Nevin Manimala

J Frailty Aging. 2025 Nov 26;14(6):100106. doi: 10.1016/j.tjfa.2025.100106. Online ahead of print.

ABSTRACT

BACKGROUND: Ketone bodies are metabolites produced during fasting or on a ketogenic diet that have pleiotropic effects on the inflammatory and metabolic aging pathways underpinning frailty in vivo models. Ketone esters (KEs) are compounds that induce hyperketonemia without dietary changes and that may impact physical and cognitive function in young adults. The functional effects of KEs have not been studied in older adults.

OBJECTIVES: Our long-term goal is to examine if KEs modulate aging biology mechanisms and clinical outcomes relevant to frailty in older adults. Here, we report the exploratory functional and quality-of-life outcome measures collected during a 12-week safety and tolerability study of KE (NCT05585762).

DESIGN: Randomized, placebo-controlled, double-blinded, parallel-group, pilot trial of 12-weeks of daily KE ingestion.

SETTING: The Clinical Research Unit at the Buck Institute for Research on Aging, California.

PARTICIPANTS: Community-dwelling older adults (≥65 years), independent in activities of daily living, with no unstable acute medical conditions (n = 30).

INTERVENTION: Participants were randomly allocated (1:1) to consume 25 g daily of either KE (bis-octanoyl (R)-1,3-butanediol) or a taste, appearance, and calorie-matched placebo (PLA) containing canola oil.

MEASUREMENTS: Longitudinal change in physical function, cognitive function and quality of life were assessed as exploratory outcomes in n = 23 completers (n = 11 PLA, n = 12 KE). A composite functional outcome intended for interventional frailty trials was derived and calculated. Heart rate and activity was measured throughout the study using digital wearables.

RESULTS: There were no statistically significant longitudinal differences between groups in exploratory functional, activity-based or quality of life outcomes.

CONCLUSION: Daily ingestion of 25 g of KE did not affect exploratory functional or quality-of-life end points in this pilot cohort of healthy older adults. Future work will address these endpoints as primary and secondary outcomes in a larger trial of pre-frail older adults.

PMID:41313689 | DOI:10.1016/j.tjfa.2025.100106

Alzheimers Dement. 2025 Nov;21(11):e70950. doi: 10.1002/alz.70950.

ABSTRACT

INTRODUCTION: Late-life depression symptoms are implicated in dementia. We examined how cumulative burden, duration, trajectory, and variability of depression symptoms are associated with incident dementia.

METHODS: A prospective cohort analysis of 23,305 dementia-free adults from four population studies (English Longitudinal Study of Ageing [ELSA], Health and Retirement Study [HRS], Survey of Health, Ageing and Retirement in Europe [SHARE], China Health and Retirement Longitudinal Study [CHARLS]) with repeated Centre for Epidemiologic Studies of Depression scale (CES-D)/Euro-Depression scale (EURO-D) assessments across three waves and a pooled median follow-up of ≈10.8 years. Exposures included CumSD/cumulative average depression symptom score (CumADS), high-symptom exposure duration, visit-to-visit variability (Standard deviation [SD], coefficient of variation [CV], variation independent of the mean [VIM]), and time-course patterns. Associations were analyzed using multivariable-adjusted Cox regression.

RESULTS: Each 1-unit increase in cumulative score was associated with a 3%-8% higher dementia hazard across cohorts. Highest versus lowest cumulative quartiles showed markedly elevated risk. Sustained high exposure for 4 years conferred ≈2.7-3.9× greater risk. Higher variability and worsening trajectories were also linked to higher incidence. Associations were robust across subgroups.

DISCUSSION: Persistent and unstable depression symptoms independently predict higher dementia risk, supporting longitudinal mood monitoring and sustained management.

HIGHLIGHTS: Multi-cohort study of 23,305 adults (ELSA, HRS, SHARE, CHARLS). Cumulative depression burden shows a dose-response with dementia risk. Highest versus lowest quartile: dementia hazard up to 18× (HRS). Sustained high symptoms (4 years) linked to ≈2.7-3.9× greater risk. Visit-to-visit variability independently associates with higher dementia risk.

PMID:41313677 | DOI:10.1002/alz.70950

J Vet Emerg Crit Care (San Antonio). 2025 Nov 28. doi: 10.1111/vec.70057. Online ahead of print.

ABSTRACT

OBJECTIVE: To analyze the effects of co-administering various drugs with canine whole blood (WB), canine fresh frozen plasma (FFP), or canine freeze-dried plasma (FDP), and determine whether alterations to the blood constituents or drugs exist within the admixture.

DESIGN: In vitro experimental study.

SETTING: Government blood and coagulation research laboratory.

INTERVENTIONS: Seven units of commercially acquired canine FFP, 7 units of canine FDP, and 8 units of canine WB were co-administered with multiple drugs, including fentanyl, midazolam, ketamine, hydromorphone, tranexamic acid (TXA), ampicillin/sulbactam, enrofloxacin, ceftriaxone, and ertapenem, and delivered simultaneously into an IV line via infusion pumps using clinically relevant doses. The resultant solutions were analyzed for coagulation factor activities and fibrinogen concentration. Liquid chromatography-tandem mass spectroscopy was used to assess drug concentration, and impedance aggregometry and cell-free hemoglobin were used to evaluate platelet function in the WB samples.

MEASUREMENT AND MAIN RESULTS: Platelet function decreased with each drug co-administered with WB in vitro. Cell-free hemoglobin increased when ketamine, fentanyl, and midazolam were co-administered with WB. Drug loss was seen when enrofloxacin was co-administered with FDP. Drug loss was also seen when hydromorphone was co-administered with FFP. Sulbactam and ertapenem resulted in drug loss when co-administered with FDP and FFP. Drug loss was seen when ceftriaxone, fentanyl, and midazolam were co-administered with each blood product. With each admixture, there were variable changes in coagulation factor activities. A statistically significant decrease in activity <50% was seen only in factors V and VIII when ceftriaxone and enrofloxacin, respectively, were co-administered with FDP.

CONCLUSIONS: Platelet function will likely be adversely affected by the co-administration of any of the selected drugs. Co-administration of ketamine, fentanyl, and midazolam with WB resulted in significant hemolysis and is not recommended. It is reasonable to consider co-administering ampicillin, TXA, and ketamine with FDP and FFP.

PMID:41313672 | DOI:10.1111/vec.70057

Rev Esc Enferm USP. 2025 Nov 17;59:e20250211. doi: 10.1590/1980-220X-REEUSP-2025-0211en. eCollection 2025.

ABSTRACT

OBJECTIVE: To analyze factors associated with the occurrence of COVID-19 in the pediatric population in hospital settings.

METHOD: This was a paired case-control study conducted with medical records of children under 14 years of age. The pediatric population with a positive COVID-19 test was considered a case, and the pediatric population with a negative COVID-19 test was considered a control. For each case, a control was used, totaling 486 medical records. Descriptive analysis, bivariate analysis, and logistic regression were performed.

RESULTS: The variables associated with the occurrence of COVID-19 were brown, black, yellow, and indigenous children, emergency room and Intensive Care Unit admission, use of mask and oxygen catheter, antimicrobials, and corticosteroids. Fever, anorexia, non-eupneic respiratory pattern with saturation between 90% and 95%, cough, runny nose, and comorbidities were associated with the outcome.

CONCLUSION: Advances by providing information on factors associated with COVID-19 in the hospitalized population under 14 years of age, including place of hospitalization, anorexia, runny nose, comorbidity, and corticosteroid use.

PMID:41313640 | DOI:10.1590/1980-220X-REEUSP-2025-0211en

Rev Esc Enferm USP. 2025 Nov 17;59:e20250022. doi: 10.1590/1980-220X-REEUSP-2025-0022en. eCollection 2025.

ABSTRACT

OBJECTIVE: To describe postoperative complications in patients undergoing oncological surgeries, and to analyze adherence to the recommendations of the project Acceleration of Total Postoperative Recovery (ACERTO) in these patients and the risk factors for death.

METHOD: Retrospective longitudinal study. Sample of 229 patients in the immediate postoperative period admitted to the intensive care unit from July to December 2021.

RESULTS: The frequency of complications was 68.5%. There was adherence to the recommendation of fluid resuscitation ≤ 30 mL/kg in 56.6% intraoperatively and greater adherence in the postoperative period (90.4%) and in the prescription of nausea and vomiting prophylaxis in the intraoperative (93%) and postoperative (100%) periods. An association was observed between adherence to recommendations and a reduction in complications. The independent risk factors for death were age (p = 0.031) and the score Sequential Organ Failure Assessment (SOFA) (p = 0.004).

CONCLUSION: A high frequency of complications was observed in the postoperative period and a mortality rate of 11.8%. Adherence to the protocol ACERTO was associated with a reduction in postoperative complications in cancer patients. Age and SOFA score were independent risk factors for death.

PMID:41313639 | DOI:10.1590/1980-220X-REEUSP-2025-0022en

Haemophilia. 2025 Nov 28. doi: 10.1111/hae.70073. Online ahead of print.

ABSTRACT

INTRODUCTION: Assessment of health-related quality of life (HRQoL) is relatively new in von Willebrand disease (VWD). So far, generic questionnaires have mainly been used for HRQoL assessment in VWD.

AIMS: To assess generic and disease-specific HRQoL in adult VWD patients and compare HRQoL with the general German population.

METHODS: Patients presenting with a personal or family history of bleeding and von Willebrand factor (VWF)-specific laboratory parameters were enrolled in the WIL-QoL study. HRQoL was assessed with generic (SF-36) and disease-specific (VWD-QoL) questionnaires. Descriptive and inferential statistical procedures were applied based on a significance level at α ≤ 5%.

RESULTS: In the retrospective, multicentre WIL-QoL study, HRQoL and clinical data in 120 adults with VWD (one adolescent completed the adult questionnaire) from 10 centres in Germany were collected. Compared to the corresponding age group in the general German population, female VWD patients had significantly worse HRQoL in all SF-36 domains and male patients only in the ‘physical functioning’ domain. In the VWD-QoL, highest impairments were seen in all VWD patients in the domains ‘other physicians’, ‘treatment’ and ‘sport & leisure’. VWD patients with a more significant disease burden, such as a bleeding score ≥ 9 (p < 0.0001), long-term prophylaxis (p = 0.003), and VWD-type 3 (p = 0.022), reported significantly worse HRQoL. No HRQoL differences were seen between male and female VWD patients.

CONCLUSION: Female VWD patients showed significant impairments in their HRQoL compared to the age group-related general population. Compared to SF-36, the VWD-QoL identified stronger significant HRQoL differences in most VWD subgroups, confirming the impact of bleeds.

PMID:41313635 | DOI:10.1111/hae.70073

JMIR Res Protoc. 2025 Nov 28;14:e71929. doi: 10.2196/71929.

ABSTRACT

BACKGROUND: Two decades of research have highlighted persistent income-related health inequities in Canada across municipal, provincial, and national levels. While there is broad consensus among researchers, advocates, and health professionals that social determinants are the primary drivers of health, the empirical foundation supporting this remains relatively limited. A current renaissance in health system data access offers an opportunity to assess the multilevel impact of social factors on health inequalities, yet this potential remains underused.

OBJECTIVE: This project aims to examine how social, economic, and political conditions shape health inequalities and investigate how structural and intermediate determinants explain disparities across national, provincial, city, neighborhood, and individual levels.

METHODS: We will create the Canadian Social Determinants Urban Laboratory (CSDUL), a multilevel, longitudinal, virtual data environment that integrates 15 existing databases from Statistics Canada, the Canadian Institute for Health Information, the Canadian Urban Environmental Health Research Consortium, and DMTI Spatial. Guided by the World Health Organization social determinants of health framework, CSDUL will initially cover 2011 to 2015 due to data completeness and expand as additional years become available. CSDUL builds on Statistics Canada’s Canadian Population Health Survey and will link survey data to administrative and health records, including hospital discharges, ambulatory care, mortality, cancer registries, and longitudinal tax files. Area-level indicators will be added using historical postal codes and geospatial boundaries. Organized through a hub-and-node model, CSDUL includes a central hub and 5 research nodes. We will develop and validate area-based indicators to study social determinants at micro (individual), meso (neighborhood, city, and province), and macro (national) levels. A core deliverable is to assess the strengths and limitations of survey and administrative data for health research and derive variables accordingly. After developing CSDUL, we will replicate World Health Organization Regional Office for Europe income-related health inequality analysis for urban Canada and analyze the impact of social determinants on outcomes. We will apply a 2-fold Oaxaca-Blinder decomposition between the lowest and highest urban income quintiles. A major strength of CSDUL is its capacity to analyze how diverse determinants shape health across subgroups (eg, gender), identifying key drivers of health outcomes.

RESULTS: The indicators to be used in CSDUL are being developed and validated by the contributing nodes. In collaboration with node 3, we are constructing measures of social capital using DMTI Spatial Points of Interest data. A prototype version of CSDUL incorporating a limited set of indicators has been developed in Statistics Canada’s Research Data Centre. We anticipate receiving the finalized indicators from the nodes by August 2025 to September 2025 and aim to complete the decomposition analysis by December 2025.

CONCLUSIONS: Multisectoral interventions are most effective when they are customized to meet the unique needs of specific subpopulations using robust and multilevel data sources such as CSDUL.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/71929.

PMID:41313634 | DOI:10.2196/71929

JMIR Res Protoc. 2025 Nov 28;14:e75199. doi: 10.2196/75199.

ABSTRACT

BACKGROUND: The COVID-19 pandemic impacted trust in public health, medical care, scientific, and governmental institutions; this influenced health, health-seeking behaviors, and adherence to public health measures. Understanding how trust evolves is necessary for informing future public health crisis management and strategies. Rebuilding public trust is key to pandemic preparedness worldwide. This research protocol examines these trust dynamics, their determinants, and their implications.

OBJECTIVE: This study aimed to investigate the evolution of public trust in scientists, public health and medical care institutions, governments, and social and personal networks during the COVID-19 pandemic. It sought to identify key factors contributing to trust maintenance or erosion, particularly in marginalized and minority communities, and understand the impact of trust level on public health adherence.

METHODS: A sequential, explanatory mixed methods approach was implemented, consisting of an initial quantitative survey followed by qualitative interviews. The nationwide representative survey included 5607 Canadian residents as of May 2024. The questionnaire assessed trust in 6 key trust sources before and during the pandemic: provincial and federal governments, public health authorities, medical care providers, health scientists, and social and personal networks. To complement, 41 qualitative interviews were conducted to understand participants’ lived experiences, perceptions, and how trust played into both. Data have been analyzed using quantitative statistical techniques and qualitative phenomenological analysis, and the results have been integrated to derive comprehensive insights. All phases of data collection and analysis were finalized by early 2025. The project then advanced to paper preparation, dissemination at national conferences, and knowledge-translation activities, including the report development and public-facing outputs, scheduled for completion in end-2025.

RESULTS: This Canadian survey included participants from all 10 provinces and 2 territories; the provinces and territories’ samples matched the proportions of each in the overall Canadian population. Age and sex or gender were well distributed across the sample. Additionally, 18.6% (1040/5607) identified as an ethnic minority, 12.7% (710/5607) identified as Indigenous, including 7.2% (403/5607) First Nations, 4.8% (270/5607) Métis, and 0.4% (25/5607) Inuit. Fifty-five percent (3094/5607, 55.2%) had received at least 1 dose and planned to stay up to date with booster recommendations, while 36.6% (2052/5607) were vaccinated but did not intend to receive additional doses. A small percentage, 0.7% (39/5607), had not yet been vaccinated but were open to it, whereas 6.4% (359/5607) had not received a vaccine and did not plan to take a vaccine.

CONCLUSIONS: The COVID-19 pandemic has underscored the critical role of trust in public health behavior and crisis response. This study explores how consistent, transparent communication and equity-driven policies may contribute to maintaining public trust, particularly among marginalized communities. By examining trust dynamics and identifying potential disparities, this study aims to inform evidence-based public health strategies and improve preparedness for future health emergencies.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/75199.

PMID:41313631 | DOI:10.2196/75199

JMIR Res Protoc. 2025 Nov 28;14:e77521. doi: 10.2196/77521.

ABSTRACT

BACKGROUND: The COVID-19 pandemic challenged families, youth, and frontline workers, including childcare providers. Studying lived experiences before, during, and near the pandemic’s end from multiple perspectives provides a more holistic and deeper understanding of its effects and impacts.

OBJECTIVE: This study investigated how parental, childcare provider, and youth stress, mental health, and role overload relate to individual coping and family functioning, as well as vaccine attitudes and uptake patterns among youth, parents, and childcare providers. Information learned from this investigation will inform policy and messaging for future public health crises.

METHODS: This study is an explanatory sequential mixed methods study designed to capture the voices of parents of children younger than 18 years of age, childcare providers, and youth aged 12-17 years through surveys and interviews. This retrospective cross-sectional study began with a web-based survey that included demographic questions and validated scales to assess personal well-being, household and family dynamics, behavioral problems, and vaccination-related perceptions, attitudes, and behaviors. Open-ended responses about pandemic experiences for themselves and their families were included. A subsample of parents, youth, and childcare providers was selected for in-depth interviews about their pandemic-related experiences. Descriptive statistics were used to summarize demographic characteristics, and internal consistency was assessed for all survey measures using Cronbach α. Future studies will use inferential statistical techniques to analyze survey measures, thematic analysis for open-ended survey responses and interview data, and mixed methods data integration to synthesize quantitative and qualitative findings.

RESULTS: Data collection for the study began in August 2022 and finished in August 2023. Data analysis is currently in progress to address research questions, and study preparation and dissemination efforts are underway. A total of 506 adults and 93 youths answered a study survey, and 45 adults and 21 youths completed in-depth interviews. Among the 506 adults, 166 were childcare providers. The adult sample had a mean age of 42.8 (SD 9.15) years and was predominantly female (467/506, 92.3%), with 9.7% (49/506) identifying as Black, 4.7% (24/506) as Hispanic, and 81.2% (411/506) being parents of children aged 17 years or younger. The youth sample had a mean age of 14.5 (SD 1.63) years, and 55.9% (52/93) were female, 6.4% (6/93) were Black, and 17.2% (16/93) were Hispanic. Several dyads and triads participated. The sample included 42 parent-child dyads, 3 parent-parent dyads, 2 parent-parent-child triads, and 21 parent-child-child triads.

CONCLUSIONS: These data will be used to understand the diverse experiences of families, youth, and childcare providers during and after the COVID-19 pandemic. This includes successful and unsuccessful adaptations, responses to policies and mandates, and the unmet needs for health messaging, programs, policies, and services. This research aims to guide the development of effective policies and public health communication, fostering scalable and sustainable messaging resources.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/77521.

PMID:41313626 | DOI:10.2196/77521

JMIR Res Protoc. 2025 Nov 28;14:e77944. doi: 10.2196/77944.

ABSTRACT

BACKGROUND: Driving performance involves multiple underlying components of psychomotor functioning, such as attention, executive functions, and vehicle control. While the effects of acute medical marijuana and prescription opioid intoxication are known, how long-term use of medical marijuana under real-world conditions affects driving performance is unknown. Additionally, there are numerous ongoing physical and cognitive changes that affect driving performance with age. Given the proliferation of medical marijuana and prescription opioid use in adults aged 50 years and older, the prevalence of polypharmacy, and declining functional abilities, it is imperative to understand the long-term effects of daily medical marijuana use. Further, we need to understand how co-occurring use of medical marijuana and prescription opioids, in the presence of comorbidities such as chronic pain, affects real-world driving outcomes.

OBJECTIVE: This study aims to document the observational trial protocol. The primary goal of this study is to identify the effects of daily long-term (ie, use for >12 months daily or most days of the week) medical marijuana use on driving performance outcomes using an open-road driving performance task under real-world conditions in adults aged 50 years and older who endorse chronic or severe nonmalignant pain and to examine the combined effect of daily long-term medical marijuana use and prescription opioid use on driving outcomes. A secondary goal is to qualitatively explore self-regulation of medical marijuana and prescription opioid use in this population.

METHODS: We plan to test medical marijuana use as the exposure variable in adults aged 50 years and older on an open-road driving task performance as the primary outcome. The study will detail tetrahydrocannabinol exposure through ecological momentary assessment and urinalysis and will compare performance with a race-sex-matched group of non-marijuana users.

RESULTS: This study is funded by a grant from the National Institute on Drug Abuse (5R01DA057965). Recruitment began on May 19, 2025. As of November 2025, a total of 30 participants had been enrolled. Recruitment is anticipated to be completed by 2029. Publication of the complete results and data from this study is expected by 2030.

CONCLUSIONS: Data from this study will identify the effects of long-term medical marijuana use and the combined effect of that use with prescription opioids to develop risk screening protocols and intervention targets for this population. The development and dissemination of screening and intervention guidelines will be the next step in this work.

TRIAL REGISTRATION: ClinicalTrials.gov NCT06995937; https://www.clinicaltrials.gov/study/NCT06995937.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/77944.

PMID:41313623 | DOI:10.2196/77944