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PubMed2026

Perceptions of Pharmacogenomic Testing Among People With Treatment Resistant Depression: Legitimization as a Facilitator of Acceptance.

Pharmacogenomic testing for psychiatric medications has been proposed as both an early intervention to optimize treatment response, and for use among patients who have tried multiple medications without symptom remission. Therefore, this testing may be particularly salient to the subset of individuals with major depressive disorder for whom depression has been labeled as "treatment resistant". Understanding the impact of this diagnostic label on illness identity and attitudes towards new therapies is important as genomic technology expands and rates of depression increase. We sought to explore perceptions and attitudes towards pharmacogenomic testing among individuals who had received a diagnosis of treatment resistant depression. We conducted a qualitative study with a constructivist orientation. Participants were recruited from a larger genomic research study and interviewed by phone or video call. We took an inductive approach to coding guided by reflexive thematic analysis. Themes were then organized into a relational framework following principles of interpretive description. Twelve individuals were interviewed. Key themes included internalized acceptance/hopelessness, and external validation/frustration, which were cyclically interconnected. These themes were situated within a larger framework illustrating the ways that illness identity and modifying factors such as relief of guilt, social support, pharmacogenomic testing and depressive symptoms can either facilitate acceptance and validation or contribute to feelings of hopelessness and frustration. Though participants expressed some skepticism around its effectiveness, pharmacogenomic testing may contribute to the shift towards acceptance and validation by legitimizing individuals' experiences with lack of treatment response. Genetic counselors and other healthcare providers should be aware of the complex balance between hope and frustration underlying conversations around pharmacogenomic testing, and factors that are more likely to foster self-acceptance.

Humans↗

PubMed2026

Effectiveness of a digi-physical tool and working method for paediatric obesity treatment in Abu Dhabi: a non-inferiority intervention study using an external historical comparator.

BACKGROUND: Effective paediatric obesity treatment requires high intensity, scalable interventions. A digi-physical tool for paediatric obesity treatment has shown positive results in Stockholm, Sweden. This study evaluates whether the same treatment method is effective in a different cultural setting. METHODS: This non-inferiority intervention study, using an external historical comparator, included 60 consecutively recruited children aged 6-15.9 years with obesity who initiated treatment at Sheikh Shakhbout Medical City in Abu Dhabi between June and December 2023. Patients were treated with Evira, a digi-physical tool and working method enabling high intensity individualized care, real-time monitoring, and interactive patient-clinician communication. The primary outcome was BMI z-score change at 26 weeks. Non-inferiority was assessed using a predefined margin of 0.10 BMI z-score, with outcomes compared to a prior published trial in Stockholm (n = 107). RESULTS: A total of 112 children were included in the analysis (Abu Dhabi cohort, n = 35; Stockholm cohort, n = 77). The adjusted mean change in BMI z-score was - 0.20 (95% CI: - 0.28, - 0.12) in the Abu Dhabi cohort and - 0.20 (- 0.26, - 0.14) in the Stockholm cohort (p = 0.88). Non-inferiority was confirmed, (predefined margin 0.10 was not exceeded). A clinically significant BMI z-score reduction (≥ 0.20 units) was achieved by 45.7% of participants in Abu Dhabi and 36.4% in Stockholm (p = 0.35). Non-retention rates at 26 weeks were 41.7% vs. 28.0%, respectively (p = 0.07). CONCLUSIONS: The findings provide promising evidence that treatment outcomes achieved with the digi-physical treatment tool were comparable in the Abu Dhabi and Stockholm cohorts, supporting its feasibility in a second cultural and healthcare setting.

Humans↗

PubMed2026

Timing of aneurysm repair and clinical outcomes after aneurysmal subarachnoid hemorrhage: a systematic review.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) causes substantial morbidity and mortality, and guidelines recommend aneurysm repair as early as feasible. However, the association between onset-to-treatment time and outcomes remains uncertain. This review synthesized evidence across multiple clinical outcomes and examined whether treatment modality modifies this association. METHODS: Searches were conducted in PubMed/MEDLINE, Scopus, and LILACS for studies comparing clinical outcomes across different onset-to-treatment windows in adults with confirmed aSAH. Findings were synthesized narratively according to the Synthesis Without Meta-analysis (SWiM) guideline. The review was prospectively registered in PROSPERO (CRD420261415084). RESULTS: Twenty reports comprising 11,096 participant records were included, with likely overlap between two reports. Treatment categories ranged from <6 h to ≥15 days. Earlier securement likely reduced pretreatment rebleeding, particularly when untreated or markedly delayed patients were included, although treated-cohort comparisons were inconsistent. More methodologically informative adjusted analyses showed no reproducible independent association between treatment timing and functional outcome or mortality. No consistent association emerged for vasospasm or related cerebral ischemia, hydrocephalus, or length of stay. Two observational studies modeled time continuously: one found a significant U-shaped mortality association with an estimated nadir at 32.6 h, whereas the other showed a similar but non-significant adjusted pattern with an estimated nadir near 12.16 h. These findings are highly susceptible to confounding by indication and survivor bias and do not establish benefit from treatment delay. Three studies formally tested modality-timing interaction; one found a significant mortality interaction and two did not. Additional stratified analyses showed no consistent modality-specific pattern. Certainty of evidence for the timing-mortality association was very low because of serious risk of bias, inconsistency, and imprecision. CONCLUSION: Earlier aneurysm securement remains supported for preventing pretreatment rebleeding. The independent association of treatment timing with mortality or functional outcome remains uncertain. The observed mortality patterns are hypothesis-generating and do not define a validated therapeutic window, support intentional treatment delay, or justify changing current guideline recommendations. Prospective multicenter studies using continuous-time modeling and rigorous methods to address confounding and survivor bias are needed.

Humans↗

PubMed2026

Postoperative complications and outcomes after surgical treatment for tophaceous gout: A systematic review and meta-analysis.

BACKGROUND: Surgical treatment remains necessary for selected patients with tophaceous gout, particularly when mechanical limitation, nerve compression, ulceration, infection, deformity, or failure of conservative treatment is present. However, postoperative outcomes after surgery for tophaceous gout have not been comprehensively quantified. This systematic review and meta-analysis evaluated postoperative complication profiles and recurrence burden after surgical treatment for tophaceous gout. METHODS: A systematic search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted from database inception to March 25, 2026. Original studies reporting postoperative outcomes after surgical treatment for tophaceous gout were included. Pooled event rates with 95% confidence intervals (CIs) were calculated using a random-effects single-arm meta-analytic approach. Primary outcomes were postoperative infection, delayed wound healing, and recurrence. Secondary outcomes were reoperation, amputation, and overall complications. Functional outcomes were summarized descriptively. RESULTS: 18 retrospective studies were included. The pooled postoperative infection rate was 11.3% (95% CI 8.0%-15.7%), delayed wound healing 9.9% (95% CI 5.1%-18.2%), and recurrence 8.5% (95% CI 4.7%-14.9%). Secondary pooled rates were 9.7% (95% CI 5.5%-16.7%) for reoperation, 3.7% (95% CI 2.0%-6.8%) for amputation, and 24.0% (95% CI 14.0%-38.1%) for overall complications. Significant subgroup differences were identified only for infection according to anatomic site and intervention type. Sensitivity analyses showed that pooled estimates were robust. The certainty of evidence was very low for all outcomes. CONCLUSIONS: Surgical treatment for tophaceous gout is associated with measurable postoperative risks, particularly infection and overall complications. These findings support careful perioperative counseling, structured postoperative surveillance, integrated long-term urate-lowering management, and more standardized reporting of perioperative risk factors and postoperative outcomes in future surgical studies of tophaceous gout.

Humans↗

PubMed2026

Treatment-related associations of nucleus accumbens connectivity within mesocorticolimbic circuits in depression.

Pharmacological treatment remains a mainstay in managing depression, yet the neural correlates associated with treatment response remain incompletely understood. This study used multimodal neuroimaging to examine nucleus accumbens (NAc)-centered structural and functional alterations associated with fluoxetine and Shugan Jieyu Capsule (SG), a traditional Chinese medicine, in patients with mild-to-moderate depression (MMD). Sixty patients were randomized to an 8-week course of fluoxetine or SG. Depression severity was assessed using the 24-item Hamilton Depression Rating Scale (HAMD-24), and structural and functional MRI scans were acquired at baseline and endpoint. Both treatments were associated with significant symptom improvement. Neuroimaging analyses revealed structural and functional alterations involving the NAc. Changes in NAc-amygdala connectivity showed an exploratory association with symptom improvement in the SG group, whereas changes in NAc-rostral anterior cingulate cortex connectivity were associated with symptom improvement in the fluoxetine group and remained significant after correction for multiple comparisons. In addition, remitters exhibited stronger baseline connectivity between the NAc and ventral tegmental area and between the NAc and middle frontal gyrus compared with non-remitters. These findings suggest that NAc-centered connectivity may be relevant to treatment-related neural changes in depression and may inform future research on imaging-based candidate markers of treatment response and personalized treatment approaches. TRIAL REGISTRATION: The study is registered in https://www.chictr.org.cn/ with a registration number ChiCTR1900024988 (date: 08.06.2019).

Humans↗

PubMed2026

Pilot randomized trial of intermittent theta-burst stimulation versus H-Coil transcranial magnetic stimulation for treatment-resistant depression.

BACKGROUND: Intermittent theta burst stimulation (figure-8-coil iTBS) and H7-coil repetitive transcranial magnetic stimulation (rTMS) are FDA-cleared treatments for major depression; yet their comparative effectiveness in treatment-resistant depression (TRD) has not been evaluated in randomized trials. This pilot randomized trial was designed to obtain preliminary comparative estimates and to explore whether baseline cognitive functioning relates to early remission. METHODS: Twenty-eight adults with TRD were randomized to six weeks of figure-8-coil iTBS delivered to the dorsolateral prefrontal cortex (DLPFC) (n = 15) or H7-coil rTMS delivered to the dorsomedial prefrontal cortex (DMPFC) (n = 13). The primary outcome was change in 17-item Hamilton Depression Rating Scale (HRSD-17) score from baseline to week 6, analyzed with ANCOVA. Additional outcomes included response, remission, and symptom trajectories through week 18. Exploratory analyses examined the association between baseline cognitive functioning, such as executive functions and memory, and remission. RESULTS: Twenty-five participants completed all 30 sessions. Adjusted week-6 HRSD-17 scores did not differ between groups (mean difference -0.40, 95% CI -5.23 to 4.43; p=.865). Response rates were 40.0% for figure-8-coil iTBS and 50.0% for H7-coil rTMS (p>.60), and remission rates were identical across groups (20.0%). Remitters showed higher baseline executive functioning than non-remitters in exploratory analyses, although these associations were not confirmed in adjusted models. CONCLUSION: In this pilot trial, figure-8-coil iTBS and H7-coil rTMS showed symptom improvement, with no clear between-group differences. Exploratory findings suggest a potential signal involving executive functioning that warrants further investigation. These results inform the feasibility and design of larger comparative trials. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05902312).

Adult↗

PubMed2026

Five-year outcomes in a randomised controlled trial of prolonged exposure therapy and supportive counselling for post-traumatic stress disorder in adolescents: a task-shifted intervention.

BACKGROUND: Cognitive-behavioural therapies with a trauma focus are effective in reducing posttraumatic stress disorder and other psychological distress in adolescents. Long-term follow-up data on adolescents treated for PTSD remain scarce, with few studies extending beyond 12 months after treatment completion. OBJECTIVE: To evaluate the maintenance of treatment gains in a comparative study of effectiveness of PE-A and SC up to 60 months post-treatment. METHOD: Sixty-three adolescents diagnosed with PTSD were randomly assigned to either treatment, provided by newly trained and supervised non-specialist health workers. The primary outcome measure was PTSD symptom severity, as independently assessed on the Child PTSD Symptom Scale (CPSS). We report on the 60-month post-treatment follow-up, building on post-treatment, 3-month, 6-month, 12-month and 24-month post-treatment data that have been published previously. RESULTS: Participants in both treatment groups maintained a significant reduction in PTSD symptoms up to 60-months post-treatment (F (7, 343) = 2.86, p < .01). Participants receiving prolonged exposure experienced greater improvement on the CPSS at all follow-up assessment timepoints, except for the 60-month FU (p = .28; g = 0.33). CONCLUSION: Adolescents with PTSD continued to maintain treatment gains up to 60-months post-treatment. These data, along with findings from the original RCT, indicate that a brief treatment protocol (averaging 9 sessions of PE-A or SC) in a LMIC, task-shifted to be delivered by nurses without prior psychotherapy experience, led to lasting improvements in PTSD and comorbid symptoms for up to five years. The sustained benefits and improved functioning over the first few years post-treatment support expanding both treatments, especially PE-A, in community settings.

Humans↗

PubMed2026

Systemic biomarkers of treatment response to methotrexate in people with painful knee osteoarthritis: A biological substudy of the PROMOTE randomised controlled clinical trial.

OBJECTIVE: Stratification of therapeutic responses may help identify efficacious therapies for osteoarthritis (OA). In the PROMOTE randomised trial, participants with elevated baseline high-sensitivity C-reactive protein (hs-CRP) showed greater pain reduction after methotrexate treatment. We set out to interrogate a broader panel of serum/plasma inflammatory response markers relevant to methotrexate actions as potential biomarkers of therapeutic effect. Our objectives were to: (i) characterize changes in these systemic markers during methotrexate treatment; determine whether (ii) baseline levels or (iii) changes in any marker during treatment were associated with treatment response; and (iv) compare these findings with the more established clinical inflammatory marker, hs-CRP. DESIGN: Plasma/serum samples from participants in PROMOTE's biological substudy were analysed for 35 inflammatory markers at baseline (pre-treatment) and at 6-months (post-treatment), by MesoScale V-plex multiplex assay. Those with paired biological and clinical data at both baseline and 6-months were included in the substudy analysis set. Relationships between markers and overall data structure were assessed by Pearson correlation and Principal Component analysis. Associations between markers (baseline levels or change over time) and change in average knee pain severity in past week (numerical rating scale, NRS) were evaluated by univariable linear regression, adjusting for baseline age, sex, and body mass index. Least Absolute Shrinkage and Selection Operator (LASSO) regression with bootstrap resampling enabled marker selection. Benjamini-Hochberg correction adjusted for multiple testing (Padj). RESULTS: 87 participants with paired blood marker and clinical data were eligible for substudy analysis. 18/35 markers were quantifiable and analysed. Systemic IL-8 and TNF-α levels decreased (Padj=0.015, 0.048 respectively) while IL-15 increased (Padj=0.033) with methotrexate treatment over 6-months. Analysing within this active treatment randomised arm, higher baseline IFN-γ was associated with greater reduction in NRS pain change (0.66 [0.01, 1.31], P=0.047), as was decreasing TNF-α over 6-months (2.25 [0.00, 4.5], P=0.049). LASSO identified higher IFN-γ, lower plasma IL-15 and IL-16, and younger age as the most important baseline predictors of pain improvement. hs-CRP was highly selected by LASSO for treatment response in both arms. In a secondary univariate treatment arm-by-biomarker interaction analysis, of the 19 markers, only hs-CRP showed consistent effects in adjusted models (at baseline, coeffic. 2.34 [0.53, 4.15], P=0.001; change over 6-months, (0.36 [0.06, 0.66], P=0.018). CONCLUSIONS: Blood measurement of IFN-γ, TNF-α, IL-15 and IL-16 as well as hs-CRP could act as potential markers to stratify the treatment response by average knee pain to methotrexate in knee osteoarthritis.

Humans↗

PubMed2026

Dynamics of antibiotic resistance genes co-occurrence with pathogenic and non-pathogenic bacteria throughout wastewater treatment processes.

Wastewater treatment plants (WWTPs) are recognized hotspots for antibiotic resistance genes (ARGs) and pathogenic bacteria. Despite advancements in treatment technologies, the persistence of ARGs and pathogenic bacteria remains a concern. In this study, we analyzed the dynamic changes in ARGs and bacterial communities throughout the treatment processes within an anaerobic-anoxic-oxic (AAO) WWTP over one week by using HT-qPCR coupled with 16S rRNA gene amplicon sequencing. The connectedness index, based on network analysis, showed that the dynamics of ARGs and mobile genetic elements (MGEs) were more strongly associated with potentially pathogenic bacteria than with non-pathogenic bacteria, suggesting that ARG immigration and dissemination in the WWTP were likely driven by potentially pathogenic taxa. The AAO treatment significantly reduced ARGs in final effluent (EF) (∼64 %) and residual sludge (RS) (∼81 %); however, potential hosts of ARGs such as Comamonas testosteroni and Clostridioides difficile persisted with minimal changes in relative abundance and remained detectable in EF and RS. Notably, the abundance of ARGs was lower in RS than in EF, and source tracking analysis identified influent as the primary source of ARGs and potentially pathogenic taxa in EF, underscoring the greater health risks associated with effluent discharge.

Wastewater↗

PubMed2026

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↗

PubMed2026

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 > 5 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 > 5 cm2 after PVI, four variables-age ≥ 75 years, left atrial diameter > 44 mm, estimated glomerular filtration rate < 60 mL/min/1.73 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 = 336), a significant treatment-by-score interaction was observed (P < 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 = 494), a qualitatively similar interaction pattern was observed for additional ablation beyond PVI (interaction P = 0.029), although the ablation strategy differed from LVA-guided ablation. CONCLUSIONS: Among patients with persistent AF and mapped LVA >5 cm2, the ALID score identified heterogeneity in response to adjunctive LVA ablation. These hypothesis-generating findings require prospective validation before clinical implementation.

Humans↗

PubMed2026

Corrigendum to: "Oral subchronic exposure to the mycotoxin ochratoxin A induces key pathological features of Parkinson's disease in mice six months after the end of the treatment" [Food Chem. Toxicol. (2021) 152 112164].

Explore the source record for details and available documents.

Published Erratum↗

PubMed2026

Determinants of Nonspecific Response to Treatment in Randomized Controlled Trials of Major Depressive Disorder: A Narrative Review.

The design, conduct, and interpretation of double-blind randomized placebo-controlled clinical trials in major depressive disorder (MDD) are complicated by determinants of nonspecific response to treatment (NSRT). This narrative review provides a comprehensive overview of the determinants of NSRT in randomized controlled trials (RCTs) for MDD, including the placebo effect, factors related to measurement of the primary endpoint, the inclusion of misdiagnosed patients, the relapsing-remitting course of MDD, and factors related to functional unblinding. Potential strategies to reduce the impact of the determinants of NSRT and to improve the interpretation of RCT outcomes in MDD are also summarized. These strategies include use of centralized rating and standardized rater training, independent diagnostic confirmation, optimized site selection, minimizing financial incentives, exclusion of subjects participating in multiple clinical trials, exclusion of patients with unstable major depressive episode trajectories, and use of active placebo and alternative trial designs. Uniformity among experts in the definitions of determinants of NSRT and related concepts, as well as in strategies to address them, may facilitate progress in the development of novel treatments for MDD.

Humans↗

PubMed2026

Therapeutic approaches for the treatment of bovine metritis: a systematic review of clinical, reproductive and productive outcomes.

Bovine metritis is a complex multifactorial disease associated with substantial clinical and economic impact due to reduced milk production, subfertility, and increased culling rates. Considerable uncertainty remains regarding the comparative efficacy of the many therapeutic strategies used to manage it. This systematic review aimed to summarize and critically evaluate the available evidence on therapeutic approaches for bovine metritis, with respect to clinical cure, reproductive performance, productive performance, and culling. A literature search conducted in PubMed, Web of Science and CABI Digital Library (2010-2025) identified 18 randomized controlled clinical trials eligible for inclusion. Risk of bias was assessed independently by two reviewers using the Cochrane RoB 2 tool. Given substantial clinical and methodological heterogeneity across studies, findings were synthesized narratively by outcome, without meta-analytic pooling, and the certainty of evidence was assessed using GRADE for the comparisons supported by more than one study. Overall, systemic antimicrobial therapies consistently improved short-term clinical cure rates, although their effects on long-term reproductive and productive performance remained inconsistent. In selected cases, nonsteroidal anti-inflammatory drugs (NSAIDs) showed clinical outcomes comparable to antimicrobial treatments, allowing reductions in antimicrobial use ranging from 50% to 92%. Alternative approaches, such as intrauterine flavonoid, chitosan or dextrose-based therapies, produced inconsistent results that appeared to correlate with disease severity and treatment protocol. The evidence base is limited by substantial heterogeneity in disease definitions, postpartum timing of diagnosis, and cure criteria across studies, and by the near-universal absence of allocation concealment in the primary literature; these limitations restrict the certainty of most conclusions to low or moderate. Therefore, effective metritis control should move beyond symptom resolution and incorporate integrated and preventive strategies targeting inflammatory and metabolic dysregulation during the transition period.

Animals↗

PubMed2026

Direct Oral Anticoagulants as Primary or Secondary Treatment for Heparin-Induced Thrombocytopenia (HIT) and Associated Thromboembolism (HITT)-A Meta-Analysis.

INTRODUCTION: Heparin-induced thrombocytopenia (HIT) is associated with a high risk for thrombosis. The role of direct oral anticoagulants (DOACs) is still emerging and data are limited considering efficacy and safety among patients with HIT. The aim of this review is to evaluate current data on DOACs as primary or secondary treatment among patients with HIT. METHODS: This is a systematic review utilising Pubmed, Scopus and Embase online databases. Eligible studies were published up to December 2024 evaluating DOACs as primary or secondary treatment among patients with HIT and/or associated thrombosis (HITT). Primary outcomes included thrombosis rate (TR) and bleeding rate (BR) during follow-up. RESULTS: A total of 44 publications were included (29 case reports, 5 case studies and 10 cohort studies [n > 10 patients]). Regarding treatment, 19 articles evaluated only rivaroxaban, 7 articles only apixaban, 11 articles only dabigatran and 7 articles more than one regimen. A total of 352 patients were included. Overall, 190 patients (53.8%) were given DOAC as primary treatment whereas 162 patients were given a parenteral treatment first and continued with a DOAC. Mean nadir platelet count at diagnosis was 63 000/μL. HITT rate was 190/352 (53.9%; 8% had arterial thrombosis). Mean follow-up was 7.6 months. TR was 20/352 (Pooled proportion = 0.064 [95% CI = 0.042-0.092]) (30% of them were new thromboses without initial thrombosis), and BR was 9/352 (Pooled proportion = 0.039 [95% CI = 0.022-0.062]). Finally, there was no difference found regarding TR and BR between primary or secondary treatment, and among different regimens. CONCLUSIONS: DOACs are associated with low rates of thrombosis and major bleeding among patients treated for HIT or HITT, either as primary or secondary treatment. However, the certainty of evidence is very low because of the quality and limitations of the available studies.

Humans↗

PubMed2026

Improving Sleep and PTSD Outcomes in Service Members: A Randomized Controlled Trial Examining the Long-Term Effects of an Integrated Treatment.

Trauma-induced sleep disturbances often persist after successful posttraumatic stress disorder (PTSD) treatment. While integrated protocols combining sleep and exposure-based treatments may maximize outcomes, prior studies are limited and have largely relied on subjective sleep measures or failed to include long-term follow up assessments. Active-duty service members with PTSD (n = 82) were randomly assigned to Compressed Prolonged Exposure (CPE) treatment or Trauma Management Therapy (TMT), which integrates exposure therapy with sleep hygiene training and other skills-based interventions. PTSD symptoms and actigraphy-based sleep were measured at baseline, posttreatment, 3- and 6-month follow-up and data were compared between groups and across time. Posttreatment, both groups showed negligible to small changes in sleep compared to baseline. However, the TMT group evidenced improvements in most sleep parameters by the 3- and 6-month follow-ups, while sleep health generally worsened in the CPE group over time. Between groups, those randomized to TMT exhibited better sleep efficiency (g = 0.24) and onset latency (g = -0.34) at 3-month follow-up, and better sleep quality (g = 0.70), efficiency (g = 0.51), and wake after sleep onset (g = -0.52) at 6-month follow-up. Within both treatment groups, poorer sleep at the 6-month follow-up was correlated with greater PTSD symptom severity measured at the same time point. Integrated treatment for sleep and PTSD produced superior objective sleep outcomes compared to exposure alone, with the most meaningful improvements in sleep observed 6 months after treatment completion. Several critical directions for future studies are discussed.

Humans↗

PubMed2025

Treatment preference for once-weekly versus once-daily DPP-4 inhibitors in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND/OBJECTIVE: Although once-weekly and once-daily DPP-4 inhibitors have gained widespread market recognition, patient preference differences remain a key focus. This meta-analysis compares treatment preferences for once-weekly versus once-daily DPP-4 inhibitors in T2DM, offering evidence to guide clinical decisions and healthcare policies. METHODS: PubMed, OVID, EBSCO, Web of Science, CNKI, Wanfang, and clinical trial registries were searched up to June 30, 2025. After screening literature against predefined criteria, a systematic review was conducted to compare the effects of once-weekly and once-daily DPP-4 inhibitors on the treatment preferences of patients with T2DM. RESULTS: 8 RCTs with 1,575 participants were analyzed. No significant difference in medication adherence and DTSQ total score between the once-weekly and once-daily groups (p > 0.05). HbA1c percentage (MD = -0.21, 95% CI [-0.42, -0.01], p < 0.05) decreased significantly with once-weekly dosing, while GA and FPG showed no change (p > 0.05), this suggests greater improvement in HbA1c percentage levels following a switch to once-weekly DPP-4 inhibitors. Once-weekly DPP-4 inhibitors showed higher musculoskeletal/connective tissue disorder risk (RR = 2.63; 95% CI [1.18, 5.83]), but no significant differences in other adverse events (p > 0.05). No significant differences in treatment burden between both groups (p > 0.05). CONCLUSION: No statistically significant association between treatment preferences for once-weekly versus once-daily DPP-4 inhibitors among T2DM patients and medication adherence, treatment satisfaction, glycemic level changes, safety, or treatment burden for these two dosing regimens. Further research is needed to elucidate the influence of physician prescribing behavior on these preferences.

Humans↗

PubMed2026

Treatment of Hot Flashes in Men With Prostate Cancer Undergoing Androgen Deprivation Therapy.

BACKGROUND: Hot flashes are common and often debilitating side effects of castration therapy; a cornerstone in the treatment of metastatic prostate cancer (PCa) as well as in localized or locally advanced PCa when combined with radiotherapy. The evidence for relieving vasomotor symptoms is limited. This systematic review presents both pharmacological and non-pharmacological interventions for treating hot flashes in men with PCa undergoing castration therapy, primarily androgen deprivation therapy (ADT). METHODS: a systematic literature search was conducted in PubMed using ("hot flash*" OR "hot flush*" OR "vasomotor*") AND ("prostate") as keywords. Studies with intervention for hot flashes due to castration therapy, estimation of treatment response (e.g., reduction in frequency or impact on quality of life) and patients with PCa (any stage) were eligible. RESULTS: Of 469 papers, 35 were included in the review. The included studies evaluated cyproterone acetate, estrogen or estrogen derivatives, progesterone derivatives, selective serotonin reuptake inhibitors (SSRIs), gabapentin, oxybutynin, and clonidine, as well as non-pharmacological interventions such as acupuncture, cognitive behavioral therapy (CBT), and dietary supplements (e.g., Dong Quai/Angelica Sinensis, Serelys Homme, soy protein, and Salvia officinalis). Across all blinded pharmacological interventions, the relative reduction in hot flash frequency ranged from -21% to -84%, and the placebo effect was between -19% and -30%. CONCLUSION: Hormonal agents such as cyproterone acetate and estrogen appear to be the most effective treatments, although they are associated with side effects. Non-pharmacological options like acupuncture and CBT may offer some benefit, while dietary supplements seem to be ineffective. Future studies are needed also to evaluate newer treatments, such as fezolinetant, in this patient population.

Humans↗