Nevin Manimala

Blood Adv. 2025 Aug 12:bloodadvances.2025017004. doi: 10.1182/bloodadvances.2025017004. Online ahead of print.

ABSTRACT

Atypical hemolytic uremic syndrome (aHUS), a life-threatening complement-mediated disorder, is now treatable with terminal complement inhibitors like eculizumab. Although effective, these therapies are costly and increase susceptibility to infections, notably meningococcal disease, raising concerns about long-term use. The optimal duration of complement inhibition remains unclear, prompting efforts to explore the possibility of treatment discontinuation. We conducted a systematic review and meta-analysis to evaluate the benefits and risks of stopping terminal complement inhibitor therapy in aHUS. We searched PubMed, Scopus, and CINAHL for studies of continuing vs. stopping anti-complement treatment in aHUS. Of 3303 identified studies, 13 observational studies (3 case-control, 10 cohort) comprising 584 patients were included. Overall, continuing treatment was associated with an approximately 76% reduction in the odds of relapse (odds ratio [OR] 0.24, 95% CI: 0.09 to 0.62; p= 0.01.) Study design influenced results: cohort studies showed a more modest effect (OR=0.40 (95% CI: 0.15 to 1.09), while case-control studies reported inflated estimates (OR=0.04 (95%CI: 0.02 to 0.08); subgroup interaction p=0.03). Patients with various genetic variants [CFH, CFHdel, MCP] had decreased relapse with continued therapy when case-control studies were included in the analysis. When the analysis was restricted to cohort studies, the effects became uncertain [statistically non-significant with large confidence intervals]. While current evidence is insufficient to provide personalized guidance on which patients with aHUS can safely discontinue anti-complement therapy, findings from higher-quality studies-which show no statistical difference between continued and discontinued treatment-suggest that discontinuation may be possible for at least some patients.

PMID:40795230 | DOI:10.1182/bloodadvances.2025017004

J Antimicrob Chemother. 2025 Aug 7:dkaf295. doi: 10.1093/jac/dkaf295. Online ahead of print.

ABSTRACT

OBJECTIVES: The spread of carbapenem-resistant Gram-negative bacteria (CR-GNB) related to nosocomial infections is an important public health challenge, and polymyxins have become the last line of defence against CR-GNB. In this study, we aimed to compare the efficacy and safety of different polymyxins.

METHODS: This retrospective cohort study included neurocritical care patients with CR-GNB pneumonia. The efficacy and safety were compared in original and inverse probability of treatment weighting cohorts. A subgroup analysis was further conducted to explore the impact of augmented renal clearance status at baseline on treatment efficacy.

RESULTS: Of the 331 patients included, 90 received colistin sulphate, 187 received polymyxin B, and 54 received colistin methanesulfonate sodium. Compared with colistin sulphate, colistin methanesulfonate sodium significantly reduced the clinical failure rate on Day 7 (20.8% versus 37.2%, P = 0.034) and 28-day mortality rate (6.2% versus 16.9%, P = 0.013) and improved the microbiological eradication rate on Day 28 (94.8% versus 84.2%, P = 0.013). The colistin methanesulfonate sodium group also had a lower mortality rate (6.2% versus 15.7%, P = 0.005) and clinical failure rate on Day 28 (17.1% versus 27.4%, P = 0.020) than the polymyxin B group. However, colistin methanesulfonate sodium was more nephrotoxic than colistin sulphate and polymyxin B (P = 0.001 and P = 0.004, respectively). Subgroup analysis revealed no statistical difference in clinical failure rate and mortality risk between the three groups.

CONCLUSIONS: For CR-GNB pneumonia in neurocritical care patients, intravenous colistin methanesulfonate sodium may provide a useful treatment option, but vigilance is warranted for nephrotoxicity.

PMID:40795180 | DOI:10.1093/jac/dkaf295

Subst Use Misuse. 2025 Aug 12:1-10. doi: 10.1080/10826084.2025.2546505. Online ahead of print.

ABSTRACT

BACKGROUND: The Centers for Disease Control and Prevention offered a multicomponent intervention called Local Opioid Overdose Prevention and Response (LOOPR). Five sites (Bell, KY, Boone, WV, Manchester, NH, St. Francois, MO, and Ware, GA) were selected to implement academic detailing (AD). AD is a strategy for communicating safer opioid prescribing practices to clinicians. This is the first study to assess changes in county-level opioid prescribing behaviors after implementing a multicomponent prevention program emphasizing AD.

OBJECTIVES: We examined three opioid prescribing behaviors (percentage of opioid prescribers in the top centile nationally, opioid prescribing rate, and average number of opioid prescriptions per prescriber) before and after program implementation in each site and a paired control. We used paired interrupted time series to examine the effect of LOOPR on each outcome for each site and control.

RESULTS: Five jurisdictions incorporated AD as part of LOOPR. In addition, Bell County, KY implemented three other interventions (coalition establishment, communication campaign, and community-based overdose prevention program). Manchester City, NH (community-based overdose prevention program and public health/public safety partnership) and St. Francois, MO (communication campaign and public health/public safety partnership) implemented two additional interventions. Boone County, WV and Ware County, GA only incorporated AD. Though not always statistically significant, all sites showed decreasing or stabilizing trends after implementation of LOOPR for most outcomes.

CONCLUSIONS/IMPORTANCE: This study shows AD is a versatile strategy and customizable activity that can be implemented in many settings as a separate activity or integrated with various prevention programs, making it particularly suitable for community-level interventions.

PMID:40795158 | DOI:10.1080/10826084.2025.2546505

J Public Health (Oxf). 2025 Aug 7:fdaf092. doi: 10.1093/pubmed/fdaf092. Online ahead of print.

ABSTRACT

BACKGROUND: Migration involves a risk of mental health problems, including stress, anxiety, and depression. This study systematically reviewed social determinants of mental health problems among South Asian migrants living in industrialized countries.

METHODS: Four databases (PubMed, CINAHL, EMBASE, and PsycINFO) were searched for observational studies published between 2000 and 2025. The social ecological model was used as a theoretical framework. Studies that included adult South Asian migrants using validated mental health tools were included. Social determinants of mental health were identified through extraction of social factors that demonstrated statistically significant associations with mental health problems. The study protocol was registered in PROSPERO and followed PRISMA guidelines.

RESULTS: Seventeen studies met the inclusion criteria. The prevalence of stress, anxiety, and depression ranged from 23% to 59%, 20% to 50%, and 9% to 47%, respectively. Common social determinants of mental health problems were age, gender, marital status, social support, language, education, and employment. Being older, female, unmarried, or unemployed or having less social support or lower education, or facing language barriers were major factors influencing mental health problems.

CONCLUSIONS: The findings warrant the development and implementation of policies focused on addressing these social determinants of mental health problems and improving access to and utilization of mental health services.

PMID:40795145 | DOI:10.1093/pubmed/fdaf092

Eur Heart J. 2025 Aug 7:ehaf441. doi: 10.1093/eurheartj/ehaf441. Online ahead of print.

NO ABSTRACT

PMID:40795129 | DOI:10.1093/eurheartj/ehaf441

JAMA Netw Open. 2025 Aug 1;8(8):e2526418. doi: 10.1001/jamanetworkopen.2025.26418.

NO ABSTRACT

PMID:40794411 | DOI:10.1001/jamanetworkopen.2025.26418

JAMA Netw Open. 2025 Aug 1;8(8):e2526616. doi: 10.1001/jamanetworkopen.2025.26616.

ABSTRACT

IMPORTANCE: Pulmonary rehabilitation (PR) improves exercise tolerance, symptom burden, and health-related quality of life for people with chronic respiratory conditions. However, demand for PR outstrips supply. Traditionally, PR has been delivered using specialist, gym-based exercise equipment.

OBJECTIVE: To investigate whether PR using minimal equipment (PR-min) is noninferior to PR using specialist gym exercise equipment (PR-gym).

DESIGN, SETTINGS, AND PARTICIPANTS: This parallel, 2-group, assessor- and statistician-blinded, noninferiority randomized clinical trial compared PR-min with PR-gym. Eligible participants were people with chronic respiratory disease referred for PR to the Regional Pulmonary Rehabilitation Unit in northwest London, UK. Recruitment occurred from October 15, 2018, to December 21, 2021, with a final follow-up to December 14, 2022. Randomization was by an independent web-based system using minimization with 1:1 allocation. Data analysis was performed from May 2023 to January 2025.

INTERVENTIONS: Both PR programs comprised 2 in-person, outpatient supervised sessions per week for 8 weeks. PR-min used minimal equipment (eg, walking circuit and body weight exercises), whereas PR-gym used specialist exercise equipment (eg, treadmills and weights machines).

MAIN OUTCOMES AND MEASURES: The primary outcome was change in incremental shuttle walk (ISW) distance after PR (ie, at 8 weeks; with a predefined noninferiority margin of -24 m). Secondary outcomes included dyspnea, health-related quality of life, costs, and adverse events.

RESULTS: A total of 436 participants (median [IQR] age, 71.7 [63.2-77.7] years; 239 [54.8%] male) were enrolled, with 218 randomized to PR-min and 218 to PR-gym. At 8 weeks, PR-min (n = 136) and PR-gym (n = 130) demonstrated significant improvements in ISW distance with no significant between-group difference in ISW distance change (mean, 1.7 m; 1-sided 97.5% CI lower bound, -16.8), which was within the -24-m noninferiority margin. The intention-to-treat analysis and a robust range of sensitivity analyses all demonstrated that PR-min was noninferior to PR-gym. Similar findings were observed for dyspnea and health-related quality of life. No excess adverse events or costs were seen with intervention.

CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that PR-min demonstrated noninferiority to PR-gym for exercise capacity, dyspnea, and health-related quality of life. PR-min can expand the number of settings where PR can be provided, thus improving patient accessibility.

TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN16196765.

PMID:40794408 | DOI:10.1001/jamanetworkopen.2025.26616

J Mol Neurosci. 2025 Aug 12;75(3):105. doi: 10.1007/s12031-025-02399-4.

ABSTRACT

This study aimed to investigate the effects of a histamine-reducing diet on five developmental domains in autism spectrum disorder subjects and the impact of variants in the AOC1 and HNMT genes on the therapeutic outcomes. Four genetic variants (rs2052129, rs10156191, rs1049742, and rs11558538) in AOC1 and HNMT were genotyped in 400 Bulgarian children with ASD. Genotype and allele frequencies were compared to control data from the GnomAD database. Further analysis was conducted on 91 ASD subjects with elevated histamine who followed the histamine-reducing diet. Significant improvements were observed across all developmental domains measured by the DP-3 test, including physical, adaptive behavior, social-emotional, cognitive, and communication skills. Paired samples T-tests indicated statistically significant increases in all categories (p < 0.001), with physical scores increasing from 82.29 to 89.18, adaptive behavior from 72.68 to 81.35, social-emotional from 71.43 to 80.22, cognitive from 69.33 to 78.66, and communication from 67.36 to 77.54. Minor allele carriers exhibited lower mean improvements across each of the five developmental parameters compared to wild-type carriers, with mean reductions of 0.90 for rs2052129, 0.70 for rs10156191, 2.07 for rs1049742, and 1.94 for rs11558538. These findings highlight the potential role of histamine regulation in autism spectrum disorder, the impact of variants in the AOC1 and HNMT genes on the therapeutic outcome and suggest dietary management as a viable intervention to improve developmental outcomes.

PMID:40794387 | DOI:10.1007/s12031-025-02399-4

Curr Top Behav Neurosci. 2025 Aug 13. doi: 10.1007/7854_2025_596. Online ahead of print.

ABSTRACT

Like other medical illnesses, psychiatric conditions are defined by the presence of characteristic signs and symptoms that cause distress and dysfunction. Unlike most medical illnesses, however, the pathophysiological mechanisms underlying psychiatric symptoms remain largely unknown. Recent work in theory-driven computational neuroscience has proposed a unified account of how organisms derive estimates of both external and internal states by integrating prior beliefs with sensory input. This framework offers a powerful means of explaining typical perception and action, while also identifying how these processes may go awry to produce a panoply of psychiatric symptoms. Disruptions in this inferential process, which we term perceptual dysregulation, span exteroceptive, proprioceptive, and interoceptive systems and manifest across conditions ranging from psychosis and autism to anxiety and trauma-related disorders, functional neurological disorder, and dementia. This volume reviews emerging evidence for maladaptive sensory inference across psychiatric and neurological illness and explores how computational models based on Bayesian statistics can illuminate shared mechanisms beneath diverse symptom presentations. We argue that targeting perceptual dysregulation may not only enable new interventions but also catalyze the development of a revised psychiatric nosology grounded in testable models of brain-body interaction.

PMID:40794380 | DOI:10.1007/7854_2025_596

Metabolomics. 2025 Aug 12;21(5):111. doi: 10.1007/s11306-025-02316-1.

ABSTRACT

INTRODUCTION: Myocardial revascularization (MR) is recommended in acute myocardial infarction. Understanding the physiological disturbances caused by MR may be pertinent for future therapeutic strategies in the postoperative period.

OBJECTIVES: This study aims to analyze the MR impact on plasma metabolites and investigate potential correlations between them with routinely measured biochemical and clinical parameters in MR, and with the cardiopulmonary bypass time (CPB).

METHODS: Twenty-five patients had plasma samples collected before and after MR for metabolomic analysis, performed by liquid chromatography coupled with high-resolution mass spectrometry.

RESULTS: One hundred eleven ions showed statistically significant differences due to MR and thirteen were identified. Only Pregnenolone Sulfate had its abundance in plasma decreased due to MR. Hydrocortisone succinate, Cortisone, and Corticosterone increased in response to the glucocorticoids administered during surgery. LysoPS 16:1, LysoPC 14:0, Phenylvaleric acid, 13-Hydroxyoctadecadienoic acid, N-Linoleoyl Glutamine, and N-Myristoyl Methionine, along with the significant increase in the white blood cell count are associated with inflammation processes, possibly caused by MR. Furthermore, Pregnenolone sulfate, Pentosidine, Phenylvaleric acid, and N-Myristoyl Methionine were correlated with biochemical/clinical parameters and CPB.

CONCLUSION: These results open new horizons in the interpretation of physiological disturbances caused by MR, as well as provide support for future studies. The scientific community is invited to build upon the outcomes obtained to confirm the associations suggested in this study, advancing the realm of metabolomics and MR.

PMID:40794378 | DOI:10.1007/s11306-025-02316-1