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PubMed2026

Novel Proactive Speech-Language Intervention Is More Effective Than Usual Care: Randomized Controlled Trial of Babble Boot Camp for Infants With Classic Galactosemia.

PURPOSE: Speech and language disorders cannot be diagnosed and treated until children are approximately 2-4 years old. To investigate whether these disorders can be prevented, we developed and trialed Babble Boot Camp (BBC), the first proactive sustained intervention starting with precursor skills including cooing and babbling. METHOD: Participants were two randomly assigned groups of 22 infants with classic galactosemia, a metabolic disease with known risks for severe speech and language disorders. One group started BBC at under 6 months of age, and the other started at 15 months of age, both completing BBC at 24 months of age. Coached by a speech-language pathologist in weekly telehealth sessions, caregivers implemented BBC activities and routines daily at home. A typical control group and a group of children with classic galactosemia who received usual care participated as well. All children completed standardized assessments of speech and language at postintervention. RESULTS: Assessment scores showed that BBC was more effective than usual care for both intervention groups. Greatest benefits were seen in the group that started at or before 6 months of age, with a proportion of clinically concerning scores equal to that in the typically developing peers. No effects of sex, genotype, or milk consumption were evident in the outcomes. CONCLUSIONS: Findings motivate a paradigm shift from deficit-based to proactive approaches for infants with classic galactosemia. BBC is extensible to many other disorders, with trials currently underway for infants with Down syndrome and infants born preterm.

Humans↗

PubMed2026

From pathobiology to prescribing in obesity-driven HFpEF: A systematic review and practical therapeutic framework.

Heart failure with preserved ejection fraction (HFpEF) is increasingly driven by obesity and cardiometabolic dysfunction. In this phenotype, the dominant biology extends beyond congestion alone and includes visceral and epicardial adiposity, systemic inflammation, impaired myocardial energetics, endothelial dysfunction, and exertional elevation in filling pressures. We performed a PRISMA-compliant systematic review with structured narrative evidence synthesis to evaluate pharmacological therapy in obesity-driven HFpEF, searching PubMed/MEDLINE, Scopus, Web of Science Core Collection, ClinicalTrials.gov, and WHO ICTRP through December 2025. Eighteen reports were included in the final qualitative synthesis. The available evidence supports sodium-glucose cotransporter 2 inhibitors as the pharmacological foundation because they provide the most mature outcome data across the preserved ejection fraction spectrum. Semaglutide improves symptoms, physical limitations, exercise capacity, and body weight in dedicated obesity-related HFpEF trials, whereas tirzepatide extends this signal by improving clinical status and reducing worsening heart failure events. Finerenone broadens the therapeutic platform in HF with mildly reduced or preserved ejection fraction, although obesity-specific data remain indirect. Conventional neurohormonal therapies retain a selective role, but they are not the principal biological match for this phenotype. Obesity-driven HFpEF should therefore be managed as a cardiometabolic syndrome with heart failure expression, using a phenotype-based sequence that links diagnosis, decongestion, SGLT2 inhibition, obesity-directed therapy, and selective adjunctive intensification.

Humans↗

PubMed2026

Structural complexity and mechanistic diversity of MECOM rearrangements in myeloid neoplasms.

Rearrangements involving MECOM at chromosome 3q26.2 are recurrent in myeloid neoplasms, classically represented by inv(3)(q21q26.2) and t(3;3)(q21;q26.2), which reposition the GATA2-distal haematopoietic enhancer and drive aberrant EVI1 overexpression. However, the full structural and mechanistic diversity of MECOM rearrangements (MECOM-r) is yet to be explored. We retrospectively analysed 97 cases with cytogenetically defined MECOM-r and identified 12 with complex rearrangements using GTG-banded karyotyping and tri-colour interphase/metaphase fluorescence in situ hybridisation analyses. These 12 cases demonstrated remarkable structural heterogeneity. The abnormalities encompassed translocations, inversions, insertions, duplications, and deletions, which often coexisted within the same specimen as multiple rearranged subclones. Insertional events emerged as a distinct mechanism of MECOM activation. These encompassed insertions of MYNN and/or MECOM into chromosomes 1 and 6, insertion of chromosome 8 segment into MECOM, and inverted insertions between homologous chromosome 3 segments. Recurrent breakpoints at 3q21 across multiple cases, together with localised copy number imbalances frequently involving the MYNN and GOLIM4 loci at 3q26.2, underscore the architectural fragility of these two regions. Co-occurring abnormalities such as -5/del(5q), -7/del(7q), and TP53 loss were common, reflecting a permissive genomic background for chromosomal reassembly. Our findings expand the mechanistic landscape of MECOM-r beyond canonical inv(3)/t(3;3), establishing 3q21 and 3q26.2 as structural 'hotspots' and genomic instability hubs. Distinct from fusion-driven oncogenes such as KMT2A, MECOM activation results from enhancer hijacking and regional structural remodelling, leading to EVI1 overexpression and clonal evolution in myeloid malignancies.

Humans↗

PubMed2026

Foot exercise plus education versus brief advice for the treatment of plantar heel pain (FEET Trial): a feasibility randomised controlled trial.

BACKGROUND: Despite foot muscle strengthening being a target of exercise interventions for plantar heel pain (PHP) no study has measured foot muscle outcomes, and existing research is limited by a lack of control (no treatment) comparisons. OBJECTIVES: To determine the feasibility of conducting a randomised controlled trial and investigate the acceptability and credibility of comprehensive progressive foot exercise and education compared to brief advice for PHP. DESIGN: Randomised parallel group feasibility trial. METHOD: People with PHP were randomised (1:1 concealed allocation) to receive either foot exercise plus education or brief advice for twelve weeks. Primary outcomes included willingness to enrol, recruitment rate, adherence, logbook completion, dropout rate, early withdrawal reasons, adverse events, additional treatments sought, and credibility/expectancy. RESULTS: Twenty people with PHP (16 women; age 50 ± 9 years; body mass index = 30.7 ± 4.6 kg/m2) were recruited over 15 weeks (1.3 participants per week). Primary outcomes were willingness to enrol (80%), adherence (physiotherapy sessions attended: foot exercise plus education 85%, brief advice 100%; home exercise program: 62% daily sessions completed, 72% thrice weekly sessions completed), logbook completion (foot exercise plus education 75%, brief advice 90%), dropout rate (15%), and additional treatments sought (69%). There were no intervention-related adverse events, and credibility scores were higher for foot exercise plus education. CONCLUSIONS: This study confirms feasibility and acceptability of a protocol comparing foot exercise plus education with brief advice in individuals with PHP, generating key insights to inform future trial design.

Humans↗

PubMed2026

Effectiveness of tobacco cessation interventions delivered in clinical settings in South Asia: a systematic review and meta-analysis.

BACKGROUND: Despite the burden of tobacco use, access to cessation support in South Asia remains scarce. OBJECTIVE: This review evaluates the effectiveness of tobacco cessation interventions delivered in clinical settings in South Asia. METHODS: Five relevant databases were searched from inception to February 2025. Eligibility criteria included randomized and non-randomized studies evaluating behavioral, pharmacotherapy, and multicomponent interventions delivered in clinical settings in South Asia. Data on study setting and design, participant information, intervention, comparator, and outcomes were extracted. Meta-analyses using random-effect models were conducted where possible. Certainty of evidence was assessed using GRADE. RESULTS: Thirty-seven studies were included (22 randomized and 15 non-randomized). Interventions involved pharmacotherapy (n = 6; 16.2%), nicotine replacement therapy (n = 7; 18.9%), behavioral counseling (n = 12; 32.4%), or combined/multicomponent interventions (n = 12; 32.4%). Most studies were conducted in India (n = 26; 70.3%), followed by Pakistan (n = 6; 16.2%), Nepal (n = 3; 8.1%), and two studies (5.4%) were multi-country in India, Pakistan, and Bangladesh. Pooled analyses demonstrated higher quit rates among intervention versus control for continuous abstinence at 0-3 months (RR: 1.21, 95%CI: 1.06 to 1.37) and >3 months (RR: 1.68, 95%CI: 1.1.4 to 2.47), and for point abstinence at >3 months post-intervention (RR: 2.03, 95%CI:1.35 to 3.08). Heterogeneity was high for all analyses (I2 range: 94% to 97%). Combined behavioral and pharmacotherapy interventions were most effective (RR: 1.70, 95%CI: 0.98 to 2.92), although not statistically significant (p = 0.06). CONCLUSION: Tobacco cessation interventions delivered in clinical settings in South Asia are effective, particularly when combining behavioral support with pharmacotherapy. However, evidence is limited by methodological weaknesses.

Humans↗

PubMed2026

Cisplatin-Induced Hearing Loss Prevention With Intratympanic Therapy Systematic Review and Meta-Analysis.

INTRODUCTION: Cisplatin-induced hearing loss (CIHL) is a well-described, long-term consequence of cisplatin treatment for malignancy. Intratympanic (IT) injections have been trialed to prevent CIHL in humans. To provide clarity on which agents have been studied through IT injection and to review their efficacy for hearing loss prevention, we performed a systematic review and meta-analysis. DATA SOURCES: OVID Medline, Embase, Web of Science, and Cochrane Library were queried. METHODS: Databases were searched in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Prospective randomized trials were included, and a systematic review was performed for all studies. Demographic, audiometric, and therapeutic data were collected. Random-effects models were used to compare across studies, and subgroup analyses were performed for each IT agent. RESULTS: The initial database search yielded 1017 articles, which were screened according to inclusion and exclusion criteria. Ten studies were identified, involving a total of 284 patients. Studies included data on IT dexamethasone, IT N-acetylcysteine (NAC), and IT sodium thiosulfate (STS). Pooled analysis across all agents and frequencies did not reveal a significant difference in hearing thresholds between treatment and control ears [prediction interval [-3.77, 3.20], negative favors treatment). Subgroup analysis of IT dexamethasone [-1.74, 3.80] and IT NAC [-1.02, 4.64] also did not demonstrate significant differences. STS data were not amenable to pooled analysis; however, one study demonstrated a significant decrease in ASHA-defined ototoxicity (40% vs. 85%, P =0.0027). CONCLUSIONS: To date, no IT agent has consistently prevented CIHL, although limited data suggest that IT STS may decrease ototoxicity. More trials are necessary to fully elucidate these effects.

Humans↗

PubMed2026

Multi-omics integrative analysis provides insight into potential molecular responses to sustained high water flow in common carp (Cyprinus carpio) cultured in recirculating aquaculture.

To investigate the potential molecular responses by which water flow intensity affects the growth of common carp (Cyprinus carpio) in a recirculating aquaculture system (RAS), a control group (CG, actual water velocity 0.3 cm/s) and three sustained flow treatment groups were established, including a low-flow group (LF, 1 body length per second, bl/s), a medium-flow group (MF, 2 bl/s), and a high-flow group (HF, 3 bl/s). After 12 weeks of culture in the RAS, growth performance was compared among groups under different flow intensities. The best-performing group and the control group were then selected for the determination of intestinal digestive enzyme activities, as well as transcriptomic and whole-genome bisulfite sequencing analyses of muscle tissue. The results showed that the specific growth rate and feed intake of the HF group were significantly higher than those of the other groups (P < 0.05), whereas no significant difference in feed conversion ratio was observed among groups. Compared with the CG group, lipase activity was significantly higher in the HF group (P < 0.05), while α-amylase and trypsin activities showed increasing trends without significant differences. RNA-seq identified a total of 273 differentially expressed genes, including 72 upregulated genes and 201 downregulated genes in the HF group relative to the CG group. These genes were mainly enriched in glycolysis, pyruvate metabolism, ATP metabolism, the pentose phosphate pathway, the insulin signaling pathway, the PPAR signaling pathway, and the adipocytokine signaling pathway, indicating that sustained high water flow induced a muscle transcriptional response characterized by remodeling of energy metabolism and substrate utilization. Whole-genome bisulfite sequencing analysis showed that DNA methylation in common carp muscle occurred predominantly in the CpG context. Differentially methylated regions between the HF and CG groups were mainly distributed in transcription-related regulatory regions, including promoters, CpG islands, and CpG island shores. In promoter regions, the number of hypermethylated regions in the HF group relative to the CG group was markedly higher than that of hypomethylated regions. Integrated analysis further identified two candidate genes showing both promoter differential methylation and differential expression, namely LOC109094644 and bcorl1, suggesting that adaptation to high water flow may involve IGF-related growth regulation and remodeling of upstream transcriptional programs. The qPCR results were consistent with the transcriptomic data. Taken together, within the tested range, a sustained water flow of 3 bl/s was more conducive to the growth of common carp in the RAS, which may be associated with enhanced lipid digestion and utilization, remodeling of the muscle energy metabolic network, changes in promoter methylation, and the coordinated regulation of key candidate genes. This study provides a theoretical basis for clarifying the exercise adaptation mechanism of common carp in recirculating aquaculture and for optimizing flow velocity parameters.

Animals↗

PubMed2026

Updated adjunctive minocycline for schizophrenia: A systematic review and meta-analysis of clinical and cognitive outcomes.

BACKGROUND: Minocycline has been proposed as an adjunctive treatment for schizophrenia due to its anti-inflammatory and neuroprotective properties. However, evidence regarding its efficacy across clinical and cognitive outcomes remains inconsistent. METHODS: A systematic review and meta-analysis of double-blind RCTs was conducted following PRISMA guidelines. PubMed, Web of Science, Embase, Ovid MEDLINE, and the Cochrane Library were searched from January 2000 to August 2025. Eligible studies included patients with schizophrenia receiving adjunctive minocycline plus stable antipsychotics. Primary outcomes were PANSS total and subscale scores and overall cognitive performance. Secondary outcomes included SANS, CDS, CGI, GAF, and seven cognitive domains. Standardized mean differences (SMDs) with 95% CIs were calculated. RESULTS: Ten RCTs involving 895 participants were included. Adjunctive minocycline was associated with improvements in negative symptoms (PANSS negative: SMD = -0.55, 95% CI: -0.96 to -0.13; SANS: SMD = -0.75, 95% CI: -1.00 to -0.49) and overall psychopathology (PANSS total: SMD = -0.49, 95% CI: -0.80 to -0.18). Cognitive benefits were limited to a modest improvement in working memory (SMD = 0.24, 95% CI: 0.08 to 0.39), with no significant effects in other cognitive domains. Subgroup analyses suggested that illness stage, antipsychotic regimen, treatment duration, sample size, and geographic region may contribute to variability in treatment effects. Adverse event rates were comparable between groups. CONCLUSIONS: Adjunctive minocycline may improve negative symptoms and provide modest working memory benefits in schizophrenia. However, the evidence is limited by substantial heterogeneity, potential small-study effects, and inconsistent findings. Although short- to medium-term tolerability appeared comparable to placebo, larger, longer-term RCTs are needed to confirm its efficacy and safety.

Humans↗

PubMed2026

New Horizons in the Development of Treatments for Substance Use Disorders.

Substance use disorders (SUDs) are a major public health problem in the United States and cause substantial morbidity and mortality. There are meaningful gaps in the available SUD treatment options, and the development of new therapies is urgently needed. While medications with U.S. Food and Drug Administration approval are available for alcohol, nicotine, and opioid use disorders, there are no approved pharmacotherapies for cannabis, cocaine, or methamphetamine use disorders. Behavioral treatments for SUDs have significant limitations in effectiveness and accessibility, and there is a need for the development of both new behavioral treatment options and new models of treatment delivery. The next generation of treatments for SUDs will likely come from a diverse set of interventions, including new drug classes, new technologies, and new methods of delivery.

Humans↗

PubMed2026

A complete hlyCABD-like RTX operon marks a virulence-associated subset of trh-positive Vibrio parahaemolyticus from Hangzhou Bay, China.

Vibrio parahaemolyticus remains a major cause of seafood-associated gastroenteritis, yet routine surveillance still relies largely on the canonical hemolysin markers thermostable direct hemolysin (tdh) and tdh-related hemolysin (trh). To determine whether this framework overlooks accessory virulence determinants in trh-positive lineages, we analyzed 193 V. parahaemolyticus isolates collected between 2022 and 2025 from clinical, environmental, and seafood-associated sources in the Hangzhou Bay region of China. Serotyping identified 45 serotypes, with O10:K4 predominating among clinical isolates. Both clinical and non-clinical populations showed open pan-genomes, although the non-clinical group carried a larger accessory gene pool. We identified a complete hlyCABD-like RTX operon in 10 trh-positive isolates with T3SS2-associated virulence backgrounds. These RTX-positive isolates were distributed across seven sequence types and three of five phylogenetic groups. This distribution was lineage-restricted but non-clonal. In the representative hybrid-assembled genome, the operon occurred within a mosaic genomic region containing additional virulence- and mobility-associated genes, indicating a composite pathogenicity island-like element. In the tested subset, RTX-positive isolates showed significantly greater hemolytic activity than RTX-negative trh-positive isolates. This significant difference was consistently observed in both plate-based and liquid assays, and within the RTX-positive subset, hlyA expression correlated with hemolytic activity, whereas the trh gene and the tlh (thermolabile hemolysin) gene did not. A complete hlyCABD-like RTX operon therefore identifies a hemolysis-associated subset of trh-positive V. parahaemolyticus and supports its further evaluation as an additional target for food safety surveillance.

Vibrio parahaemolyticus↗

PubMed2026

Does future-oriented imagery rescripting increase willingness to carry out a social anxiety-related behavioral experiment? An extended replication.

BACKGROUND AND OBJECTIVES: Mental images of threat are common in social anxiety disorder and could impede exposure to fear-relevant situations. Landkroon et al. (2022) found that imagery rescripting of anticipated future threat, compared to no-task, increases willingness of non-clinical individuals to conduct a social anxiety-related behavioral experiment. The aim of this two-day preregistered extended replication study was to examine whether the effects persist beyond the intervention session by scheduling the behavioral experiment 1-7 days after the intervention. METHODS: On Day 1, 60 pre-screened participants were asked to design a behavioral experiment to test an idiosyncratic negative belief about a feared social situation. They were then randomly assigned to imagery rescripting (focused on their worst feared outcome of the behavioral experiment) or no-task. Participants' willingness to do the behavioral experiment and their threat beliefs was measured. On Day 2, they were asked to carry out the behavioral experiment. RESULTS: The imagery rescripting group, compared to the control group, did not show increased willingness or compliance to do the behavioral experiment on Day 1 or 2. Furthermore, the imagery rescripting did not lead to greater reductions in threat beliefs on either day. LIMITATIONS: The quality of the imagery rescripting intervention was not assessed, and given the brief nature of the intervention, any effects may have dissipated before participants decided whether to carry out the behavioral experiment. CONCLUSIONS: There was no evidence that imagery rescripting leads to changes in willingness or compliance to do a fear-relevant behavioral experiment. More research is needed to examine interventions that can enhance exposure in socially anxious people.

Humans↗

PubMed2026

Integrated assessment of biocontrol potential and genome analysis of endophytic Bacillus velezensis MGL-B1 against mango stem-end rot.

Mango stem-end rot is a globally significant postharvest disease that severely threatens the mango industry, primarily caused by Botryosphaeria dothidea. However, information on biocontrol agents targeting this pathogen in mango remains limited. In this study, we isolated and identified a strain of Bacillus velezensis MGL-B1 from mango leaf tissues for the first time, which exhibited broad-spectrum antifungal activity. Both in vitro and in vivo assays demonstrated that MGL-B1 effectively inhibited the growth of B. dothidea, with an in vivo biocontrol efficacy reaching 83.72 ± 5.10%, comparable to that of the commonly used chemical fungicide thiabendazole. Further mechanistic analysis revealed that MGL-B1 acts by directly disrupting the integrity of the pathogen's mycelial cell membrane. In addition, its released volatile organic compounds (VOCs) also displayed significant antifungal activity, with components such as 2-nonanone, 2-nonanol, and phenylethyl alcohol being confirmed to exert antifungal effects in in vitro fumigation assays. qPCR analysis showed that MGL-B1 treatment significantly upregulated the transcriptional levels of genes involved in plant-pathogen interaction, phenylpropanoid biosynthesis, and antioxidant defense pathways in mango fruits, with upregulation folds of 16.32, 37.19, and 75.93, respectively; meanwhile, the expression of browning-related genes such as polyphenol oxidase (PPO) was markedly suppressed. Whole-genome sequencing further revealed 14 biosynthetic gene clusters for antimicrobial compounds, including five unknown gene clusters. Collectively, B. velezensis MGL-B1 represents a promising biocandidate strain with multiple antifungal mechanisms and excellent control efficacy, providing a valuable resource for green and sustainable management of mango diseases.

Mangifera↗

PubMed2026

Unraveling the c-Myc-CASC19/HDAC1-NPM1 epigenetic axis: A novel regulatory circuitry and therapeutic target in gastric carcinogenesis.

Mounting evidence implicates long non-coding RNA cancer susceptibility candidate 19 (CASC19) in the pathogenesis of diverse malignancies. However, its functional role and molecular mechanisms in gastric cancer (GC) remain elusive. Herein, we identified a novel 717-bp transcript isoform of CASC19 in GC cells. This study aimed to delineate the biological functions and underlying mechanisms of this novel CASC19 transcript in GC pathogenesis. CASC19 was significantly upregulated in GC tissues and cell lines, correlating with adverse clinicopathological features and poor prognosis in GC patients. Functional investigations demonstrated that CASC19 overexpression potentiated GC cell proliferation, metastasis, and epithelial-mesenchymal transition, whereas CASC19 knockdown attenuated these malignant phenotypes and suppressed tumorigenesis in xenograft models. Mechanistically, CASC19 functioned as a molecular scaffold by recruiting histone deacetylase 1 (HDAC1) to the nucleophosmin 1 (NPM1) promoter. This recruitment sustained H3K27 deacetylation, thereby transcriptionally repressing NPM1 promoter activity and accelerating gastric carcinogenesis. Crucially, Depletion of HDAC1 or NPM1 partial rescued CASC19-mediated oncogenic effects. Intriguingly, the transcription factor c-Myc was found to transcriptionally activate CASC19 through direct binding to its promoter region. Collectively, our findings indicate that the c-Myc-CASC19/HDAC1-NPM1 axis acts as a potential prognostic biomarker candidate for GC and may represent a therapeutic vulnerability worthy of future investigation.

Humans↗

PubMed2026

Comprehensive multi-post-translational modifications profiling reveals age-associated remodeling in skeletal muscle.

Sarcopenia, characterized by the progressive loss of skeletal muscle mass and function, is a major hallmark of aging. Post-translational modifications (PTMs) play essential roles in regulating protein activity and cellular homeostasis; however, how multiple PTMs are remodeled during skeletal muscle aging remains incompletely characterized. Here, we performed comprehensive multi-layered proteomic profiling of skeletal muscle from young (3-month-old) and aged (24-month-old) mice, systematically quantifying the global proteome together with five major PTMs: acetylation, phosphorylation, N-glycosylation, O-glycosylation, and ubiquitination. In total, we identified 5 337 proteins and mapped thousands of PTM sites, generating an integrated atlas of age-associated proteomic and PTM remodeling in skeletal muscle. Pathway enrichment analyses revealed distinct modification-specific patterns: acetylation and phosphorylation were predominantly associated with metabolic and mitochondrial-related pathways; N-glycosylation was enriched in immune- and secretory pathway-related processes; O-glycosylation was associated with muscle contraction-related pathways; and ubiquitination was preferentially linked to cytoskeletal organization in muscle cells. Correlation analyses further uncovered diverse association patterns among different PTMs across protein- and modification-level datasets. Phosphorylation and ubiquitination exhibited consistent positive associations, whereas acetylation and ubiquitination showed both inverse and concordant co-variation patterns across subsets of proteins. Phosphorylation and O-glycosylation displayed heterogeneous association patterns across different proteins, and acetylation and phosphorylation demonstrated positive correlations with distinct age-associated directional changes across protein subsets. Together, these results provide a comprehensive, multi-dimensional view of age-associated remodeling of the skeletal muscle proteome and multiple PTM layers, offering a valuable resource for understanding molecular alterations accompanying muscle aging and sarcopenia.

Animals↗

PubMed2026

Study of prescription-indication of antivirals for herpesviruses in a Colombian population: a cross-sectional study.

BACKGROUND: To describe the utilization patterns and therapeutic indications of antivirals used for herpesvirus infections in Colombian patients. RESEARCH DESIGN/METHODS: A cross-sectional study on the use of antivirals for treating outpatients with herpesviruses between November 2023 and January 2024 in a Colombian population database. The Micromedex® database was used to identify Food and Drug Administration (FDA)-approved indications, off-label uses, and potentially inappropriate indications. RESULTS: A total of 14,816 individuals were included (median age:53.0 years [IQR:35.0-65.0]; 60.5% women). Acyclovir was the most frequently prescribed antiviral (oral:77.3%; topical:43.4%). Overall, 56.1% received oral therapy only, 25.2% combined oral and topical therapy, and 18.7% topical therapy only. FDA-approved indications accounted for 29.1% of use (herpes zoster), off-label use for 26.9% (mainly prophylaxis in immunocompromised patients), and potentially inappropriate use for 25.3% (primarily topical treatment of herpes zoster). Acyclovir use (OR:5.93; 95%CI:4.60-7.64) and specialist care (OR:2.17; 95%CI:1.73-2.71) were associated with off-label use. CONCLUSIONS: Antiviral prescribing for herpesvirus infections in a group of patients in Colombia is largely driven by acyclovir, with a substantial proportion of off-label and potentially inappropriate use, particularly involving topical therapies for herpes zoster. These findings highlight significant gaps in adherence to evidence-based recommendations and underscore the need for targeted interventions to optimize prescribing practices.

Humans↗

PubMed2026

Patient expectations assessed before randomisation and after the first treatment session, and their associations with pain outcome at 3 months in patients with tennis elbow: a secondary analysis of a randomised controlled feasibility trial in Norwegian secondary care.

OBJECTIVE: To evaluate patients' expectations of pain improvement before randomisation (T1) and after the first treatment (T2), and to examine how expectations at these two time points were associated with pain outcome measured at 3 months (T3). DESIGN: Exploratory secondary analyses of a three-arm, randomised controlled feasibility trial in patients with tennis elbow comparing heavy slow resistance training, shock wave therapy and advice (1:1:1). SETTING: Outpatient clinic at Oslo University Hospital. PARTICIPANTS: Adults with lateral epicondylalgia, commonly known as tennis elbow. MAIN OUTCOME MEASURES: Expected pain was rated on a Numeric Rating Scale (NRS, 0-10) at T1 and T2. Present pain (NRS, 0-10) was reported at 3 months (T3). Changes in expectations from T1 to T2 were summarised descriptively. Univariable linear regressions assessed associations between T3 pain and expectations at T1 and T2, treatment group and baseline factors. Explained variance was quantified by R2. Multivariable models including demographics and baseline pain were evaluated via adjusted R2. RESULTS: Fifty-four participants were included. In the shock wave group, nine (47%) came to expect greater improvement from T1 to T2; by contrast, in the advice group, seven (41%) expected less improvement. Expectations at T1 were not associated with T3 pain, whereas expectations at T2 were positively associated with T3 pain (b=0.61, 95% CI 0.33 to 0.89, p<0.01, R2=0.27), suggesting that higher expected pain at T2 was associated with higher reported pain at T3. Adding education and baseline pain increased explained variance modestly (R2 from 0.27 to 0.32). CONCLUSION: In this study, expectations measured after randomisation and one treatment session were associated with pain at 3 months for patients with tennis elbow. Larger, prospectively designed studies should investigate how postrandomisation expectations relate to clinical outcomes in non-blinded musculoskeletal trials. TRIAL REGISTRATION NUMBER: NCT04803825.

Humans↗

PubMed2026

Outcomes of Stage IVA Cervical Cancer Treated with Radiation Therapy: A Systematic Review and Meta-Analysis.

FIGO stage IVA cervical cancer, defined by bladder or rectal mucosal invasion without distant metastasis, is an uncommon but clinically challenging disease with limited high-quality evidence to guide management. We performed a systematic review and meta-analysis to evaluate survival outcomes, treatment-related morbidity, and prognostic factors in patients with stage IVA cervical cancer treated with definitive radiotherapy. Following PRISMA 2020 guidelines and PROSPERO registration (CRD42024602426), PubMed, Embase, and Web of Science were searched through February 2025. Eleven studies comprising 492 patients met eligibility criteria. Pooled random-effects analyses demonstrated 2-, 3-, and 5-year disease-free survival rates of 41.5% (95% CI, 28.1-55.0), 34.2% (95% CI, 21.1-47.3), and 30.9% (95% CI, 16.0-45.8), respectively. Corresponding overall survival rates were 56.0% (95% CI, 46.2-65.9), 45.9% (95% CI, 35.9-55.9), and 34.8% (95% CI, 26.4-43.3). Weighted median disease-free survival and overall survival were 15.6 and 33.6 months, respectively. The pooled incidence of vesicovaginal or rectovaginal fistula was 23.7% (95% CI, 12.9-34.6). Adverse prognostic factors included pelvic nodal involvement, hydronephrosis, rectal invasion, omission of brachytherapy, and total EQD2 below 80-85 Gy. Concurrent chemoradiation and completion of brachytherapy were consistently associated with improved outcomes. Despite curative-intent treatment, long-term survival remains poor and treatment-related morbidity substantial. Durable pelvic control remains the principal therapeutic challenge. Concurrent chemoradiation with adequate-dose brachytherapy appears essential for optimal outcomes, while future stage IVA-specific studies incorporating image-guided adaptive brachytherapy, advanced radiotherapy techniques, and systemic treatment intensification are needed to improve survival and reduce treatment-related morbidity.

Humans↗

PubMed2026

The Impact of Upper Extremity Rehabilitation on Fatigue in Individuals With Multiple Sclerosis: A Systematic Review.

BACKGROUND: Although numerous interventions have been investigated to alleviate fatigue in people with multiple sclerosis (PwMS), evidence regarding the effects of upper extremity rehabilitation on fatigue remains limited. OBJECTIVE: The objective of this review was to evaluate and synthesize the available evidence on the effects of upper extremity rehabilitation interventions on fatigue in PwMS. METHODS: This review was conducted in accordance with the PRISMA guidelines and was prospectively registered in the PROSPERO database. A systematic search of PubMed, Web of Science, and Scopus was performed up to August 2026. Studies were eligible if they investigated the effects of upper extremity rehabilitation interventions on fatigue in PwMS. The risk of bias of randomized controlled trials was assessed using the Risk of Bias 2 (RoB 2), and the certainty of the evidence was appraised using the GRADE methodology. RESULTS: Nine studies including 250 participants (136 intervention, 114 control) met the inclusion criteria. The included studies evaluated a range of technology-assisted, exercise-based, home-based, and task-oriented upper extremity rehabilitation approaches, with some interventions incorporating more than one therapeutic or technological component. Fatigue outcomes were measured using the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS). Risk of bias was low in three randomized controlled trials, with some concerns in two and high in two; among the two crossover studies, one was rated as low risk and one as high risk. GRADE assessment showed low certainty of evidence for studies using the FSS and very low certainty for those using the MFIS, indicating an overall low certainty of the available evidence. CONCLUSIONS: The available evidence is insufficient to draw definitive conclusions regarding the effects of upper extremity rehabilitation on fatigue in PwMS. Further high-quality randomized controlled trials are required.

Humans↗