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Neurosurgery-Led Digital Emergency Referral System in Khyber Pakhtunkhwa, Pakistan: Protocol for a Mixed Methods Implementation Study

JMIR Res Protoc. 2026 Jul 17;15:e90331. doi: 10.2196/90331.

ABSTRACT

BACKGROUND: Emergency referral systems in low- and middle-income countries (LMICs) are characterized by systemic inefficiencies, including prolonged transfer delays, interfacility miscommunication, and inadequate receiving-end preparation. In Khyber Pakhtunkhwa (KP), a province of Pakistan with a population exceeding 40 million, referral pathways remain predominantly paper-based and operationally fragmented. Tertiary medical institutions, including Lady Reading Hospital (LRH), Khyber Teaching Hospital (KTH), and Hayatabad Medical Complex (HMC), sustain a disproportionate burden of medically unnecessary referrals from peripheral facilities, culminating in institutional overcrowding, resource depletion, and attenuation of specialist neurosurgical and emergency care delivery.

OBJECTIVE: This study aims to design, implement, and evaluate a neurosurgery-led digital emergency referral platform-the KP Medical Teaching Institution (MTI) Referral Application-across primary, secondary, and tertiary tiers of health care delivery in KP, with the primary intent of reducing unnecessary referral rates, abbreviating referral response intervals, optimizing inpatient bed utilization, and strengthening bidirectional inter-facility communication.

METHODS: A convergent mixed methods design will be employed, incorporating a quantitative prospective cohort study alongside a qualitative exploratory component. The quantitative arm will adopt a census-based methodology, enumerating all emergency referrals processed through the digital platform over a 6-month pilot period commencing June 2026, with preimplementation historical referral data serving as the comparator. An estimated 5000-7000 referral episodes are anticipated. Primary outcomes include reduction in unnecessary referral rates and referral-to-response time. Secondary outcomes encompass inpatient bed occupancy rates, unanswered referral proportions, case acceptance and declination rates, remotely managed cases precluding physical transfer, patient mortality indices where ascertainable, and health care provider satisfaction scores. Statistical analysis will be performed using IBM SPSS, incorporating descriptive statistics, chi-square, or Fisher exact tests, paired comparisons, and multivariate logistic regression. The qualitative component will comprise structured surveys, semistructured interviews, and focus group discussions among purposively sampled health care professionals and patients, with thematic analysis conducted independently by 2 coders and findings integrated via a convergent mixed methods framework.

RESULTS: System development, stakeholder engagement, user-centered iterative design, beta testing, and platform validation have been completed. Participant recruitment is pending pilot deployment in June 2026. Data collection is projected to conclude by November 2026, followed by analysis from December 2026 through February 2027. Peer-reviewed dissemination is anticipated in spring 2027. No external funding was received.

CONCLUSIONS: This protocol outlines an integrated, multimodal assessment of a neurosurgery-based digital emergency referral system in a resource-constrained low- to middle-income country. In case the expected gains in referral efficiency and communication are realized, the results can be valuable evidence to justify the wider implementation of digital referral platforms in KP and other similar environments.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/90331.

PMID:42467936 | DOI:10.2196/90331

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Identification of Mitochondria- and Macrophage Activation-Related Hub Genes in Sarcopenia

IET Syst Biol. 2026 Jan-Dec;20(1):e70081. doi: 10.1049/syb2.70081.

ABSTRACT

To explore the hub genes and pathways associated with sarcopenia progression from the perspective of mitochondrial dysfunction and macrophage activation. The GEO datasets GSE8479, GSE1428 and GSE136344 were obtained from the GEO database. Mitochondria-related genes (MRGs) and macrophage activation-related genes (MARGs) were identified. Functional enrichment analyses, PPI analysis, diagnostic model construction, molecular subtyping and ssGSEA-based immune enrichment analysis were performed. Key genes were further validated by RT-qPCR. A total of 62 mitochondria- and macrophage activation-related differentially expressed genes (M&MARDEGs) were identified. Nine key genes (IGF1, FTL, MAPK8, MAPK9, TF, CREB1, FAS, VEGFA and NFKB1) were retained in the final diagnostic model. Immune enrichment analysis suggested distinct immune-related transcriptional characteristics among different risk groups and molecular subtypes. RT-qPCR validation demonstrated that IGF1, FAS and MAPK9 were significantly downregulated, whereas FTL, TF, CREB1 and NFKB1 were significantly upregulated in the sarcopenia model group. MAPK8 and VEGFA showed decreasing trends without statistical significance. Integrated transcriptomic analysis identified key genes potentially associated with sarcopenia through the intersection of mitochondrial dysfunction and macrophage activation. These findings provide insights into the molecular characteristics of sarcopenia and may offer candidate targets for future mechanistic and translational studies.

PMID:42467925 | DOI:10.1049/syb2.70081

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Prophylactic clip closure for the prevention of delayed bleeding after colorectal endoscopic submucosal dissection: a systematic review and meta-analysis of randomized controlled trials

Eur J Gastroenterol Hepatol. 2026 Jun 12. doi: 10.1097/MEG.0000000000003234. Online ahead of print.

ABSTRACT

Prophylactic clip closure after endoscopic submucosal dissection (ESD) may be beneficial in the prevention of adverse events. In this meta-analysis of randomized controlled trials, we have evaluated the role of prophylactic clipping after ESD. We reviewed multiple databases from inception to 24 January 2026. Outcomes of interest included post-ESD bleeding, perforation, and post-ESD coagulation syndrome. Risk ratios with 95% confidence intervals (CIs) were calculated. Data were analyzed using a random-effects model. Heterogeneity was assessed using the I2 statistic. Five randomized controlled trials with 772 patients were included. Prophylactic clipping was associated with a lower risk of post-ESD bleeding (risk ratio: 0.35, 95% CI: 0.18, 0.65). There was no significant difference in risk of post-ESD coagulation syndrome (risk ratio: 1.06, 95% CI: 0.73, 1.53), and perforation (risk ratio: 0.72, 95% CI: 0.23, 2.30) between the groups. In conclusion, this meta-analysis demonstrates the benefits of prophylactic clipping after colorectal ESD in the prevention of post-ESD bleeding.

PMID:42467919 | DOI:10.1097/MEG.0000000000003234

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Divergent dietary thresholds for all-cause versus cardiovascular mortality in sarcopenia and advanced cardiovascular-kidney-metabolic syndrome: a national prospective cohort study

Singapore Med J. 2026 Jul 17. doi: 10.4103/singaporemedj.SMJ-2025-292. Online ahead of print.

ABSTRACT

INTRODUCTION: Sarcopenia and cardiovascular-kidney-metabolic (CKM) syndrome are common comorbidities. We evaluated their cumulative impact on all-cause and cardiovascular mortality, and the modifying effect of a Composite Dietary Antioxidant Index (CDAI).

METHODS: This prospective study used data from the National Health and Nutrition Examination Survey linked to the National Death Index. Sarcopenia (Foundation for the National Institutes of Health criteria) and CKM syndrome (American Heart Association stages, dichotomised into advanced/non-advanced) defined the primary exposure. Outcomes were all-cause and cardiovascular mortality. Cox models estimated hazard ratios (HRs). Maximally selected rank statistics determined optimal outcome-specific CDAI thresholds.

RESULTS: Among 8782 participants (median follow-up 131 months), advanced CKM syndrome was associated with sarcopenia (odds ratio 2.29, 95% confidence interval [CI] 1.48-3.53). This study demonstrated a cumulative risk of comorbid advanced CKM syndrome and sarcopenia on mortality, with this group exhibiting the highest risk for all-cause (HR 3.11, 95% CI 1.72-5.61) and cardiovascular (HR 1.80, 95% CI 1.04-3.12) mortality. Furthermore, we identified an inverse relationship between disease burden and protective CDAI thresholds for all-cause mortality, whereas cardiovascular mortality exhibited a distinctly higher threshold. Specifically, the comorbidity group required lower antioxidant intake (CDAI >-3.80) than the non-comorbidity group (CDAI >-1.19) for all-cause mortality. Conversely, cardiovascular mortality required a substantially higher threshold (CDAI >3.04).

CONCLUSION: Coexisting advanced CKM syndrome and sarcopenia present a significant cumulative mortality risk. Exploratory analyses suggest that this risk may be mitigated by dietary antioxidants, but the protective threshold is context-dependent. Modest dietary improvement was associated with improved all-cause survival in high-risk patients, whereas higher antioxidant intake correlated with better cardiovascular outcomes. These results suggest that precision nutrition strategies may vary depending on the specific health outcome.

PMID:42467916 | DOI:10.4103/singaporemedj.SMJ-2025-292

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Management of endoscopic rectal activity in ulcerative colitis: real-world adherence to guidelines and clinical outcomes

Eur J Gastroenterol Hepatol. 2026 Jun 2. doi: 10.1097/MEG.0000000000003228. Online ahead of print.

ABSTRACT

OBJECTIVE: Rectal disease activity in ulcerative colitis is associated with a high symptom burden. The British Society of Gastroenterology (BSG) provides evidence-based recommendations for the management of ulcerative proctitis, which are relevant to patients with rectal disease activity; however, real-world adherence and outcomes remains unclear. This study aimed to evaluate adherence to BSG guideline-recommended management and its relationship with treatment timing and clinical outcomes.

METHODS: We conducted a retrospective observational cohort study at a single tertiary center (2022-2024). Adults with endoscopically confirmed rectal disease activity in ulcerative colitis were included. Guideline adherence was assessed using predefined criteria derived from the BSG algorithm. Clinical, biochemical, endoscopic, and histological remission were evaluated at 12 months.

RESULTS: Of 119 patients, 63 (52.9%) received guideline-adherent management. Adherence was significantly higher when treatment decisions were made at endoscopy compared with deferral to clinic (73 vs. 22%, RR: 0.30, 95% CI: 0.16-0.51; P < 0.001). At 12 months, clinical remission was achieved in 97/119 (81.5%), biochemical remission in 80/96 (83.3%), endoscopic remission in 36/68 (52.9%), and histological remission in 30/68 (44.1%). Guideline-adherent management showed numerically higher clinical remission rates, though not statistically significant. Deferral of treatment decisions was associated with a lower rate of clinical remission (72 vs. 86%), although not statistically significant (P = 0.06).

CONCLUSION: Guideline adherence is suboptimal in real-world practice. Endoscopy-led decision-making were strongly associated with guideline adherence and represents a modifiable system-level factor in care delivery. High overall remission rates suggest that guideline adherence alone may be an incomplete surrogate for care quality.

PMID:42467913 | DOI:10.1097/MEG.0000000000003228

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The Efficacy of Hypnotherapy in Reducing Burnout and Related Psychopathologies: Protocol for a Systematic Review and Meta-Analysis

JMIR Res Protoc. 2026 Jul 17;15:e69733. doi: 10.2196/69733.

ABSTRACT

BACKGROUND: Hypnosis is a focused state of consciousness that enhances concentration, attention, and responsiveness to suggestion. It has shown efficacy in treating psychiatric disorders such as depression, anxiety, and posttraumatic stress disorder (PTSD). However, its potential for addressing burnout and related symptoms remains underexplored. This systematic review and meta-analysis aims to assess the effectiveness of hypnotherapy in alleviating symptoms of burnout and associated conditions, including depression, anxiety, and PTSD.

OBJECTIVE: This study aims to evaluate the efficacy of hypnotherapy in treating burnout and its related psychopathologies, including depression, anxiety, and PTSD.

METHODS: A comprehensive search was conducted across PubMed, Scopus, and PsycINFO for peer-reviewed, English-language observational and experimental studies published up to February 2024. Only studies with adults (>18 y) who received hypnotherapy for psychiatric symptoms will be included. Data extraction will focus on treatment effects related to burnout and associated psychiatric conditions. Statistical analysis will be performed using Comprehensive Meta-Analysis (version 4.0). A random-effects model will be used to account for heterogeneity, with Cochran Q and I² statistics used to assess variability. Subgroup analyses will explore moderators such as sociodemographic factors, country, and study quality. Sensitivity analyses will identify influential studies, and publication bias will be assessed using funnel plots and the Egger test. All analyses will be 2-sided (P<.05), and the results will be presented in forest plots.

RESULTS: The search strategy underwent a PRESS (Peer Review of Electronic Search Strategies) review in December 2023 and was registered in PROSPERO (International Prospective Register of Systematic Reviews) in January 2024. Database searches were completed between February and April 2024, followed by title and abstract screening from May to November 2024. Full-text screening began in December 2024, with data extraction conducted from January through April 2025. A preliminary narrative synthesis was completed between May and August 2025. Quantitative analysis began in September 2025 and is ongoing, with completion anticipated in early summer 2026. The final findings are expected to be submitted for publication by fall 2026.

CONCLUSIONS: This review aims to synthesize existing evidence on the potential role of hypnotherapy for burnout and related psychiatric symptoms. This systematic review will provide an updated synthesis of evidence on hypnotherapy for burnout and associated psychological outcomes. Limitations include variability in study designs and measurement tools. The results will be disseminated through peer-reviewed journals and scientific meetings to guide future clinical and research applications.

PMID:42467904 | DOI:10.2196/69733

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Development and Application of Lyophilized Bacillus Atrophaeus Spore Pellets as an Reference Material of Enumeration for Onsite Validation of Medical Sterilization Equipment

J Appl Microbiol. 2026 Jul 17:lxag180. doi: 10.1093/jambio/lxag180. Online ahead of print.

ABSTRACT

AIMS: To develop a user-friendly and portable reference material (RM) for onsite validation of medical sterilization equipment, addressing the limitations of conventional biological indicators that require specialized laboratory facilities.

METHODS AND RESULTS: A lyophilized microsphere-based RM containing Bacillus atrophaeus spores was developed by optimizing lyoprotectant formulation. The RM demonstrated excellent homogeneity (F statistic < F critical) and satisfactory stability over 14 days at 4°C and 25°C, rigorously according to ISO 33405: 2024 standard method. When applied to validate UV sterilization devices by quantifying viable spore reduction, it further provided precise and reliable log reduction value measurements. The simple reconstitute-and-culture procedure enabled non-specialists to perform onsite checks. For instance, in UV validation, optimal conditions (e.g., ≥3-log reduction within 30 min at a distance of 150 cm) were easily determined using this RM. Preliminary assessments also confirmed its applicability for ozone and ethylene oxide sterilizers.

CONCLUSIONS: This study presents the first preparation of a convenient, lyophilized spore RM that fulfills ISO 33405: 2024 criteria. Its successful application in validating multiple sterilization modalities demonstrates significant potential for routine quality control and compliance testing in healthcare settings, particularly where advanced laboratory facilities are unavailable.

PMID:42467903 | DOI:10.1093/jambio/lxag180

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Guidelines for home-based enzyme replacement therapy in children and adolescents with mucopolysaccharidosis: a scoping review

Rev Esc Enferm USP. 2026 Jul 17;60:e20250589. doi: 10.1590/1980-220X-REEUSP-2025-0589en. eCollection 2026.

ABSTRACT

OBJECTIVE: To identify and map the main guidelines for carrying out home-based enzyme replacement therapy (ERT) administered to children and adolescents diagnosed with mucopolysaccharidosis.

METHOD: A scoping review, conducted according to JBI Manual for Evidence Synthesis (Edition 2024). Twelve data sources were consulted using specific search strategies. Data were extracted using a specific form and analyzed using simple descriptive statistics and a qualitative PAGER approach.

RESULTS: The final sample consisted of 13 articles published between 2007 and 2020, mostly conducted in European countries, with a predominance of authors affiliated with the Royal Manchester Children’s Hospital. Five patterns were identified for consolidating qualified and safe care in the context of homebased ERT administered to children and adolescents with types I, II, IV-A, and VII mucopolysaccharidoses. The nurse emerges as an essential professional in all stages and activities presented.

CONCLUSION: Despite the progress made regarding guidelines for the decentralization of ERT, challenges to its implementation still persist, among which the need for dissemination of technical and scientific knowledge stands out.

PMID:42467880 | DOI:10.1590/1980-220X-REEUSP-2025-0589en

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Postshortage Compounded GLP-1 RA Market in 2 States With Potentially High Demand

JAMA Health Forum. 2026 Jul 2;7(7):e262207. doi: 10.1001/jamahealthforum.2026.2207.

ABSTRACT

IMPORTANCE: Supply-side challenges combined with high costs and limited insurance coverage led to a robust market for compounded glucagon-like peptide-1 receptor agonists (GLP-1 RAs). However, assessment of this market since the end of the semaglutide and tirzepatide shortages is needed.

OBJECTIVE: To characterize available compounded GLP-1 RA products, describe aspects of patient care and monitoring, and identify source pharmacies of available compounded products.

DESIGN, SETTING, AND PARTICIPANTS: From August to October 2025, a cross-sectional secret shopper study was conducted of brick-and-mortar weight-loss clinics and medical spas advertising GLP-1 RAs for weight loss and offering compounded GLP-1 RAs. These businesses were identified in January 2025 using a web mapping application to perform location-based searches that were supplemented with a review of business websites and publicly available data regarding compounding facilities. The businesses were located in 2 states (West Virginia and Oklahoma) with potentially high demand for compounded GLP-1 RAs that were purposively selected based on obesity rate and insurance mix.

MAIN OUTCOMES AND MEASURES: Compounded GLP-1 RAs offered by weight-loss clinics and medical spas; aspects of patient care and monitoring; and characteristics of compounding suppliers, including facility type, licensing status, objectionable conditions noted by investigators, and disciplinary actions.

RESULTS: A total of 75 weight-loss clinics and medical spas offering compounded GLP-1 RAs were identified and included in the analysis. Of these businesses, 7 (9.3%) reported offering oral compounded GLP-1 RA formulations and 42 (56.0%) reported offering compounded GLP-1 RA products combined with B vitamins. Twenty-three compounding facilities were identified as suppliers, 4 (of 21; 19.0%) of which were not licensed to perform sterile compounding. Since 2023, 1 facility (4.3%) had received multiple US Food and Drug Administration warning letters and 3 of 22 (13.6%) had been subject to state-level disciplinary action.

CONCLUSIONS AND RELEVANCE: Findings of this study show that, after the end of the semaglutide and tirzepatide shortages, compounding facilities have continued to manufacture GLP-1 RAs with added ingredients. Compounded GLP-1 RA sourcing is diverse but includes facilities without licenses to perform sterile compounding or that have been subject to recent disciplinary action, posing clinical and regulatory challenges.

PMID:42467450 | DOI:10.1001/jamahealthforum.2026.2207

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State Medicaid Bed-Hold Policies and Hospitalizations and ED Visits Among Long-Stay Nursing Home Residents

JAMA Health Forum. 2026 Jul 2;7(7):e262226. doi: 10.1001/jamahealthforum.2026.2226.

ABSTRACT

IMPORTANCE: Forty-three state Medicaid programs have bed-hold policies that reimburse nursing homes (NHs) to reserve a resident’s bed during a hospitalization or other temporary absence. Although bed-hold policies are intended to increase continuity of care, some evidence suggests they may incentivize NHs to hospitalize residents; however, these data are outdated, and the impact of bed-hold policies on resident outcomes remains understudied.

OBJECTIVE: To examine the association between Medicaid bed-hold policies and hospitalizations and emergency department (ED) visits among NH residents receiving long-term care.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study of long-stay NH residents in the US used claims data for a 20% national sample of Medicare fee-for-service beneficiaries from 2013 through 2018. Adjusted comparisons between states that did and did not adopt bed-hold policies were conducted using a staggered difference-in-differences design. Sensitivity analyses were conducted that (1) used composite outcomes combining death with hospitalization and ED visits, (2) restricted the sample to dually eligible residents, (3) excluded hospital-based NHs, (4) restricted the sample to NHs that were present for the entire study period, (5) restricted the sample to for-profit NHs, and (6) used alternate approaches to adjust standard errors. Data were analyzed between April and November 2025.

EXPOSURES: State adoption of a Medicaid bed-hold policy.

MAIN OUTCOMES AND MEASURES: Hospitalizations and ED visits in a given month were the 2 primary outcomes.

RESULTS: The sample included 219 719 long-stay NH residents (mean [SD] age, 80.2 [12.6] years; 67.2% female) in 22 states and the District of Columbia, of which 16 states adopted bed-hold policies. There were no significant changes in differences in resident and NH characteristics between those in states that did and did not adopt the policies from the pre- to the post-adoption period. Adjusted estimates did not show statistically significant changes in the likelihood of hospitalization (-0.1 percentage points [pp]; 95% CI, -0.3 to 0.1 pp; P = .41) or an ED visit (0.0 pp; 95% CI, -0.1 to 0.2 pp; P = .68) associated with adoption of bed-hold policies. Results of sensitivity analyses were consistent with the primary analyses.

CONCLUSIONS AND RELEVANCE: This cohort study found that states’ adoption of Medicaid bed-hold policies was not associated with hospitalizations or ED visits among long-stay NH residents, suggesting that the goal of bed-hold policies may not be undermined by increases in these events.

PMID:42467449 | DOI:10.1001/jamahealthforum.2026.2226