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Introduction: Gait is a critical indicator of neurological health, with changes often signaling underlying decline. We developed a remote gait monitoring protocol using off-the-shelf shoe-based sensors (RunScribe) to assess gait parameters in real-world home settings. This protocol, known as Gait Assessment with Innovative Technologies – Home-based Use and Benefit (GAIT-HUB), was tested in individuals with multiple sclerosis (MS), a population at high risk for gait impairment due to the disease’s variable progression. Methods: Participants with MS completed an in-clinic baseline gait assessment using a validated sensor (G-Sensor®) and three weekly, remotely supervised gait assessments at home using the RunScribe sensors. Gait parameters were compared across devices using intra-class correlation coefficients (ICCs) and Bland-Altman analyses. Longitudinal reliability of remote assessments and system usability score (SUS) were evaluated. Results: Twenty-nine participants (76% women, ages 19–67, PDDS range 0–5) successfully completed the home-based assessments. High agreement between devices was observed for gait speed, stride length, and cadence (ICCs >0.90), though phases like stance and swing showed more variability. Bland-Altman analyses indicated minimal bias in most parameters. Longitudinal assessments demonstrated strong reliability (ICCs >0.87) for key metrics, and SUS indicated good-to-excellent usability of the remote protocol. Conclusion: The GAIT-HUB protocol enables reliable and feasible home-based gait monitoring using wearable sensors that patients can easily self-apply. This approach provides valuable insights into daily mobility patterns beyond clinical visits, supporting more precise and timely assessments of functional status between appointments and offering the potential for seamless integration into telemedicine routine care.

Objectives. We sought to determine the effectiveness of a systems-based intervention designed to increase Chlamydia trachomatis (CT) screening among adolescent boys. Methods. An intervention aimed at increasing CT screening among adolescent girls was extended to adolescent boys (14–18 years). Ten pediatric clinics in a health maintenance organization with an ethnically diverse population were randomized. Experimental clinics participated in a clinical practice improvement intervention; control clinics received traditional information on screening. Results. The intervention significantly increased CT screening at the experimental sites from 0% (baseline) to 60% (18-month posttest); control sites evidenced a change only from 0% to 5%. The overall prevalence of CT was 4%. Conclusions. Although routine CT screening is currently recommended only for young sexually active women, the present results show that screening interventions can be successful in the case of adolescent boys, among whom CT is a moderate problem.

In recent years, self-supervised learning has been studied to deal with the limitation of available labeled-dataset. Among the major components of self-supervised learning, the data augmentation pipeline is one key factor in enhancing the resulting performance. However, most researchers manually designed the augmentation pipeline, and the limited collections of transformation may cause the lack of robustness of the learned feature representation. In this work, we proposed Multi-Augmentations for Self-Supervised Representation Learning (MA-SSRL), which fully searched for various augmentation policies to build the entire pipeline to improve the robustness of the learned feature representation. MA-SSRL successfully learns the invariant feature representation and presents an efficient, effective, and adaptable data augmentation pipeline for self-supervised pre-training on different distribution and domain datasets. MA-SSRL outperforms the previous state-of-the-art methods on transfer and semi-supervised benchmarks while requiring fewer training epochs.

This study quantifies the impact of utilization management (UM) programs and alternative delivery systems offered by the Blue Cross and Blue Shield Plans on hospital utilization and payments during the 1980's. It also explores the possible existence of a substitution effect defined as the shift of inpatient services to outpatient settings resulting from these programs. Further, the relationship between each UM program and HMO/PPO (Health Maintenance Organization / Preferred Provider Organization) enrollment is investigated to determine whether the growth in HMO/PPO enrollment influences the effectiveness of UM programs. Three econometric models which control for a number of exogenous variables such as (1) government regulations, (2) demography, (3) health care market characteristics, (4) time trend, (5) differences in seasonality, and (6) regional variations are specified and estimated. The results indicate that Plans having adopted preadmission certification combined with concurrent review and/or retrospective review with payment denial programs have experienced fewer hospital admissions, days, lower inpatient and total payments per thousand Plan enrollees. Retrospective review with payment denial programs have also reduced hospital outpatient visits and outpatient payments. Discharge planning programs have a statistical impact on inpatient days and average length of stay. Over the ten-year period, growth in HMO membership within Plans was significantly associated with the reduction of average length of stay, inpatient, outpatient, and total hospital payments per thousand enrollees. Although growth in PPO penetration rate within Plans was related to higher hospital outpatient visits and payments, it was statistically related to the decline of inpatient utilization, inpatient payments, and total payments. The findings also suggest that hospital outpatient department may be an area where outpatient services are substituted for inpatient care. Finally, the results of HMO and PPO interaction models show that Plans with high HMO enrollment are those in which UM programs are associated with greater reductions in hospital utilization and payments in the Blue Cross and Blue Shield System. Plans with high PPO membership appear to enhance the effectiveness of UM programs with regard to reducing inpatient hospital utilization but not hospital payments. These results provide clear evidence that HMO/PPO penetration rates within Plans play an important role in determining the effects of UM programs.

This study evaluates the aggregate and temporal impact seven Blue Cross and Blue Shield Plan utilization management (UM) programs have on hospital utilization and payments over a nine-year period, 1980 through 1988. The impact of these programs is determined using a statistical model that controls for variations in organizational characteristics of 56 Blue Cross and Blue Shield Plans, the health care market of the individual Plan, and several state and federal health care regulations. The statistical results indicate that over the entire period 1980 to 1988, preadmission certification, concurrent review, and denial of payment (as a part of the retrospective review program) programs were associated with lower hospital admissions, and fewer inpatient days and payments per 1,000 members. Mandatory second surgical opinion did not have a statistical impact on hospital utilization and payments. The aggregate reduction in hospital payments for all Blue Cross and Blue Shield Plans with both a preadmission certification and concurrent review program was estimated at $2.55 billion in 1988 dollars. For those Plans conducting preadmission certification, concurrent review, denial of payment, and case management programs in 1988, the total per enrollee reduction of inpatient payments was $52.94.

Abnormal tumour vasculature has a significant impact on tumour progression and response to therapy. Nitric oxide (NO) regulates angiogenesis and maintains vascular homeostasis and, thus, can be delivered to normalize tumour vasculature. However, a NO-delivery system with a prolonged half-life and a sustained release mechanism is currently lacking. Here we report the development of NanoNO, a nanoscale carrier that enables sustained NO release to efficiently deliver NO into hepatocellular carcinoma. Low-dose NanoNO normalizes tumour vessels and improves the delivery and effectiveness of chemotherapeutics and tumour necrosis factor-related, apoptosis-inducing, ligand-based therapy in both primary tumours and metastases. Furthermore, low-dose NanoNO reprogrammes the immunosuppressive tumour microenvironment toward an immunostimulatory phenotype, thereby improving the efficacy of cancer vaccine immunotherapy. Our findings demonstrate the ability of nanoscale NO delivery to efficiently reprogramme tumour vasculature and immune microenvironments to overcome resistance to cancer therapy, resulting in a therapeutic benefit.

Despite the transformative impact of cancer immunotherapy, the need for improved patient stratification remains critical due to suboptimal response rates. While neoantigens are central to anti-tumor immunity, current metrics, such as tumor mutation burden (TMB), are limited by their neglect of immunogenicity and tumor heterogeneity. Here we present NeoPrecis, a computational framework designed to improve immunotherapy response prediction by refining neoantigen characterization across MHC-I and MHC-II pathways and by integrating tumor clonality information. NeoPrecis features an interpretable T-cell-recognition model that reveals the critical influence of MHC molecules on TCR recognition beyond mere antigen presentation. Benefit HLA alleles, identified through model-driven contribution analysis, exhibit significant predictive power for patient outcomes in immune checkpoint inhibitor treatment (melanoma: p -value = 0.04; NSCLC: p -value = 0.01). NeoPrecis, via its clonality-aware neoantigen landscape feature, improves immunotherapy response prediction in tumor types with varying prevalence of neoantigens, including heterogeneous NSCLC, which retains more subclonal neoantigens due to lower immunoediting pressure. We thus propose NeoPrecis as a comprehensive evaluative framework for neoantigen assessment by incorporating both immunogenicity and tumor clonality, offering insights into the link between the collective quality of neoantigen landscapes and immunotherapy response. Response to immune therapy varies among cancer types and individual cancer patients; thus, predictive biomarkers of success are urgently needed. Here, the authors present a computational framework that integrates tumor clonality and neoantigen characterization data to predict patient outcomes upon immune checkpoint inhibitor treatment.

Patients who had a positive laboratory test for influenza were six times as likely to be hospitalized for acute myocardial infarction during the 7 days after specimen collection (the “risk interval”) as during the year before and the year after the risk interval.

BackgroundThere have been no randomised controlled trials that specifically evaluate the effect of a comprehensive programme with multidisciplinary input on patients who have just been discharged from hospital after treatment of acute exacerbation of COPD (AECOPD). The aim of this study was to assess whether a comprehensive care programme would decrease hospital readmissions and length of hospital stay (LOS) for patients with COPD.MethodsPatients discharged from hospital after an episode of AECOPD were randomised to an intervention group (IG) or usual care group (UG). The IG received a comprehensive, individualised care plan which included education from a respiratory nurse, physiotherapist support for pulmonary rehabilitation, 3-monthly telephone calls by a respiratory nurse over 1 year, and follow-up at a respiratory clinic with a respiratory specialist once every 3 months for 1 year. The UG were managed according to standard practice. The primary outcome was hospital readmission rate at 12 months.Results180 patients were recruited (IG, N=90; UG, N=90; mean±SD age 74.7±8.2 years, 172 (95.6%) men; mean±SD FEV1 45.4±16.6% predicted). At 12 months, the adjusted relative risk of readmission was 0.668 (95% CI 0.449 to 0.995, p=0.047) for the IG compared with the UG. At 12 months, the IG had a shorter LOS (4.59±7.16 vs 8.86±10.24 days, p≤0.001), greater improvement in mean Modified Medical Research Council Dyspnoea Scale (−0.1±0.6 vs 0.2±0.6, p=0.003) and St George's Respiratory Questionnaire score (−6.9±15.3 vs −0.1±13.8, p=0.003) compared with the UG.ConclusionsA comprehensive COPD programme can reduce hospital readmissions for COPD and LOS, in addition to improving symptoms and quality of life of the patients.Trial registration numberNCT 01108835, Results.

ObjectivesTo obtain more powerful assessment of the prognostic value of fractional flow reserveCT testing we performed a systematic literature review and collaborative meta-analysis of studies that assessed clinical outcomes of CT-derived calculation of FFR (FFRCT) (HeartFlow) analysis in patients with stable coronary artery disease (CAD).MethodsWe searched PubMed and Web of Science electronic databases for published studies that evaluated clinical outcomes following fractional flow reserveCT testing between 1 January 2010 and 31 December 2020. The primary endpoint was defined as ‘all-cause mortality (ACM) or myocardial infarction (MI)’ at 12-month follow-up. Exploratory analyses were performed using major adverse cardiovascular events (MACEs, ACM+MI+unplanned revascularisation), ACM, MI, spontaneous MI or unplanned (>3 months) revascularisation as the endpoint.ResultsFive studies were identified including a total of 5460 patients eligible for meta-analyses. The primary endpoint occurred in 60 (1.1%) patients, 0.6% (13/2126) with FFRCT>0.80% and 1.4% (47/3334) with FFRCT ≤0.80 (relative risk (RR) 2.31 (95% CI 1.29 to 4.13), p=0.005). Likewise, MACE, MI, spontaneous MI or unplanned revascularisation occurred more frequently in patients with FFRCT ≤0.80 versus patients with FFRCT >0.80. Each 0.10-unit FFRCT reduction was associated with a greater risk of the primary endpoint (RR 1.67 (95% CI 1.47 to 1.87), p<0.001).ConclusionsThe 12-month outcomes in patients with stable CAD show low rates of events in those with a negative FFRCT result, and lower risk of an unfavourable outcome in patients with a negative test result compared with patients with a positive test result. Moreover, the FFRCT numerical value was inversely associated with outcomes.