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Nevin Manimala Statistics

Mediation Analysis to Identify Individual Component Effects of the Care Bundle to Improve Functional Outcome After ICH in the INTERACT3 Study

Neurology. 2025 Oct;105(7):e214070. doi: 10.1212/WNL.0000000000214070. Epub 2025 Sep 12.

ABSTRACT

BACKGROUND AND OBJECTIVES: The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT3) showed that the implementation of a care bundle improves the functional outcome of patients who experience acute intracerebral hemorrhage (ICH). However, uncertainty exists over the relative contribution of each component of the care bundle for the benefit.

METHODS: INTERACT3 used a stepped-wedge, cluster randomized controlled trial design, which was conducted in 5 lower and 4 upper middle-income countries and 1 high-income country. Compared with usual care, there was a statistically significant beneficial effect of the intervention, a care bundle comprising early control of elevated blood pressure (BP), glucose, and temperature and reversal of warfarin-related anticoagulation, on the primary outcome of functional recovery of ICH. We performed a model-based causal mediation analysis to assess the contribution of each component of the care bundle to the overall effect, as measured by the modified Rankin Scale (mRS) at 6 months after randomization. The mediation analysis considered whether protocol-specified treatment targets were reached as well as the actual achieved levels of physiologic control according to the summary measures of systolic BP (mean, variation over 1-24 hours, and reduction in 1 hour) and mean of blood glucose, body temperature, and international normalized ratio over 24 hours. The analyses were performed in the modified intention-to-treat population with available mRS data.

RESULTS: A total of 6,225 patients (mean age 61.9 years [SD 12.6], 2,284 women [36.5%]) with available primary outcome data were included in these analyses. Overall, only the control of BP and blood glucose contributed positively to the beneficial effect, with mediated proportions of 8.9% (95% CI 4.8-20.0) and 7.0% (1.1-17.0) for achieved systolic BP and blood glucose over 24 hours after randomization, respectively, and 4.0% (1.2-14.0) and 7.6% (2.2-15.0) for reaching the specified targets for systolic BP and blood glucose, respectively.

DISCUSSION: The major contributors to the effectiveness of the care bundle in INTERACT3 for improved functional outcomes after acute ICH were the control of systolic BP and blood glucose, as indicated by both the achieved levels and protocol targets being met.

TRIAL REGISTRATION INFORMATION: The name of the registry is “the Third, Intensive Care Bundle With Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT3).” This trial was submitted for registration at ClinicalTrials.gov (NCT03209258) on July 1, 2017, and the Chinese Clinical Trial Registry (ChiCTR-IOC-17011787) on June 28, 2017. The first patient was enrolled on December 12, 2017.

PMID:40939125 | DOI:10.1212/WNL.0000000000214070

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Nevin Manimala Statistics

Impacts of Climate, Organic Management, and Degradation Status on Soil Biodiversity in Agroecosystems Worldwide

Glob Chang Biol. 2025 Sep;31(9):e70486. doi: 10.1111/gcb.70486.

ABSTRACT

Unsustainable soil management, climate change, and land degradation jeopardize soil biodiversity and soil-mediated ecosystem functions. Although the transition from conventional to organic agriculture has been proposed as a potential solution to alleviate these pressures, there is limited evidence of its effectiveness in enhancing belowground biodiversity across different biogeographical regions, climates, and land degradation levels. In this study, we holistically assessed the status of soil biodiversity, from microorganisms to meso- and macrofauna, in agroecosystems distributed across four continents. We identified the primary environmental community composition drivers and assessed the effects of the transition from conventional to organic management (no chemical inputs) on soil ecology. Our findings highlight the mean temperature and precipitation of the warmest and coldest quarters of the year, aridity, pH, and soil texture as the primary drivers of the different soil biodiversity components. Overall, organic farming has a significant but small impact on soil biodiversity compared to the other community drivers. On top of that, the results demonstrate the importance of a regional-specific context for a future generalized transition towards organic soil management. Specifically, under the most arid conditions in our study, organic management showed potential to buffer biodiversity loss in highly degraded soils, with a significant increase in diversity for prokaryotes and protists compared to conventionally managed soils. Therefore, the combination of a global and, simultaneously, regional-specific approach supports the hypothesis that a shift towards organic agriculture would maximize its beneficial impact on belowground diversity in highly degraded soils under arid conditions over the coming years, being a crucial tool to increase resilience and adaptation to global change for agriculture.

PMID:40939096 | DOI:10.1111/gcb.70486

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Nevin Manimala Statistics

The Cerebral Haemorrhage and SARS-CoV-2: An Emerging Virus From a Meta-Analysis Perspective

Rev Med Virol. 2025 Sep;35(5):e70069. doi: 10.1002/rmv.70069.

ABSTRACT

The central nervous system is a potential target of the COVID-19 virus, and one of the devastating neurological consequences of this infection is cerebral haemorrhage (ICH). Cerebral haemorrhage is a leading cause of death worldwide. This study aimed to systematically review and analyse the existing literature on this topic and provide insights into the potential neurological consequences of COVID-19. A comprehensive search was conducted across the PubMed, Scopus, Web of Science, and Embase databases to extract relevant published data up to February 2025. This meta-analysis included 11 studies involving a total of 197,060 individuals. Subgroup analyses were performed based on the year of publication, hospital sampling wards, and study design. A critical appraisal was carried out using the Newcastle-Ottawa Scale (NOS) score. Risk was utilised as a measure of pooled effect size based on a random-effects model. In this analysis, we identified 11 articles that directly assessed the risk of cerebral haemorrhage. The reported risk of cerebral haemorrhage was five cases per 10,000 COVID-19 patients [0.005 (95% CI: 0.002-0.009), p < 0.001]. Notably, studies published in 2022 and 2023 indicated a significantly higher risk of cerebral haemorrhage compared to earlier years. COVID-19 patients admitted to the intensive care unit (ICU) faced an increased risk of cerebral haemorrhage compared to those admitted to general wards. Meta-regression analysis revealed a statistically significant association between the risk of cerebral haemorrhage and the type of wards in a hospital [0.0089 (95% CI: 0.0067-0.0112), p < 0.001], as well as the year of publication [0.0004 (95% CI: 0.0003-0.0008), p = 0.048]. Therefore, it is essential to evaluate COVID-19 patients admitted to the ICU in recent years for the potential occurrence of cerebral haemorrhage.

PMID:40939094 | DOI:10.1002/rmv.70069

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Nevin Manimala Statistics

Discovery of a Novel Cyclopeptide as Tyrosinase Inhibitor for Skin Lightening

Skin Res Technol. 2025 Sep;31(9):e70207. doi: 10.1111/srt.70207.

ABSTRACT

BACKGROUND: Melanin synthesis plays a crucial role in skin pigmentation, and inhibiting tyrosinase, the key enzyme in melanin production, is a primary strategy for developing skin-lightening agents. This study investigates the tyrosinase inhibitory potential of CHP-9, a novel cyclopeptide, and evaluates its cytotoxicity and efficacy as a cosmetic depigmenting agent.

METHODS: CHP-9 was synthesized via a solid-phase peptide synthesis strategy. The tyrosinase inhibitory activity was assessed using an enzymatic assay, while its effects on melanin content were evaluated in cultured human melanocytes. The MTT assay was performed to assess cytotoxicity across a range of CHP-9 concentrations (0.0781-10 mg/mL). Molecular docking simulations were conducted to elucidate the interaction between CHP-9 and human tyrosinase (PDB ID: 5M8M). Statistical analysis was performed using GraphPad Prism Software, and significance was determined via one-way ANOVA.

RESULTS: CHP-9 exhibited significant tyrosinase inhibition (28.57% at 1% concentration) and reduced melanin content in treated melanocytes from 30.90 ± 1.13 to 23.51 ± 1.14 µg/mL. Cytotoxicity assays confirmed CHP-9’s high biocompatibility, with cell viability exceeding 90% at concentrations up to 2.5 mg/mL. Docking studies revealed strong binding affinity between CHP-9 and key tyrosinase residues via hydrogen bonding, supporting its inhibitory mechanism.

CONCLUSIONS: CHP-9 exhibited significant tyrosinase inhibition (28.57% at 1% concentration) and reduced melanin content in melanocytes, while maintaining over 90% cell viability at effective doses. These findings suggest that CHP-9 is a safe and effective candidate for cosmetic skin-lightening applications. Further research is needed to enhance formulation stability and evaluate long-term efficacy in vivo.

PMID:40939092 | DOI:10.1111/srt.70207

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Nevin Manimala Statistics

Longitudinal Associations of Social Isolation, Systemic Inflammation, and Cognitive Function Among Older Adults With Diabetes: Cross-Lagged Examination

Sci Diabetes Self Manag Care. 2025 Sep 12:26350106251371080. doi: 10.1177/26350106251371080. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of the study was to examine the cross-lagged longitudinal associations between social isolation and cognitive function among older adults with diabetes and to investigate the mediating role of systemic inflammation in these associations.

METHODS: Secondary data from the Health and Retirement Study were utilized across 3 waves (2006, 2010, and 2014). To examine the longitudinal relationships between social isolation and cognitive function, a cross-lagged panel modeling approach was employed, with particular attention to the mediating role of C-reactive protein. A sequential predictor procedure was used; initially, only social isolation and cognitive function were analyzed; subsequently, sociodemographic covariates were controlled for; and finally, health-related covariates were added.

RESULTS: Data from 1336 older adults with diabetes in the United States were analyzed. In the partially adjusted model, reciprocal negative associations between social isolation and cognitive function were identified. However, these reciprocal negative associations were no longer statistically significant after accounting for health-related covariates. C-reactive protein did not serve as a mediator in the link between social isolation and cognitive function regardless of adjustments for covariates.

CONCLUSION: Given the reciprocal associations between social isolation and poorer cognitive function, a feedback loop may exist between these 2 factors. It is crucial to identify mediating mechanisms to disrupt this vicious cycle.

PMID:40939083 | DOI:10.1177/26350106251371080

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Nevin Manimala Statistics

Just-in-Time Adaptive Interventions: Where Are We Now and What Is Next?

Annu Rev Psychol. 2025 Sep 12. doi: 10.1146/annurev-psych-121024-044244. Online ahead of print.

ABSTRACT

The past decade has seen a surge in developing just-in-time adaptive interventions (JITAIs)-an intervention approach that leverages advancements in digital technologies to address the rapidly changing needs of individuals in daily life. This article provides an overview of the state of science on JITAI development and highlights important directions for future research. We explain what a JITAI is (and what it is not) and review the scientific and practical rationales underlying this approach. We also call attention to three key challenges relating to the development of JITAIs. The first challenge is that individuals may not be able to engage with (i.e., invest energy in) an intervention when they need it most in daily life. The second concerns the generally suboptimal engagement of individuals in interventions that leverage digital technologies as currently implemented. The third concerns the paucity of research on ways to harness the power of social relationships in JITAIs. We conclude that much research effort is needed to build more sophisticated and effective JITAIs.

PMID:40939059 | DOI:10.1146/annurev-psych-121024-044244

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Nevin Manimala Statistics

Malnutrition Mortality Among Older Adults by County and Race and/or Ethnicity in the United States, 2000-2019

J Am Geriatr Soc. 2025 Sep 12. doi: 10.1111/jgs.70042. Online ahead of print.

ABSTRACT

BACKGROUND: Older adults are at an increased risk of malnutrition due to chronic diseases and social vulnerabilities. This study estimates protein-energy malnutrition mortality rates among adults aged 65-74 and ≥ 75 by race and ethnic population group and county.

METHODS: We analyzed death data from the National Vital Statistics System and population data from the National Center for Health Statistics from 2000 to 2019. We calculated county-level mortality rates using small-area estimation methods, adjusting for misclassifications in death certificates. The primary outcome was deaths attributed to malnutrition. The exposures were to populations (American Indian/Alaskan Native [AIAN], Asian, Black, Hispanic/Latino, and White) and the county.

RESULTS: From 2000 to 2019, malnutrition mortality rates increased in individuals aged ≥ 75 from 19.5 (95% uncertainty interval [UI]: 18.8-20.1) to 49.2 (48.4-50.0) deaths per 100,000, and in those aged 65-74 from 2.2 (2.0-2.3) to 4.6 (4.4-4.7). In 2019, Black individuals had the highest national mortality rates: 60.8 (58.2-63.3) for ≥ 75 years and 7.7 (7.3-8.2) for 65-74 years. In 2019, a county in Georgia had the highest rate for White individuals aged ≥ 75 at 334.9 (236.6-464.8), and a county in Montana had the highest for AIAN individuals aged 65-74 at 34.9 (13.1-72.0). Counties in the New York metro had the lowest mortality rates across all population groups and ages.

CONCLUSION: Malnutrition mortality rates have increased among older adults, varying by geography and population group, underscoring the need for targeted nutritional interventions.

PMID:40939057 | DOI:10.1111/jgs.70042

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Nevin Manimala Statistics

Personal Care Aides in Adult Day Services Centers and Residential Care Communities: United States, 2022

Natl Health Stat Report. 2025 Jul 29;(217):1. doi: 10.15620/cdc/174600.

ABSTRACT

INTRODUCTION: Personal care aides (aides) are a key part of the long-term care infrastructure and provide hands-on care and support with essential activities of daily living to older and disabled Americans. This report presents the number of aides employed in adult day services centers (ADSC) and residential care communities (RCC), the hours they spend with their service users, and their training and benefits.

METHODS: Data are from the ADSC and RCC provider components of the 2022 National Post-acute and Long-term Care Study, conducted biennially by the National Center for Health Statistics. The study includes several questions on staffing, including about the number of registered nurses (RNs), licensed practical nurses (LPNs) or licensed vocational nurses (LVNs), and aides employed directly by ADSCs and RCCs. Full-time equivalent (FTE) staff is based on the number of full-time and part-time employees. A measure of hours per user (participant or resident) per day was used to compare staffing levels in the two settings relative to the number of users. Responses to questions on number of hours of training required and types of training and benefits offered to aides were used to compare in and across ADSC and RCC settings.

RESULTS: Of the 15,600 nursing (RN, LPN or LVN, and aide) FTEs employed in ADSCs and 452,000 employed in RCCs, the majority were aides (63.2% and 76.0%, respectively). Both settings often employed at least one aide (56.2% and 75.6%). The average total of all nursing staffing hours per participant or resident per day was 1 hour and 34 minutes for ADSCs and 4 hours and 25 minutes for RCCs. A lower percentage of ADSCs than RCCs offered training in dementia care (50.8% and 72.3%) and end-of-life issues (19.7% and 58.4%).

PMID:40939053 | DOI:10.15620/cdc/174600

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Nevin Manimala Statistics

The Efficacy and Safety of Transcranial Photobiomodulation for Mild Cognitive Impairment Due to Alzheimer’s Disease: A Randomized, Double-Blind, Sham-Controlled Study

Photobiomodul Photomed Laser Surg. 2025 Sep;43(9):411-416. doi: 10.1177/15578550251369575.

ABSTRACT

Background: Transcranial photobiomodulation (tPBM) is a promising noninvasive neuromodulation modality with potential therapeutic benefits for neurodegenerative diseases. Infrared light delivered by a tPBM device penetrates the cortex, stimulating neuronal activity by increasing mitochondrial adenosine triphosphate production and enhancing regional cerebral blood flow. Objective: This study investigated the efficacy and safety of a self-administered, at-home, wearable tPBM device for improving cognitive function in individuals with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD). Methods: Individuals with MCI due to AD, diagnosed according to the National Institute on Aging and Alzheimer’s Association criteria, with a Korean version of Mini-Mental State Examination-2 (K-MMSE2) score of 23-27 and a global Clinical Dementia Rating (CDR) score of 0.5-1.0 were enrolled. Subjects self-administered tPBM six times per week for 12 weeks. Assessments were conducted at weeks 7 and 13 using the Korean version of the Montreal Cognitive Assessment (K-MoCA), K-MMSE2, the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease, and the Geriatric Depression Scale. Results: A total of 26 participants were enrolled. The treatment group showed a statistically significant improvement in K-MoCA scores at week 13 (p < 0.05) compared with the sham group. Although K-MMSE2 scores improved in the treatment group, the difference was not statistically significant. No serious adverse events were reported. Conclusion: Findings suggest that tPBM is an effective and safe home-use intervention for individuals with MCI, with promising therapeutic and preventative roles in Alzheimer’s dementia.

PMID:40939031 | DOI:10.1177/15578550251369575

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Nevin Manimala Statistics

Accelerating Systematic Reviews: A Novel One-Week Screening Protocol Using Rule-Based Automation with AI-Assisted Python Coding

Am J Physiol Heart Circ Physiol. 2025 Sep 12. doi: 10.1152/ajpheart.00374.2025. Online ahead of print.

ABSTRACT

The exponential growth in academic publishing – exceeding 2 million papers annually 2023 – has rendered traditional systematic review methods unsustainable1-3. These conventional approaches typically require 6-24 months for completion4-6, creating critical delays between evidence availability and clinical implementation. While existing automation tools demonstrate workload reductions of 30-72.5%, their machine learning dependencies create barriers to immediate implementation7-10. Additionally, direct AI screening methods involve substantial computational costs, lack real-time adaptability, suffer from inconsistent performance across different research domains, and provide no clear audit trail for regulatory compliance. We present a one-week systematic review acceleration protocol using rule-based automation where artificial intelligence (AI) assists with code generation. Researchers define screening criteria, then use AI language models (Claude, ChatGPT) as coding assistants. This protocol employs a two-phase screening process: (1) rule-based title/abstract screening and (2) rule-based full-text analysis, while adhering to established systematic review guidelines such as Cochrane methodology and PRISMA reporting5, 6. The rule-based system provides immediate implementation with complete transparency, while validation framework guides researchers in systematically testing screening sensitivity to minimize false negatives and ensure comprehensive study capture; meta-analysis and statistical synthesis remain manual processes requiring human expertise. We demonstrate the protocol’s application through a case study examining cardiac fatty acid oxidation in heart failure with preserved ejection fraction (HFpEF)11, and validated through a separate review examining e-cigarette versus traditional cigarette cardiopulmonary effects, which successfully processed 3,791 records12. This protocol represents a substantial advancement in systematic review methodology, making high-quality evidence synthesis more accessible across a broad range of scientific disciplines.

PMID:40939020 | DOI:10.1152/ajpheart.00374.2025