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Journal of the American Medical Directors Association

Elsevier BV

Preprints posted in the last 30 days, ranked by how well they match Journal of the American Medical Directors Association's content profile, based on 13 papers previously published here. The average preprint has a 0.01% match score for this journal, so anything above that is already an above-average fit.

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Assessment of safe wheeled walker use in frail older adults: Development of a video-based rating instrument

Leonhardt, R.; Lindemann, U.; Schneider, M.; Rapp, K.; Klenk, J.

2026-06-08 geriatric medicine 10.64898/2026.06.04.26354904 medRxiv
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Background: Wheeled walkers can improve safety during walking, but improper use may increase fall risk among frail older adults. No suitable tool exists to assess safe indoor wheeled walker use in this population. This study aimed to develop and validate a video-based expert assessment tool. Methods: Based on the literature and expert consensus, seven problematic indoor situations were identified, and an assessment tool with five safety criteria per situation was developed (maximum score = 35). Fifty participants (mean age 83.9 years, 64% women) from a geriatric rehabilitation clinic and a nursing home were video-recorded while using a rollator. Expert ratings were compared with nursing staff ratings, self-ratings, and the Timed Up and Go test to evaluate validity. Intra- and inter-rater reliability were determined from independent ratings by two physiotherapists and a repeated expert rating after seven days. Sensitivity to change was assessed after two weeks of rehabilitation, and feasibility by the time required for assessment. Results: The expert score of rater 1 at baseline was 28.5 points, and assessment required a mean of 17.5 minutes. Intra-rater reliability was excellent (ICC = 0.98) and inter-rater reliability was good (ICC = 0.80). Validity analyses showed the strongest association with nursing staff assessments (r = 0.74) and a moderate association with the Timed Up and Go test (r = -0.45). After two weeks, patients improved by an average of 2.38 points (8.4% of baseline score). Conclusions: The new instrument demonstrated high reliability, acceptable validity, sensitivity to change, and good feasibility for assessing safe wheeled walker use in frail older adults. Trial registration number and date of registration: DRKS00038358, 07/11/2025

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Inflammation and late life depressive symptoms

Forbes, M.; Lotfaliany, M.; Miteku, B. M.; Yu, C.; Lacaze, P.; Isvoranu, A.-M.; Kang, M.; Nguyen, T.; Woods, R.; McNeil, J.; Neumann, J.; Mohebbi, M.; Berk, M.

2026-06-10 psychiatry and clinical psychology 10.64898/2026.06.05.26354416 medRxiv
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Background Low-level systemic inflammation has been associated with late-life depressive symptoms. Whether individuals with higher inflammation derive preventive benefit from low-dose aspirin therapy is unknown. Methods We performed a post-hoc analysis of the ASPiring in Reducing Events in the Elderly (ASPREE) randomised, double-blind, placebo-controlled trial. Baseline C-reactive protein (hsCRP) was measured in plasma and depressive symptoms were assessed annually using the Center for Epidemiologic Studies Depression 10 Scale with elevated symptoms defined as CES-D-10 >= 8. Participants with elevated depressive symptoms at baseline were excluded. We fitted population-averaged logistic generalised estimating equation models adjusted for baseline sociodemographic and lifestyle covariates, including an hsCRP x treatment interaction to test effect modification by aspirin. Results Higher baseline hsCRP was associated with increased odds of elevated depressive symptoms during follow-up (OR 1.07 per SD increase in hsCRP, 95% CI 1.03-1.11). Low-dose aspirin allocation did not modify the hsCRP-depressive symptoms association (interaction OR 1.02, 95% CI 0.94-1.10). Findings were similar after additional adjustment for comorbidity and other covariates. Conclusions In community-dwelling older adults during the ASPREE randomised trial period, higher baseline hsCRP was modestly associated with elevated depressive symptoms. There was no evidence that low-dose aspirin was associated with reduced risk of depressive symptoms among participants with higher baseline inflammation.

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Ethnic and Socioeconomic Inequalities in Health and Social Care Utilisation Among People with Dementia: A Population-Based Study

Mathlin, G.; Cooper, C.; Teoh, L.; Mukadam, N.; Banerjee, S.; Birks, Y.; Demnitz-King, H.; Hunter, R.

2026-06-08 psychiatry and clinical psychology 10.64898/2026.06.04.26354916 medRxiv
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Background: People affected by dementia experience intersecting care inequalities. We explored relationships between ethnicity and health and social care resource use among people with dementia in an ethnically diverse urban region. Methods: We conducted a retrospective observational cohort study using Discover-NOW, including patients with dementia between 1.4.2015 and 1.4.2025. We calculated ethnic density as the percentage of the Middle Layer Super Output Area (SOA) population self-identifying with the same ethnic group. Regression models, clustered by Local SOA, tested whether ethnic density moderated relationships between ethnicity and primary care, outpatient, inpatient, emergency and social care service use, controlling for sociodemographic characteristics, deprivation, comorbidities and time of diagnosis. Findings: We included 30,704 people with dementia. People from Black and Mixed ethnic groups used more primary care, and those from Asian ethnic groups less primary and secondary care, than White ethnic groups. Rates of local authority social care packages were similar across ethnic groups. High ethnic density predicted fewer GP consultations in Black ethnic groups, but more in South Asian groups. Interpretation: Among Black ethnic groups, primary care use was relatively high, especially in areas of low ethnic density, perhaps reflecting greater needs among communities at risk of racism and isolation. The trend towards increased primary care use among South Asian people in areas of higher ethnic density may reflect communities mitigating help-seeking hesitancy related to cultural and language barriers. Greater care integration could reduce care inequalities among minority ethnic communities who may experience fewer barriers to social relative to health care.

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Loss of a Spouse and Risk of Cognitive Decline: Insights from Six Prospective Cohort Studies

Guo, C.; Wang, Y.; Sun, X.; Ge, F.

2026-06-01 psychiatry and clinical psychology 10.64898/2026.05.20.26353668 medRxiv
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Aims. The risk of cognitive decline after losing a spouse remained mixed. This study aims to investigate the association between spousal loss and risk of cognitive decline, assess whether this association varies by sex and age, and identify modifiable factors. Methods. We conducted a prospective cohort study using harmonized data from six population-based aging surveys: the US Health and Retirement Study and its sister surveys in England, Mexico, China, India, and South Africa, incorporating their respective Harmonized Cognitive Assessment Protocol (HCAP) sub-studies. Spousal loss (yes vs no) was the exposure. Cognitive outcomes (i.e., orientation, memory, executive function, and language), were assessed using HCAP neuropsychological batteries. We conducted parallel analyses in six cohorts. Associations between spousal loss and cognitive outcomes were estimated using generalized linear models, and summarised estimates were derived via random-effects meta-analyses. Sex stratification and restricted cubic spines were used to examine how these associations vary by sex and age, respectively. Results. The analytical cohort consisted of 18,551 individuals aged 61.22 (SD 6.30) to 71.37 (SD 7.33) years. Widowhood prevalence ranged from 14.1% in CHARLS to 53.9% in HAALSI and was consistently higher in women. Spousal loss was associated with poorer memory (multivariable-adjusted {beta} = -0.07, 95% CI -0.12 to -0.01) and executive function (multivariable-adjusted {beta} = -0.08, 95% CI -0.13 to -0.03) in the meta-analysis, with no significant associations for orientation or language. While results were generally consistent in five cohorts, the ELSA showed divergent patterns (orientation: {beta} = 0.10, 95% CI 0.06 to 0.13; memory: {beta} = 0.05, 95% CI 0.02 to 0.08; language: {beta} = 0.16, 95% CI 0.12 to 0.19). Sex-stratified analyses indicated poorer executive function among men (multivariable-adjusted {beta} = -0.14, 95% CI -0.19 to -0.08) and poorer memory among women (multivariable-adjusted {beta} = -0.07, 95% CI -0.14 to -0.01) following widowhood. Nonlinear age-related effects on cognition were observed in ELSA, LASI, and HAALSI. Higher education, internet use, and BMI were negatively associated with the risk of cognitive decline among widowed participants. Conclusions. Spousal loss is associated with domain- and sex-specific differences in cognitive performance, with substantial heterogeneity across study populations. Future research should integrate biopsychosocial markers to develop context-sensitive interventions for widowed older adults.

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Frailty-based prognostication of clinical outcomes in geriatric burn patients: a retrospective study

Lee, J. H.; Jinsi, M.; Feldman, M. J.; Hobgood, S.

2026-05-15 geriatric medicine 10.64898/2026.05.12.26353034 medRxiv
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Burn trauma disproportionately impacts older adults, yet existing burn severity models emphasize age, total body surface area (TBSA), and inhalation injury without accounting for geriatric-specific vulnerabilities such as frailty. We conducted a retrospective cohort study of 326 geriatric patients admitted with burn injuries between 2020 and 2024 to evaluate how TBSA, burn location, inhalation injury, renal insufficiency, comorbidities, and functional dependence in activities of daily living (ADLs) and instrumental activities of daily living (IADLs) affect in- hospital mortality and discharge disposition. Based on multivariable logistic regression and chi- square analyses, TBSA, as expected, emerged as the strongest predictor across models. Each 1% increase in TBSA was associated with a 7% increase in the odds of in-hospital mortality (p=0.006) and a 12 to 19% increase in odds of post-acute care placement (p<0.001). Inhalation injury and renal insufficiency were also independently associated with increased odds of both mortality and post-acute care disposition, whereas respiratory comorbidity predicted mortality alone. Functional status demonstrated outcome-specific prognostic value: ADL dependence predicted mortality, while IADL dependence predicted discharge disposition. Patients with some ADL dependence had five-fold higher odds of in-hospital mortality (p=0.011), while some (OR=2.48, p= 0.039) and full IADL dependence (OR=2.61, p=0.025) were associated with higher odds of post-acute care placement. Integrating structured functional assessments that distinguish basic from instrumental limitations alongside established burn severity metrics may enhance prognostication and guide individualized care planning for older adults with burn injuries.

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Effect of levodopa treatment on gait in older adults with mild parkinsonian signs

Pongmala, C.; Roytman, S.; van Emde Boas, M.; Vangel, R.; Rosano, C.; Bohnen, N.

2026-06-06 geriatric medicine 10.64898/2026.06.04.26354926 medRxiv
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Background Slow walking in older adults with mild parkinsonian signs (MPS) is a complex, multifactorial phenomenon arising from the cumulative burden of subclinical age-associated pathologies. This decline reflects age-associated neuronal loss in the dopaminergic system. A recent study suggests that levodopa treatment may enhance gait parameters. The goal of this small pilot study is to explore the effect of levodopa treatment on slow walking gait in older adults with MPS. Method This study was a randomized, placebo-controlled clinical pilot trial. Slow walking older adults without clinical evidence of PD were recruited and randomized into 2 groups (active treatment group or placebo control group). Participants in the active group were pre-treated with carbidopa for three days, followed by carbidopa-levodopa for seven days. Spatiotemporal gait parameters were evaluated at baseline and post-intervention. Results Gait factor analysis identified three main factors explaining gait characteristics at baseline, which included gait efficiency, gait rhythmicity, and gait turning.No effect of treatment was observed in the placebo group (p=0.111, p=0.616), no group difference was observed between the placebo and active group at baseline ({beta}=0.310, p=0.547), but a strong trend for a treatment-related increase was observed in the active treatment group ({beta}=0.506, p=0.076). Conclusion Our preliminary data suggest that sustained levodopa treatment (one week) in conjunction with carbidopa pre-treatment and concomitant carbidopa supplementation is feasible in slow walking older adults with MPS. Moreover, the data indicate potential efficacy, showing improvements in cadence, and step durations.

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Malnutrition and healthcare costs in older adults in Sweden: a longitudinal study based on a population-based cohort and Swedish registers

Xia, X.; Balcha, Y. M.; Carballo-Casla, A.; Aho, E.; Willers, C.; Rydwik, E.; Calderon-Larranaga, A.; Kugelberg, S.; Berggreen-Clausen, A.; Garpsater, J.; Jonsson, L.

2026-06-01 health economics 10.64898/2026.05.29.26354412 medRxiv
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Background The study aimed to estimate healthcare costs associated with malnutrition in Swedish older adults. Methods We conducted a cohort study using data from the population-based Swedish National Study on Aging and Care in Kungsholmen (SNAC-K, N = 2982), a geriatric inpatient cohort of complex patients (N = 7680), and a cohort of individuals with cognitive impairment from the Swedish Register of Cognitive/Dementia Disorders (SveDem, N = 64192). At risk of malnutrition and malnutrition were ascertained by the Mini-Nutritional Assessment in SNAC-K and the geriatric inpatient cohort. In SveDem, body mass index was used for identifying malnutrition. Healthcare resource use was derived from regional and national registers. Associations between malnutrition and healthcare costs in 2024 Swedish kronor (SEK) were analyzed using two-part models and generalized linear regression models, adjusting for demographic and clinical factors. Findings In the community, at risk of malnutrition and malnutrition were associated with an increase in annual healthcare costs of 2267 SEK (95% CI: 64,4469) and 1846 SEK (95% CI: -6802,10493), respectively. In geriatric patients, healthcare costs over 6 months in individuals at risk of malnutrition and individuals with malnutrition were 60205 SEK (45613,74798) and 86619 SEK (68362,104875) higher than those without malnutrition. In people with cognitive impairment, malnutrition was associated with higher annual healthcare costs (22170 SEK, 95% CI: 15152,29188). Interpretation Both at risk of malnutrition and malnutrition are associated with higher healthcare costs in Swedish older adults. The study findings are important for informing future economic evaluations of malnutrition interventions in Swedish older adults.

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Using opioid analgesia for chronic pain in adults aged 85+: a qualitative study

Faux-Nightingale, A.; Woodcock, C.; Walker, C.; Smith, H. E.; Welsh, V. K.

2026-06-08 geriatric medicine 10.64898/2026.06.08.26354706 medRxiv
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Background Chronic pain is common in adults aged 85 years and older (85+) and is associated with detrimental outcomes. Chronic pain guidelines advise first line management with non-pharmacological measures; paracetamol and non-steroidal anti-inflammatory drugs are the preferred analgesics. Challenges in accessing non-pharmacological therapies for adults aged 85+, and the presence of multimorbidity and polypharmacy, mean that opioid medication is often prescribed for chronic pain despite the potential for opioid-related adverse effects and guidance identifying long-term opioids for chronic pain as a potentially inappropriate prescription. Aim This study aims to explore patient, caregiver, and healthcare professional perspectives on the prescription of opioid medications for pain management for chronic pain in adults aged 85+ to support development of resources for optimising opioid prescribing. Design and Setting In this qualitative study, participants were recruited through primary care, in the community or in care home settings. Method 36 semi-structured interviews were conducted with care home residents and community dwellers aged 85+ (n=12), caregivers (informal and care home staff) (n=12), and healthcare professionals (n=12). Interviews were transcribed and analysed using reflexive thematic analysis. Results Four themes were developed: contextual complexity, satellite influences, balancing act, and pragmatic prescribing. Using opioids in adults aged 85+ is a balancing act to support patients best possible quality of life within their unique circumstances whilst using the pain management tools available. Conclusion Opioids continue to have an important role in pain management in adults aged 85+ largely due to paucity of alternatives and the drive to support quality of life.

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Emergency dementia crisis care: Exploring health care staff views on crisis care optimisation across emergency services in England

Mirea Conley, E.; Bell, G.; Fountain, J.; Cadar, D.; Tabet, N.; Bosco, A.

2026-06-09 psychiatry and clinical psychology 10.64898/2026.06.08.26355155 medRxiv
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Background: In the UK, over 36 million contacts are made annually by people living with dementia (PLWD) to either primary or secondary community mental health services. As dementia progresses, PLWD may experience increased distress and resort to 999 calls for an ambulance, which may in turn result in conveyance to Accident & Emergency (A&E). Nearly 1 million A&E attendances are made by PLWD. This trend is set to rise sharply as the prevalence rates of dementia increase over time and as the condition progresses, with associated healthcare costs impacting overall care delivery. This may lead to reduced resource allocation for dementia emergency services, negatively affecting the experiences of both providers and service users. Aim(s): To explore ways to improve access and quality of care to emergency crisis care for PLWD from the perspective of healthcare staff providing this type of support. Methods: This qualitative study explored (1) the experiences, resources, and needs of healthcare professionals in emergency and community settings to support access for PLWD, and (2) the mechanisms influencing dementia crisis response. The COREQ Checklist was used to improve transparency, credibility, and reproducibility. Inter-rater reliability was calculated. PPIE contributors co-developed recommendations for healthcare professionals, and study findings informed a comic-based dissemination resource shared with third-sector organisations to support community awareness and engagement. Results: Fifteen interviews were held with emergency services staff. Inter-rater reliability was substantial between two raters (k = 0.62). Four overarching themes, with associated subthemes, were identified relating to crisis care delivery, barriers to effective response, and strategies employed to address these challenges. Additional themes captured decision-making processes at key points in the care pathway, including initial crisis response, during intervention, and at discharge from emergency and community services. Decision-making was characterised by the need to balance patient safety with autonomy in determining care in the best interests of PLWD and their informal carers. Discussion: This exploratory study reveals frontline staff perspectives on challenges and actionable strategies for dementia crisis care. Findings support targeted service improvements, cross-sector collaboration, and co-produced resources to enhance outcomes for PLWD and their informal carers.

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Psychosocial outcomes of a multidomain lifestyle and empowerment program for mild cognitive impairment

Vickers, K. L.; De Wit, L.; Goldstein, F. C.; Thelin, J.; Giannotto, E. L.; Saurman, J. L.; Levey, A. I.; Rodriguez, A. D.

2026-05-26 psychiatry and clinical psychology 10.64898/2026.05.21.26353503 medRxiv
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Background: Individuals with mild cognitive impairment (MCI) experience cognitive and functional declines that can negatively impact mood and reduce feelings of self-efficacy. These changes can also lead to elevated distress in care partners (CPs). Therefore, interventions that address quality of life and psychosocial factors in people with MCI and their CPs are needed. Objective: The present study evaluated the impact of a multidomain lifestyle program, the Cognitive Empowerment Program (CEP), on changes in psychosocial functioning, particularly empowerment, in people with MCI and their CPs. Methods: Participants were 94 people with MCI (Mean= 75.1 years old, 45.7% female, 81.9% white) and their CPs (Mean= 69.1 years old, 71.3% female, 87.3% white) that completed the 12-month CEP program comprised of physical, cognitive, and psychosocial interventions. Questionnaires were administered pre- and post-program to assess empowerment, self-efficacy, meaning and purpose, depression, and stress in participants with MCI alongside empowerment, depression, stress, and caregiving burden in CPs. Results: After completing the CEP program, participants with MCI endorsed higher empowerment and self-efficacy as well as fewer symptoms of depression and perceived stress. CPs endorsed feeling more empowered despite elevated caregiver burden. Conclusions: These results suggest multidomain lifestyle programs can positively impact wellbeing in MCI. Future research should focus on refining delivery models, exploring integration with pharmacological treatments, prioritizing inclusion of diverse populations, and measuring long-term outcomes to strengthen the reach and impact of programs like CEP.

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Comparing palliative care quality between designated and non-designated cancer hospitals: A secondary analysis of bereaved family surveys

Ito, S.; Miyashita, M.; Takahashi, R.; Nakazawa, Y.; Ogawa, A.; Yotani, N.; Hamano, J.

2026-05-19 palliative medicine 10.64898/2026.05.14.26353232 medRxiv
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Background: The quality of palliative care in non-designated cancer hospitals, where approximately 70% of deaths of patients with cancer occur, remains unevaluated. This study aimed to clarify the quality of palliative care in these hospitals by comparing patient characteristics and evaluating the quality of palliative care provided by bereaved families. Methods: A questionnaire survey was conducted among bereaved family members of patients with cancer who died in 2018 at designated and non-designated cancer hospitals (excluding palliative care units). We compared the two groups regarding patient and bereaved family characteristics, quality assessment of palliative care (including Memorial Symptom Assessment Scale [MSAS]), care satisfaction, and the presence of end-of-life discussions. Results: In total, 27,944 bereaved family members agreed to participate. The mean age at death was 73.2 ({+/-}11.9) and 79.7 ({+/-}10.9) years for designated and non-designated cancer hospitals, respectively (p < 0.001, Effect Size [ES] = 0.55). The mean MSAS total score (symptom intensity) was significantly higher for designated cancer hospitals than for non-designated cancer hospitals, even after adjusting for patient characteristics (p < 0.001, ES = 0.39). Conversely, the mean adjusted overall satisfaction was significantly higher in non-designated cancer hospitals (p < 0.001, ES = 0.21) than in designated cancer hospitals. Conclusions: Non-designated cancer hospitals had older and less symptomatic patients than designated cancer hospitals. However, there was no significant clinical difference in the quality of palliative care, as assessed by the bereaved families.

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Comparing cannabinoid extracts for treating cancer-related symptoms: a randomized placebo-controlled, triple-blind aggregate n-of-1 clinical trial

Hawley, P. H.; Wade, K.; Daeninck, P.; Fitzgibbon, E.; Kerba, M.; Goldie, C.; Kopoplovic, I.

2026-06-02 palliative medicine 10.64898/2026.05.31.26354558 medRxiv
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Context Despite widespread use of medical cannabinoids for cancer-related symptom management, systematic reviews consistently call for more clinical trial evidence. Objectives This study aimed to determine and explore responses to medical cannabis extracts for cancer-related symptoms using patient-centred methodology. Methods An aggregate N-of-1 study of clinically stable but symptomatic outpatients from 8 Canadian cancer centres, comparing three blinded sublingual extracts (THC; CBD; 1:1) with placebo, self-titrated within a prescribed schedule for four consecutive days each in randomized sequence for up to three cycles (total 16-48 days). The primary outcome was the frequency of at least a 1.4-point (20%) improvement in a 7-point Patient Global Impression of Change (PGIC) for at least one extract over placebo. Results The primary outcome was achieved in 50/89 (56%) participants (p<0.001), with no significant preference of one extract over another on average, but a clear preference between extracts for most individuals. Changes in a modified Edmonton Symptom Assessment score and participant preference (n=91) confirmed these findings. Improved sleep, tiredness and anxiety contributed most to the overall improvement regardless of primary symptom. There were no demographic predictors of response. Mild adverse effects were common with all extracts including placebo but resolved rapidly on dose reduction/cessation. Moderate/severe adverse effects were rare but associated with THC. Conclusions Medical cannabis extracts can be meaningfully beneficial for cancer-related symptoms in approximately 50% of patients, particularly for sleep and related symptoms. A starting dose of 2.5mg of THC/CBD three times a day was well-tolerated. Personalization of treatment is required to optimize response.

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The effect of physical activity timing on insomnia and sleep quality: a randomized cross-over trial in older adults

Albalak, G.; Noordam, R.; van der Elst, M.; Drop, T.; Caneda Cabrera, E.; Oudendijk, L.; Lammers, G. J.; Gordijn, M.; Kervezee, L.; Exadaktylos, V.; van Bodegom, D.; van Heemst, D.

2026-05-20 geriatric medicine 10.64898/2026.05.18.26353463 medRxiv
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Background Insomnia symptoms are common in older adults. While observational studies suggest physical activity (PA) timing affects health outcomes, its effect on sleep remains unclear. We compared morning versus evening PA effects on insomnia severity and sleep quality in older adults with insomnia symptoms. Methods Eligible participants were aged 60 to 80 years with (sub)clinical insomnia (Insomnia Severity Index [ISI] score [&ge;]10). In a randomized cross-over trial, participants engaged in coached PA in the morning (10:00 - 11:00) or evening (19:30 - 20:30) for 14 days each. ISI scores were assessed post-intervention. Objective sleep parameters; duration, latency, efficiency, and timing, were assessed with a Withings Sleep Analyzer under the mattress. Subjective sleep quality was reported daily via smartphone app. Salivary dim light melatonin onset (DLMO) was measured on the final day of each intervention. Results Of 37 participants (mean ISI 14.3 {+/-} 3.3), 27 completed the study (mean age 69.8 {+/-} 5; 63% women). ISI scores improved after both morning ({Delta} - 2.5; 95% CI: - 1.14, - 3.83) and evening ({Delta} - 2.0; 95% CI: - 0.63, - 3.38) activity relative to baseline, but were not different between interventions. Compared to evening activity, sleep midpoint occurred earlier with morning activity (03:40 vs 04:00; {Delta} - 20 min; 95% CI: - 31, - 8). No differences in subjective sleep quality or DLMO were found. Exploratory analyses suggested insomnia scores improved specifically in late chronotypes following morning activity. Conclusions While morning vs. evening PA timing did not impact most sleep quality measures, it influenced sleep timing. Larger studies are needed to define optimal and personalized PA timing for improving sleep.

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Dementia and Frailty Impact Postoperative Care Trajectories and Burden among Older Adults Undergoing Radical Cystectomy for Bladder Cancer

Ernandez, J.; Xiang, L.; Adler, R.; Hsu, J.; Shah, S. K.; Kim, D.; Gershman, B.; Mossanen, M.; Weissman, J. S.

2026-06-06 urology 10.64898/2026.06.04.26354768 medRxiv
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OBJECTIVE: Bladder cancer (BC) is predominantly a disease of older, comorbid adults, and radical cystectomy (RC), which is the gold standard treatment, carries considerable morbidity. We sought to determine the impact of baseline dementia and frailty on the care trajectory beyond the immediate postoperative period. We hypothesized that frail patients and those with dementia undergoing RC for BC will have poorer care trajectories. METHODS AND MATERIALS: We identified Medicare beneficiaries [&ge;] 66 years old who underwent RC for BC in 2017 with 12 months of pre- and post-RC enrollment. Frailty and dementia were characterized using validated, claims-based measures. Associations between baseline frailty and dementia with postoperative care trajectory outcomes were determined using Fine-Gray competing risk models. RESULTS: We identified 3,600 beneficiaries of whom 11.6% were frail and 3.4% met criteria for dementia. Patients with dementia were more likely to be frail, comorbid, and not receive standard-of-care neoadjuvant chemotherapy. Frailty was independently associated with [&ge;] 2 transitions in care level after index discharge from RC and skilled nursing facility (SNF) admissions within 1 year of RC, exposure to intensive post-RC interventions, including dialysis and feeding tube placement, and poorer survival. Dementia remained associated with SNF admissions regardless of frailty level. CONCLUSIONS: Among a contemporary cohort of older adults undergoing RC for BC, preoperative dementia and frailty were independently associated with poorer care trajectory beyond the immediate postoperative period after RC. Our work highlights a role for preoperative geriatric assessment in identifying and optimizing patients at greatest risk.

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A Pilot Randomized Controlled Trial to Evaluate the Preliminary Efficacy of PAL-CHW-PDAC, a Digitally Enhanced CHW-led Intervention to Facilitate Stepped Palliative Care in Patients with Pancreatic Cancer.

Thiruvengadam, N.; Celestin-Joachim, M.; Rivas, L.; Bahmani, A.; Orosa, M.; Matangi, N.; Montgomery, S.; Ferrell, B.

2026-05-22 palliative medicine 10.64898/2026.05.20.26353748 medRxiv
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Background Pancreatic Ductal Adenocarcinoma will be the 2nd-most common cause of cancer mortality by 2030. It is associated with rapid deterioration, severe symptoms, and significant quality-of-life concerns. Using input from patients, family caregivers (FCGs), and provider stakeholders, we designed an intervention, PAL-CHW-PDAC, delivered by a community health worker that involves proactive symptom monitoring and management, care navigation, and disease education. Methods We conducted a pilot randomized controlled trial of 60 patients with newly diagnosed PDAC (within 2 weeks of diagnosis) and their caregivers at Loma Linda University Health from 09/2025 to 05/2026. Patients were randomized 1:1 to receive the PAL-CHW-PDAC intervention (6 CHW visits over 3 months) or an attention control. The control comparator involved receiving standard handouts and videos on pancreatic cancer, along with check-in visits with research staff. The primary outcome was symptom burden, defined using the NCCN/FACT Hepatobiliary Symptom Index. Secondary outcomes included quality of life (QoL) measured by the FACT-Hep and psychological distress (measured by the NCCN-Distress Thermometer). Caregiver outcomes included burden, preparedness, quality of life, and psychological distress. Results: 60 out of 74 eligible (81%) were enrolled. The median age was 71, 60% of patients were Hispanic. 68% of patients presented with metastatic PDAC, 23% with borderline resectable disease and 9% with resectable PDAC. There was a trend towards improved symptom burden at 12 weeks (mean increase of 5.3 points vs. decrease of 3.2 points; p=0.093) with the intervention compared to the attention control. The intervention group also had improved psychological distress at 12 weeks (3.31 vs. 5.95, p=0.01), caregiver psychological distress (3.26 vs. 6.86, p<0.001) and caregiver preparedness (2.92 vs. 2.11) at 12 weeks. Telehealth utilization for symptom-focused visits improved with the intervention (82%) compared to the control. (14%, p=0.01) Hospice utilization also improved with the intervention (41% vs 7%, p-0.12). Conclusions: A pilot RCT of the PAL-CHW-PDAC intervention demonstrated preliminary efficacy with a trend towards improved symptom burden, psychological distress, and caregiver psychological distress and preparedness. A larger definitive clinical trial is needed to understand the impact of this promising intervention. ClinicalTrials.gov number, NCT07591571

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Systematic Analysis of Housing Referral Outcomes in New York City's WholeYouNYC Social Care Network: Identifying Barriers to Service Connection

Conde, F.

2026-05-22 health systems and quality improvement 10.64898/2026.05.19.26353634 medRxiv
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Background: Health-related social needs (HRSNs), particularly housing instability, are significant drivers of poor health outcomes among Medicaid populations. New York State's Social Care Networks (SCNs) aim to systematically connect members to housing services through coordinated referral systems. However, limited systematic analysis of referral patterns hinders quality improvement efforts. We analyzed housing referral outcomes and workflows to identify barriers to successful service connections. Methods: We conducted a mixed-methods quality improvement study at Public Health Solutions' WholeYouNYC SCN Coordination Center. Quantitative analysis examined 4,258 housing referrals submitted between June 2025 and January 2026, extracted from the Unite Us platform via Power BI dashboard. We calculated acceptance rates, analyzed time metrics, and examined outcomes by receiving organization. Qualitative data were collected through structured consultations with 7 staff members (5 navigators, 2 supervisors) and review of internal workflow documentation. Process mapping identified workflow bottlenecks. Results: Of 4,258 housing referrals, only 45% (n=1,936) were accepted by receiving organizations, while 19% (n=815) were rejected and 32% (n=1,382) remained awaiting response with no recorded action. Average time to acceptance was 8 days for accepted referrals. Acceptance rates were consistent across top receiving organizations (44-46%), suggesting systemic rather than partner-specific barriers. Analysis of unresolved referrals revealed prolonged cases, with the longest pending 271 days. Three critical workflow bottlenecks were identified: CBO response delays, missing housing documentation, and challenges with client engagement. Conclusions: Low housing connection rates (45%) and prolonged unresolved referrals (up to 271 days) indicate systemic barriers requiring interventions at multiple levels. Recommendations include establishing CBO response time benchmarks, implementing automated follow-up protocols, standardizing documentation requirements, and enhancing real-time data monitoring. These findings provide an evidence-based framework for quality improvement in social care coordination programs.

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APOE-specific Cognitive Effects of Levetiracetam in Mid-Age Adults

Lancaster, C.; Dowell, N. G.; Tertikas, G.; Bakker, A.; Bird, C. M.; Tabet, N.; Rusted, J.

2026-05-21 psychiatry and clinical psychology 10.64898/2026.05.14.26352135 medRxiv
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Background: Low-dose levetiracetam is under investigation as a potential treatment for slowing Alzheimer's Disease progression. This study tests whether levetiracetam enhances executive function in mid-age adults, and whether drug effects differ by Apolipoprotein e4 (APOE4+) genetic risk status. Methods: Fifty-eight adults (aged 45-65 years; 27 APOE33; 31 APOE4+) participated in a double-blind, placebo-controlled study of low-dose levetiracetam (125mg bidaily for two-weeks). At the end of each treatment phase, participants completed a switch-inhibition task. Results: Mid-age APOE4+ carriers were significantly slower and showed a greater cost of increasing executive demand than APOE33 individuals. Response times were quicker under levetiracetam, with increased benefits reported in APOE33 individuals, at younger ages, and in individuals with reduced levels of plasma-based biomarkers. Levetiracetam selectively benefitted accuracy in APOE33 individuals. Conclusion: Low-dose levetiracetam enhances executive function in midlife, particularly in individuals at lower risk of Alzheimer's Disease based on age, APOE4 genotype, and proxies of neuropathology.

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Delirium and Increased Risk of Developing Dementia: An Emulated Target Trial Analysis

Rathmell, C. S.; Sun, H.; Ge, W.; Magdamo, C.; Das, S.; Moura, L. M. V. R.; Zafar, S. F.; Akeju, O.; Mukherji, S. S.; Shaw, K. M.; Westover, M. B.

2026-05-14 neurology 10.64898/2026.05.11.26352925 medRxiv
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BackgroundMultiple studies suggest bidirectional links between delirium and Alzheimers Disease and Related Dementias (ADRD). Although they establish a strong association between delirium and subsequent ADRD, it has not been explored using statistical causal inference which makes the best use of observational data to minimize biases. MethodsWe conducted an emulated clinical trial to estimate the effect of experiencing delirium during hospitalization between April 2017 and September 2019 on the cumulative incidence of ADRD over two years following hospital admission in patients 65 and older. The emulated trial used observational data from individuals in the Mass General Brigham Electronic Medical Record (EMR). We carried out statistical causal survival analysis using methods that adjust for confounding, censoring, competing risks, and immortal-time bias, including inverse propensity weighting (IPW) and g-formula approaches. ResultsOf the 6029 patients hospitalized in this time frame who were 65 or older with evidence of a PCP in the EMR, 5901 were included in the analysis based on no history of dementia diagnosis or medications 12 months prior to admission. At two years post-admission, the adjusted cumulative incidence of ADRD in individuals who did not experience delirium was 7.6% (95% Confidence Interval [CI] 4.0-12.1%) while it was 20.2% (95% CI 13.2-27.9%) for those who did experience delirium when calculated using the IPW method. ConclusionsOur emulated trial results argue for a strong association between delirium during hospitalization and the risk of developing ADRD in the two years following hospital admission in individuals 65 and older. Key PointsO_ST_ABSQuestionC_ST_ABSWe sought to answer whether statistical causal inference would show the same association between delirium and the onset of dementia in the two years following hospitalization. FindingsOur emulated trial results argue for a strong association between delirium during hospitalization and the risk of developing ADRD in the two years following hospital admission in individuals 65 and older. MeaningThe implications of demonstrating this relationship underscore the importance of delirium-mitigating interventions for long-term cognitive outcomes.

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Burden Of Community-Acquired Pneumonia In Hungary: A Nationwide Analysis Of Incidence, Hospitalization Rates And Mortality Between 2016 And 2020

Kiss, Z.; Meszner, Z.; Kulcsar, A.; Bogos, K.; Habon, T.; Moldvay, J.; Papai-Szekely, Z.; Tamasi, L.; Torzsa, P.; Voko, Z.; Wittmann, I.; Molnar, G. A.; Rokszin, G.; Kovacs, V.; Abonyi-Toth, Z.; Barcza, Z.; Szabo, T. G.; Varnai, M.; Odhiambo, R.; Berta, A.; Darida, M.; Horvath, I.; Kovacs, K. A.; Neuhauser, N.; Lakatos, B.; Muller, V.

2026-05-28 infectious diseases 10.64898/2026.05.27.26354111 medRxiv
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Background: Community-acquired pneumonia (CAP) remains a major global health burden disproportionately affecting older adults and people with comorbidities, with Streptococcus pneumoniae as one of the leading bacterial causes in Europe. The Hungarian Occurrence and Burden of PnEumonia (Hungarian-HOPE) study examined the incidence, hospitalization rates, and mortality of CAP between 2016 and 2020 in Hungary. Methods: The National Health Insurance Fund database was used to identify adult CAP patients (all-cause) based on ICD-10 codes J10-18. Outcomes included CAP incidence, 0-15-day hospitalization, and 0-30-day mortality after hospitalization, stratified by age, sex, and comorbidities (chronic obstructive pulmonary disease [COPD], asthma, cardiovascular disease [CVD], and type 1 and 2 diabetes [T1DM, T2DM]). Risk maps visualized relative risk gradients across population strata. Results: During the pre-pandemic period (2016-2019), over 100,000 CAP cases and more than 50,000 hospitalizations were recorded annually. In 2020, recorded cases fell to approximately 98,000, while hospitalizations increased to 66,200. Hospitalization rates increased from 25.1% in 2016 to 29.1% in 2019, then increased to 43.1% in 2020. The 30-day mortality among hospitalized patients rose from 22.7% in 2016 to 23.6% in 2019. Incidence, hospitalization, and mortality all increased with age. Relative to healthy males aged 30-39 years, CAP risk escalated steeply in the [&ge;]80 years cohort (incidence 5-15-fold; hospitalization >3-fold; mortality 11-24-fold) and was further amplified by COPD, CVD, or T2DM, with a lesser effect for T1DM. Conclusions: The results highlight the substantial age- and comorbidity-driven CAP burden in Hungary and support prioritization of preventive strategies including pneumococcal vaccination for older adults and high-risk groups.

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VACS 2.0 Frailty Index Correlates with Soluble TNF Receptor Levels in Aging Veterans

Carbone, S.; Wilson, B.; Kowal, C.; Dolinar, T.; Kostadinova, L.; Anthony, D. D.; Shive, C. L.

2026-05-26 geriatric medicine 10.64898/2026.05.24.26353987 medRxiv
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The VACS 2.0 Frailty Index was developed using the VA health records system to identify frailty and predict mortality in older Veterans that were living with HIV. Systemic inflammatory indices have been associated with frailty, but little is known about the association between frailty and immunosenescence. We aim to investigate the potential link between soluble inflammatory indices, T cell expression of exhaustion and senescence markers, and frailty as measured by the VACS 2.0 index. We analyzed a one-time blood draw for plasma levels of inflammatory indices, T cell subsets and expression of exhaustion and senescence markers, and calculated VACS 2.0 index scores in a cohort of 30 older (>65 years) Veteran participants. We found that VACS 2.0 scores correlated with the number of prescribed medications in the older Veterans. Soluble TNF receptor levels strongly correlated with VACS 2.0 frailty scores. How these soluble TNF receptors are generated and whether they mechanistically contribute to frailty warrants further investigation.