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Background and Aims: Liver fibrosis staging is challenging in patients with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Liver biopsies are invasive, whereas non-invasive tests such as vibration-controlled transient elastography (VCTE) can be inaccurate in patients with obesity. We hypothesized that endoscopic ultrasound shear wave elastography (EUS-SWE) is more accurate for liver fibrosis staging in patients with MASLD and obesity, and in this pilot study we aimed to test this hypothesis and establish optimal fibrosis stage cutoffs for EUS-SWE., Methods: This was a multicenter, cross-sectional study from prospectively collected data. Consecutive patients who underwent EUS-SWE with subsequent liver biopsy were included. EUS-SWE was compared to Fibrosis-4 Index (FIB-4) and VCTE. Area under the receiver operator characteristic (AUROC) curve analysis was performed, and 90% sensitivity and specific cutoffs were calculated to determine optimal cutoffs., Results: 62 patients were included. Mean body mass index was 40.74kg/m 2 . EUS-SWE was superior to FIB-4 in discriminating significant fibrosis (F2; AUROC 0.87 vs 0.61, p<0.0048) and advanced fibrosis (F3; AUROC 0.93 vs 0.63 p<0.0001), but not cirrhosis (F4; AUROC 0.95 vs 0.81, p=0.099). EUS-SWE was superior to VCTE in predicting advanced fibrosis and cirrhosis (p=0.0067 and 0.0022 respectively). 90% sensitivity cutoffs for EUS-SWE were 7.50, 8.48, and 11.30 for F2-F4 respectively, and 90% specificity cutoffs were 9.82, 10.20, and 14.60 respectively., Conclusions: In this pilot study, EUS-SWE was superior to FIB-4 and VCTE for liver fibrosis staging in patients with MASLD and obesity (Clinical trial registration number: NCT05728697)., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Difficult biliary cannulation (DBC) is a known risk factor for developing post-ERCP pancreatitis (PEP). To better understand how DBC increases PEP risk, we examined the interplay between technical aspects of DBC and known PEP risk factors., Methods: This was a secondary analysis of a multicenter, randomized controlled trial comparing rectal indomethacin alone with the combination of rectal indomethacin and prophylactic pancreatic duct (PD) stent placement for PEP prophylaxis in high-risk patients. Participants were categorized into 3 groups: 1) DBC with high pre-procedure risk for PEP, 2) DBC without high pre-procedure risk, and 3) non-DBC at high pre-procedure risk., Results: In all, 1601 (84.1%) participants experienced DBC, which required a mean of 12 (SD 10) cannulation attempts and mean duration of 14.7 minutes (SD 14.9). PEP rate was highest (20.7%) in DBC with high pre-procedure risk, followed by non-DBC with high pre-procedure risk (13.5%) and then DBC without high pre-procedure risk (8.8%). Increasing number of PD-wire passages (aOR:1.97, 95% CI:1.25-3.1) was associated with PEP in DBC, but PD injection, pancreatic sphincterotomy and number of cannulation attempts were not associated with PEP. Combining indomethacin with PD stenting lowered PEP risk (aOR:0.61, 95% CI:0.44-0.84) in DBCs. This protective effect was evident in up to at least 4 PD wire passages., Conclusions: DBC confers higher PEP risk in additive fashion to pre-procedural risk factors. PD wire passages appear to add the greatest PEP risk in DBCs, but combining indomethacin with PD stenting reduces this risk, even with increasing PD wire passages., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Data on endoscopic outcomes in adults without diabetes who are taking glucagon like peptide receptor agonist (GLP-1 RA) is limited so we aimed to compare repeat esophagogastroduodenoscopy (EGD) in this population to those without GLP-1 using retrospective matched case-control study., Methods: Using TriNetX (Cambridge, MA), adults with BMI of ≥27 kg/m2 without diabetes who underwent diagnostic EGD were analyzed. Study group included individuals with ≥3 GLP-1 prescriptions and EGD ≥30 days after initial GLP-1 prescription. Control group was never prescribed GLP-1 RAs but had EGD after prescription of other weight loss medications. Outcomes were compared using risk-ratio in matched cohorts., Result: No significant difference in repeat EGD (5.4% vs 4.2%, RR 1.28, 0.95-1.71) or new diagnosis of gastroparesis (1.1% vs 0.6%, RR 2.00, 0.94-4.27) was noted between the groups., Conclusion: GLP-1 RAs may not substantially increase the risk of repeat endoscopy in individuals without diabetes., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Objectives: As thyroid disorders are common amongst the elderly, this study aims to evaluate the reference interval (RI) for thyroid stimulating hormone (TSH) in healthy adults aged 70 years and over., Methods: A proposed RI was determined from the Australian participants of the ASPirin in Reducing Events in the Elderly (ASPREE) randomised trial. Participants had no history of cardiovascular disease, thyroid cancer, dementia, or life-threatening illnesses. Participants prescribed with any thyroid-related medication at baseline were excluded. TSH levels were measured using a commercial chemiluminescence microparticle immunoassay. The RI was determined using the middle 95th percentile of the logarithmic transformed data of baseline TSH. Cox proportional hazard regression models were used to validate the RI by assessing disease incidence over time., Results: A total of 10,995 participants had baseline TSH measures. Median (IQR) age was 73.9 (71.8-77.3) years. We propose a RI of 0.34-3.75 mU/L. TSH levels did not differ by age or sex. At baseline, there was no association between symptoms associated with thyroid disease and levels of TSH. Over the follow-up period of up to 11 years, no association was seen between baseline TSH levels and relevant disease outcomes for participants within the RI., Conclusions: From a group of initially healthy, community-dwelling adults aged >=70 years, we propose a RI of TSH to best represent euthyroidism. This concentration was not associated with an increased risk of thyroid related symptoms or outcomes, confirming its appropriateness for clinical use., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Objective: This study investigated the association between gait speed, handgrip strength, and their combination, and the risk for developing clinically relevant depressive symptoms in community-dwelling older adults., Methods: A secondary analysis was conducted using data from the ASPirin in Reducing Events in the Elderly study. Participants were community-dwelling older adults in Australia and the United States of America followed for a median (interquartile range) of 3.97 (2.26) years. Baseline handgrip strength and gait speed were used as exposure variables, and their combination categories were also explored. Depression was measured using the modified Center for Epidemiological Studies Depression 10-item scale (CES-D 10). Cox regression was used to estimate Adjusted Hazard Ratios (AHR) with 95 % Confidence Intervals (CI) after adjusting for a range of potential confounders., Result: A total of 17,231 participants (55.3 % women) were included in the analysis. Slow gait and weak grip at baseline were associated with the risk of depression (AHR: 1.20; CI: 1.11-1.29 and 1.14; 1.06-1.23, respectively). The combination of the two physical performance measures was associated with a 31 % increase in the risk of depression (1.31; 1.16-1.47) and a significant dose-response association was observed for quintiles of gait and grip with depression., Limitations: Although the CES-D 10 is a validated scale, it is a self-reported tool rather than a clinical diagnosis of depression., Conclusion: Low physical function may be a risk factor for depression in older adults. This highlights the inextricable link between the physical and mental health of older adults, which can inform potential clinical and public health prevention strategies for depression in later life., Competing Interests: Declaration of competing interest TC has received honoraria for lectures from Roche. The authors declare no conflicts of interest., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Background: During the COVID-19 pandemic, weight loss programs rapidly transitioned to a virtual model, replacing in-person clinic visits. We sought to compare the observed weight loss and adherence to treatment between patients referred for intensive behavioral therapy (IBT) who were treated via telemedicine and those treated in person., Methods: After IRB approval, we conducted a retrospective observational study of patients referred for clinical bariatric IBT between January 2019 and June 2021 who were followed in person or via telemedicine. The primary endpoint was the percentage of excess BMI loss (EBL%); secondary endpoints included treatment adherence, duration of follow-up, and number of completed visits., Results: During the study period, 139 patients were seen for at least one IBT session for weight management: 62 were followed up in person (IP) and 77 via telemedicine (TM). The mean age, baseline BMI, and follow-up duration between the groups were similar. In the IP and TM groups, the EBL% was -24.7 ± 24.7 and -22.7 ± 19.5 (P = 0.989) and loss to follow-up after the first visit was 27.4% and 19.5% (P = 0.269), respectively., Conclusion: For the management of obesity, weight loss programs delivered via telemedicine can achieve similar outcomes to those provided via classical in-person visits. This study suggests that the integration of telecare into clinical practice in bariatric medicine should be considered in the future. Emerging technologies may allow adequate patient follow-up in multiple scenarios, specifically non-critical chronic disorders, and bring unanticipated benefits for patients and healthcare providers., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Studies on middle-aged or individuals with cognitive or cardiovascular impairments, have established that intensive blood pressure (BP) control reduces cognitive decline risk. However, uncertainty exists on differential effects between antihypertensive medications (AHM) classes on this risk, independent of BP-lowering efficacy, particularly in community-dwelling hypertensive older adults., Methods: A post-hoc analysis of the ASPREE study, a randomized trial of low-dose aspirin in adults aged 70+ years (65+ if US minorities) without baseline dementia, and followed for two years post-trial. Cox proportional-hazards regression models were used to estimate associations between baseline and time-varying AHM exposure and incident dementia (an adjudicated primary trial endpoint), in participants with baseline hypertension. Subgroup analyses included prespecified factors, APO ε4 carrier status and monotherapy AHM use., Results: Most hypertensive participants (9,843/13,916; 70.7%) used AHMs. Overall, 'any' AHM use was not associated with lower incident dementia risk, compared with untreated participants (HR 0.84, 95%CI 0.70-1.02, p=0.08), but risk was decreased when angiotensin receptor blockers (ARBs) were included (HR 0.73, 95%CI 0.59-0.92, p=0.007). ARBs and β-blockers decreased dementia risk, whereas angiotensin-converting enzyme inhibitors (ACEIs) and diuretics increased risk. There was no association with RAS modulating or blood-brain-barrier crossing AHMs on dementia risk., Conclusions: Overall, AHM exposure in hypertensive older adults was not associated with decreased dementia risk, however, specific AHM classes were with risk direction determined by class; ARBs and β-blockers were superior to ACEIs and other classes in decreasing risk. Our findings emphasize the importance of considering effects beyond BP-lowering efficacy when choosing AHM in older adults., Competing Interests: DISCLOSURES Dr. Shah reports being the site principal investigator or sub-investigator for Alzheimer’s disease clinical trials for which his institution (Rush University Medical Center) is compensated [Amylyx Pharmaceuticals, Inc., Athira Pharma, Inc., Edgewater NEXT, Eli Lilly & Co., Inc., Genentech, Inc.]. The remaining authors declare that they have no conflict of interests.

Introduction: Prophylactic pancreatic stent placement (PSP) is effective for preventing pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk cases, but the optimal technical approach to this intervention remains uncertain., Methods: In this secondary analysis of 787 clinical trial patients who underwent successful stent placement, we studied the impact of (i) whether pancreatic wire access was achieved for the sole purpose of PSP or naturally during the conduct of the case, (ii) the amount of effort expended on PSP, (iii) stent length, (iv) stent diameter, and (v) guidewire caliber. We used logistic regression models to examine the adjusted association between each technical factor and post-ERCP pancreatitis (PEP)., Results: Ninety-one of the 787 patients experienced PEP. There was no clear association between PEP and whether pancreatic wire access was achieved for the sole purpose of PSP (vs occurring naturally; odds ratio [OR] 0.82, 95% confidence interval [CI] 0.37-1.84), whether substantial effort expended on stent placement (vs nonsubstantial effort; OR 1.58, 95% CI 0.73-3.45), stent length (>5 vs ≤5 cm; OR 1.01, 95% CI 0.63-1.61), stent diameter (≥5 vs <5 Fr; OR 1.13, 95% CI 0.65-1.96), or guidewire caliber (0.035 vs 0.025 in; 0.83, 95% CI 0.49-1.41)., Discussion: The 5 modifiable technical factors studied in this secondary analysis of large-scale randomized trial data did not appear to have a strong impact on the benefit of prophylactic PSP in preventing PEP after high-risk ERCP. Within the limitations of post hoc subgroup analysis, these findings may have important implications in procedural decision making and suggest that the benefit of PSP is robust to variations in technical approach., (Copyright © 2024 by The American College of Gastroenterology.)

Background: Emerging data suggest that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve kidney outcomes for people with type 2 diabetes (T2D). Direct comparisons of the kidney and cardiovascular effectiveness of GLP-1 RA with sodium-glucose cotransporter 2 inhibitors (SGLT2i), a first-line therapy for this population, are needed., Objectives: The authors compared kidney and cardiovascular outcomes for new users of SGLT2i and GLP-1 RAs with T2D., Methods: Using propensity score overlap weighting, we analyzed electronic health record data from 20 U.S. health systems contributing to PCORnet between 2015 and 2020. The primary kidney outcome was a composite of sustained 40% estimated glomerular filtration rate (eGFR) decline, incident end-stage kidney disease, or all-cause mortality over 2 years or until censoring. In addition, we examined cardiovascular and safety outcomes., Results: The weighted study cohort included 35,004 SGLT2i and 47,268 GLP-1 RA initiators. Over a median of 1.2 years, the primary outcome did not differ between treatments (HR: 0.91; 95% CI: 0.81-1.02), although SGLT2i were associated with a lower risk of 40% eGFR decline (HR: 0.77; 95% CI: 0.65-0.91). Risks of mortality (HR: 1.08; 95% CI: 0.92-1.27), a composite of stroke, myocardial infarction, or death (HR: 1.03; 95% CI: 0.93-1.14), and heart failure hospitalization (HR: 0.95; 95% CI: 0.80-1.13) did not differ. Genital mycotic infections were more common for SGLT2i initiators, but other safety outcomes did not differ. The results were similar regardless of chronic kidney disease status., Conclusions: SGLT2i and GLP-1 RAs led to similar kidney and cardiovascular outcomes in people with T2D, though SGLT2i initiation was associated with a lower risk of 40% eGFR decline. (Evaluating Comparative Effectiveness of Empagliflozin in Type 2 Diabetes Population With and Without Chronic Kidney Disease; NCT05465317)., Competing Interests: Funding Support and Author Disclosures This study was funded by the Boehringer Ingelheim & Lilly Diabetes Alliance. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). Boehringer Ingelheim was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations. Dr Butler has received consultant honoraria from Abbott, American Regent, Amgen, Applied Therapeutic, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardiac Dimension, Cardior, CVRx, Cytokinetics, Edwards, Element Science, Innolife, Impulse Dynamics, Imbria, Inventiva, Lexicon, Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Roche, Sequana, SQ Innovation, and Vifor. Dr Pagidipati has received research support from Alnylam, Amgen, Boehringer Ingelheim, Eggland’s Best, Eli Lilly, Novartis, Novo Nordisk, and Verily Life Sciences; has served on consultation/advisory panels for Bayer, Boehringer Ingelheim, CRISPR Therapeutics, Eli Lilly, Esperion, AstraZeneca, Merck, Novartis, and Novo Nordisk; has served as an executive committee member for trials sponsored by Novo Nordisk and Amgen; has served on the Data Safety Monitoring Boards for trials sponsored by Johnson and Johnson and Novartis; and has served on the medical advisory board for Miga Health. Dr Fonseca has received research support (to Tulane) from Fractyl and Jaguar Gene Therapy; has received consultant honoraria from Asahi, Bayer, Abbott, Boehringer Ingelheim, and Corcept; has stock or stock options in Mellitus Health, BRAVO4Health, Amgen, and Abbott; and has patents pending for BRAVO risk engine for predicting diabetes complications and PAX4 gene therapy for type 1 diabetes. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Endoscopic liver "palpation" can be performed by indenting the liver surface under EUS. Indentation depth is measured with the use of sonographic calipers. We hypothesized that fibrotic livers are more difficult to indent, and that indentation can accurately predict liver fibrosis staging. We compared EUS-guided liver palpation and conventional screening modalities in patients with suspected metabolic dysfunction-associated steatotic liver disease., Methods: This was a cross-sectional pilot study. Consecutive patients at 3 hospitals from 2021 to 2023 underwent EUS-guided palpation with liver biopsy. Liver palpation was compared with fibrosis-4 index (FIB-4), aspartate transaminase to platelet ratio index (APRI), nonalcoholic fatty liver disease fibrosis score (NFS), and transient elastography in predicting fibrosis staging on histology. Area under the receiver operating characteristic curve analysis was performed., Results: Seventy-three patients were included. Mean age was 49.1 years, and 71.2% were female. Mean body mass index was 41.1 kg/m. 2 Indentation depth was negatively correlated with fibrosis stage (Kruskal-Willis test, P < .0001). EUS palpation demonstrated c-statistics of 0.79 and 0.95 in discriminating advanced fibrosis and cirrhosis, respectively. EUS liver palpation was superior to NFS in predicting advanced fibrosis (P = .0057) and superior to APRI and NFS in predicting cirrhosis (P = .0099 and P = .045, respectively). EUS palpation was not significantly different from FIB-4. EUS palpation was superior to transient elastography in predicting cirrhosis (P = .045). When optimal cutoffs were used, indentation measurement ≤3.5 mm yielded 100% predictive value for ruling in advanced fibrosis, and ≥4.0 mm yielded 100% predictive value for ruling out cirrhosis., Conclusions: EUS liver palpation is a novel, accurate, and easy-to-use screening tool for advanced fibrosis and cirrhosis in patients with metabolic dysfunction-associated steatotic liver disease., Competing Interests: Disclosure The following authors disclosed financial relationships: C. C. Thompson: Consultant, Apollo Endosurgery and Covidien/Medtronic; Venture Fund General Partner, BlueFlame Healthcare; Consultant/Research Support, Boston Scientific; Founder/Consultant/Board Member, Enterasense Ltd; Founder/Consultant/Board Member, EnVision Endoscopy; Research Support, ERBE; Consultant/Advisory Board, Fractyl; Consultant/Research Support, GI Dynamics; Founder/Consultant/Board Member, GI Windows; Consultant/Research Support, Olympus/Spiration; Consultant/Advisory Board Member/Research Support, USGI Medical; Consultant/Research Support, Fujifilm, Consultant/Research Support, Lumendi; Consultant, Xenter; Consultant/Research Support, Endoquest Robotics. K. Chang: Consultant for Olympus and Fujifilm. M. Ryou: Consultant for Olympus, Fujifilm, Cook, Boston Scientific, GI Windows Surgical, and EnteraSense. P. Jirapinyo: Consultant/Advisory Board Member/Research Support, Apollo Endosurgery; Consultant/Research Support, Boston Scientific; Consultant, ERBE; Consultant/Advisory board Member/Research Support, Fractyl; Research Support, GI Dynamics; Consultant, Spatz Medical; Research Support, USGI Medical. The other authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Introduction: There is limited evidence about factors related to the timeliness of dementia diagnosis in healthcare settings., Methods: In five prospective cohorts at Rush Alzheimer's Disease Center, we identified participants with incident dementia based on annual assessments and examined the timing of healthcare diagnoses in Medicare claims. We assessed sociodemographic, health, and psychosocial correlates of timely diagnosis., Results: Of 710 participants, 385 (or 54%) received a timely claims diagnosis within 3 years prior to or 1 year following dementia onset. In logistic regressions accounting for demographics, we found Black participants (odds ratio [OR] = 2.15, 95% confidence interval [CI]: 1.21 to 3.82) and those with better cognition at dementia onset (OR = 1.48, 95% CI: 1.10 to 1.98) were at higher odds of experiencing a diagnostic delay, whereas participants with higher income (OR = 0.89, 95% CI: 0.81 to 0.97) and more comorbidities (OR = 0.94, 95% CI: 0.89 to 0.98) had lower odds., Discussion: We identified characteristics of individuals who may miss the optimal window for dementia treatment and support., Highlights: We compared the timing of healthcare diagnosis relative to the timing of incident dementia based on rigorous annual evaluation. Older Black adults with lower income, higher cognitive function, and fewer comorbidities were less likely to be diagnosed in a timely manner by the healthcare system., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Importance: Black or African American (hereinafter, Black) and Hispanic or Latino/a/x (hereinafter, Latinx) adults are disproportionally affected by Alzheimer disease, but most research studies do not enroll adequate numbers of both of these populations. The Alzheimer's Disease Neuroimaging Initiative-3 (ADNI3) launched a diversity taskforce to pilot a multipronged effort to increase the study inclusion of Black and Latinx older adults., Objective: To describe and evaluate the culturally informed and community-engaged inclusion efforts to increase the screening and enrollment of Black and Latinx older adults in ADNI3., Design, Setting, and Participants: This cross-sectional study used baseline data from a longitudinal, multisite, observational study conducted from January 15, 2021, to July 12, 2022, with no follow-up. The study was conducted at 13 ADNI3 sites in the US. Participants included individuals aged 55 to 90 years without cognitive impairment and those with mild cognitive impairment or Alzheimer disease., Exposures: Efforts included (1) launch of an external advisory board, (2) changes to the study protocol, (3) updates to the digital prescreener, (4) selection and deployment of 13 community-engaged research study sites, (5) development and deployment of local and centralized outreach efforts, and (6) development of a community-science partnership board., Main Outcomes and Measures: Screening and enrollment numbers from centralized and local outreach efforts, digital advertisement metrics, and digital prescreener completion., Results: A total of 91 participants enrolled in the trial via centralized and local outreach efforts, of which 22 (24.2%) identified as Latinx and 55 (60.4%) identified as Black (median [IQR] age, 65.6 [IQR, 61.5-72.5] years; 62 women [68.1%]). This represented a 267.6% increase in the monthly rate of enrollment (before: 1.11 per month; during: 4.08 per month) of underrepresented populations. For the centralized effort, social media advertisements were run between June 1, 2021, and July 31, 2022, which resulted in 2079 completed digital prescreeners, of which 1289 met criteria for subsequent site-level screening. Local efforts were run between June 1, 2021, to July 31, 2022. A total of 151 participants underwent site-level screening (100 from local efforts, 41 from centralized efforts, 10 from other sources)., Conclusions and Relevance: In this cross-sectional study of pilot inclusion efforts, a culturally informed, community-engaged approach increased the inclusion of Black and Latinx participants in an Alzheimer disease cohort study.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in patients with diabetes; limited data suggested that statins may reduce the risk of NAFLD progression. This study aimed to examine the association between statins and the development or progression of NAFLD in veterans with diabetes. In a new-user negative control design, we conducted a retrospective propensity score (PS)-matched cohort study of patients with diabetes between 2003 and 2015. After excluding patients with other causes of liver disease, we formed PS using 85 characteristics. The primary outcome was a composite NAFLD progression outcome. Primary analysis examined odds of outcome in PS-matched cohort. Post-hoc analysis included a PS-matched cohort of statin users with intensive lowering of low-density lipoprotein-cholesterol (LDL-C) vs low-intensity lowering. We matched 34,102 pairs from 300,739 statin users and 38,038 non-users. The composite outcome occurred in 8.8% of statin users and 8.6% of non-users (odds ratio (OR) 1.02, 95% confidence interval (95% CI) 0.97-1.08). In the post-hoc analysis, intensive lowering of LDL-C compared to low-intensity showed increased NAFLD progression (OR 1.21, 95% CI 1.13-1.30). This study showed that statin use in patients with diabetes was not associated with decreased or increased risk of NAFLD progression. Intensive LDL-C lowering, compared to low-intensity LDL-C lowering, was associated with an increased risk of NAFLD progression., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The net benefit of aspirin cessation in older adults remains uncertain. This study aimed to use observational data to emulate a randomized trial of aspirin cessation versus continuation in older adults without cardiovascular disease (CVD)., Methods: Post hoc analysis using a target trial emulation framework applied to the immediate post-trial period (2017-2021) of a study of low-dose aspirin initiation in adults aged ≥ 70 years (ASPREE; NCT01038583). Participants from Australia and the USA were included if they were free of CVD at the start of the post-trial intervention period (time zero, T0) and had been taking open-label or randomized aspirin immediately before T0. The two groups in the target trial were as follows: aspirin cessation (participants who were taking randomized aspirin immediately before T0; assumed to have stopped at T0 as instructed) versus aspirin continuation (participants on open-label aspirin at T0 regardless of their randomized treatment; assumed to have continued at T0). The outcomes after T0 were incident CVD, major adverse cardiovascular events (MACE), all-cause mortality, and major bleeding during 3, 6, and 12 months (short-term) and 48 months (long-term) follow-up. Hazard ratios (HRs) comparing aspirin cessation to continuation were estimated from propensity-score (PS) adjusted Cox proportional-hazards regression models., Results: We included 6103 CVD-free participants (cessation: 5427, continuation: 676). Over both short- and long-term follow-up, aspirin cessation versus continuation was not associated with elevated risk of CVD, MACE, and all-cause mortality (HRs, at 3 and 48 months respectively, were 1.23 and 0.73 for CVD, 1.11 and 0.84 for MACE, and 0.23 and 0.79 for all-cause mortality, p > 0.05), but cessation had a reduced risk of incident major bleeding events (HRs at 3 and 48 months, 0.16 and 0.63, p < 0.05). Similar findings were seen for all outcomes at 6 and 12 months, except for a lowered risk of all-cause mortality in the cessation group at 12 months., Conclusions: Our findings suggest that deprescribing prophylactic aspirin might be safe in healthy older adults with no known CVD., (© 2024. The Author(s).)

Development of late-life mobility disability is a dynamic process of transitions between worsening and improving. We tested associations between participation in physical, social, and cognitive activity with mobility disability transitions. Participants (N=2,758, age 78.1 years [SD: 7.7]) from two Rush Alzheimer's Disease Center cohorts completed annual mobility disability questionnaires for 7.6 (SD: 4.4) years. First-order Markov transition models tested associations between baseline self-reported physical, social, and cognitive activity with bidirectional transitions in mobility disability score increases (worsening) and decreases (improving) between consecutive visits. Overall, 75.5% of participants experienced ≥1 transition among 18,318 pairs of consecutive visits-4,174 of which were worsening and 2,606 were improving transitions. Adjusting for covariates, higher participation in each activity type was associated with lower odds of worsening (physical OR=0.71, 95% CI: 0.67-0.75; social OR=0.64, 95% CI: 0.58-0.70; and cognitive OR=0.79, 95% CI: 0.74-0.85), and higher odds of improving (physical OR=1.20, 95% CI: 1.11-1.28; social OR=1.45, 95% CI: 1.30-1.61; and cognitive OR=1.12, 95% CI: 1.03-1.22) in separate models. In combined models, physical and social activity remained associated with worsening and improving; cognitive activity was only associated with worsening. Physical, social, and cognitive activity engagement contributes to lower odds of worsening mobility disability and may promote recovery., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In randomized clinical trials, treatment effects may vary, and this possibility is referred to as heterogeneity of treatment effect (HTE). One way to quantify HTE is to partition participants into subgroups based on individual's risk of experiencing an outcome, then measuring treatment effect by subgroup. Given the limited availability of externally validated outcome risk prediction models, internal models (created using the same dataset in which heterogeneity of treatment analyses also will be performed) are commonly developed for subgroup identification. We aim to compare different methods for generating internally developed outcome risk prediction models for subject partitioning in HTE analysis., Methods: Three approaches were selected for generating subgroups for the 2,441 participants from the United States enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) randomized controlled trial. An extant proportional hazards-based outcomes predictive risk model developed on the overall ASPREE cohort of 19,114 participants was identified and was used to partition United States' participants by risk of experiencing a composite outcome of death, dementia, or persistent physical disability. Next, two supervised non-parametric machine learning outcome classifiers, decision trees and random forests, were used to develop multivariable risk prediction models and partition participants into subgroups with varied risks of experiencing the composite outcome. Then, we assessed how the partitioning from the proportional hazard model compared to those generated by the machine learning models in an HTE analysis of the 5-year absolute risk reduction (ARR) and hazard ratio for aspirin vs. placebo in each subgroup. Cochran's Q test was used to detect if ARR varied significantly by subgroup., Results: The proportional hazard model was used to generate 5 subgroups using the quintiles of the estimated risk scores; the decision tree model was used to generate 6 subgroups (6 automatically determined tree leaves); and the random forest model was used to generate 5 subgroups using the quintiles of the prediction probability as risk scores. Using the semi-parametric proportional hazards model, the ARR at 5 years was 15.1% (95% CI 4.0-26.3%) for participants with the highest 20% of predicted risk. Using the random forest model, the ARR at 5 years was 13.7% (95% CI 3.1-24.4%) for participants with the highest 20% of predicted risk. The highest outcome risk group in the decision tree model also exhibited a risk reduction, but the confidence interval was wider (5-year ARR = 17.0%, 95% CI= -5.4-39.4%). Cochran's Q test indicated ARR varied significantly only by subgroups created using the proportional hazards model. The hazard ratio for aspirin vs. placebo therapy did not significantly vary by subgroup in any of the models. The highest risk groups for the proportional hazards model and random forest model contained 230 participants each, while the highest risk group in the decision tree model contained 41 participants., Conclusions: The choice of technique for internally developed models for outcome risk subgroups influences HTE analyses. The rationale for the use of a particular subgroup determination model in HTE analyses needs to be explicitly defined based on desired levels of explainability (with features importance), uncertainty of prediction, chances of overfitting, and assumptions regarding the underlying data structure. Replication of these analyses using data from other mid-size clinical trials may help to establish guidance for selecting an outcomes risk prediction modelling technique for HTE analyses., (© 2024. The Author(s).)

Per-oral pancreatoscopy (POP) is a pancreas-preserving modality that allows for targeted pancreatic duct interventions, particularly in cases where standard techniques fail. POP specifically has an emerging role in the diagnosis, risk stratification, and disease extent determination of main duct intraductal papillary mucinous neoplasms (IPMNs). It has also been successfully used for laser ablation of IPMNs in poor surgical candidates, lithotripsy for complex stone disease, and laser stricturoplasty. As experience with POP increases beyond select referral center practices, further studies validating POP efficacy with long-term follow-up will help clarify when POP-guided intervention is most beneficial in relation to surgical intervention., Competing Interests: Disclosure Y. Hanada—None. R.J. Shah—Consultant for Boston Scientific, Olympus, and Dragonfly., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Importance: Age-related hearing loss is common in an aging population, affecting communication and contributing to a worsened quality of life. It occurs as a result of cochlear degeneration and may be further exacerbated by inflammation and microvascular changes, as observed in animal models., Objective: To compare the effect of daily low-dose aspirin vs placebo on the progression of age-related hearing loss in healthy older adults., Design, Setting, and Participants: A prespecified secondary analysis was conducted of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized clinical trial. Participants were 279 healthy community-dwelling individuals living in Australia who were aged 70 years or older and free of overt cardiovascular diseases, dementia, and life-limiting illnesses. Participants were recruited between January 1, 2010, and December 31, 2014, and followed up over 3 years. Statistical analysis was completed from June to December 2023., Intervention: A 100-mg daily dose of enteric-coated aspirin or matching placebo., Main Outcomes and Measures: Hearing measures were air conduction audiometry and binaural speech perception in noise. Assessments were conducted at baseline, 18 months, and 3 years. The change from baseline hearing measures were analyzed using an intention to treat approach. Aspirin and placebo were compared using mixed linear regression models adjusting for age, sex, diabetes, and smoking., Results: Of 279 participants, 154 (55%) were male, and the median age at baseline was 73.1 years (IQR, 71.5-76.2 years). A total of 98 of 138 participants (71%) in the aspirin group and 94 of 141 participants (67%) in the placebo group reported experiencing hearing loss at baseline. Compared with placebo, aspirin did not affect the changes in mean (SD) 4-frequency average hearing threshold from baseline to year 3 (aspirin: baseline, 27.8 [13.3] dB; year 3, 30.7 [13.7] dB; difference, 3.3 [3.9] dB; placebo: baseline, 27.5 [12.6] dB; year 3, 30.9 [13.8] dB; difference, 3.0 [4.8] dB; P = .55) nor any other tested frequencies. An increase in air conduction threshold indicates a deterioration in hearing. Similarly, for the mean (SD) speech reception threshold, there was no significant difference observed between the aspirin and placebo group at the year 3 follow-up assessment (aspirin: baseline, -9.9 [3.8] dB; year 3, -9.1 [3.8] dB; difference, 0.9 [2.9] dB; placebo: baseline, -10.5 [7.1] dB; year 3, -9.6 [4.1] dB; difference, 0.9 [5.9] dB; P = .86). The findings were consistent across sex, age groups, diabetic and smoking status., Conclusions and Relevance: In this secondary analysis of the ASPREE randomized clinical trial, low-dose aspirin did not affect the progression of age-related hearing loss. More investigation is warranted on whether a longer follow-up or the use of a more powerful anti-inflammatory agent might prove beneficial., Trial Registration: anzctr.org.au Identifier: ACTRN12614000496617.

Introduction: Poor social connection is considered a risk factor for dementia. Since socializing behaviors may cluster together or act compensatorily, we aimed to investigate social connection patterns and their association with dementia, for men and women separately., Methods: A total of 12,896 community-dwelling older adults (mean ± SD age: 75.2 ± 4.3 years, 54% women) without major cognitive impairment were included. Latent class analysis was conducted using 24 baseline social connection indicators. Cox proportional hazards regression was used to estimate the association between latent classes and incident dementia over 12 (median: 8.4) years follow-up., Results: Three distinct classes were identified in both genders: strong social connections with an intermediate friend-relative network (Class 1: men, 43.8%; women, 37.9%), weak social connections (Class 2: men, 29.6%; women, 27.4%), and strong social connections with a larger friend-relative network (Class 3: men, 26.6%; women, 34.7%). Compared to Class 1, men in Class 2 (HR: 1.38, 95% CI: 1.08-1.77) and women in Class 3 (HR: 1.27, 95% CI: 1.01-1.60) had an increased risk of dementia., Discussion: Dementia risk varies with different social connection patterns among older men and women., Highlights: Three distinct social connection patterns were identified based on 24 indicators. These patterns were related to dementia risk differently in men and women. In men, a weak social connection pattern was associated with a higher dementia risk. In women, a strong social connection with a relatively larger friend-relative network was associated with a greater dementia risk., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Placebo-controlled trials of sodium-glucose co-transporter-2 inhibitors demonstrate kidney and cardiovascular benefits for patients with type 2 diabetes and chronic kidney disease (CKD). We used real-world data to compare the kidney and cardiovascular effectiveness of empagliflozin to dipeptidyl peptidase-4 inhibitors (DPP4is), a commonly prescribed antiglycemic medication, in a diverse population with and without CKD. Using electronic health record data from 20 large US health systems, we leveraged propensity overlap weighting to compare the outcomes for empagliflozin and DPP4i initiators with type 2 diabetes between 2016 and 2020. The primary composite kidney outcome included 40% estimated glomerular filtration rate decrease, incident end-stage kidney disease, or all-cause mortality through 2 years or censoring. We also assessed cardiovascular and safety outcomes. Of 62,197 new users, 20,279 initiated empagliflozin and 41,918 initiated DPP4i. Over a median follow-up of 1.1 years, empagliflozin prescription was associated with a lower risk of the primary outcome (hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.65 to 0.87) than DPP4is. The risks for mortality (HR 0.76, 95% CI 0.62 to 0.92) and a cardiovascular composite of stroke, myocardial infarction, or all-cause mortality (HR 0.81, 95% CI 0.70 to 0.95) were also lower for empagliflozin initiators. No difference in heart failure hospitalization risk between groups was observed. Genital mycotic infections were more common in patients prescribed empagliflozin (HR 1.72, 95% CI 1.58 to 1.88). Empagliflozin was associated with a lower risk of the primary outcome in patients with CKD (HR 0.68, 95% CI 0.53 to 0.88) and those without CKD (HR 0.79, 95% CI 0.67 to 0.94). In conclusion, the initiation of empagliflozin was associated with a significantly lower risk of kidney and cardiovascular outcomes than DPP4is over a median of just over 1 year. The association with a lower risk for clinical outcomes was apparent even for patients without known CKD at baseline., Competing Interests: Declaration of competing interest Boehringer Ingelheim was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations. Dr. Butler reports consultant honoraria from Abbott, American Regent, Amgen, Applied Therapeutic, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardiac Dimension, Cardior, CVRx, cytokinetics, Edwards, Element Science, Innolife, Impulse Dynamics, Imbria, Inventiva, Lexicon, Eli Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Roche, Sequana, SQ Innovation, and Vifor. Dr. Pagidipati reports research support from Alnylam, Amgen, Boehringer Ingelheim, Eggland's Best, Eli Lilly, Novartis, Novo Nordisk, and Verily Life Sciences; consultation/advisory panels for Bayer, Boehringer Ingelheim, CRISPR Therapeutics, Eli Lilly, Esperion, AstraZeneca, Merck, Novartis, and Novo Nordisk; executive committee member for trials sponsored by Novo Nordisk and Amgen; data safety monitor board for trials sponsored by Johnson and Johnson and Novartis; medical advisory board for Miga Health. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Importance: Chronic kidney disease (CKD) is an often-asymptomatic complication of type 2 diabetes (T2D) that requires annual screening to diagnose. Patient-level factors linked to inadequate screening and treatment can inform implementation strategies to facilitate guideline-recommended CKD care., Objective: To identify risk factors for nonconcordance with guideline-recommended CKD screening and treatment in patients with T2D., Design, Setting, and Participants: This retrospective cohort study was performed at 20 health care systems contributing data to the US National Patient-Centered Clinical Research Network. To evaluate concordance with CKD screening guidelines, adults with an outpatient clinician visit linked to T2D diagnosis between January 1, 2015, and December 31, 2020, and without known CKD were included. A separate analysis reviewed prescription of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) and sodium-glucose cotransporter 2 (SGLT2) inhibitors in adults with CKD (estimated glomerular filtration rate [eGFR] of 30-90 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio [UACR] of 200-5000 mg/g) and an outpatient clinician visit for T2D between October 1, 2019, and December 31, 2020. Data were analyzed from July 8, 2022, through June 22, 2023., Exposures: Demographics, lifestyle factors, comorbidities, medications, and laboratory results., Main Outcomes and Measures: Screening required measurement of creatinine levels and UACR within 15 months of the index visit. Treatment reflected prescription of ACEIs or ARBs and SGLT2 inhibitors within 12 months before or 6 months following the index visit., Results: Concordance with CKD screening guidelines was assessed in 316 234 adults (median age, 59 [IQR, 50-67] years), of whom 51.5% were women; 21.7%, Black; 10.3%, Hispanic; and 67.6%, White. Only 24.9% received creatinine and UACR screening, 56.5% received 1 screening measurement, and 18.6% received neither. Hispanic ethnicity was associated with lack of screening (relative risk [RR], 1.16 [95% CI, 1.14-1.18]). In contrast, heart failure, peripheral arterial disease, and hypertension were associated with a lower risk of nonconcordance. In 4215 patients with CKD and albuminuria, 3288 (78.0%) received an ACEI or ARB; 194 (4.6%), an SGLT2 inhibitor; and 885 (21.0%), neither therapy. Peripheral arterial disease and lower eGFR were associated with lack of CKD treatment, while diuretic or statin prescription and hypertension were associated with treatment., Conclusions and Relevance: In this cohort study of patients with T2D, fewer than one-quarter received recommended CKD screening. In patients with CKD and albuminuria, 21.0% did not receive an SGLT2 inhibitor or an ACEI or an ARB, despite compelling indications. Patient-level factors may inform implementation strategies to improve CKD screening and treatment in people with T2D.

Background: Cognitive impairment is common after stroke, and a large proportion of stroke patients will develop dementia. However, there have been few large prospective studies which have assessed cognition both prior to and after stroke. This study aims to determine the extent to which incident stroke impacts different domains of cognitive function in a longitudinal cohort of older community-dwelling individuals., Methods: 19,114 older individuals without cardiovascular disease or major cognitive impairment were recruited and followed over a maximum 11 years. Stroke included ischaemic and haemorrhagic stroke and was adjudicated by experts. Cognitive function was assessed regularly using Modified Mini-Mental State Examination (3MS), Hopkins Verbal Learning Test-Revised (HVLT-R), Symbol Digit Modalities Test (SDMT), and Controlled Oral Word Association Test (COWAT). Linear mixed models were used to investigate the change in cognition at the time of stroke and decline in cognitive trajectories following incident stroke., Results: During a median follow-up period of 8.4 [IQR: 7.2, 9.6] years, 815 (4.3%) participants experienced a stroke. Over this time, there was a general decline observed in 3MS, HVLT-R delayed recall, and SDMT scores across participants. However, for individuals who experienced a stroke, there was a significantly greater decline across all cognitive domains immediately after the event immediately after the event (3MS: -1.03 [95%CI: -1.45, -0.60]; HVLT-R: -0.47 [-0.70, -0.24]; SDMT: -2.82 [-3.57, -2.08]; COWAT: -0.67 [-1.04, -0.29]) and a steeper long-term decline for three of these domains (3MS -0.62 [-0.88, -0.35]; COWAT: -0.30 [-0.46, -0.14]); HVLT-R: -0.12 [95%CI, -0.70, -0.24]). However individuals with stroke experienced no longer-term decline in SDMT compared to the rest of the participants., Conclusions: These findings highlight the need for comprehensive neuropsychology assessments for ongoing monitoring of cognition following incident stroke; and potential early intervention., (© 2024. The Author(s).)

Objectives: This study examines the gender-specific associations between a wide range of social activities and dementia risk., Methods: A prospective cohort study was conducted involving community-dwelling older Australians (≥70 years) without significant cognitive impairment at enrolment. During the first year of enrolment, we assessed 25 self-reported social activities covering various aspects, including support from relatives and friends, community participation, social interactions with surroundings, and loneliness. Dementia diagnosis followed DSM-IV criteria, adjudicated by an international expert panel. To estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between social activities and dementia, we performed Cox proportional hazards models, adjusting for age, educational attainment, baseline global cognition, and depressive symptoms., Results: Among 9,936 participants who completed all social activity questionnaires (median [IQR] age: 73.4 [71.6-77.1] years; 47.4% men), dementia was diagnosed in 3.8% of men (n = 181/4,705) and 2.6% of women (n = 138/5,231) over a median 6.4 years (IQR: 5.3-7.6, range: 0.2-10.1) follow-up. Gender-specific relationships emerged: caregiving for a person with illness/disability in women (HR: 0.65, 95% CI: 0.42-0.99), and having ≥9 relatives feeling close to call for help in men (HR: 0.56, 95% CI: 0.33-0.96; reference <9 relatives) were associated with reduced dementia risk. Unexpectedly, in women, having ≥5 friends with whom they felt comfortable discussing private matters were associated with a greater dementia risk (HR: 1.69, 95% CI: 1.10-2.59; reference ≤2 friends). Imputed models further identified that babysitting/childminding was associated with lower dementia risk in men (HR: 0.75, 95% CI: 0.56-0.99). No other social activities showed significant associations with dementia., Discussion: This study provides evidence of social activities influencing dementia risk. Further investigations are required to uncover the mechanisms driving these observed relationships., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Background: This study examined the associations of body mass index (BMI) and waist circumference (WC), as well as their short- and long-term changes over time, with incident dementia in older individuals., Methods: Data came from 18,837 community-dwelling individuals aged 65+ years from Australia and the United States, who were relatively healthy without major cognitive impairment at enrolment. Anthropometric measures were prospectively assessed at baseline, as well as change and variability from baseline to year two (three time-points). In a subgroup (n = 11,176), self-reported weight at age 18 and 70+ years was investigated. Dementia cases satisfied DSM-IV criteria. Cox regression was used to examine the associations between anthropometric measures and incident risk of dementia., Results: Compared to normal weight, an overweight (HR: 0.67, 95%CI: 0.57-0.79, p < 0.001) or obese BMI (HR: 0.73, 95%CI: 0.60-0.89, p = 0.002), or a larger WC (elevated, HR: 0.71, 95%CI: 0.58-0.86, p < 0.001; highly elevated, HR: 0.65, 95%CI: 0.55-0.78, p < 0.001; relative to low) at baseline was associated with lower dementia risk. In contrast, substantial increases in BMI (>5%) over 2 years after baseline were associated with higher dementia risk (HR: 1.49, 95% CI: 1.17-1.91, p = 0.001). Increased dementia risk was also seen with an underweight BMI at baseline and a 2-year BMI decrease (>5%), but these associations appeared only in the first 4 years of follow-up. Compared to normal weight at both age 18 and 70+ years, being obese at both times was associated with increased dementia risk (HR: 2.27, 95%CI: 1.22-4.24, p = 0.01), while obesity only at age 70+ years was associated with decreased risk (HR: 0.70, 95%CI: 0.51-0.95, p = 0.02)., Conclusions: Our findings suggest that long-term obesity and weight gain in later life may be risk factors for dementia. Being underweight or having substantial weight loss in old age may be early markers of pre-clinical dementia., (© 2024 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Background & Aims: Chronic pancreatitis (CP) causes an abdominal pain syndrome associated with poor quality of life. We conducted a clinical trial to further investigate the efficacy and safety of camostat, an oral serine protease inhibitor that has been used to alleviate pain in CP., Methods: This was a double-blind randomized controlled trial that enrolled adults with CP with a baseline average daily worst pain score ≥4 on a numeric rating system. Participants were randomized (1:1:1:1) to receive camostat at 100, 200, or 300 mg 3 times daily or placebo. The primary end point was a 4-week change from baseline in the mean daily worst pain intensity score (0-10 on a numeric rating system) using a mixed model repeated measure analysis. Secondary end points included changes in alternate pain end points, quality of life, and safety., Results: A total of 264 participants with CP were randomized. Changes in pain from baseline were similar between the camostat groups and placebo, with differences of least squares means of -0.11 (95% CI, -0.90 to 0.68), -0.04 (95% CI, -0.85 to 0.78), and -0.11 (95% CI, -0.94 to 0.73) for the 100 mg, 200 mg, and 300 mg groups, respectively. Multiple subgroup analyses were similar for the primary end point, and no differences were observed in any of the secondary end points. Treatment-emergent adverse events attributed to the study drug were identified in 42 participants (16.0%)., Conclusion: We were not able to reject the null hypothesis of no difference in improvements in pain or quality of life outcomes in participants with painful CP who received camostat compared with placebo. Studies are needed to further define mechanisms of pain in CP to guide future clinical trials, including minimizing placebo responses and selecting targeted therapies., Clinicaltrials: gov, Number: NCT02693093., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: The prognostic implication of cholesterol levels in older adults remains uncertain. This study aimed to examine the relationship between low-density-lipoprotein cholesterol (LDL-c) and mortality outcomes in older individuals., Methods: This post hoc analysis examined the associations of LDL-c levels with mortality risks from all-cause, cardiovascular disease (CVD), cancer, and combined non-CVD/noncancer conditions in a cohort of individuals aged ≥65 years from the ASPirin in Reducing Events in the Elderly trial (NCT01038583). At baseline, participants had no diagnosed dementia, physical disability, or CVD, and were not taking lipid-lowering agents. Outcome analyses were performed using multivariable Cox models., Results: We analyzed 12 334 participants (mean age: 75.2 years). Over a median 7-year follow-up, 1 250 died. Restricted cubic splines found a U-shaped relation for LDL-c and all-cause mortality, cancer mortality, and noncancer/non-CVE mortality (nadir: 3.3-3.4 mmol/L); the risk of CVD mortality was similar at LDL-c below 3.3 mmol/L and increased above 3.3 mmol/L. Similar trends were observed in analyses modeling LDL-c by quartiles. When modeling LDL-c as a continuous variable, the risk of all-cause mortality, cancer mortality, and noncancer/non-CVD mortality was decreased by 9%, 16%, and 18%, respectively, per 1-mmol/L higher LDL-c, and the risk of CVD mortality was increased by 19% per 1-mmol/L higher LDL-c. Reduced all-cause and non-CVD/noncancer mortality risks were only significant in males but not females (pinteraction < .05)., Conclusions: There were U-shaped relationships between LDL-c and all-cause mortality, cancer mortality, and noncancer/non-CVD mortality in healthy older adults. Higher LDL-c levels were associated with an increased risk of CVD mortality. Future studies are warranted to confirm our results., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Background: The combination of rectally administered indomethacin and placement of a prophylactic pancreatic stent is recommended to prevent pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients. Preliminary evidence suggests that the use of indomethacin might eliminate or substantially reduce the need for stent placement, a technically complex, costly, and potentially harmful intervention., Methods: In this randomised, non-inferiority trial conducted at 20 referral centres in the USA and Canada, patients (aged ≥18 years) at high risk for post-ERCP pancreatitis were randomly assigned (1:1) to receive rectal indomethacin alone or the combination of indomethacin plus a prophylactic pancreatic stent. Patients, treating clinicians, and outcomes assessors were masked to study group assignment. The primary outcome was post-ERCP pancreatitis. To declare non-inferiority, the upper bound of the two-sided 95% CI for the difference in post-ERCP pancreatitis (indomethacin alone minus indomethacin plus stent) would have to be less than 5% (non-inferiority margin) in both the intention-to-treat and per-protocol populations. This trial is registered with ClinicalTrials.gov (NCT02476279), and is complete., Findings: Between Sept 17, 2015, and Jan 25, 2023, a total of 1950 patients were randomly assigned. Post-ERCP pancreatitis occurred in 145 (14·9%) of 975 patients in the indomethacin alone group and in 110 (11·3%) of 975 in the indomethacin plus stent group (risk difference 3·6%; 95% CI 0·6-6·6; p=0·18 for non-inferiority). A post-hoc intention-to-treat analysis of the risk difference between groups showed that indomethacin alone was inferior to the combination of indomethacin plus prophylactic stent (p=0·011). The relative benefit of stent placement was generally consistent across study subgroups but appeared more prominent among patients at highest risk for pancreatitis. Safety outcomes (serious adverse events, intensive care unit admission, and hospital length of stay) did not differ between groups., Interpretation: For preventing post-ERCP pancreatitis in high-risk patients, a strategy of indomethacin alone was not as effective as a strategy of indomethacin plus prophylactic pancreatic stent placement. These results support prophylactic pancreatic stent placement in addition to rectal indomethacin administration in high-risk patients, in accordance with clinical practice guidelines., Funding: US National Institutes of Health., Competing Interests: Declaration of interests The following authors have received honoraria, consulting fees, or research support from companies that manufacture prophylactic pancreatic stents or indomethacin within the last 2 years: SAE (consulting fees from Olympus, honoraria from Boston Scientific), NF (consulting fees and payment or honoraria for lectures or receipt of equipment or materials from Boston Scientific and Pentax), FFW (consulting fees from Cook/Boston Scientific), SV (consulting fees from Boston Scientific/Olympus), JYB (consulting fees from Boston Scientific/Olympus), MK (consulting fees from Boston Scientific), RK (consulting fees from Boston Scientific), Y-IC (consulting fees, honoraria, research grants, and travel payments from Boston Scientific), AB (financial interest in Olympus), ARo (payment or honoraria for lectures or presentations and travel from Boston Scientific), and study group members SGK (honoraria and grant support from Taewoong Medical) and SG (consulting fees and honoraria from Boston Scientific). All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

To determine the prevalence of non-use and limited use of cochlear implants. To find out the reasons for the same. This study was carried out among the paediatric patients who underwent cochlear implantation under the SHP* scheme in Civil Hospital, Ahmedabad between 2013 and 2020., Study Design: Retrospective cross-sectional study., Study Setting: Civil Hospital Ahmedabad., Sample Size: 150 paediatric patients. Patients were selected based on a random number generator. The data was collected through a telephonic interview based upon a preformed questionnaire. The study indicates that out of a total 150 participants, 109 (72.7%) used their cochlear implant regularly while 41 (27.3%) did not. Major issue faced by the participants was in the external device -damage to the device and monetary issues for its repair. The participants who have dropped the usage of their implants faced issues mostly after 2 years of usage. The age group of less than 3 years showed 15.6% of non-usage, while the age group of 3-6 years showed an increase to 34.5% of non-users. The age group of more than 6 years showed an even higher proportion (41.3%) of non-users. It is recommended that the government ensures the follow-up of the patients undergoing cochlear implantation for at least 2 years after the surgery. The proportion of non-users in the consecutive increasing age groups saw a rise in number. Therefore, it is recommended to divert the resources towards lower age groups to facilitate a better outcome., Competing Interests: Conflict of interestNo any conflicts of interest involved., (© Association of Otolaryngologists of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Endoscopic papillectomy (EP) offers a safe and effective method for resection of ampullary adenomas. Data regarding the long-term resolution of adenoma following EP are limited. The aim of this study therefore was to examine the timing of recurrence after EP of ampullary adenomas., Methods: This was a single-center retrospective study including patients who received EP for ampullary adenomas from 8/2000 to 1/2018. Patients with confirmed complete eradication of adenoma were included in the recurrence analysis with recurrence defined as finding adenomatous histology after 1 negative surveillance endoscopy. Kaplan-Meier estimates were calculated to determine recurrence rates., Results: Of the 165 patients who underwent EP, 136 patients (mean age 61.9, 51.5% female) had adenomatous histology with a mean lesion size of 21.2 mm. A total of 124 (91.2%) achieved complete eradication with a follow-up of 345.8 person-years. Recurrence occurred in 20 (16.1%) patients at a mean of 3.2 (± 3) years (range 0.5-9.75 years) for a recurrence rate of 5.8 (95% CI 3.6-8.8) per 100 person-years. Nine (45%) recurrences occurred after the 1st 2 years of surveillance. Recurrence rate did not differ by baseline pathology [low-grade dysplasia: 5.2 (95% CI 3.0-9.0), high-grade dysplasia: 6.9 (95% CI 2.3-15.5), adenocarcinoma: 7.7 (95% CI 0.9-25.1)]., Conclusion: Recurrence remains a significant concern after EP. Given the timing of recurrence, long surveillance periods may be necessary. Larger multicenter studies are needed, however, to determine appropriate surveillance intervals., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A percutaneous cholecystostomy tube (PCT) is the conventionally favored nonoperative intervention for treating acute cholecystitis. However, PCT is beset by high adverse event rates, need for scheduled reintervention, and inadvertent dislodgement, as well as patient dissatisfaction with a percutaneous drain. Recent advances in endoscopic therapy involve the implementation of endoscopic transpapillary drainage (ETP-GBD) and endoscopic ultrasound-guided gallbladder drainage (EUS-GBD), which are increasingly preferred over PCT due to their favorable technical and clinical success combined with lower complication rates. In this article, we provide a comprehensive review of the literature on EUS-GBD and ETP-GBD, delineating instances when clinicians should opt for endoscopic management and highlighting potential risks associated with each approach.

Introduction: Risk factors for cardiovascular disease (CVD) also increase the risk of dementia. However, whether commonly used CVD risk scores are associated with dementia risk in older adults who do not have a history of CVD, and potential gender differences in this association, remains unclear. The aim of this study was to determine whether CVD risk scores are prospectively associated with cognitive decline and dementia in initially healthy older men and women., Methods: A total of19,114 participants from a prospective cohort of individuals aged 65+ years without known CVD or dementia were recruited. The atherosclerotic cardiovascular disease risk score (ASCVDRS), Systematic Coronary Risk Evaluation 2-Older Persons (SCORE2-OP), and the Framingham risk score (FRS) were calculated at baseline. Risk of dementia (according to DSM-IV criteria) and cognitive decline (defined as a &gt;1.5 standard deviation decline in global cognition, episodic memory, psychomotor speed, or verbal fluency from the previous year) were assessed using hazard ratio., Results: Over a median follow-up of 6.4 years, 850 individuals developed dementia and 4,352 cognitive decline. Men and women in the highest ASCVDRS tertile had a 41% (95% CI 1.08, 1.85) and 45% (1.11, 1.89) increased risk of dementia compared to the lowest tertile, respectively. Likewise, men and women in the highest SCORE2-OP tertile had a 64% (1.24, 2.16) and 60% (1.22, 2.11) increased risk of dementia compared to the lowest tertile, respectively. Findings were similar, but the risk was slightly lesser when examining risk of cognitive decline for both ASCVDRS and SCORE2-OP. However, FRS was only associated with the risk of cognitive decline among women (highest vs. lowest tertiles: 1.13 [1.01-1.26])., Conclusion: These findings suggest the utility of the ASCVDRS and SCORE2-OP in clinical practice, to not only assess future risk of CVD, but also as potential early indicators of cognitive impairment, even in relatively healthy older men and women., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Khellin is the key furanocoumarin of Ammi visnaga L. (Lam.) that exhibits various biological properties. This unique natural product has inspired the discovery of two first-in-class drugs, amiodarone and sodium cromoglycate. A wide range of analytical methods were generated while translating khellin scaffold into clinically used drugs; however, they have never been reviewed and critically assessed. The present review aims to review and evaluate the analytical techniques for the natural products, khellin, visnagin, and their inspired drugs, amiodarone and sodium cromoglycate. High-performance liquid chromatography (HPLC) is the extensively used technique in most analytical methods reported for these compounds; however, other techniques including the fluorimetry, luminescence spectrophotometry, potentiometry, voltammetry, FT-Raman spectroscopy, and ELISA were also employed. The review will be helpful for further basic and translational research on furanochromone and related scaffolds.

Competing Interests: Financial/Nonfinancial Disclosures None declared.

Introduction: Recent genome-wide association studies identified new dementia-associated variants. We assessed the performance of updated polygenic risk scores (PRSs) using these variants in an independent cohort., Methods: We used Cox models and area under the curve (AUC) to validate new PRSs (PRS-83SNP, PRS-SBayesR, and PRS-CS) compared with an older PRS-23SNP in 12,031 initially-healthy participants ≥70 years of age. Dementia was rigorously adjudicated according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria., Results: PRS-83SNP, PRS-SBayesR, and PRS-CS were associated with incident dementia, with fully adjusted (including apolipoprotein E [APOE] ε4) hazard ratios per standard deviation (SD) of 1.35 (1.23-1.47), 1.37 (1.25-1.50), and 1.42 (1.30-1.56), respectively. The AUC of a model containing conventional/non-genetic factors and APOE was 74.7%. This was improved to 75.7% (p = 0.007), 76% (p = 0.004), and 76.1% (p = 0.003) with addition of PRS-83SNP, PRS-SBayesR, and PRS-CS, respectively. The PRS-23SNP did not improve AUC (74.7%, p = 0.95)., Conclusion: New PRSs for dementia significantly improve risk-prediction performance, but still account for less risk than APOE genotype overall., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background and Objectives: It has been suggested that higher triglyceride levels were associated with a lower risk of Alzheimer disease. This study aimed to examine the association of triglycerides with dementia and cognition change in community-dwelling older adults., Methods: This prospective longitudinal study used data from the Aspirin in Reducing Events in the Elderly (ASPREE) randomized trial of adults aged 65 years or older without dementia or previous cardiovascular events at enrollment. The main outcome was incident dementia. Other outcomes included changes in composite cognition and domain-specific cognition (global cognition, memory, language and executive function, and psychomotor speed). The association between baseline triglycerides and dementia risk was estimated using Cox proportional hazard models adjusting for relevant risk factors. Linear mixed models were used to investigate cognitive change. The analysis was repeated in a subcohort of participants with available APOE -ε4 genetic data with additional adjustment for APOE -ε4 carrier status and an external cohort (UK Biobank) with similar selection criteria applied., Results: This study included 18,294 ASPREE participants and 68,200 UK Biobank participants (mean age: 75.1 and 66.9 years; female: 56.3% and 52.7%; median [interquartile range] triglyceride: 106 [80-142] mg/dL and 139 [101-193] mg/dL), with dementia recorded in 823 and 2,778 individuals over a median follow-up of 6.4 and 12.5 years, respectively. Higher triglyceride levels were associated with lower dementia risk in the entire ASPREE cohort (hazard ratio [HR] with doubling of triglyceride: 0.82, 95% CI 0.72-0.94). Findings were similar in the subcohort of participants with APOE-ε4 genetic data (n = 13,976) and in the UK Biobank cohort (HR was 0.82 and 0.83, respectively, all p ≤ 0.01). Higher triglycerides were also associated with slower decline in composite cognition and memory over time ( p ≤ 0.05)., Discussion: Older adults with higher triglyceride levels within the normal to high-normal range had a lower dementia risk and slower cognitive decline over time compared with individuals with lower triglyceride levels. Higher triglyceride levels may be reflective of better overall health and/or lifestyle behaviors that would protect against dementia development. Future studies are warranted to investigate whether specific components within the total circulating pool of plasma triglycerides may promote better cognitive function, with the hope of informing the development of new preventive strategies., (© 2023 American Academy of Neurology.)

Diagnostic delay in dementia is common in the U.S. Drivers of diagnostic delay are poorly understood, but appear related to misconceptions about dementia, stigma, concerns about autonomy, the nature of the diagnostic process, and provider-related factors. There is little quantitative evidence underlying cited risks and benefits of receiving a diagnosis around the time of dementia onset, including impacts on physical health, impacts on mental health, care partner interactions, costs of care, increased time for care planning, or earlier access to treatment. While various groups continue to push for reductions in diagnostic delay, realization of benefits and mitigation of harms will require new research on potential benefits and harms. Workforce and resource constraints, coupled with the expected growth in the number of persons living with dementia, may be a barrier to realization of potential benefits and mitigation of identified harms, which will require adequate access to providers, services, and supports., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Melinda C. Power reports grants from the United States (US) National Institutes of Health (NIH), U.S. Department of Defense (DOD), and District of Columbia Department of Health (DC Health) and prior service on the Biogen Healthy Lives, Healthy Climate Scientific Advisory Board. Victoria Willens and Dr. Yi Chen report no conflicts of interest. Dr. Christina Prather reports grants from the United States (U.S.) National Institutes of Health (NIH), Agency for Healthcare Research and Quality (AHRQ), and District of Columbia Department of Health (DC Health) and serves as a consultant to the Alzheimer’s Association Project Echo program. Dr. Ali Moghtaderi reports grants from the US National Institutes of Health. Dr. Kan Z. Gianattasio reports current funding support from grants and contracts from the United States (U.S.) National Institutes of Health (NIH), the Centers for Medicare and Medicaid Services (CMS), the Maryland Health Care Commission (MHCC), and the SCAN Foundation Dr. Francine Grodstein reports grants from the US National Institutes of Health. Dr. Raj C. Shah reports grants from the US National Institutes of Health and being the site principal investigator or sub-investigator for Alzheimer’s disease clinical trials for which his institution (Rush University Medical Center) is compensated [Amylyx Pharmaceuticals, Inc., Athira Pharma, Inc., Edgewater NEXT, Eli Lilly & Co., Inc., and Genentech, Inc.]. Dr. Bryan D. James reports grants from the United States (U.S.) National Institutes of Health (NIH), serves as a consultant to the Alzheimer’s Association, serves on the Vivid Genomics, Inc. Scientific Advisory Board, and has served on a drug advisory board for Eisai, Inc., (© The Author(s) 2023.)

Introduction/purpose: The two most common procedures performed to treat obesity are Roux-En-Y gastric bypass (RNYGB) and laparoscopic sleeve gastrectomy (LSG). Due to changes in enteric absorption, bariatric surgery increases rates of nephrolithiasis. As population-based data are limited, we aimed to compare the incidence of kidney stones after RNYGB and LSG., Materials and Methods: We queried Explorys (Cleveland, OH), a database that aggregated data from 26 healthcare systems. We identified patients who were newly diagnosed with nephrolithiasis 3, 6, and 12 months after their RNYGB or LSG. Additionally, a multivariate analysis was conducted to investigate the association of nephrolithiasis with RNYGB as compared to LSG. This analysis adjusted for other risk factors, including age above 65, male gender, Caucasian race, diabetes mellitus, hypertension, primary hyperparathyroidism, gout, and obesity., Results: From 1999 to 2019, there were 11,480 patients who underwent RNYGB and 22,770 patients who underwent LSG. The incidence of nephrolithiasis in the RNYGB cohort at all three time points was higher than in the LSG cohort (3 months, 7.1% vs. 2.4%; 6 months, 6.6% vs. 2.0%; 1 year, 5.8% vs. 1.4%; P < 0.001). After the multivariate analysis, it was found that, though both RNYGB and LSG were independently associated with the development of nephrolithiasis, the risk of nephrolithiasis was higher in those who underwent RNYGB compared to those who underwent LSG (OR 1.594, 95% CI 1.494 to 1.701, P < 0.001)., Conclusion: RNYGB is associated with a higher risk of nephrolithiasis when compared to LSG., (© 2023. The Society for Surgery of the Alimentary Tract.)

Mouse models that reflect human disorders provide invaluable tools for the translation of basic science discoveries to clinical therapies. However, many of these in vivo therapeutic studies are short term and do not accurately mimic patient conditions. In this study, we used a fully immunocompetent, transgenic mouse model, TGS, in which the spontaneous development of metastatic melanoma is driven by the ectopic expression of a normal neuronal receptor, mGluR1, as a model to assess longitudinal treatment response (up to 8 months) with an inhibitor of glutamatergic signaling, troriluzole, which is a prodrug of riluzole, plus an antibody against PD-1, an immune checkpoint inhibitor. Our results reveal a sex-biased treatment response that led to improved survival in troriluzole and/or anti-PD-1-treated male mice that correlated with differential CD8 + T cells and CD11b + myeloid cell populations in the tumor-stromal interface, supporting the notion that this model is a responsive and tractable system for evaluating therapeutic regimens for melanoma in an immunocompetent setting., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The Controlled Oral Word Association Test (COWAT) is a commonly used measure of verbal fluency. While a normal decline in verbal fluency occurs in late adulthood, significant impairments may indicate brain injury or diseases such as Alzheimer's disease. Normative data is essential to identify when test performance falls below expected levels based on age, gender, and education level., Objective: This study aimed to establish normative performance data on single-letter COWAT for older community-dwelling adults., Methods: Over 19,000 healthy men and women, without a diagnosis of dementia or a Modified Mini-Mental State Examination score below 77/100, were recruited for the ASPREE trial. Neuropsychological assessments, including the COWAT with letter F, were administered at study entry., Results: Median participant age was 75 years (range 65-98), with 56.5% being women. The majority of participants had 9-11 years of education in Australia and over 12 years in the U.S. The COWAT performance varied across ethno-racial groups and normative data were thus presented separately for 16,335 white Australians, 1,084 white Americans, 896 African-Americans, and 316 Hispanic/Latinos. Women generally outperformed men in the COWAT, except for Hispanic/Latinos. Higher education levels consistently correlated with better COWAT performance across all groups, while the negative association with age was weaker., Conclusions: This study provides comprehensive normative data for the COWAT stratified by ethno-racial groups in Australia and the U.S., considering age, gender, and education level. These norms can serve as reference standards for screening cognitive impairments in older adults in both clinical and research settings., Competing Interests: The authors report no conflicts of interest., (© 2023 – The authors. Published by IOS Press.)

Objective: To evaluate the safety and efficacy of endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) using a lumen-apposing metal stent (LAMS)., Background: For patients with acute cholecystitis who are poor surgical candidates, EUS-GBD using a LAMS is an important treatment alternative to percutaneous gallbladder drainage., Methods: We conducted a regulatory-compliant, prospective multicenter trial at 7 tertiary referral centers in the United States of America and Belgium. Thirty consecutive patients with mild or moderate acute cholecystitis who were not candidates for cholecystectomy were enrolled between September 2019 and August 2021. Eligible patients had a LAMS placed transmurally with 30 to 60-day indwell if removal was clinically indicated, and 30-day follow-up post-LAMS removal. Endpoints included days until acute cholecystitis resolution, reintervention rate, acute cholecystitis recurrence rate, and procedure-related adverse events (AEs)., Results: Technical success was 93.3% (28/30) for LAMS placement and 100% for LAMS removal in 19 patients for whom removal was attempted. Five (16.7%) patients required reintervention. Mean time to acute cholecystitis resolution was 1.6±1.5 days. Acute cholecystitis symptoms recurred in 10.0% (3/30) after LAMS removal. Five (16.7%) patients died from unrelated causes. Procedure-related AEs were reported to the FDA in 30.0% (9/30) of patients, including one fatal event 21 days after LAMS removal; however, no AEs were causally related to the LAMS., Conclusions: For selected patients with acute cholecystitis who are at elevated surgical risk, EUS-GBD with LAMS is an alternative to percutaneous gallbladder drainage. It has high technical and clinical success, with low recurrence and an acceptable AE rate. Clinicaltrials.gov, Number: NCT03767881., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Cardiovascular disease (CVD) is a recognized risk factor for dementia. Here we determined the extent to which an incident CVD event modifies the trajectory of cognitive function and risk of dementia., Methods: 19,114 adults (65+) without CVD or dementia were followed prospectively over 9 years. Incident CVD (fatal coronary heart disease, nonfatal myocardial infarction [MI], stroke, hospitalization for heart failure) and dementia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) were adjudicated by experts., Results: Nine hundred twenty-two participants had incident CVD, and 44 developed dementia after CVD (4.9% vs. 4.4% for participants without CVD). Following a CVD event there was a short-term drop in processing speed (-1.97, 95% confidence interval [CI]: -2.57 to -1.41), but there was no significant association with longer-term processing speed. In contrast, faster declines in trajectories of global function (-0.56, 95% CI: -0.76 to -0.36), episodic memory (-0.10, 95% CI: -0.16 to -0.04), and verbal fluency (-0.19, 95% CI: -0.30 to -0.01) were observed., Discussion: Findings highlight the importance of monitoring cognition after a CVD event., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Large-scale applications of nanotechnology have been extensively studied within the last decade. By exploiting certain advantageous properties of nanomaterials, multifunctional products can be manufactured that can contribute to the improvement of everyday life. In recent years, one such material has been nanocellulose. Nanocellulose (NC) is a naturally occurring nanomaterial and a high-performance additive extracted from plant fibers. This sustainable material is characterized by a unique combination of exceptional properties, including high tensile strength, biocompatibility, and electrical conductivity. In recent studies, these unique properties of nanocellulose have been analyzed and applied to processes related to membrane technology. This article provides a review of recent synthesis methods and characterization of nanocellulose-based membranes, followed by a study of their applications on a larger scale. The article reviews successful case studies of the incorporation of nanocellulose in different types of membrane materials, as well as their utilization in water purification, desalination, gas separations/gas barriers, and antimicrobial applications, in an effort to provide an enhanced comprehension of their capabilities in commercial products.

Importance: Low-dose aspirin has been widely used for primary and secondary prevention of stroke. The balance between potential reduction of ischemic stroke events and increased intracranial bleeding has not been established in older individuals., Objective: To establish the risks of ischemic stroke and intracranial bleeding among healthy older people receiving daily low-dose aspirin., Design, Setting, and Participants: This secondary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized, double-blind, placebo-controlled trial of daily low-dose aspirin was conducted among community-dwelling people living in Australia or the US. Participants were older adults free of symptomatic cardiovascular disease. Recruitment took place between 2010 and 2014, and participants were followed up for a median (IQR) of 4.7 (3.6-5.7) years. This analysis was completed from August 2021 to March 2023., Interventions: Daily 100-mg enteric-coated aspirin or matching placebo., Main Outcomes and Measures: Stroke and stroke etiology were predetermined secondary outcomes and are presented with a focus on prevention of initial stroke or intracranial bleeding event. Outcomes were assessed by review of medical records., Results: Among 19 114 older adults (10 782 females [56.4%]; median [IQR] age, 74 [71.6-77.7] years), 9525 individuals received aspirin and 9589 individuals received placebo. Aspirin did not produce a statistically significant reduction in the incidence of ischemic stroke (hazard ratio [HR], 0.89; 95% CI, 0.71-1.11). However, a statistically significant increase in intracranial bleeding was observed among individuals assigned to aspirin (108 individuals [1.1%]) compared with those receiving placebo (79 individuals [0.8%]; HR, 1.38; 95% CI, 1.03-1.84). This occurred by an increase in a combination of subdural, extradural, and subarachnoid bleeding with aspirin compared with placebo (59 individuals [0.6%] vs 41 individuals [0.4%]; HR, 1.45; 95% CI, 0.98-2.16). Hemorrhagic stroke was recorded in 49 individuals (0.5%) assigned to aspirin compared with 37 individuals (0.4%) in the placebo group (HR, 1.33; 95% CI, 0.87-2.04)., Conclusions and Relevance: This study found a significant increase in intracranial bleeding with daily low-dose aspirin but no significant reduction of ischemic stroke. These findings may have particular relevance to older individuals prone to developing intracranial bleeding after head trauma., Trial Registration: ISRCTN.org Identifier: ISRCTN83772183.

Importance: Lifestyles enriched with socially and mentally stimulating activities in older age may help build cognitive reserve and reduce dementia risk., Objective: To investigate the association of leisure activities and social networks with dementia risk among older individuals., Design, Setting, and Participants: This longitudinal prospective cohort study used population-based data from the ASPREE Longitudinal Study of Older Persons (ALSOP) for March 1, 2010, to November 30, 2020. Community-dwelling individuals in Australia aged 70 years or older who were generally healthy and without major cognitive impairment at enrollment were recruited to the ALSOP study between March 1, 2010, and December 31, 2014. Data were analyzed from December 1, 2022, to March 31, 2023., Exposures: A total of 19 measures of leisure activities and social networks assessed at baseline were classified using exploratory factor analysis., Main Outcomes and Measures: Dementia was adjudicated by an international expert panel according to Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria. Cox proportional hazards regression examined dementia risk over 10 years, adjusting for education, socioeconomic status, and a range of health-related factors., Results: This study included 10 318 participants. Their median age was 73.8 (IQR, 71.6-77.2) years at baseline, more than half (52.6%) were women, and most self-identified as White (98.0%). In adusted analyses, more frequent engagement in adult literacy activities (eg, writing letters or journaling, using a computer, and taking education classes) and in active mental activities (eg, playing games, cards, or chess and doing crosswords or puzzles) was associated with an 11.0% (adjusted hazard ratio [AHR], 0.89 [95% CI, 0.85-0.93]) and a 9.0% (AHR, 0.91 [95% CI, 0.87-0.95]) lower risk of dementia, respectively. To a lesser extent, engagement in creative artistic activities (craftwork, woodwork, or metalwork and painting or drawing) (AHR, 0.93 [95% CI, 0.88-0.99]) and in passive mental activities (reading books, newspapers, or magazines; watching television; and listening to music or the radio) (AHR, 0.93 [95% CI, 0.86-0.99]) was also associated with reduced dementia risk. In contrast, interpersonal networks, social activities, and external outings were not associated with dementia risk in this sample., Conclusions and Relevance: These results suggest that engagement in adult literacy, creative art, and active and passive mental activities may help reduce dementia risk in late life. In addition, these findings may guide policies for geriatric care and interventions targeting dementia prevention for older adults.

Background: Aspirin as a primary preventative in healthy older adults did not prolong disability-free survival in the ASPREE randomized trial. Observational studies following randomized trials allow assessment of benefits and harms which may not appear during the trial. We describe health characteristics, physical function, and aspirin use in the ASPREE-eXTension (ASPREE-XT) observational study cohort., Methods: Descriptive statistics compared health characteristics of those consented to ASPREE-XT at their first post-trial baseline (XT01) to corresponding ASPREE baseline values, and to those not consented. Likelihood of an indication for aspirin was assessed in participants reporting aspirin use at XT01., Results: 16,317 (93%) of the remaining and eligible 17,546 ASPREE participants were consented into ASPREE-XT; 14,894 completed XT01. Mean participant age had increased from 74.9 to 80.6 years. Overall health and physical function declined from the original ASPREE baseline; more participants were living alone, there was higher prevalence of chronic kidney disease, diabetes, and frailty, grip strength was lower and gait speed slower. Those not consented into ASPREE-XT were slightly older, and had lower cognitive scores and higher prevalence of age-related conditions than those who continued. 1015/11,717 (8.7%) participants without an apparent indication for aspirin reported using aspirin at XT01., Conclusions: The ASPREE-XT cohort was slightly less healthy at the XT01 visit than at ASPREE trial initiation, and rates of aspirin use without indication were similar to ASPREE baseline. Participants will be followed long-term to investigate aspirin's potential legacy towards dementia and cancer prevention and explore determinants of healthy aging., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest in the publication of this manuscript., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Open intensive care unit (ICU) visitation policies facilitate communication between clinicians and patients' families. Restrictive visitation policies (eg, during a pandemic) may reduce families' comprehension of information., Objectives: To determine whether written communication increased awareness of medical issues among ICU families and whether the effect size depended on the visitation policies in place when participants were enrolled., Methods: Families of ICU patients were randomly assigned to receive usual care with or without daily written patient care updates from June 2019 to January 2021. Participants were asked whether patients had experienced 6 ICU problems at up to 2 time points during the ICU stay. Responses were compared with the study investigators' consensus., Results: Of 219 participants, 131 (60%) were restricted from visiting. Participants in the written communication group were more likely than participants in the control group to correctly identify shock, renal failure, and weakness and were just as likely as participants in the control group to correctly identify respiratory failure, encephalopathy, and liver failure. Participants in the written communication group were more likely than participants in the control group to correctly identify the patient's ICU problems when all 6 were grouped as a composite outcome, with the adjusted odds ratio of correct identification tending to be higher among participants enrolled during restricted versus open visitation periods: 2.9 (95% CI, 1.9-4.2; P < .001) vs 1.8 (95% CI, 1.1-3.1; P = .02), P = .17 for difference., Conclusions: Written communication helps families correctly identify ICU issues. The benefit may be enhanced when families cannot visit the hospital. ClinicalTrials.gov Identifier: NCT03969810., (©2023 American Association of Critical-Care Nurses.)