 8.08 to 0.91) or first defecation (MD - 3.23 h, 95% CI - 6.63 to 0.18), both with low certainty. LOS evidence was very uncertain (MD - 0.18 days, 95% CI - 0.70 to 0.33). Subgroup analyses suggested shorter LOS after abdominal surgery (MD - 0.60 days, 95% CI - 1.99 to 0.79) but not after spinal fusion (MD 0.10 days, 95% CI - 0.29 to 0.50; p for interaction = 0.0362). The benefits of postoperative chewing gum in children remain uncertain, with potential surgery-specific differences in LOS warranting investigation.

Humans

Efficacy of Janus kinase inhibitor combined with phototherapy in non-segmental vitiligo: systematic review and meta-analysis.

BACKGROUND: Vitiligo is a chronic autoimmune disease causing skin depigmentation and psychosocial issues. Non-segmental vitiligo often shows limited response to standard therapies. The IFN-&#x3b3;-JAK-STAT pathway plays a key role, and combining JAK inhibitors with NB-UVB may improve repigmentation. AIM: To evaluate the efficacy of JAK inhibitors (baricitinib or tofacitinib) plus NB-UVB versus NB-UVB without JAK inhibitors in adult NSV. METHODS: PubMed, Cochrane, and ClinicalTrials.gov were searched till August 2024 for randomized controlled trials. Four studies, comprising 217 adults (121 in the combination group and 96 in the control group), were analyzed using RevMan 5.4. Bias was assessed via Newcastle-Ottawa, Cochrane ROB-2, and ROBINS-I tools. RESULTS: Combination therapy significantly reduced total VASI compared to controls (MD = -4.96, 95% CI [-9.29, -0.63], p&#x2009;=&#x2009;0.02), with a greater effect on sensitivity analysis (MD = -6.84, p&#x2009;=&#x2009;0.0007). Significant reductions were seen in face/neck (MD = -0.17, p&#x2009;=&#x2009;0.002), trunk (MD = -3.62, p&#x2009;=&#x2009;0.0001); acral (MD = -0.85, p&#x2009;=&#x2009;0.0002) and extremity (MD = -4.61, p&#x2009;<&#x2009;0.00001) regions after sensitivity analysis. Patients were more likely to achieve &#x2265;50% (RR = 6.87, p&#x2009;<&#x2009;0.00001) and &#x2265;75% (RR = 15.13, p&#x2009;=&#x2009;0.006) repigmentation. CONCLUSIONS: JAK inhibitor plus NB-UVB markedly improves the repigmentation in adult NSV compared to NB-UVB alone.

Humans

Safety and Effectiveness of Direct Oral Anticoagulants Versus Low-Molecular-Weight Heparin for Cancer-Associated Thrombosis: A Systematic Review and Meta-analysis.

BACKGROUND: Cancer-associated thrombosis is a condition associated with high mortality rates, yet limited evidence exists regarding the safety and effectiveness of low-molecular-weight heparin (LMWH) and direct oral anticoagulants (DOACs), focusing on a fixed follow-up period based on clinical practice guideline recommendations. OBJECTIVE: This study aimed to compare the safety and effectiveness of DOACs versus LMWH in patients with cancer-associated thrombosis over a 6-month follow-up period. METHODS: PubMed, Embase, and Cochrane Library databases were systematically searched up to 30 June, 2025. Recurrent venous thromboembolism, major bleeding, and all-cause mortality were pooled using a random-effects meta-analysis. RESULTS: Seven randomized controlled trials and 28 cohort studies were included in our systematic review. After applying the criteria for a 6-month follow-up period, five randomized controlled trials and 16 cohort studies with 49,824 patients were analyzed in the meta-analysis. In randomized controlled trials, DOACs showed a lower incidence of venous thromboembolism recurrence (relative risk [RR] 0.66, 95% confidence interval [CI] 0.49-0.87) compared with LMWH, with a non-significant increase in major bleeding (RR 1.28, 95% CI 0.87-1.88) and no significant difference in all-cause mortality (RR 1.00, 95% CI 0.86-1.18). Cohort studies demonstrated a lower incidence of venous thromboembolism recurrence (RR 0.69, 95% CI 0.62-0.76) with DOACs, a non-significant reduction in major bleeding (RR 0.85, 95% CI 0.68-1.07), and a lower risk of all-cause mortality (RR 0.47, 95% CI 0.31-0.72). CONCLUSIONS: In patients with cancer-associated thrombosis, DOACs demonstrated a decrease in recurrent venous thromboembolism without increasing the risk of all-cause mortality. A non-significant increase in the risk of major bleeding was recorded in randomized controlled trials, but not in cohort studies. DOACs may provide greater effectiveness for cancer-associated thrombosis compared with LMWH.

Humans

Weight regain following discontinuation of glucagon-like peptide-1 receptor agonists in adults who are overweight or obese: a systematic review and meta-analysis.

OBJECTIVE: This study aims to explore the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on weight changes and the occurrence of adverse reactions in overweight or obese adults after drug withdrawal. METHODS: Computerized searches were conducted in evidence-based databases such as PubMed, Embase, Cochrane Library and Scopus. The search period was from the establishment of the database to December 2025. Collect randomised controlled trials (RCTs) and controlled trials on GLP-1RAs, including tirzepatide, semaglutide, liraglutide, and dulaglutide, for the treatment of overweight or obese adult patients. The risk of bias in the included studies was assessed using the Cochrane Risk of Bias V2.0 tool provided by the Cochrane Collaboration, and meta-analysis was performed using the R programming language. RESULTS: A total of 699 studies were initially retrieved. Eventually, six studies involving 8,993 patients were included in the quantitative analysis, comprising 5,553 patients in the discontinuation group and 3,440 in the continued treatment group. The results of the meta-analysis showed that, compared with the continued treatment group, the weight difference in the discontinuation group was mean difference (MD) = 17.90%, 95% confidence interval (CI) [14.11-21.69], P&#xa0;<&#xa0;0.0001. It can be seen that there was a significant rebound in weight after drug withdrawal, and there was statistical heterogeneity among the studies (P&#xa0;=&#xa0;0.0082). Subgroup analysis further revealed that the weight rebound amplitude after discontinuation of tirzepatide was significantly higher than that of semaglutide. This result suggests that the differences in the mechanism of action of different GLP-1RAs may be the reason for the differences in weight changes after discontinuation. In addition, the percentage difference in body weight between after and before drug withdrawal was MD = 9.11%, 95% CI [7.91-10.30], P&#xa0;<&#xa0;0.0001, further verifying the trend of weight rebound after drug withdrawal. The summary of adverse reaction reports analyzed and studied indicates that after drug withdrawal, the overall adverse reactions of patients decreased, gastrointestinal adverse reactions decreased, and the incidence of cardiovascular events was not affected by drug withdrawal. CONCLUSION: There is a significant weight rebound phenomenon after discontinuation of GLP-1RAs, and the rebound magnitudes vary among different types of drugs. At the same time, there is a risk of adverse reactions during the use of such drugs.

Humans

Risk-Benefit of Phase 2 Monotherapy Trials in Adult Solid Cancers: A Systematic Review and Meta-Analysis.

Phase 2 (and phase 1 dose expansion, which we label phase 2 for the purposes of this study) cancer trials are the first direct tests of a new drug's efficacy. Because efficacy evidence is lacking, the therapeutic status of drug administration during ethical review is uncertain. We compared the efficacy and safety of cancer monotherapies in phase 2&#xa0;with phase 3, where clinical equipoise underwrites a therapeutic status for drug administration. In this systematic review and meta-analysis, we searched Clinicaltrials.gov for phase 2 and 3 investigational monotherapy drug trials in six solid malignancies, with primary completion dates 2015-2020, inclusive. Two independent reviewers completed data extraction. Effects were estimated using an inverse-variance weighted random-effects model meta-analysis of proportions using the R package meta. We analyzed 130 phase 2 and 52 phase 3 trial arms, enrolling 6665 and 18,694 patients. The pooled objective response rate was 7% (95% CI 5%-11%) in phase 2 versus 24% in phase 3 (95% CI 17%-31%; p&#x2009;<&#x2009;0.0001). The median PFS and OS were shorter in phase 2 compared to phase 3 (3.23 vs. 5.43&#x2009;months, p&#x2009;<&#x2009;0.0001; 9.46 vs. 14.44&#x2009;months, p&#x2009;=&#x2009;0.0001). The pooled rate of drug-related grade 3-4 adverse events was 30% (95% CI 23%-37%) in phase 2 and 25% (95% CI 19%-32%) in phase 3. Monotherapies delivered in phase 2 cancer trials present diminished risk-benefit compared with phase 3 and align with historic estimates for phase 1. Though there may be exceptions, risks for drug administration in phase 2 should generally be justified by appeals to research rather than therapeutic value.

Humans

Systematic meta-analysis of the toxicities and side effects of the targeted drug lenvatinib.

BACKGROUND: Lenvatinib, an effective targeted drug for various cancers, has clinical medication safety concerns due to its toxicities and side effects. OBJECTIVE: This study evaluated lenvatinib-induced any adverse events (any AEs) and nine aspects: vascular toxicities related to the circulatory system (vascular toxicities, blood system, and heart), toxicities of the skin and its appendages (skin/subcutaneous tissue and taste system), toxicities of the respiratory system (respiratory, thoracic, and mediastinal and respiratory tract), toxicities of the nervous system (nervous system and general), toxicities of the digestive system (gastrointestinal and liver), toxicities of the urinary system, toxicities of the endocrine and metabolic system (endocrine and metabolism/nutrition), toxicities of the musculoskeletal system, and other severe toxicities. Toxicities and side effects were stratified by severity into any and &#x2265;3 grades for analysis. PATIENTS/MATERIALS AND METHODS: Multiple databases were searched for lenvatinib cancer clinical studies (cohort studies and randomized controlled trials) from inception to December 31, 2024; toxicity and side effect data were extracted and analyzed. RESULTS: Nine high-quality studies were included, showing that lenvatinib is effective in cancers but has notable toxicities. Taking hypertension as an example, for any grade, the risk ratio (RR) was 2.34 with a 95% confidence interval (CI) of [2.09, 2.62], a Z-value of 14.74, and a P-value <0.00001; for grade &#x2265;3, the RR was 2.60 with a 95% CI of [2.21, 3.06], a Z-value of 11.44, and a P-value <0.00001. CONCLUSION: Lenvatinib is effective for cancer but toxic, and this study supports its rational clinical use.

Humans

Hyper-oncotic albumin administration reduces mortality in acute Respiratory Distress Syndrome compared to crystalloid: a systematic review and meta-analysis.

BACKGROUND: To evaluate the association between albumin administration as volume replacement and mortality in adult ARDS patients, we performed this meta-analysis and trial sequential analysis (TSA). METHODS: We searched databases including PubMed, Science Direct, Scopus, Web of Science databases and Cochrane Central Register of Controlled Trials up to 12 December 2024. We screened trials that included adult ARDS patients and compared albumin with crystalloid. The 28-day mortality served as the primary endpoint, while the oxygenation change, the length of ICU stay and the length of hospital stay were designated as secondary outcomes. To clarify the differing concentrations of albumin, we formed two distinct subgroups: the hyper-oncotic albumin subgroup (&#x2265;20%) and the iso-oncotic albumin subgroup (4%&#x223c;5%). Statistical synthesis was performed with Cochrane Review Manager 5.4.1, employing random-effects models. To mitigate random errors, TSA was implemented with &#x3b1;&#x2009;=&#x2009;0.05 and &#x3b2;&#x2009;=&#x2009;0.20 parameters. RESULTS: The analysis incorporated 5 publications: 3 randomized controlled trials (RCTs) and 2 non-randomized studies (NRSs). Overall mortality was lower in the albumin group (33.2%, 97/292) than in the crystalloid group (44.9%, 133/296) (OR = 0.61, 95%CI 0.43-0.85, p&#x2009;=&#x2009;0.004). RCTs (n&#x2009;=&#x2009;204) showed no benefit (OR = 0.83, p&#x2009;=&#x2009;0.54), but NRSs (n&#x2009;=&#x2009;384) demonstrated reduced mortality (OR = 0.52, p&#x2009;=&#x2009;0.002). Hyper-oncotic albumin was associated with lower mortality in NRSs (OR = 0.40, p&#x2009;=&#x2009;0.02) but not in RCTs (OR = 0.74, p&#x2009;=&#x2009;0.57). Iso-oncotic albumin showed no benefit (OR = 0.88, p&#x2009;=&#x2009;0.72). Regarding the impact of albumin on oxygenation, significant improvements in oxygenation were observed only on the first (p&#x2009;=&#x2009;0.05) and second days (p&#x2009;<&#x2009;0.0001). The TSA indicated a continued need for high-quality RCTs. CONCLUSIONS: Our analysis suggests that hyper-oncotic albumin may reduce mortality and improve early oxygenation in ARDS patients compared to crystalloids. Larger RCTs are urgently needed to validate these findings and define their potential role in clinical management.

Humans

A Dynamic Nomogram to Predict Metabolic Dysfunction-Associated Fatty Liver Disease in Patients with Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MetS) involves multiple metabolic disorders. This study aimed to identify high-risk populations for metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with MetS and to establish a dynamic predictive nomogram. METHODS: A total of 627 patients with MetS from six regions in Zhejiang Province were enrolled and categorized into MAFLD and non-MAFLD groups, then randomly assigned to training and validation sets at a ratio of 7:3. Independent predictors of MAFLD were identified using least absolute shrinkage and selection operator regression and multivariable logistic regression analyses. These predictors were then used to construct a dynamic nomogram. RESULTS: A total of 627 patients with MetS were included in the final analysis, of whom 77.0% (483/627) were diagnosed with MAFLD. Multivariable logistic regression analysis identified body mass index (BMI), waist circumference (WC), total cholesterol (TC), alanine aminotransferase (ALT), MetS-defined dysglycemia, and education level as independent risk factors for MAFLD. MetS-defined dysglycemia showed the highest odds ratio (OR) for MAFLD development [OR = 1.87, 95% confidence interval (CI): 1.07-3.29]. Although the number of MetS components and the metabolic syndrome score were significantly associated with MAFLD in univariate analysis, they were not independently associated with MAFLD in the multivariate model. A dynamic nomogram for predicting MAFLD risk in patients with MetS was developed and internally validated. The area under the receiver operating characteristic curve was 0.834 (95% CI: 0.787-0.880) in the training set and 0.839 (95% CI: 0.771-0.899) in the validation set, indicating strong predictive performance. Bootstrap internal validation demonstrated good agreement between predicted and observed outcomes in calibration curves. Decision curve analysis further indicated favorable clinical applicability of the nomogram. CONCLUSION: BMI, WC, TC, ALT, MetS-defined dysglycemia, and education level are independent risk factors for MAFLD. A dynamic nomogram for predicting MAFLD risk in patients with MetS was successfully developed and validated.

Humans

Indigenous body image amid rapid social and economic change: A reflexive thematic analysis of Wayuu narratives.

The Wayuu, Colombia's largest Indigenous group, are experiencing rapid social, economic, and technological change, including expanding internet access, educational opportunities, and increasing exposure to globalised media. Though the harmful effects of appearance-idealised media imagery on body image are well documented, indigenous body image research remains unevenly distributed across global contexts, with Latin American Indigenous communities particularly underrepresented. This study explored how Wayuu people understand and experience appearance ideals and body image in the context of expanding digital media exposure and rapid sociocultural and economic change. Five focus groups of up to 9 participants were conducted with 29 Wayuu participants (18-68 years; 23 women, 6 men). Using reflexive thematic analysis, three overarching themes were identified: (1) Intersecting sources of appearance pressure: encompassing influences from social media, Wayuu family expectations, and discrimination from non-Indigenous peers; (2) Negotiating and resisting appearance ideals: from body dissatisfaction and restrictive eating to affirmation of cultural identity as protection; and (3) The changing role of appearance in today's Wayuu culture: participants linked globalised appearance ideals to expanding educational opportunities, migration, digital connectivity, and broader socioeconomic transformations occurring within Wayuu territories. While exposure to global ideals fostered comparison and dissatisfaction, cultural pride and collective belonging appeared to buffer against internalised colonial values. Culturally grounded media literacy and education initiatives co-developed with Wayuu communities could foster critical reflection while strengthening heritage. These results highlight the need for decolonial, community-based approaches to body image research and intervention in Indigenous contexts.

Adolescent

Simultaneous determination of imiquimod and terbinafine in skin permeation studies: Validation of a liquid chromatography method with fluorescence detection.

Chromoblastomycosis is a chronic, neglected subcutaneous mycosis posing significant therapeutic challenges. A topical strategy combining terbinafine (TBF), an antifungal, with imiquimod (IMQ), a TLR-7/8 agonist immunomodulator, has emerged a promising alternative. However, no validated analytical method is currently available to simultaneously quantify both drugs in skin, which is crucial for novel formulation development. This study reports the development and validation of a simple HPLC method with fluorescence detection (excitation 236&#xa0;nm, emission 340&#xa0;nm) for the simultaneous determination of TBF and IMQ extracted from porcine skin. Separation was achieved on a C8 reversed-phase column (125&#xa0;&#xd7;&#xa0;4.0&#xa0;mm, 5&#xa0;&#x3bc;m) using a mobile phase of methanol and water (60,40, v/v), both containing 0.1% formic acid at a flow rate of 0.8&#xa0;mL/min. The method showed excellent linearity (r&#xa0;>&#xa0;0.999) over 0.01-1.0&#xa0;&#x3bc;g/mL for IMQ and 0.1-2.0&#xa0;&#x3bc;g/mL for TBF. Intra- and inter-day precision demonstrated coefficients of variation below 5%, and recovery rates from skin (79-105%) confirmed accuracy. Limits of detection were 0.001&#xa0;&#x3bc;g/mL for IMQ and 0.004&#xa0;&#x3bc;g/mL for TBF, with quantification limits of 0.02&#xa0;&#x3bc;g/mL and 0.16&#xa0;&#x3bc;g/mL, respectively. This selective, sensitive, and reproducible method represents a valuable analytical tool for supporting the development and quality control of topical formulations for chromoblastomycosis and other fungal skin diseases.

Animals

Evaluating the utility of melatonin in spine surgery: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Spine surgery is increasingly performed worldwide, and acute postoperative stressors such as pain and anxiety remain highly prevalent despite historical management with opioids and other pharmacological agents. Recently, interest has emerged in melatonin administration given its endogenous physiological roles, low cost, favorable adverse event profile, and documented benefits throughout surgical literature. PURPOSE: This study aims to consolidate the existing evidence on melatonin's utility specifically in spine surgery, an area not yet comprehensively evaluated, to inform clinical practice and enhance spine surgeon comprehension. STUDY DESIGN/SETTING: Preregistered on PROSPERO, this systematic review queried PubMed/MEDLINE, CINAHL, SPORTDiscus, and Web of Science on November 21st, 2025, for studies reporting outcomes following melatonin administration in patients undergoing spine surgery. METHODS: Study quality was assessed using the Cochrane Risk-of-Bias 2 tool. Extracted variables included demographics, comparator medications, dosages, and other relevant details. Statistical analyses included frequency-weighted means (FWMs), associated standard deviations, narrative syntheses, and limited meta-analyses, where appropriate. RESULTS: A total of 6 moderate-quality randomized trials were included from 749 screened. Melatonin (3-10 mg) was administered to 227 patients (FWM age=43.3&#xb1;8.6 years; 46.2% male; BMI=26.6&#xb1;3.2 kg/m2), placebo to 125 patients (age=43.2&#xb1;10.1 years; 60% male; BMI=28.5&#xb1;4.3 kg/m2), and active pharmacologic comparators (fentanyl, gabapentin, dexmedetomidine, zolpidem) to 151 patients (age=46.6&#xb1;8.9 years; 40.5% male; BMI=26.3&#xb1;3.5 kg/m2). Procedures primarily involved uncomplicated lumbar laminectomies (1-4 levels), with outcomes assessed up to 24 hours postoperatively. Melatonin was associated with significant improvements in early postoperative VAS-pain scores, blood-pressure-related, analgesic-related, and anxiety-related outcomes versus placebo across most reporting studies. Compared with active pharmacologic agents, significant benefits were observed only in select nausea- and anxiety-related instances. Limited meta-analysis (n=2) demonstrated higher 24-hour VAS-pain for melatonin versus gabapentin, though mean difference was near-negligible and harbored extensive statistical constraints. CONCLUSION: Melatonin demonstrates variable utility following spine surgery, with generally consistent anxiolysis and frequent benefit versus placebo but less consistent and comparatively weaker efficacy relative to active pharmacologic comparators. Future outcome-homogenous studies incorporating more granular, expansive comparator arms and more robust quantitative analyses are needed to further elucidate melatonin's role in advancing spine care. LEVEL OF EVIDENCE: Level II.

Humans

Comparative effectiveness of percutaneous coronary intervention strategies for coronary small-vessel disease: a network meta-analysis of randomized trials.

BACKGROUND: Coronary small-vessel disease (SVD) remains challenging for percutaneous coronary intervention (PCI) because small lumens magnify restenosis and ischemic risk. Multiple devices are available, yet their comparative performance is uncertain. This study evaluated and ranked PCI strategies for SVD. METHODS: A systematic review and network meta-analysis was conducted in accordance with PRISMA. PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and Google Scholar were searched from inception to 15 August 2025. Eligible studies were English-language randomized controlled trials enrolling adults with angiographic SVD defined as reference vessel diameter &#x2264;3.0&#x2009;mm, comparing PCI strategies, and reporting target lesion revascularization (TLR), binary restenosis (BR), or myocardial infarction (MI). A frequentist random-effects network meta-analysis generated odds ratios (ORs) with 95% confidence intervals (CIs) and treatment rankings using the surface under the cumulative ranking curve (SUCRA). RESULTS: Thirty-nine trials including 14,503 patients met the criteria. For TLR (37 studies; 11,980 patients), the highest SUCRA values were observed with sirolimus-eluting stents (SES 90.1%), zotarolimus-eluting stents (ZES 83.9%), and everolimus-eluting stents (EES 82.2%). For BR (32; 6,468), SES, ZES, and paclitaxel-coated balloons (DCB-PTX) ranked highest (95.0%, 80.0%, and 78.3%). For MI (37; 11,602), SES, DCB-PTX, and ZES ranked highest (79.0%, 78.7%, and 68.5%). Representative effects showed SES reduced TLR versus bare-metal stents (BMS) (OR, 0.25; 95% CI, 0.15-0.43) and MI versus BMS (OR, 0.41; 95% CI, 0.21-0.79). Conventional approaches such as BMS, plain old balloon angioplasty (POBA), and gold-plated balloon angioplasty (GPBA) ranked lowest across outcomes. CONCLUSION: SES provides the most consistent clinical benefit for coronary SVD. ZES, EES, and DCB-PTX are effective alternatives in selected settings, whereas BMS, POBA, and GPBA are less effective. These findings offer comparative evidence to guide device selection in SVD.

Humans

The musculoskeletal pain literacy questionnaire (MSK-PLq) - Part 1: Development of a preliminary version through a systematic review and Delphi consensus.

OBJECTIVE: Chronic musculoskeletal (MSK) pain is a leading cause of disability worldwide, and self-management is a first-line approach recommended by international clinical guidelines. Access to evidence-based information that enhances health literacy may support patients' engagement in their self-management and treatment decision-making, potentially reducing disease burden and pain. However, no tool currently exists to assess health literacy specifically in MSK pain. This study aimed to develop and describe the preliminary version of a knowledge-based questionnaire to evaluate MSK pain literacy, the Musculoskeletal Pain-Literacy questionnaire (MSK-PLq). METHODS: A systematic literature review identified existing health literacy instruments and generated a preliminary list of domains. A two-round Delphi study with 22 panellists (19 experts and three people living with chronic MSK pain), followed by consensus meetings, was used to refine domains and items (&#x2265;70% agreement). Readability was assessed using the Flesch Reading Ease (FRE) score and three stakeholders were consulted to review the questionnaire for comprehensibility, clarity, and face validity. RESULTS: Six domains were retained (Understand, Access, Appraise, Apply, Digital, Beliefs), comprising 20 items in the preliminary version of MSK-PLq. Readability was acceptable (mean FRE 74, indicating fairly easy reading), and subject feedback supported the questionnaire's clarity and face validity. CONCLUSIONS: The preliminary version of the MSK-PLq is proposed as the first knowledge-based tool to assess functional, interactive, and critical aspects of MSK pain literacy. It may have applications in clinical practice, research, education, and digital health, by informing tailored patient education and supporting self-management strategies, although further psychometric validation is required.

Humans