Amyotrophic lateral sclerosis (ALS) is associated with substantial financial burden. How financial concerns are documented or addressed in ALS multidisciplinary clinics (MDC) is unclear. We aimed to characterize financial concerns among people living with ALS (pALS) and how they are identified and documented by multidisciplinary clinic staff. We performed a retrospective electronic medical record (EMR) review for people living with ALS (pALS) attending at least two visits at the MDC, identifying documentation of financial concerns across all MDC notes throughout 2024. Semi-structured interviews with MDC staff explored experiences with financial concern discussions and documentation. Rapid qualitative analysis was used to analyze interview content. Among 67 pALS with at least 2 MDC visits, 45 (67.2%) had ≥ 1 documented financial concerns. Financial concerns were most documented in neurology physician notes and portal messages (both 77.8%) and included insurance denials, medication costs, disability/Medicare navigation, caregiving expenses, and home modifications. Social work and patient portal notes provided greater detail than other staff notes. Staff interviews highlighted insurance and equipment costs as frequent financial concerns. Four qualitative themes emerged: insurance challenges and reliance on non-insurance resources, financial barriers limiting care and quality of life, limited proactive conversations/documentation, and the central role of social work. Financial concerns are common among pALS but are inconsistently discussed and documented in the EMR, often arising through asynchronous communication or social work. Integrating financial screening and promoting proactive multidisciplinary documentation may improve identification of financial concerns and support more equitable, person-centered ALS care.
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We investigated information needs and current knowledge on conflicts of interests (COIs) and funding in guidelines among guideline contributors. We invited contributors, including methodologists, medical staff, journal editors, and health policymakers, from China, Japan, and South Korea to an online survey on the knowledge and information needs related to COI and funding in guidelines. The results were presented descriptively using frequencies and percentages. A total of 342 (94.2% of the 363 questionnaires that were initiated) were considered valid and included in the analysis: 188 were from China, 92 from Japan, and 62 from South Korea. Most respondents (n = 307, 89.8%) were aware of issues related to COIs and funding in guidelines. Of these 307 respondents, 44 (14.3%) had participated in guideline development without filling out a declaration of interest form, and 287 (93.5%) believed that it would be necessary to standardize the reporting of information on COIs and funding in guidelines. Most respondents found the division into financial and nonfinancial interests the most appropriate way to categorize COIs (n = 155, 50.5%) and agreed that all guideline contributors should disclose their interests (n = 245, 79.8%). Most respondents would agree to set thresholds for individual financial COIs (n = 240, 78.2%) and funding (n = 239, 77.8%), amounts below which would not need to be disclosed. Nearly 80% of the respondents supported mandatory disclosure of potential COI for all guideline contributors. The RIGHT-COI&F reporting guideline is an important step in the right direction, improving the transparency and comprehensiveness of guidelines.
Medical scribes are increasingly used in outpatient clinics in the United States to reduce physician documentation burden, but their economic and operational impact remains inconsistently characterized. This scoping review synthesized evidence on the impact of medical scribes in outpatient care in the United States, focusing on physician productivity, documentation efficiency, and financial outcomes. Nine databases were searched from January 2010 to September 2024 for English-language studies reporting economic or productivity outcomes of medical scribe use in outpatient settings. Two reviewers independently screened 1,945 unique records; data were charted using a piloted template and synthesized thematically. Twenty United States-based studies met the inclusion criteria: nine pre-post evaluations, five controlled cohort studies, two randomized controlled trials (RCTs), two microsimulation models, and two systematic reviews. Scribes consistently improved physician productivity: 19 of 20 studies (95%) reported increased work relative value units (wRVUs), higher patient throughput, and reduced documentation time. Clinician satisfaction improved across 9 studies; patient experience remained stable. Economic outcomes varied: 13 of 20 studies attempted return on investment (ROI) analysis, but only 6 included comprehensive costs (wages, training, licensing, turnover). Cost neutrality was achievable in high-volume clinics with predictable scheduling and unutilized capacity, but financial returns depended heavily on specialty, baseline productivity, and cost accounting rigor. Medical scribes enhance operational efficiency and physician workflow in United States outpatient clinics, though economic value is context-dependent and incompletely documented. Standardised cost frameworks and controlled evaluations in non-United States health systems are needed to guide implementation decisions.
Hospice care is associated with improved end-of-life outcomes. Recent shifts in hospice utilization highlight several key trends. Alzheimer's disease and related dementias (ADRD) (25%) have surpassed cancer (23%) as the leading primary diagnosis. Concurrently, industry ownership has transitioned from predominantly nonprofit to for-profit (70%) and private equity (PE) ownership has grown dramatically from 3% to 15%. To date, no study has synthesized evidence on PE ownership in hospice care. We conducted a systematic review of English-language, peer-reviewed studies published 2012-2026, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Of 630 screened articles, 114 underwent full-text review and 6 met inclusion criteria. All studies used national data; sample sizes ranged from 80 to 536 PE-owned hospices. Three studies examined PE prevalence and market trends; two assessed caregiver-reported care experiences, and one evaluated financial outcomes by PE ownership. The evidence regarding PE ownership of hospices remains limited. It highlights the increasing role of PE in hospice markets. It consistently found (across two studies) worse care experiences at PE-owned hospices vs nonprofit hospices, except for emotional and religious support which was similar across ownership type. The evidence suggests PE ownership is associated with complex, often worse patterns related to market structure, care experiences, and financial allocation. Additionally, it underscores the limited evidence base to inform policy development. Research is needed to examine associations between PE ownership and hospice care quality, both overall and among vulnerable populations. Research should clarify modifiable factors influencing hospice quality and better characterize evolving ownership structures.
Subjective cognitive decline (SCD) is under-addressed in survivorship care despite associations with other adverse patient-reported outcomes and poor long-term cognitive health. Research on SCD and social determinants of health (SDOH) is limited among cancer survivors. This study examined associations of SCD, and its impacts, with cancer-related characteristics and SDOH among survivors. The study analyzed cross-sectional data from survivors ages ≥ 45 years in the nationally representative 2023/2024 Behavioral Risk Factor Surveillance System. Survey-weighted modified Poisson regression modeling with robust standard errors was employed. Exposures were cancer-related characteristics (cancer type, age at diagnosis, multiple cancer diagnoses) and SDOH (employment instability, food insecurity, low social connection, financial strain, limited transportation, number of SDOH). Outcomes were SCD and four SCD-related impacts (worrying, discussing with a healthcare provider, interference with day-to-day activities, interference with work/volunteer activities). Prevalence ratios (PRs) with 95% confidence intervals (CIs) are reported. Among 11,713 survivors, the weighted prevalence of SCD was 19.6%. Being diagnosed before age 40 and with multiple cancers were associated with greater prevalence of SCD in bivariate analyses, however, no cancer-related characteristics were associated with SCD measures in multivariable analyses. Each SDOH measure except employment instability was associated with SCD (aPRs = 1.37 to 2.25; all p ≤ 0.0039), versus no SDOH. Compared to no SDOH, number of SDOH was associated with each SCD-related impact (aPRs = 1.35 to 3.36; all p ≤ 0.0007) except provider discussion. Findings highlight the role SDOH plays in influencing SCD among survivors. Greater attention to SCD may improve long-term outcomes among survivors.
Hepatitis B virus (HBV) infection remains a major public health challenge in sub-Saharan Africa despite the availability of a safe and effective vaccine. In Nigeria, adult vaccination coverage and completion rates are not well characterized within hospital-based populations. A hospital-based cross-sectional study was conducted among 1,200 adults attending Federal Medical Centre (FMC) Keffi, Nasarawa State, Nigeria. Data on socio-demographics, HBV-related knowledge, attitudes, perceived barriers, vaccination uptake, and completion were collected using a structured questionnaire. Knowledge and attitude scores were categorized into poor, fair, and good levels. Associations between socio-demographic characteristics and vaccination uptake were examined using chi-square and Fisher's exact tests, with statistical significance set at p < 0.05. The mean age of respondents was predominantly 36-40 years (32.5%), with males constituting 72.3%. Most respondents had tertiary education (91.8%) and were civil servants (83.4%). Overall awareness of HBV was high (95.5%), with a mean knowledge score of 12.37 ± 1.42. Good knowledge was observed in 74.2% of respondents, while 57.2% demonstrated good attitudes toward HBV prevention. Vaccination uptake was high, with 93.5% reporting receipt of at least one vaccine dose. However, only 22.3% had completed the recommended three-dose schedule, while 48.2% and 23.1% had received one and two doses, respectively. Willingness to complete vaccination was reported by 81.6% of respondents. Perceived barriers included high vaccine cost (72.4%), inadequate access to health facilities (96.9%), fear of side effects (71.9%), and insufficient information (73.5%). No significant associations were found between socio-demographic variables and vaccination uptake (p > 0.05 for all). Despite high HBV vaccination initiation and knowledge levels, substantial gaps in vaccine completion persist. Addressing financial, informational, and access-related barriers is essential to improve full vaccination coverage among Nigerian adults.
Chronic wounds constitute a global crisis that has a substantial financial and social impact on healthcare systems. Many attempts have been made in recent decades to create bioceramic-based wound dressing materials to aid in the healing process. Bioceramics are frequently used as materials or alternatives for bone repair because of their strong mechanical qualities. Both soft and hard tissues can be repaired thanks to the release of various metallic ions from bioceramics. Cell motility, proliferation, differentiation, adhesion, angiogenesis, and antibiosis may all benefit from these ions. These substances can be added to sophisticated composite systems like hydrogels, porous scaffolds, films, and membrane-based dressings, or they can be used on their own as powders or suspensions of nanoparticles. Bioceramic-based wound dressings have a lot of potential, but their clinical application is still constrained by a number of issues, such as their inherent brittleness, low mechanical flexibility, poor degradation control, and occasionally inadequate interaction with the dynamic wound environment. However, incorporating bioceramics into scaffold-based platforms may help get around many of these restrictions. Furthermore, the scaffold architecture can improve the overall therapeutic performance of bioceramic systems by better simulating the extracellular matrix and enabling controlled delivery of bioactive components. This review focuses on advanced ceramic-based wound dressings and their role in enhancing structural support, promoting cell attachment and proliferation, and creating a favorable environment for skin regeneration.
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.
Rare genetic diseases (RDs), though individually uncommon, collectively impose a substantial global burden with significant social, emotional and economic implications. Understanding the lived experiences of RD patients, caregivers and service providers is essential to fully address the challenges they face. This study presents a narrative synthesis of original qualitative research on RDs published between 2004 and 2024, identifying 317 studies across multiple databases. Reflexive thematic analysis was used to synthesise and interpret the findings, allowing for an integrative understanding of both commonalities and disparities in experiences and research focus globally. While studies from Europe (45%) and North America (32%) dominated the field, markedly fewer included participants from Africa (3%), Asia (11%) and South America (2%), particularly from low- to middle-income countries. Across studies, recurring themes included navigating emotional resilience; the redefinition of identity in the face of RD; the social experience of illness; healthcare experiences, including access to and quality of healthcare services; the financial and logistical burden of care; the experience of research and new technologies; and the influence of society, culture and power structures. The pronounced underrepresentation of LMIC settings, persisting despite targeted search efforts, is itself a substantive finding, raising critical questions about where rare disease knowledge is produced and whose experiences are considered worthy of formal documentation. The synthesis underscores the urgent need for geographically inclusive, methodologically diverse and community-engaged approaches to qualitative RD research.
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Carrier screening is used to determine reproductive risk for autosomal recessive or X-linked conditions, and its clinical implementation varies widely. We evaluated recurring clinical patterns observed at an independent, university-affiliated, high-volume maternal-fetal medicine center in Los Angeles receiving referrals from diverse practice settings. In our view, carrier screening is far too frequently performed later than ideal, which narrows timelines for partner testing, prenatal diagnosis, and decision making and increases patient distress. Carrier screening practices differ by referring clinician, resulting in inequities in detecting genetic risk. Within a single couple, partners are often screened on discordant panels (and sometimes sequentially, maternal-first), which delays risk clarification and increases the chance of misinterpretation. Based on these observations, we believe prepregnancy carrier screening should be prioritized; otherwise, carrier screening should be performed as early as possible in pregnancy with concurrent partner testing. We also believe patients should receive counseling on the benefits and limitations of all available screening options to preserve patient autonomy.
Finite element (FE) foot models are increasingly used to support clinical decision-making in hallux valgus (HV) surgery, yet most rely only on static standing simulations. Such calibration remains under-constrained, validating non-unique mechanical model parameters that fit static data but may fail to represent dynamic mechanics limiting clinical reliability. This study evaluated whether introducing dynamic gait loading and multi-metric validation improves parameter identifiability and increases patient-specific clinical validity. Prior to surgery, a patient with HV underwent plantar pressure and motion analysis in static and walking. Patient-specific model was developed by morphing a standard FE foot mesh to the CT geometry. Then, thirteen biomechanical foot parameters were varied by Latin Hypercube Sampling. The 160 static simulations obtained were evaluated against fourteen targets from static experimental data. Sets with < 5% mean static error were finally used in FE time-dependent dynamic gait simulation driven by patient data. Predictions were compared for bone motion, center-of-pressure path, and plantar pressures at three instants of the gait. Static study produced 9.9% average error across all models (eight models < 5% error) while input values differed widely. Dynamic validation split these candidates: one set kept mean errors < 13% whereas others rose to 25%, with substantial discrepancies in forefoot loading and kinematics. Static plausibility does not guarantee dynamic validity. Dual loading combined with multi-metric validation proved to be essential to isolate physiologically coherent parameter sets. Resulting pipeline strengthens the credibility of HV digital twins for future clinical decision-making.
Hem-o-lok clips and endoloops are commonly used techniques for appendiceal stump closure during laparoscopic appendectomy. However, evidence regarding their relative safety and efficacy remains inconsistent. This meta-analysis compared clinical outcomes between the two techniques. PRISMA guidelines were followed. PubMed, Google Scholar, and other electronic databases were searched for comparative studies evaluating Hem-o-lok clips versus endoloops in laparoscopic appendectomy. Primary outcomes were intra-abdominal abscess and surgical site infection; secondary outcomes were operative time and hospital length of stay. Risk of bias was assessed using RoB 2 and the Newcastle-Ottawa Scale. Pooled estimates were calculated using fixed- or random-effects models. A total of 23 studies involving 4296 patients were included. No statistically significant differences were observed between the groups regarding surgical site infection (p = 0.112) or hospital length of stay (p = 0.355). Operative time was significantly shorter in the Hem-o-lok clip group (MD 5.41 min, 95% CI 3.40-7.42; p = 0.019). Intra-abdominal abscess formation was significantly less frequent in the Hem-o-lok group compared with the endoloop group (OR 1.87, 95% CI 1.05-3.32; p = 0.035). Heterogeneity was low for intra-abdominal abscess and SSI analyses, whereas substantial heterogeneity was observed for operative time and LOS outcomes. Both Hem-o-lok clips and endoloops are safe and effective methods for appendiceal stump closure. Hem-o-lok clips were associated with shorter operative time, while postoperative outcomes were largely comparable between techniques. Further randomized studies are warranted.
Current pediatric heart valve protheses lack growth potential, leading to repeated surgeries and long-term complications. Tissue-engineered heart valves (TEHVs), composed of living tissue, offer the ability to remodel and may accommodate somatic growth. This study introduces a sutureless fabrication strategy for TEHV designed to eliminate suture-related weak points and preserve valve geometry during in vitro maturation through a novel evolutive support system. This system was used to form and maintain the geometry of a fibrin-based valve scaffold embedded with human adipose-derived stromal cells during in vitro culture by mechanically constraining tissue contraction in all directions except thickness. Dimensional analysis confirmed geometry preservation throughout 28 days of perfusion bioreactor culture. At the end of the culture period, the matured valve was released from the evolution support system, after which the valve contracted to stable dimensions of approximately 16 mm in diameter, 23 mm in height, and 400 µm in thickness, corresponding to reductions of 26%, 43%, and 84% in diameter, height, and thickness, respectively, relative to the initial molded geometry. These ratios provide critical design guidance for pediatric target dimensions. Cell viability exceeded 90% upon molding, and cell density increased nearly 100-fold during culture. Histology revealed progressive collagen deposition, which correlated with improved mechanical properties. Stiffness increased nearly 9-fold and puncture strength 2.5-fold from fabrication to day 28. This reproducible sutureless strategy enables geometry retention of TEHV by guiding tissue contraction during in vitro culture, paving the way for pulsatile conditioning and further maturation to achieve mechanical properties approaching those of native valves and ensure long-term functionality.
Flexible cystoscopy is integral to outpatient urology, particularly for surveillance of non-muscle-invasive bladder cancer. Real-world economic data comparing reusable (RU) and single-use (SU) cystoscopes in German outpatient practice are scarce. We evaluated procedure-level costs and multidisciplinary user perceptions under routine conditions. A micro-costing analysis was performed in a German outpatient urology centre (337 cystoscopies/year). Capital investment (5-year amortisation), maintenance, reprocessing, consumables, and labour were included. Baseline and full-equipment replacement scenarios were modelled, and break-even thresholds calculated. A standardised survey of 13 physicians and 25 nursing staff from five practices assessed technical performance and workflow domains (5-point Likert scale). Groups were compared using Mann-Whitney U tests with Cliff's delta. Mean per-procedure cost was €27.25 for RU and €179.00 for SU. RU became cost-effective beyond 67 procedures annually; this threshold increased to 265 procedures when modelling full equipment renewal (€43,050). Physicians rated RU superior for manoeuvrability (p = 0.02) and SU superior for logistics (p = 0.02), with no differences in image quality, ergonomics, diagnostic confidence, or overall impression. Nursing staff favoured SU across all domains (all p < 0.001), particularly reprocessing workload and reliability. Limitations include single-centre design, evaluation of one device per category, context-specific reimbursement structures, and absence of primary environmental or patient-reported outcomes. In high-volume outpatient settings, RU cystoscopes are economically advantageous. However, SU devices offer substantial workflow benefits. Device selection should be context-specific, integrating case volume, infrastructure, and multidisciplinary perspectives.
Despite distinct receptor targets, both ketamine and serotonergic psychedelics produce a rapid clinical response and share biological signatures that suggest convergence on common downstream molecular mediators. To identify shared biomarkers of rapid antidepressant response, this study integrated CSF proteomics from healthy volunteers (HVs) who received intravenous ketamine with transcriptomic analyses from induced pluripotent stem cells (iPSCs) derived from participants with treatment-resistant depression (TRD) and HVs; iPSCs were treated with ketamine, its metabolite (2 R,6 R)-hydroxynorketamine, lysergic acid diethylamide (LSD), or psilocybin. Multimodal clinical characterization (transcriptomics (n = 16 TRD; 11 HV), magnetoencephalography (MEG) (n = 30 TRD; 25 HV), and plasma cytokines (n = 39 TRD; 25 HV) were also performed on TRD and HV participants who received a single dose of intravenous ketamine (0.5 mg/kg) or placebo. Conserved immune pathways were identified across CSF and iPSC neurons with interleukin-15 (IL)-15 and monocyte chemoattractant protein-1 (MCP-1) emerging as key regulatory hubs. Transcriptomically, in whole blood, ketamine responders exhibited decreased IL-15 and elevated B-cell signaling pathways at baseline that were reversed post-treatment. At the protein level, plasma IL-7 levels (primary B-cell driver) correlated with baseline MEG gamma power, reaching brain-wide significance across all participants (main effect pFDR < 0.05). The association was most pronounced in the TRD participants across subcortical regions (diagnosis x IL-7 pFDR < 10-14). Post-ketamine, the TRD IL-7-gamma relationship inverted, paralleling widespread gamma power reductions throughout default-mode network regions (session x IL-7 pclc < 0.05). In mixed-effects models, cytokine ratios linked to IL-7/IL-15 signaling predicted antidepressant response (IL-4/interferon gamma (IFN-γ) pFDR < 0.041) and non-response (MCP-1/IL-7 pFDR < 0.009), suggesting that rebalancing within the IL-7/IL-15 axis may contribute to therapeutic efficacy. Clinicaltrials.gov identifier: NCT00088699; NCT02484456.
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Fc-gamma receptors (FcγRs) regulate IgG antibody activity, and Fc-engineering is a proven method to improve the efficacy of tumor-targeting antibodies. Here, we explore tailored FcγR blockade to enhance the therapeutic efficacy and tolerability of immune checkpoint-blocking (ICB) antibodies. Mechanistically matched murine surrogate and human lead FcγR-blocking and immune checkpoint-blocking antibodies were used to study whether tailored FcγR-blockade, targeting FcγRIIB selectively or all FcγRs, can enhance the efficacy and overcome resistance to immune checkpoint therapy in vivo and in vitro. Mechanistic studies were performed with clinical reagents, including ipilimumab, nivolumab, pembrolizumab, and human FcγRIIB-selective (BI-1607) and pan-FcγR-blocking (BI-1206) antibodies, using human cells and transgenic animals with clinically relevant expression of immune checkpoint receptors. We demonstrate that FcγRIIB-selective and pan-FcγR-blocking antibodies increase the in vivo efficacy of αCTLA-4 and αPD-1 antibodies, respectively. FcγRIIB-selective antibody enhancement of αCTLA-4 was associated with increased intratumoral Treg depletion, myeloid reprogramming, interferon-γ and CXCL10-induction, and increased activated effector CD8+ T cells, correlating with higher activating-to-inhibitory (A:I) FcγR engagement ratios. Conversely, pan-FcγR blockade protected αPD-1-coated T cells from macrophage phagocytosis, increasing intratumoral activated CD8+ T cells by decreasing activating and inhibitory FcγRs. Our studies provide in vivo proof of concept that tailored FcγR blockade enhances immune checkpoint therapy and overcomes resistance through mechanistically distinct pathways. Clinical trials with tailored human FcγRIIB-blocking antibodies are ongoing.
Antimicrobial resistance (AMR) has emerged as a major threat to global public health, while conventional research methods face severe bottlenecks in deciphering its complex mechanisms and accelerating new drug development. Artificial intelligence (AI), particularly deep learning, is revolutionizing AMR research by enabling the processing of high-dimensional multi-omics data, uncovering hidden patterns, and generating novel hypotheses. This review systematically elaborates on the biomedical big data ecosystem that drives the AI revolution, including multi-omics data, phenotypic and clinical data, and literature-based knowledge data. We then discuss in detail cutting-edge AI methods and their applications in multi-level resistance mechanism analysis (knowledge-enhanced retrieval, resistance gene identification, and phenotype prediction) and intelligent design of novel antimicrobial molecules. Furthermore, we analyze core challenges in data quality, algorithm interpretability, clinical translation, and ethical governance. Finally, we propose key future directions, such as building equitable data ecosystems, developing interpretable AI models, and deepening interdisciplinary collaborations. This review aims to provide researchers with a comprehensive perspective on the current landscape, existing challenges, and future paths for AI applications in the AMR field. 抗微生物药物耐药性(antimicrobial resistance, AMR)已经成为全球公共卫生的重大威胁，传统的研究方法在解析其复杂机制、加速新药研发方面遇到了严峻的问题。人工智能(artificial intelligence, AI)技术，尤其是深度学习，由于可以处理高维多模态数据、发现隐藏的模式、产生新的假设，正在对AMR的策略产生革命性的影响。本文对驱动AI革命的生物医学大数据生态进行了系统阐述，包括多组学数据、表型和临床数据、文献知识数据;详细论述了AI在多层次耐药性机制解析(知识增强检索、耐药基因识别、表型预测)和新型抗菌分子智能设计中的前沿方法和实践;最后对目前数据质量、算法可解释性、临床转化、伦理监管等核心挑战进行了剖析，并对未来构建公平数据生态、开发可解释模型、深化跨学科合作等关键发展方向进行了展望。本文能够帮助相关研究人员全面了解AI在AMR领域的应用全景、存在的问题和未来的发展方向。.