Nevin Manimala

JMIR Biomed Eng. 2025 Aug 20;10:e70938. doi: 10.2196/70938.

ABSTRACT

BACKGROUND: Accurately assessing pain severity is essential for effective pain treatment and desirable patient outcomes. In clinical settings, pain intensity assessment relies on self-reporting methods, which are subjective to individuals and impractical for noncommunicative or critically ill patients. Previous studies have attempted to measure pain objectively using physiological responses to an external pain stimulus, assuming that the participant is free of internal body pain. However, this approach does not reflect the situation in a clinical setting, where a patient subjected to an external pain stimulus may already be experiencing internal body pain.

OBJECTIVE: This study investigates the hypothesis that an individual’s physiological response to external pain varies in the presence of preexisting pain.

METHODS: We recruited 39 healthy participants aged 22-37 years, including 23 female and 16 male participants. Physiological signals, electrodermal activity, and electromyography were recorded while participants were subject to a combination of preexisting heat pain and cold pain stimuli. Feature engineering methods were applied to extract time-series features, and statistical analysis using ANOVA was conducted to assess significance.

RESULTS: We found that the preexisting pain influences the body’s physiological responses to an external pain stimulus. Several features-particularly those related to temporal statistics, successive differences, and distributions-showed statistically significant variation across varying preexisting pain conditions, with P values <.05 depending on the feature and stimulus.

CONCLUSIONS: Our findings suggest that preexisting pain alters the body’s physiological response to new pain stimuli, highlighting the importance of considering pain history in objective pain assessment models.

PMID:40834427 | DOI:10.2196/70938

JMIR Public Health Surveill. 2025 Aug 20;11:e71494. doi: 10.2196/71494.

ABSTRACT

BACKGROUND: Pre-exposure prophylaxis (PrEP) programs have been implemented in multiple countries. Evidence from clinical trials and cohort studies has proven the safety and effectiveness of PrEP. However, minimizing drug-related adverse effects and cost should be primarily considered in PrEP. Most trials used tenofovir combined with emtricitabine as the intervention; yet, the use of tenofovir disoproxil fumarate (TDF) (ie, Tenofovir) alone has not been thoroughly evaluated. Furthermore, the medication regimen in most trials was used every day, with a few studies proposing an optimal medication regimen for PrEP.

OBJECTIVE: This study was designed to systematically evaluate the preventive efficacy and safety profile of TDF-based PrEP in the Chinese population. We also aimed to explore medication compliance, changes in sexual behavior, and hazard factors of HIV infection.

METHODS: We conducted a pragmatic randomized controlled trial (RCT) to evaluate the effectiveness and safety of TDF for HIV PrEP. Participants were randomly assigned (1:1:1) to a time-driven group (TDF 300 mg administered orally once daily), an event-driven group (TDF 300 mg administered orally 24 to 48 h before sexual activity and 2 hours after sexual activity, not exceeding 300 mg within 24 h), or an untreated control group. The primary outcomes were the effectiveness and safety of TDF during periods of PrEP use. Secondary outcomes focused on the effectiveness of TDF among participants with good compliance during PrEP use. Tertiary outcomes included the risk factors of HIV infection and behavioral changes from PrEP initiation to the last visit. For ethical reasons, all participants received condoms and health education. This study was registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-13003849).

RESULTS: A total of 1914 participants underwent randomization. During the follow-up of 3513.5 person-years from June 2013 to May 2016, HIV seroconversion was observed in 30 persons (2.02 per 100 person-years) in the time-driven group (time-driven vs control group: hazard ratio [HR] 0.93, 95% CI 058-1.51; P=.78), 35 (1.73 per 100 person-years) in the event-driven group (event-driven group vs control group: HR 0.83, 95% CI 0.52-1.31; P=.42), and 37 (2.06 per 100 person-years) in the control group. Post hoc analysis showed that participants with good medication compliance reduced their HIV infection risk by 53% (P=.01) and event-driven medication with good compliance reduced the risk by 62% (P=.009). We recorded no severe adverse events during the trial. For tertiary outcomes, low medication compliance, sexual role, no condom use, and more number of sexual partners remained significantly associated with HIV risk.

CONCLUSIONS: The TDF-based PrEP is ineffective without good adherence. However, when medication compliance is achieved, event-driven dosing is recommended as an optimal PrEP regimen.

PMID:40834420 | DOI:10.2196/71494

JMIR Infodemiology. 2025 Aug 20;5:e67825. doi: 10.2196/67825.

ABSTRACT

BACKGROUND: Antimicrobial resistance (AMR) is a major global health issue heavily influenced by human behavior. Effective communication and awareness-raising are crucial in curbing AMR, with social network sites (SNSs) significantly shaping health behaviors. Despite their potential, current analyses of AMR on SNSs have focused mainly on top-down communication initiatives.

OBJECTIVE: This study aims to examine AMR on Instagram (Meta Platforms), identifying key actors, content themes, and the nature of the communication to understand how AMR is portrayed and perceived.

METHODS: Based on the sender-message-channel-receiver model, this study used content analysis to review publicly accessible posts on Instagram. The data refer to 24 months, focusing on the hashtag “#antibioticresistance.” After cleaning the data, 610 posts (10% of the total 6105) were analyzed.

RESULTS: Content creators were predominantly information drivers or professionals in science and health. Posts frequently featured text-dominated visuals or images of bacteria and laboratory tests. However, the AMR posts were found to be siloed, with limited engagement beyond specific interest groups. The study highlighted the neutrality and accuracy of the content but noted the challenge of reaching a broader audience.

CONCLUSIONS: While Instagram serves as a platform for accurate and informative AMR communication, the post of it remains confined to niche groups, limiting its broader impact. To enhance engagement, AMR discussions should be integrated into more general interest content, use visually compelling formats, and encourage institutional participation and interactive user engagement.

PMID:40834419 | DOI:10.2196/67825

J Proteome Res. 2025 Aug 20. doi: 10.1021/acs.jproteome.5c00075. Online ahead of print.

ABSTRACT

Hypertensive nephropathy (HN) complicates hypertension with subtle early symptoms, hindering diagnosis. To address this, an integrated urinary metabolomics and peptidomics analysis was conducted comparing HN patients to hypertensive (HTN) controls, aiming to identify molecular signatures indicative of disease progression and clarify the pathophysiological mechanisms driving HN development. Urine samples were analyzed from both discovery (51 HTN vs 51 HN patients, including 27 early stage and 24 advanced-stage) and validation (21 HTN vs 21 HN) cohorts. Multivariate statistical analysis identified 40 differential metabolites across various stages: hypertension, early stage HN, and advanced-stage HN. These metabolites were associated with metabolic pathways including amino acid, carbohydrate, short-chain fatty acid, and nucleotide metabolism, such as cysteine and methionine, tyrosine, and nicotinate metabolism. Moreover, 10 differential urinary peptides were linked to coagulation regulation, immune processes, and plasminogen activation. Combining 43 clinical-correlated molecules, a high-performance diagnostic model was developed, demonstrating remarkable discrimination: AUCs of 0.973 (HTN vs early-HN), 0.998 (HTN vs advanced-HN), and 0.941 (early vs advanced-HN) in the discovery cohort, which were maintained at 0.847-0.970 in validation. Advanced-HN detection achieved exceptional accuracy (90.5%), specificity (95.2%), precision (94.7%), and an F1-score of 0.900. These urinary biomarkers aid HN diagnosis and advance mechanistic understanding.

PMID:40834388 | DOI:10.1021/acs.jproteome.5c00075

Pancreas. 2025 Aug 21. doi: 10.1097/MPA.0000000000002556. Online ahead of print.

ABSTRACT

INTRODUCTION: Schwannomas, paragangliomas, and gangliocytic paragangliomas are rare tumors of the pancreas and peripancreas. Diagnosis and management of these tumors remain challenging.

METHODS: A retrospective review was conducted at a single institution. Nineteen cases were identified from 1990 to 2022. Descriptive statistics summarized the demographic, clinicopathologic, and long-term outcome data.

RESULTS: Schwannomas were encountered within the pancreatic parenchyma, whereas half of the paragangliomas were intraparenchymal and the other half were in the peripancreatic connective tissue. Symptoms varied and occurred in half of the patients encountered. Imaging characteristics were nonspecific. When obtained, EUS-FNA (n=16) and nuclear imaging (n=3) assisted with making a preoperative diagnosis. Intraparenchymal tumors were predominantly managed with a pancreatectomy (n=12) while tumors in the peripancreatic connective tissue were managed with tumor resection without a pancreatectomy (n=4). The median follow-up for Schwannomas and gangliocytic paragangliomas was 66.8 and 13.6 months, respectively, during which time zero recurrences occurred. Paraganglioma patients had a median follow-up of 21.4 months, and tumor recurrence was encountered in 50% of patients.

CONCLUSION: Schwannomas and gangliocytic paragangliomas are benign tumors. Paragangliomas have malignant potential and should be managed with an oncologic resection. Accurate preoperative diagnosis using EUS-FNA and nuclear imaging is crucial for recommending the appropriate surgical intervention and minimizing surgical morbidity.

PMID:40834354 | DOI:10.1097/MPA.0000000000002556

Neurology. 2025 Sep 9;105(5):e213984. doi: 10.1212/WNL.0000000000213984. Epub 2025 Aug 20.

ABSTRACT

BACKGROUND AND OBJECTIVES: The most common cause of convexity subarachnoid hemorrhage (cSAH) in younger patients (younger than 60 years) is reversible cerebral vasoconstriction syndrome (RCVS). Evidence on the long-term outcomes of future vascular events and functional outcome after cSAH due to RCVS is limited. We aimed to assess the rates and baseline predictors of our primary outcomes (cSAH, intracerebral hemorrhage (ICH), and ischemic stroke), functional outcome, and mortality after cSAH attributed to RCVS.

METHODS: Individual patient data pooled analysis in patients with cSAH attributed to RCVS. A systematic literature search was conducted in PubMed and EMBASE. Two independent reviewers screened studies and extracted data. Quality assessment was assessed using the Newcastle-Ottawa Scale. Early events during the accepted time frame of an RCVS episode (<3 months) were classified as progression rather than recurrence. Follow-up was truncated at 5 years. Primary outcomes were recurrent cSAH, ICH, and ischemic stroke. Secondary outcomes were mortality and functional status measured by modified Rankin Score (mRS).

RESULTS: We identified 21 eligible cohorts finally including 138 patients from 9 collaborative centers, which provided individual patient data. The mean age was 49.3 ± 12.1 years, and 110 (79.7%) were female. During a mean follow-up of 1.8 years, annual rates were cSAH recurrence 0.81% (95% CI 0.1-2.91), ICH 0.81% (95% CI 0.1-2.91), and ischemic stroke 0.81% (95% CI 0.1-2.91). Progression during the initial episode (shortly after admission) occurred in 10 patients for cSAH, 2 for ICH, and 8 for ischemic stroke, respectively. Of 106 patients (76.8%) with available outcome data, 100 (94.3%) achieve a mRS of ≤1 at follow-up, indicating no significant disability. Two patients died (annual rate 0.5%, 95% CI 0.09-2.9): one within 10 days and the other within 2 months of the cSAH.

DISCUSSION: Our data suggest a favorable prognosis for most patients after RCVS-associated cSAH with low rates of recurrent events and a high proportion achieving functional independence. Major limitations include retrospective data collection and potential selection bias from centers providing individual patient data. Nevertheless, these findings provide prognostic information to inform clinical practice.

PMID:40834342 | DOI:10.1212/WNL.0000000000213984

Prehosp Emerg Care. 2025 Aug 20:1-16. doi: 10.1080/10903127.2025.2547651. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate video-assisted dispatcher cardiopulmonary resuscitation (CPR) versus audio-assisted dispatcher CPR effects on compression quality in simulated out-of-hospital cardiac arrest (OHCA) scenarios.

METHODS: Network meta-analysis of randomized controlled trials (RCTs) comparing video-assisted dispatcher CPR (V-DACPR) versus audio-assisted dispatcher CPR (A-DACPR) and control. Primary outcome was compression rate; secondary outcomes included compression depth, time to first compression, and interruption time. Network meta-analysis of randomized controlled trials comparing dispatcher-guided CPR with video feedback versus telephone-only instructions in simulated out-of-hospital cardiac arrest scenarios using high-fidelity manikins. Three intervention arms were compared: video-assisted CPR, audio-assisted CPR, and unguided CPR (control). Standardized mean differences (SMD) and Surface Under the Cumulative Ranking curve (SUCRA) were calculated using Bayesian network meta-analysis methodology. Primary outcome was compression rate; secondary outcomes included compression depth, time to first compression, and interruption time.

RESULTS: Fifteen trials (n = 1,556) were analyzed. V-DACPR showed superior compression rates versus A-DACPR (effect size: -21.37, 95% CI: -36.10, -7.41) and control (-43.04, 95% CI: -63.05, -22.52). V-DACPR demonstrated better time to first compression versus control (-42.23, 95% CI: -83.31, -1.42) and favorable trends in compression depth (-5.06, 95% CI: -12.40 to 2.12) and interruption time, though several comparisons between V-DACPR and A-DACPR did not reach statistical significance. Heterogeneity was low to moderate (I²=12-63%). CINeMA assessment supported moderate to high-quality evidence.

CONCLUSIONS: Video-assisted dispatcher cardiopulmonary resuscitation (CPR) demonstrated significant advantages in compression rate in simulated scenarios, with favorable trends in other quality metrics compared to A-DACPR. These findings support the potential for video assistance technology in dispatcher-guided CPR, particularly for optimizing compression rates. However, these results were observed in simulation studies and require validation in real-world clinical settings to determine their impact on patient outcomes.

PMID:40834332 | DOI:10.1080/10903127.2025.2547651

JCO Precis Oncol. 2025 Aug;9:e2500406. doi: 10.1200/PO-25-00406. Epub 2025 Aug 20.

ABSTRACT

PURPOSE: Biopsy tissue-based genomic classifiers (GCs) for prostate cancer are commercially available tools to enhance prognostication. They may corroborate candidacy for active surveillance/watchful waiting (AS/WW) or identify men who are more likely to benefit from radiotherapy (RT) with androgen deprivation therapy (ADT). We analyze real-world use of GC and associations with clinical decision making.

PATIENTS AND METHODS: We examined US commercial (n = 134,561) and Medicare (n = 68,431) insurance claims of men with newly diagnosed, localized prostate cancer between 2013 and 2022. We evaluated utilization of GCs over time and compared use of AS/WW, RT with or without ADT, radical prostatectomy (RP), or focal ablative therapy (FT) based on the receipt and type of GC.

RESULTS: GC utilization increased from <1% to 17% in 8 years with a median payment of $3,001 (IQR, $0-3,873). Younger age, higher median household income, and high-deductible health insurance were associated with higher odds of receiving a GC (all P < .001). Patients with GC were more likely to pursue AS/WW than treatment (odds ratio, 2.00 [95% CI, 1.85 to 2.1]; P < .001). Patients receiving OncotypeDX, Prolaris, and Decipher were most likely to pursue AS/WW, RP, and RT with ADT, respectively (all P < .001). Prolaris was ordered more than three times as often in Detroit as in any other city, whereas OncotypeDx was ordered more than twice as often in New York City as in any other city.

CONCLUSION: We show contemporary, real-world GC utilization trends, costs, and associations with treatment patterns. Prospective trials are ongoing to validate GC-informed treatment, but US uptake has expanded and management is associated with the use and type of GC.

PMID:40834325 | DOI:10.1200/PO-25-00406

J Econ Entomol. 2025 Aug 20:toaf210. doi: 10.1093/jee/toaf210. Online ahead of print.

ABSTRACT

Dietary-administered probiotics may address poor health and performance in honey bees (Apis mellifera L. [Hymenoptera: Apidae]). Human-grade probiotics are an affordable source of general probiotics. We examined the effects of human-grade probiotics by comparing colony and individual level health and performance between colonies administered a probiotic every other week, and those not given probiotic supplementation (control treatment group). We found that probiotics did not statistically increase individual honey bee health and performance as measured by body lipid level, tibial length, and weight of bees, nor colony performance as measured by monthly assessments of brood area, colony weight, and Varroa destructor Anderson and Trueman (Mesostigmata: Varroidae) mite infestation rate.

PMID:40834321 | DOI:10.1093/jee/toaf210

N Engl J Med. 2025 Aug 21;393(8):764-773. doi: 10.1056/NEJMoa2410542.

ABSTRACT

BACKGROUND: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by progressive surfactant accumulation and hypoxemia caused by autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), which alveolar macrophages require to clear surfactant. Molgramostim is a formulation of inhaled recombinant human GM-CSF, but its efficacy and safety in patients with aPAP have not been studied sufficiently.

METHODS: In this phase 3, double-blind, placebo-controlled trial, we randomly assigned patients with aPAP to receive molgramostim at a dose of 300 μg or placebo once daily for 48 weeks. The primary end point was the change from baseline to week 24 in the diffusing capacity of the lungs for carbon monoxide (DLCO), which was adjusted for hemoglobin concentration and expressed as a percentage of the predicted value. Secondary end points adjusted for multiplicity were the change from baseline in DLCO at 48 weeks and the change from baseline in the St. George’s Respiratory Questionnaire total (SGRQ-T) and activity (SGRQ-A) scores (scores range from 0 to 100, with lower scores indicating better quality of life) and in exercise capacity at 24 and 48 weeks.

RESULTS: A total of 164 patients underwent randomization: 81 were assigned to receive molgramostim and 83 to receive placebo. The least-squares mean change in DLCO from baseline to week 24 was 9.8 percentage points (95% confidence interval [CI], 7.3 to 12.3) with molgramostim and 3.8 percentage points (95% CI, 1.4 to 6.3) with placebo (estimated treatment difference, 6.0 percentage points; 95% CI, 2.5 to 9.4; P<0.001). The least-squares mean change in DLCO from baseline to week 48 was 11.6 percentage points (95% CI, 8.7 to 14.5) with molgramostim and 4.7 percentage points (95% CI, 1.8 to 7.6) with placebo (P<0.001), and the least-squares mean change in the SGRQ-T score at week 24 was -11.5 points (95% CI, -15.0 to -8.0) and -4.9 points (95% CI, -8.3 to -1.5), respectively (P = 0.007). No significant between-group difference in the change in SGRQ-A score was observed at 24 weeks, so no statistical inference was drawn with respect to subsequent secondary end points. The percentage of patients with at least one adverse event and the percentage with at least one serious adverse event were similar in the two groups.

CONCLUSIONS: Once-daily inhaled molgramostim led to a greater increase in pulmonary gas transfer than placebo in patients with aPAP. (Funded by Savara; IMPALA-2 ClinicalTrials.gov number, NCT04544293; European Union Clinical Trials Information System number, 2024-511052-41-00.).

PMID:40834301 | DOI:10.1056/NEJMoa2410542