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Closed-loop insulin delivery for glycaemic control in hospitalised and perioperative adults: A systematic review and meta-analysis of randomised controlled trials.

We evaluated whether closed-loop insulin delivery improves glycaemic control in hospitalised and perioperative adults. PubMed/MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov were searched from inception to 29 June 2026 for randomised controlled trials comparing closed-loop or automated insulin delivery with usual care or conventional insulin therapy. Random-effects meta-analyses were conducted; risk of bias was assessed using RoB 2 and certainty of evidence using GRADE. Seven trials involving 375 analysed participants were included. Closed-loop insulin delivery increased time in target glucose range by 23.91 percentage points (95% CI 19.40 to 28.43; I2 = 0%) and reduced mean glucose by 1.79 mmol/L (95% CI 1.06 to 2.53 lower; I2 = 36.3%); certainty was moderate for both outcomes. Two trials involving 69 participants reported compatible participant-level data for clinically significant hyperglycaemia, and both estimates favoured closed-loop insulin delivery, although the evidence was exploratory and imprecise. No severe hypoglycaemic events occurred in either group, precluding reliable estimation of comparative safety. Closed-loop insulin delivery may improve glycaemic process measures, but larger pragmatic trials are needed to establish clinical benefits, safety, and implementation feasibility.

Humans

Multidisciplinary mHealth Rehabilitation for Patients With Abdominal Cancer Who Are Receiving Chemoradiotherapy: Randomized Phase II Trial.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) for abdominal cancer frequently induces muscle loss, weight loss, and malnutrition. OBJECTIVE: This exploratory randomized phase II trial evaluated whether a multidisciplinary, mobile health (mHealth)-based multimodal rehabilitation program could preserve handgrip strength and muscle mass in patients with abdominal cancer undergoing CCRT. METHODS: In this prospective, multicenter, randomized, open-label phase II trial (NCT05325554), 111 eligible patients with abdominal malignancies scheduled for CCRT were randomly assigned (1:1) to receive either multidisciplinary mHealth rehabilitation care (MRC; n=57) or standard care (SC; n=54). The MRC program was delivered by a dedicated multidisciplinary team using the AiNST mHealth platform and wearable heart rate monitors. The primary end point was handgrip strength at the end of CCRT (analyzed with analysis of covariance adjusting for baseline). Secondary end points were exploratory and analyzed without multiplicity adjustment; sensitivity analysis using false discovery rate (FDR) correction was performed. RESULTS: Between February 2022 and April 2023, 111 patients were enrolled. Adherence was high (n=93, 83.9% achieved exercise targets). After adjusting for baseline handgrip strength, the MRC group had significantly higher handgrip strength at the end of CCRT than the SC group (adjusted mean difference 4.87 kg, 95% CI 3.36-6.38; P<.001). Exploratory analyses of secondary end points (without multiplicity adjustment) showed that the MRC group also had better preservation of body weight (P=.005), skeletal muscle mass (P<.001), serum albumin (P=.009), prealbumin (P=.02), and lower rates of hematological toxicity (P<.05), as well as improved psychological status (distress thermometer [DT] and Hospital Anxiety and Depression Scale [HADS]) and nutritional scores (Nutritional Risk Screening 2002 [NRS-2002] and Patient-Generated Subjective Global Assessment [PG-SGA]) at the end of CCRT (all P<.05). All nominally significant secondary end points remained significant after FDR correction (q<.05). These findings are preliminary and should be interpreted with caution due to the open-label design, population heterogeneity, and exploratory secondary analyses. CONCLUSIONS: In this exploratory phase II trial, a multidisciplinary, mHealth-based multimodal rehabilitation program was associated with better preservation of handgrip strength, muscle mass, and nutritional status, as well as lower rates of certain treatment toxicities, compared with SC. However, definitive conclusions are limited by the open-label design, heterogeneity of tumor types, and short follow-up. Larger, blinded phase III trials are needed to confirm these findings.

Humans

Triazole resistance in clinical Aspergillus fumigatus isolates in India, a multicenter surveillance study.

BACKGROUND: Triazole resistance in Aspergillus fumigatus is a global public health concern associated with treatment failure, notably in invasive aspergillosis. However, population-level data on triazole resistance from India remain limited, with most reports originating from single-center studies. METHODS: We conducted a multicenter surveillance study to assess the prevalence of triazole resistance among clinical A. fumigatus isolates across India. Antifungal susceptibility testing was performed using the CLSI broth microdilution method (M38-Ed3), and molecular characterization was conducted on resistant isolates. A total of 518 isolates were analyzed: 115 prospectively collected from 13 tertiary-care hospitals from 2015-2020, and 403 archived isolates obtained from the National Culture Collection of Pathogenic Fungi (1994-2020). RESULTS: The overall pooled prevalence of non-wildtype isolates was 4.1% for itraconazole (95% CI: 2.54-6.17%), 3.9% for posaconazole (95% CI: 2.39-5.94%), while 1.4% were resistant to voriconazole (95% CI: 0.55-2.77%). One multi-azole-resistant isolate from an immunocompromised, mold-active triazole-na&#xef;ve patient carried the TR34/L98H mutation, suggesting environmental acquisition. Prevalence of resistance did not differ significantly across geographic regions or between public and private sector hospitals. Linear regression analysis revealed a significant temporal increase in median MICs of all three licensed triazoles between 1994 and 2020. Approximately 29% of isolates exhibited amphotericin B MICs exceeding the epidemiological cutoff value; however, the clinical significance of this finding remains uncertain. CONCLUSIONS: Azole resistance among clinical A. fumigatus isolates in India remains uncommon (<5%), supporting the continued use of triazoles as first-line therapy. However, the observed temporal increase in triazole MICs underscores the need for sustained national surveillance to detect emerging resistance trends.

Aspergillus fumigatus

Music therapy in artificial insemination by husband: Effects on psychological distress and clinical pregnancy rate.

BACKGROUND: Infertility treatment can be psychologically burdensome. Evidence on music listening during artificial insemination by husband (AIH) remains limited. We evaluated whether a standardized periprocedural music intervention reduced psychological distress and explored its association with clinical pregnancy. METHODS: In this single-center, open-label randomized trial, 254 women undergoing AIH were allocated 1:1 to routine care or routine care plus two 30-minute music-listening sessions, immediately before and after AIH. The prespecified primary outcome was the continuous 21-item Depression Anxiety Stress Scales (DASS-21) score at follow-up; clinical pregnancy was secondary. DASS-21 was completed at baseline and at day 35 after AIH. Clinical pregnancy was assessed by ultrasonography at days 30 to 35. RESULTS: Continuous DASS-21 anxiety, depression, and stress scores did not differ between groups after adjustment for baseline scores (all P&#x2005;&#x2265;&#x2005;.868). Absolute postintervention differences were 0.01 point or less for anxiety and depression and 0.08 point for stress, indicating neither statistical nor clinically meaningful improvement. Clinical pregnancy occurred in 34/127 participants (26.77%) in the intervention group and 14/127 (11.02%) in the control group (exploratory secondary outcome; P&#x2005;=&#x2005;.001). CONCLUSION: The intervention did not improve the primary psychological outcome. The higher clinical pregnancy rate is hypothesis-generating because the trial was not powered for pregnancy, the proposed psychological mechanism was not demonstrated, and nonspecific attention and other unmeasured factors cannot be excluded. Replication using an attention-matched control, immediate state-anxiety and physiological measures, participant-preference assessment, and live-birth follow-up is required.

Humans

Post-intervention effectiveness of a computerized personalized cognitive stimulation program adapted according to cognitive reserve in older adults without cognitive impairment in Primary Care: A randomized clinical trial.

BACKGROUND: Cognitive reserve may influence responsiveness to cognitive interventions, yet it is rarely used to tailor computerized stimulation. OBJECTIVE: To evaluate the effectiveness of a computerized cognitive stimulation program personalized according to cognitive reserve on cognition, reserve-related activities, and digital competence in community-dwelling older adults without cognitive impairment in Primary Care. METHODS: In this randomized clinical trial, 102 adults aged &#x2265;65 years with normal cognitive performance were recruited from three primary care centers in Zaragoza, Spain, and stratified by cognitive reserve level before random allocation to intervention or control. The intervention comprised digital literacy sessions followed by 8 weeks of home-based computerized cognitive stimulation tailored to participants' cognitive reserve profiles and life history. Controls received a single group-based health education session focused on maintaining everyday cognitive activity. Outcomes were assessed at baseline and post-intervention using global cognition (MEC-35), the Cognitive Reserve Questionnaire, the Mobile Device Proficiency Questionnaire-16, and domain-specific neuropsychological tests. A total of 100 participants completed the final evaluation and were included in complete-case analyses. RESULTS: Compared with controls, the intervention group showed greater adjusted post-intervention improvements in global cognition (MEC-35 between-group difference: 1.8 points) and several cognitive measures, including temporal orientation, calculation, attention, praxis, verbal fluency, processing speed, executive functions, and verbal learning. CRQ scores and digital competence also improved, with small-to-large effect sizes. CONCLUSIONS: A computerized cognitive stimulation program adapted according to cognitive reserve appears feasible in Primary Care and may improve cognition, engagement in reserve-related activities, and digital competence in older adults without cognitive impairment.

Humans

Effectiveness of symptom map-based education in the management of premenstrual syndrome: a randomized controlled trial.

PURPOSE: To evaluate the effectiveness of a symptom map-based educational intervention for the non-pharmacological management of premenstrual syndrome (PMS), with a focus on symptom reduction among women with differing baseline symptom severity. METHODS: This randomized controlled study was conducted between May and December 2024. A total of 110 women meeting diagnostic criteria for PMS were randomly assigned to an intervention group (n = 55) or a control group (n = 55) using block randomization, and 101 participants completed follow-up assessments. The intervention comprised structured education based on a PMS symptom map and evidence-based self-care strategies. Outcomes included PMS symptom severity (Premenstrual Syndrome Scale), pain intensity (Visual Analog Scale), psychological symptoms (Depression Anxiety Stress Scale-21), and PMS-specific life satisfaction. CLINICAL TRIAL REGISTRATION: NCT06585475. RESULTS: Compared with the control group, women in the intervention group reported significantly lower pain (adjusted mean 4.21 vs. 6.81, p < .001) and stress levels (8.54 vs. 12.03, p < .001) at follow-up. The intervention was particularly effective in reducing PMS symptom severity and depressive symptoms among participants with higher baseline symptom burden. Improvements in PMS-specific life satisfaction were observed, with reductions in depressive symptoms contributing to this effect. CONCLUSION: A symptom map-based educational intervention is a clinically applicable, non-pharmacological approach for PMS management. This structured education appears especially beneficial for women with more severe baseline symptoms and may be integrated into routine gynecological care to support individualized symptom management.

Humans

Intentions to use different modalities of long-acting HIV PrEP among men who have sex with men and transgender and gender diverse persons in the Netherlands.

Insight into intentions to use long-acting HIV pre-exposure prophylaxis (PrEP) is essential for successful implementation. We assessed intention to use three hypothetical long-acting PrEP modalities (oral, intramuscular and subdermal) among HIV-negative men who have sex with men (MSM) and transgender and gender diverse persons in Amsterdam, recruited through the Amsterdam Cohort Studies (ACS-participants) and social media (survey-participants). Intention was measured per modality using a 7-point Likert scale. We modeled the probability of high intention to use long-acting PrEP using relative risk regression. Of 1258 participants [1231 (97.9%) MSM; 557 ACS and 701 survey; median age 40 years (IQR 32-50)], 76% had ever used oral short-acting PrEP. Intention to use was highest for monthly oral long-acting PrEP [ACS: median 4.5 (IQR 2-6), 38% high intention; survey: median 7 (IQR 6-7), 81% high intention], followed by 2-monthly intramuscular PrEP [ACS: median 3 (IQR 2-5), 19% high intention; survey: median 5 (IQR 3-7), 47% high intention], and implants [ACS: median 2 (IQR 1-4), 9% high intention; survey: median 4 (IQR 2-7), 37% high intention]. PrEP-experienced participants had higher intention to use oral long-acting PrEP and injectables than PrEP-na&#xef;ve participants. Offering multiple PrEP modalities may improve the acceptability of HIV prevention strategies and increase PrEP uptake and retention in PrEP care.

Humans

Tele-Oncology in the Post-Pandemic Era: Clinical Integration, Access Disparities and Medico-Legal Accountability.

PURPOSE OF THE REVIEW: Tele-health has evolved from a marginal tool confined to rural populations and selected follow-up programs into a structurally integrated component of modern cancer care. Prior to COVID-19, its adoption was constrained by regulatory fragmentation, non-uniform reimbursement, and licensure barriers. This narrative review evaluates the evolutionary integration of tele-health in oncology post-COVID-19, examines digital disparities across patient populations, and addresses the medico-legal implications of this integration, with the objective of providing a comprehensive and clinically actionable framework for the governance of virtual oncology care. RECENT FINDINGS: The pandemic acted as a global catalyst, driving telehealth to over 50% of oncology outpatient encounters in some settings, before stabilising post-pandemic at approximately 10-20% of consultations within hybrid care models. Evidence supports meaningful clinical benefits - improved access to specialist services, reduced travel burden, and sustained continuity of care - with outcomes comparable to in-person care in postoperative follow-up, symptom monitoring, and survivorship. However, persistent disparities in device availability, connectivity, and digital literacy disproportionately affect older, rural, and socioeconomically disadvantaged patients, raising the risk that geographic inequalities are replaced by technological ones. From a medico-legal standpoint, the remote modality does not modify the applicable standard of care, yet restricted physical examination and reliance on patient-reported data introduce risks of diagnostic delay and incomplete clinical assessment, with direct implications for professional liability, data protection under HIPAA and GDPR, cross-border licensure, and multi-party accountability across physicians, institutions, and technology providers. Tele-oncology has become a permanent structural feature of modern cancer care, offering demonstrable benefits in access, continuity, and patient satisfaction. Yet its integration has been uneven, its governance remains fragmented, and its medico-legal landscape is still evolving. Realising the full potential of virtual oncology care - equitably and safely - requires coherent regulatory frameworks, sustained investment in digital infrastructure, and explicit attention to the populations at greatest risk of being left behind.

Humans

Psychiatric mental health nurse practitioner outcomes after completion of a 1-year postgraduate fellowship.

Psychiatric mental health nurse practitioners (PMHNPs) are an essential and growing part of the health care workforce, especially in community settings. To address PMHNPs' increasing presence in community psychiatry, a 1-year postgraduate PMHNP fellowship in community psychiatry was developed with the goals of enhancing clinical competency and employment retention in underserved public sector settings. Data on 5 cohorts and 31 fellows are presented in this article. PMHNP fellows, preceptors, didactics, and clinical sites were evaluated across several time points including baseline and 6 and 12 months. The program has graduated 100% of fellows with largely positive feedback. Fellows reported significant improvements in competency across the domains of 1) assessment and diagnosis, 2) treatment, and 3) professionalism and leadership. These items were substantiated by clinical preceptors' ratings of fellows' clinical skills from 6-month and 12-month time points. Relatedly, clinical sites, preceptors, and didactics were all rated highly by fellows. After the program, 90.3% of graduates remained working in the public sector including correctional settings, community clinics, and safety net hospitals.

Community psychiatry

Randomized Trial of Intensive Nurse-Led Follow&#x2011;Up Versus Standard Care in Inflammatory Bowel Disease.

BACKGROUND: &#xa0;Nurses play a key role in inflammatory bowel disease (IBD) management. This randomized controlled trial evaluated intensive nurse-led program in patients with IBD starting advanced therapy. METHODS: &#xa0;Patients were randomized (1:1) to intensive nurse follow&#x2011;up (Arm&#xa0;A) or standard care (Arm&#xa0;B). Both arms received baseline nurse education; Arm A additionally had scheduled nurse calls and visits. Primary outcome was reduction in IBD&#x2011;Disk score in W12. Secondary outcomes were W52 reduction, robust response (>&#x2009;20-point improvement), and IBD-Disk remission (score&#x2009;<&#x2009;40). RESULTS: Overall, 98 patients were randomized (Arm&#xa0;A:&#xa0;n&#x2009;=&#x2009;50; Arm&#xa0;B:&#xa0;n&#x2009;=&#x2009;48) with similar baseline characteristics. Mean baseline IBD&#x2011;Disk scores were 49.2&#x2009;&#xb1;&#x2009;20.7 in Arm&#xa0;A and 42.0&#x2009;&#xb1;&#x2009;19.8 in Arm&#xa0;B (p&#x2009;=&#x2009;0.07). At W12, both groups improved, with greater IBD-Disk reductions in Arm A (16.1&#x2009;&#xb1;&#x2009;22.9 vs. 10.1&#x2009;&#xb1;&#x2009;20.1, p&#x2009;=&#x2009;0.09). At W52, improvement was greater in Arm&#xa0;A (18.4&#x2009;&#xb1;&#x2009;20.7 vs 9.4&#x2009;&#xb1;&#x2009;17.8; p&#x2009;=&#x2009;0.08). More patients achieved robust response in Arm A (49% vs 21%, p&#x2009;=&#x2009;0.013) at W12. By W52, IBD-Disk remission was achieved by 22/25 (88%) patients in Arm A vs 18/28 (64%) in Arm B (p&#x2009;=&#x2009;0.045). CONCLUSIONS: &#xa0;In this pilot randomized trial, intensive nurse-led follow-up did not significantly improve IBD-Disk at week 12, yet favorable trends of functional outcomes were observed. Intensive nurse&#x2011;led follow&#x2011;up program may improve quality of life in patients with IBD. These findings support the integration of specialist IBD nurses to improve patient&#x2011;centered outcomes.

Humans

The application of artificial intelligence in healthcare practice: A mapping review of systematic reviews.

Artificial intelligence (AI) is rapidly transforming healthcare practice, with growing evidence supporting its use in diagnosis, prognosis, treatment planning, and operational decision-making. The proliferation of systematic reviews in recent years underscores the need for an updated synthesis of the literature to inform research, policy, and practice. We searched PubMed, Web of Science, Scopus, IEEE Xplore, and CINAHL for systematic reviews and meta-analyses published between 2019 and February 2026. Eligible reviews focused on AI applications in healthcare practice, were peer-reviewed, and written in English. A total of 368 reviews met the inclusion criteria. Publication volume increased steadily, peaking in 2025. AI research was concentrated in high-density domains, such as radiology, oncology, and critical care. Across reviews, diagnostic imaging, electronic health record (EHR) data, and biomarkers/laboratory results accounted for 68% of training data sources, though newer data types, such as wearable device and sensor data, emerged from 2022 onward. Diagnosis, prognosis, and treatment comprised over 80% of AI applications, with novel uses emerging in recent years, such as AI-assisted clinical documentation (e.g., ambient documentation tools) and patient education. Ethical concerns were reported in 78.5% of reviews, with privacy, model accuracy, data and algorithmic bias, and explainability as recurrent themes. The proportion of reviews reporting ethical concerns increased from 2021 to 2025. AI applications in healthcare are expanding in scope, diversifying in data sources, and evolving toward novel clinical and operational uses. The human-centered AI or augmented intelligence paradigm, integrating computational precision with clinical expertise, holds significant promise but will require parallel advances in governance, regulatory frameworks, and ethical oversight to ensure safe adoption.

Artificial Intelligence

The effectiveness of digital health interventions for type 2 diabetes in underserved populations: A systematic review and meta-analysis.

This systematic review and meta-analysis of 12 randomized controlled trials (1835 participants) evaluated whether digital health interventions (DHIs) improve glycemic control among underserved adults with type 2 diabetes (T2D), including racial/ethnic minority, low-income, Medicaid-insured, rural, and low-health-literacy populations. Searches of PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to December 20, 2025 identified eligible parallel-group randomized controlled trials reporting change in hemoglobin A1c (HbA1c). Two reviewers independently screened studies, extracted data, and assessed risk of bias using the revised Cochrane Risk of Bias 2 tool. Random-effects meta-analysis showed that DHIs produced a modest but statistically significant HbA1c reduction versus control (mean difference, -0.37 %age points; 95% CI, -0.44 to -0.30; P&#x202f;<&#x202f;.0001; equivalent to -4.0&#x202f;mmol/mol). Heterogeneity was moderate-to-substantial (I&#xb2; = 69.9%). Subgroup analyses suggested directionally similar effects by population group and intervention modality, but interpretation was limited by study-level data and the small number of trials. Funnel-plot inspection and Egger's test (P&#x202f;=&#x202f;.31) did not suggest major small-study effects, although power was limited. Overall certainty for HbA1c was moderate. DHIs may support more equitable diabetes care when implemented with cultural tailoring, language access, digital-literacy support, and technology-access safeguards.

Humans

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&#x2009;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&#x2009;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%&#x2009;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&#x2009;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

Development and validation of a comprehensive prognostic model for 28-day ICU mortality in non-traumatic subarachnoid hemorrhage: an analysis based on the MIMIC-IV database.

BACKGROUND: Due to the complex pathophysiology of non-traumatic subarachnoid hemorrhage (SAH), accurate risk prediction remains a challenge. Our aim is to develop and validate a comprehensive prognostic model that integrates demographic characteristics, vital signs, laboratory parameters, and more, to provide clinical decision-making support in real-world practice. METHODS: We conducted a retrospective cohort study of 785 Non-traumatic subarachnoid hemorrhage patients. The cohort was randomly divided into a training set (n&#xa0;=&#xa0;549) and a validation set (n&#xa0;=&#xa0;236). Feature selection was performed using LASSO regression, followed by backward stepwise Cox regression for optimization. A nomogram was constructed based on independent predictive factors, and model performance was assessed using discrimination, calibration, and decision curve analysis. To prevent immortal-time bias, all predictors were anchored to a fixed early (first-24-hour) measurement window, treatment variables were modelled as binary indicators rather than cumulative exposures, and a five-model sensitivity analysis with baseline-severity adjustment was performed. RESULTS: The development of our model followed a systematic approach: first, 15 potential predictive factors were selected via LASSO regression, which were then refined to 12 independent predictors using backward stepwise Cox regression. The final predictive factors included: Ventilation, AHT, Nimodipine 60&#xa0;mg, Age, SAPS.II, Input amount, Calcium total, Platelet count, White blood cells, Anion gap, pH, and Chloride. The integrated model demonstrated excellent predictive ability for 7-day, 14-day, and 21-day mortality in both the training set (AUC: 0.972, 0.934, 0.898) and the validation set (AUC: 0.968, 0.948, 0.911). Calibration curves and decision curve analysis confirmed the model's reliability and clinical utility across different time points. We constructed a nomogram for individualized risk prediction. Univariate Kaplan-Meier survival analysis demonstrated significant stratification of survival outcomes by each predictor, while restricted cubic spline analysis revealed non-linear relationships between continuous variables and mortality risk. Random survival forest analysis identified the top three predictive factors (Nimodipine 60&#xa0;mg, Ventilation, AHT) and compared them with our full 12-variable model, confirming superior performance of the integrated model at all time points. At the 28-day primary endpoint, the model achieved a time-dependent AUC of 0.898 (training) and 0.904 (validation); after restricting predictors to the early baseline window, the leakage-controlled model retained good discrimination (validation C-index 0.803). CONCLUSIONS: Our ICU 28-day mortality prognosis model demonstrated robust performance in predicting ICU 28-day mortality in non-traumatic subarachnoid hemorrhage. The model, through the nomogram, provides individualized risk assessment, aiding clinical decision-making and patient stratification.

Humans

A translational framework for early-phase inner-ear gene therapy: clinical trial design, regulatory strategy, and ethical considerations.

PURPOSE OF REVIEW: Hereditary hearing loss has historically been approached as a diagnostic category rather than a therapeutically modifiable disease. Recent advances in molecular genetics, cochlear gene delivery, and first-in-human clinical trials are changing that. This review summarizes contemporary progress in the genetics of hearing loss, with emphasis on emerging gene-based therapies, clinical trial design, regulatory and ethical considerations, and practical implications for otolaryngologists as biologic treatment enters clinical practice. RECENT FINDINGS: Early clinical trials targeting OTOF -related DFNB9 deafness have demonstrated satisfactory safety profiles and meaningful auditory recovery, establishing the first proof-of-concept for cochlear gene therapy in humans, culminating in the April 2026 FDA approval of Otarmeni. Genetic diagnoses are increasingly informing prognosis, cochlear implant counseling, and therapeutic candidacy. Preclinical research continues to expand toward recessive, dominant, and syndromic hearing loss using gene replacement, antisense, RNA interference, and genome-editing strategies. Substantial challenges remain, including heterogeneous outcome measures, uncertain long-term efficacy, regulatory complexity, and inequitable global access. SUMMARY: The genetics of hearing loss is transitioning from a diagnostic modality to an interventional one. Widespread clinical impact will require advances in vector engineering, equitable implementation, multidisciplinary counseling, and integration with established rehabilitation pathways. For otolaryngologists, genetic literacy is becoming essential to contemporary hearing care.

Humans

Comparison between measured and synthesized posterior lead electrocardiograms during percutaneous coronary intervention-induced myocardial ischemia.

BACKGROUND: Posterior/inferolateral myocardial ischemia is frequently underrecognized on standard 12&#x2011;lead electrocardiography (ECG). Synthesized posterior leads derived from the standard 12&#x2011;lead ECG have been proposed as an alternative to directly measured posterior leads; however, their accuracy under controlled ischemic conditions has not been fully validated. METHODS: We prospectively enrolled 26 consecutive patients undergoing percutaneous coronary intervention (PCI) in whom simultaneously recorded measured and synthesized posterior lead ECGs (V7-V9) were obtained during balloon-induced myocardial ischemia. ST-segment deviation was measured at the ST junction (STJ), 40&#xa0;ms (ST1), and 80&#xa0;ms (ST2) thereafter. Agreement between measured and synthesized posterior leads was assessed using Pearson correlation and Bland-Altman analyses. As an exploratory patient-level analysis, diagnostic performance was compared with reciprocal anterior ST-segment depression (V1-V4). RESULTS: Strong correlations were observed between measured and synthesized posterior lead ST-segment deviations (V7: r&#xa0;=&#xa0;0.89; V8: r&#xa0;=&#xa0;0.86; V9: r&#xa0;=&#xa0;0.83; all P&#xa0;<&#xa0;0.001). Bland-Altman analysis demonstrated minimal systematic bias (within &#xb1;0.004&#xa0;mV) and narrow limits of agreement. Synthesized posterior leads showed higher diagnostic performance than reciprocal anterior ST-segment depression (AUC 0.917 vs. 0.708), although the difference was not statistically significant (DeLong test, P&#xa0;=&#xa0;0.197). Using a 0.05&#xa0;mV threshold, synthesized posterior leads demonstrated 83.3% sensitivity, 100% specificity, and 96.2% overall accuracy. CONCLUSIONS: Synthesized posterior leads closely reproduced measured posterior lead ST-segment deviations during percutaneous coronary intervention (PCI)-induced myocardial ischemia, supporting the technical validity of posterior lead reconstruction. Larger prospective studies are warranted to determine whether synthesized posterior leads provide incremental diagnostic value beyond careful interpretation of the standard 12&#x2011;lead ECG.

Humans

A Standardized Nursing-Led Protocol Integrated Pain, Sleep, Medication Adherence, and Symptom Management in Postherpetic Neuralgia.

Postherpetic neuralgia (PHN) is a persistent neuropathic pain condition after herpes zoster that frequently coexists with sleep disturbance, medication-related problems, and fluctuating symptoms. This study evaluated whether a standardized nursing-led protocol could improve multidimensional short-term outcomes beyond usual care. In this prospective, parallel-group randomized controlled trial, 128 adults with PHN were allocated 1:1 to usual care or usual care plus an eight-week protocol integrating structured pain assessment, sleep monitoring, medication-adherence support, and rule-based digital symptom monitoring. The primary outcome was the between-group difference in change in Numeric Rating Scale (NRS) pain score from baseline to Week 8. Secondary outcomes included Pittsburgh Sleep Quality Index (PSQI), MMAS-8 medication adherence, symptom burden, pain-related nocturnal awakenings, breakthrough pain, rescue analgesic use, adverse events, rule-based alerts, and nursing satisfaction. Week-8 data were available for 116 participants (57 usual care; 59 protocol). Mean NRS scores decreased from 7.19 &#xb1; 1.08 to 4.82 &#xb1; 1.53 in the usual-care group and from 7.28 &#xb1; 1.05 to 3.24 &#xb1; 1.28 in the protocol group. An NRS reduction of at least 2 points occurred in 49.1% and 76.3% of participants, respectively. The protocol group also showed larger improvements in PSQI, MMAS-8, symptom burden, and nocturnal awakenings, with fewer breakthrough-pain episodes and less rescue-analgesic use. These findings support further evaluation of the standardized nursing-led protocol in preregistered multicenter trials with intention-to-treat analyses and longer follow-up.

Humans

A systematic review of human avoidance learning: Cognition, computation, and methods.

Avoidance behaviour is fundamental for survival but can become maladaptive in clinical conditions. A large body of literature has accumulated on the dynamics of human avoidance learning. However, current theories and overviews do not provide an exhaustive account of this evidence. In this systematic review, we identify N = 116 studies on human avoidance learning. We analyse these studies with the goal of distilling robust empirical phenomena as a basis for theory-building, and examine their diagnostic value in differentiating between competing theories. We find that the evidence is difficult to reconcile with foundational two-factor and classical safety-signal accounts, and most strongly supports expectancy- and inference-based views, in which avoidance responses are selected with respect to represented consequences. At the same time, no current framework provides a complete account of the evidence: several findings point to an additional role for operant valuation, Pavlovian influences, and contextual or latent-state control over the expression of avoidance. Methodologically, we observe that the problem setting in the most common experimental paradigms is radically simpler than real-world avoidance and therefore unlikely to expose the limits of inferential or reflective mechanisms. Consequently, we argue that paradigms with greater computational demands and more realistic action affordances are required to identify the mechanisms underlying avoidance learning. Collectively, these insights provide a foundation for theoretical refinement, computational modelling, and methodological innovation, with implications for advancing interventions targeting maladaptive avoidance.

Humans