Pub Date : 2025-12-01DOI: 10.1016/j.lanhl.2025.100798
Federico Bellelli MD , Jeremy Raffin PhD , Prof Matteo Cesari MD PhD , Sophie Guyonnet PhD , David Furman PhD , Prof Yves Rolland MD PhD , Prof Bruno Vellas MD PhD , Prof Philipe de Souto Barreto PhD , IHU HealthAge INSPIRE Platform Group, IHU HealthAge Open Science group
<div><h3>Background</h3><div>Although pain singularly impacts most critical domains of health status, its relationship with intrinsic capacity has been poorly investigated. Inflammation is central to pain biology, and longitudinal evidence indicates that pain can amplify inflammatory activity over time. This study evaluated the cross-sectional association of pain with intrinsic capacity and its domains in a cohort of community-dwelling people across the lifespan, as well as the moderating role of the inflammatory ageing (iAge) clock in this association. The secondary objective was to explore whether the pain–intrinsic capacity associations varied as a function of age and sex.</div></div><div><h3>Methods</h3><div>The analyses included 971 participants from the INSPIRE-T cohort. INSPIRE-T is an ongoing 10-year observational study in Toulouse, France, that recruited individuals aged 20 years and older who were not affected by severe illness that could compromise life expectancy within 5 years (or within 1 year for individuals who were already disabled and at old age). Pain was assessed based on self-reported presence over the previous 8 days, using a numeric scale (0–4, where higher is worse). A composite intrinsic capacity score (calculated as the arithmetic mean of the scores across the five domains) and intrinsic capacity domains (locomotion, cognition, vitality, psychology, and sensory capacity, including visual and hearing capacities) were assessed. Estimates from the regression models should be interpreted inversely (eg, a positive regression coefficient indicates a negative association), except for the vitality domain. Multiple linear regressions analyses were conducted to examine the association of pain with intrinsic capacity and its domains, as well as the interaction with iAge (pain × iAge), age (pain × age) and sex (pain × sex). The INSPIRE Platform is registered with <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, <span><span>NCT04224038</span><svg><path></path></svg></span>.</div></div><div><h3>Findings</h3><div>Enrolment began on Oct 16, 2019, and the majority of participants were recruited by December, 2021. A total of 1014 individuals were recruited in the INSPIRE-T cohort; of those, 971 individuals (median age 64 years [IQR 48–77], range 20–102 years; 366 [38%] male and 605 female [62%] individuals) with complete pain data and intrinsic capacity evaluation data were included in the analysis. Both moderate pain (β 0·264, SE 0·076, p=0·0006) and intense pain (0·479, 0·105, p<0·0001) were negatively associated with intrinsic capacity values. Pain at all intensities, mild (0·512, 0·163, p=0·0017), moderate (1·111, 0·191, p<0·0001), or intense (1·532, 0·263, p<0·0001), was significantly associated with lower scores in the psychological domain. Intense pain was associated with reduced scores in all intrinsic capacity domains (locomotor: 0·857, 0·219, p<0·0001; vitality: –4·159, 1·742, p=0·017; cognitive:
背景:虽然疼痛会影响健康状态的大多数关键领域,但其与内在能力的关系却很少被研究。炎症是疼痛生物学的核心,纵向证据表明,随着时间的推移,疼痛会放大炎症活动。本研究评估了一组社区居民在整个生命周期中疼痛与内在能力及其域的横断面关联,以及炎症老化时钟在这种关联中的调节作用。第二个目的是探讨疼痛-内在能力的关联是否随年龄和性别的变化而变化。方法:分析了来自INSPIRE-T队列的971名参与者。INSPIRE-T是一项正在法国图卢兹进行的为期10年的观察性研究,招募年龄在20岁及以上的个体,这些个体没有可能在5年内影响预期寿命的严重疾病(或已经残疾和老年的个体在1年内)。疼痛的评估是基于自我报告的过去8天的存在,使用数字量表(0-4,越高越差)。综合内在能力得分(计算为五个领域得分的算术平均值)和内在能力领域(运动、认知、活力、心理和感觉能力,包括视觉和听觉能力)进行评估。回归模型的估计应该反向解释(例如,正回归系数表示负关联),除了活力域。采用多元线性回归分析疼痛与内在能力及其域的关系,以及与图像(疼痛×图像)、年龄(疼痛×年龄)和性别(疼痛×性别)的相互作用。INSPIRE平台已在ClinicalTrials.gov注册,注册号为NCT04224038。研究结果:招募于2019年10月16日开始,大多数参与者于2021年12月招募。在INSPIRE-T队列中共招募了1014名个体;其中971例患者(中位年龄64岁[IQR 48-77],年龄范围20-102岁;男性366例(38%),女性605例(62%))具有完整的疼痛资料和内在能力评估资料纳入分析。中度疼痛(β 0.264, SE 0.076, p= 0.0006)和剧烈疼痛(0.479,0.105,p= 0.0006)解释:疼痛与内在能力下降有关,没有证据表明图像在这种关联中起调节作用。疼痛强度越高,在所有界定内在能力的领域得分越低,除了感觉领域。在中等强度下,这种关联在活力、运动和心理领域尤为明显。需要进一步的研究来确定有效的疼痛管理是否有助于防止内在能力的下降。资助:国家研究机构。
{"title":"The association of pain with intrinsic capacity and the moderating role of inflammation in France: a cross-sectional analysis of the INSPIRE-T project","authors":"Federico Bellelli MD , Jeremy Raffin PhD , Prof Matteo Cesari MD PhD , Sophie Guyonnet PhD , David Furman PhD , Prof Yves Rolland MD PhD , Prof Bruno Vellas MD PhD , Prof Philipe de Souto Barreto PhD , IHU HealthAge INSPIRE Platform Group, IHU HealthAge Open Science group","doi":"10.1016/j.lanhl.2025.100798","DOIUrl":"10.1016/j.lanhl.2025.100798","url":null,"abstract":"<div><h3>Background</h3><div>Although pain singularly impacts most critical domains of health status, its relationship with intrinsic capacity has been poorly investigated. Inflammation is central to pain biology, and longitudinal evidence indicates that pain can amplify inflammatory activity over time. This study evaluated the cross-sectional association of pain with intrinsic capacity and its domains in a cohort of community-dwelling people across the lifespan, as well as the moderating role of the inflammatory ageing (iAge) clock in this association. The secondary objective was to explore whether the pain–intrinsic capacity associations varied as a function of age and sex.</div></div><div><h3>Methods</h3><div>The analyses included 971 participants from the INSPIRE-T cohort. INSPIRE-T is an ongoing 10-year observational study in Toulouse, France, that recruited individuals aged 20 years and older who were not affected by severe illness that could compromise life expectancy within 5 years (or within 1 year for individuals who were already disabled and at old age). Pain was assessed based on self-reported presence over the previous 8 days, using a numeric scale (0–4, where higher is worse). A composite intrinsic capacity score (calculated as the arithmetic mean of the scores across the five domains) and intrinsic capacity domains (locomotion, cognition, vitality, psychology, and sensory capacity, including visual and hearing capacities) were assessed. Estimates from the regression models should be interpreted inversely (eg, a positive regression coefficient indicates a negative association), except for the vitality domain. Multiple linear regressions analyses were conducted to examine the association of pain with intrinsic capacity and its domains, as well as the interaction with iAge (pain × iAge), age (pain × age) and sex (pain × sex). The INSPIRE Platform is registered with <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, <span><span>NCT04224038</span><svg><path></path></svg></span>.</div></div><div><h3>Findings</h3><div>Enrolment began on Oct 16, 2019, and the majority of participants were recruited by December, 2021. A total of 1014 individuals were recruited in the INSPIRE-T cohort; of those, 971 individuals (median age 64 years [IQR 48–77], range 20–102 years; 366 [38%] male and 605 female [62%] individuals) with complete pain data and intrinsic capacity evaluation data were included in the analysis. Both moderate pain (β 0·264, SE 0·076, p=0·0006) and intense pain (0·479, 0·105, p<0·0001) were negatively associated with intrinsic capacity values. Pain at all intensities, mild (0·512, 0·163, p=0·0017), moderate (1·111, 0·191, p<0·0001), or intense (1·532, 0·263, p<0·0001), was significantly associated with lower scores in the psychological domain. Intense pain was associated with reduced scores in all intrinsic capacity domains (locomotor: 0·857, 0·219, p<0·0001; vitality: –4·159, 1·742, p=0·017; cognitive:","PeriodicalId":34394,"journal":{"name":"Lancet Healthy Longevity","volume":"6 12","pages":"Article 100798"},"PeriodicalIF":14.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145709592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.lanhl.2025.100804
Chun-Ting Yang PhD , James M Wilkins MD DPhil , Kevin T Pritchard PhD , Qiaoxi Chen PhD , Xiaojuan Liu PhD , Dae Hyun Kim MD ScD , Kueiyu Joshua Lin MD ScD
Background
Trazodone has emerged as a potentially safer alternative to atypical antipsychotic medications for managing delirium-related symptoms in older adults after hospital admission. This study aimed to compare safety outcomes in older adults who were prescribed trazodone versus atypical antipsychotic medication after hospital discharge.
Methods
This population-based cohort study was done using US Medicare data from Jan 1, 2013, to Dec 31, 2022, and Optum de-identified Clinformatics Data Mart Database data from Jan 1, 2013, to Aug 31, 2025, with a target trial emulation framework. Patients aged at least 65 years without psychiatric disorders who were prescribed a new trazodone or atypical antipsychotic medication (quetiapine, risperidone, or olanzapine) prescription within 30 days of hospital discharge with a claims-based delirium diagnosis were included. We applied propensity score overlap weighting to adjust for 162 covariates. The primary outcome was all-cause rehospitalisation. Secondary outcomes included rehospitalisation for delirium, falls (including fall-related emergency department visits), pneumonia, urinary tract infections, stroke, and all-cause mortality. Treatment-outcome associations were estimated using the Fine–Gray model for non-fatal outcomes (presented as subdistribution hazard ratio [SDHR]) and the Cox model for all-cause mortality (presented as hazard ratio [HR]). Estimates from the two databases were pooled using inverse-variance weighting.
Findings
11 678 trazodone and 29 590 atypical antipsychotic medication users were included. Compared with antipsychotic medications, trazodone was associated with lower risks of rehospitalisation (SDHR 0·95 [95% CI 0·91–0·98]), rehospitalisation for delirium (SDHR 0·80 [0·75–0·86]), urinary tract infection (SDHR 0·84 [0·72–0·99]), and all-cause mortality (HR 0·84 [0·79–0·90]); no significant difference was observed for falls (SDHR 0·93 [0·85–1·02]), pneumonia (SDHR 0·96 [0·79–1·16]), and stroke (SDHR 0·92 [0·77–1·11]). The reduced risk of rehospitalisation with trazodone was consistent when compared with risperidone (SDHR 0·89 [0·84–0·95]), and olanzapine (SDHR 0·88 [0·82–0·94]) but no difference was seen with quetiapine (SDHR 0·97 [0·93–1·01]).
Interpretation
These results revealed reduced risks of rehospitalisation and all-cause mortality associated with trazodone versus atypical antipsychotic medications. Trazodone is a potentially safer alternative to antipsychotic medications in the management of delirium-related symptoms after hospital discharge.
{"title":"Safety outcomes of trazodone versus antipsychotics for delirium after hospital admission in adults aged 65 years and older: a nationwide cohort study using a target trial emulation framework","authors":"Chun-Ting Yang PhD , James M Wilkins MD DPhil , Kevin T Pritchard PhD , Qiaoxi Chen PhD , Xiaojuan Liu PhD , Dae Hyun Kim MD ScD , Kueiyu Joshua Lin MD ScD","doi":"10.1016/j.lanhl.2025.100804","DOIUrl":"10.1016/j.lanhl.2025.100804","url":null,"abstract":"<div><h3>Background</h3><div>Trazodone has emerged as a potentially safer alternative to atypical antipsychotic medications for managing delirium-related symptoms in older adults after hospital admission. This study aimed to compare safety outcomes in older adults who were prescribed trazodone versus atypical antipsychotic medication after hospital discharge.</div></div><div><h3>Methods</h3><div>This population-based cohort study was done using US Medicare data from Jan 1, 2013, to Dec 31, 2022, and Optum de-identified Clinformatics Data Mart Database data from Jan 1, 2013, to Aug 31, 2025, with a target trial emulation framework. Patients aged at least 65 years without psychiatric disorders who were prescribed a new trazodone or atypical antipsychotic medication (quetiapine, risperidone, or olanzapine) prescription within 30 days of hospital discharge with a claims-based delirium diagnosis were included. We applied propensity score overlap weighting to adjust for 162 covariates. The primary outcome was all-cause rehospitalisation. Secondary outcomes included rehospitalisation for delirium, falls (including fall-related emergency department visits), pneumonia, urinary tract infections, stroke, and all-cause mortality. Treatment-outcome associations were estimated using the Fine–Gray model for non-fatal outcomes (presented as subdistribution hazard ratio [SDHR]) and the Cox model for all-cause mortality (presented as hazard ratio [HR]). Estimates from the two databases were pooled using inverse-variance weighting.</div></div><div><h3>Findings</h3><div>11 678 trazodone and 29 590 atypical antipsychotic medication users were included. Compared with antipsychotic medications, trazodone was associated with lower risks of rehospitalisation (SDHR 0·95 [95% CI 0·91–0·98]), rehospitalisation for delirium (SDHR 0·80 [0·75–0·86]), urinary tract infection (SDHR 0·84 [0·72–0·99]), and all-cause mortality (HR 0·84 [0·79–0·90]); no significant difference was observed for falls (SDHR 0·93 [0·85–1·02]), pneumonia (SDHR 0·96 [0·79–1·16]), and stroke (SDHR 0·92 [0·77–1·11]). The reduced risk of rehospitalisation with trazodone was consistent when compared with risperidone (SDHR 0·89 [0·84–0·95]), and olanzapine (SDHR 0·88 [0·82–0·94]) but no difference was seen with quetiapine (SDHR 0·97 [0·93–1·01]).</div></div><div><h3>Interpretation</h3><div>These results revealed reduced risks of rehospitalisation and all-cause mortality associated with trazodone versus atypical antipsychotic medications. Trazodone is a potentially safer alternative to antipsychotic medications in the management of delirium-related symptoms after hospital discharge.</div></div><div><h3>Funding</h3><div>National Institute on Aging.</div></div>","PeriodicalId":34394,"journal":{"name":"Lancet Healthy Longevity","volume":"6 12","pages":"Article 100804"},"PeriodicalIF":14.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.lanhl.2025.100778
Jessica B Langbaum PhD , Prof Angela R Bradbury MD , Prof Brian L Egleston PhD , Elisabeth McCarty Wood MS LCSG , Carolyn M Langlois MS , Emily A Largent JD PhD RN , Kristin Harkins MPH , Claire M Erickson PhD MPA , Shana D Stites PsyD , Emma Oyen BS , Marie-Emmanuelle Riviere PhD , Fonda Liu PharmD , Ana Graf MD , Scott Y H Kim MD PhD , Prof Joshua D Grill PhD , Prof Eric M Reiman MD , Prof Pierre N Tariot MD , Prof J Scott Roberts PhD , Jason Karlawish MD
<div><h3>Background</h3><div>The apolipoprotein E (<em>APOE</em>) gene is the best established genetic risk factor for Alzheimer’s disease in later life, with the ε4 allele conferring higher risk. <em>APOE</em> disclosure is becoming increasingly common in the clinical care of people with Alzheimer’s disease and in cognitively unimpaired adults. In this study, we aimed to describe changes in measures of genetic disease knowledge and psychiatric symptoms following <em>APOE</em> disclosure to cognitively unimpaired adults.</div></div><div><h3>Methods</h3><div>Data were collected as part of the screening phase of the global, multicentre, Alzheimer’s Prevention Initiative Generation Study 1 (<span><span>NCT02565511</span><svg><path></path></svg></span>). Eligible individuals were cognitively unimpaired (Mini-Mental State Exam total score ≥24), aged 60–75 years, and psychologically pre-screened for readiness (by measures of depressive symptoms and anxiety) to receive their <em>APOE</em> genotype from a health-care provider. Participants were assessed before disclosure, and 2–7 days, 6 weeks, 6 months, and 12 months after disclosure. Multivariable linear and ordinal logistic regressions were used to compare changes in genetic disease knowledge, anxiety, depression, and distress by <em>APOE4</em> genotype status, adjusting for key covariates, with a focus on 2–7 days after disclosure. Multiple imputation by chained equations methods was used to account for missing outcome data.</div></div><div><h3>Findings</h3><div>The trial took place between Nov 30, 2015, and Sept 23, 2019. In total, 9496 participants (including 790 <em>APOE4</em> homozygotes, 4869 heterozygotes, and 3837 non-carriers) learned their <em>APOE</em> genotype from a health-care provider as part of Generation Study 1 screening. 4038 (42·5%) participants were in the 65–69-year age group, 5790 (61·0%) were female, 3706 (39·0%) were male, and 8862 (93·3%) self-identified as White. Increase in genetic disease knowledge 2–7 days after disclosure was greater in <em>APOE4</em> homozygotes (mean 1·19 [SD 3·95]) than in heterozygotes (0·78 [3·95], p=0·042) and non-carriers (0·29 [3·96], p=0·0002). Disease-specific distress 2–7 days after disclosure increased more in homozygotes (2·25 [6·42]) than in heterozygotes (0·53 [5·08], p<0·0001) and non-carriers (0·79 [4·95], p<0·0001). Levels of anxiety 2–7 days after disclosure increased in homozygotes (0·17 [2·95]) but decreased in heterozygotes (–0·67 [2·68], p<0·0001) and non-carriers (–0·66 [2·67], p<0·0001). There were no significant changes in depressive symptoms following disclosure for any <em>APOE4</em> group. Notably, for all <em>APOE4</em> groups, increases in distress and anxiety were small and did not reach predefined levels of clinical concern.</div></div><div><h3>Interpretation</h3><div>In cognitively unimpaired, psychologically pre-screened adults, <em>APOE</em> disclosure by a trained health-care provider was generally safe an
{"title":"Impact of learning APOE genotype on cognitively unimpaired adults: a pre-screening cohort study of the Alzheimer’s Prevention Initiative Generation Study 1","authors":"Jessica B Langbaum PhD , Prof Angela R Bradbury MD , Prof Brian L Egleston PhD , Elisabeth McCarty Wood MS LCSG , Carolyn M Langlois MS , Emily A Largent JD PhD RN , Kristin Harkins MPH , Claire M Erickson PhD MPA , Shana D Stites PsyD , Emma Oyen BS , Marie-Emmanuelle Riviere PhD , Fonda Liu PharmD , Ana Graf MD , Scott Y H Kim MD PhD , Prof Joshua D Grill PhD , Prof Eric M Reiman MD , Prof Pierre N Tariot MD , Prof J Scott Roberts PhD , Jason Karlawish MD","doi":"10.1016/j.lanhl.2025.100778","DOIUrl":"10.1016/j.lanhl.2025.100778","url":null,"abstract":"<div><h3>Background</h3><div>The apolipoprotein E (<em>APOE</em>) gene is the best established genetic risk factor for Alzheimer’s disease in later life, with the ε4 allele conferring higher risk. <em>APOE</em> disclosure is becoming increasingly common in the clinical care of people with Alzheimer’s disease and in cognitively unimpaired adults. In this study, we aimed to describe changes in measures of genetic disease knowledge and psychiatric symptoms following <em>APOE</em> disclosure to cognitively unimpaired adults.</div></div><div><h3>Methods</h3><div>Data were collected as part of the screening phase of the global, multicentre, Alzheimer’s Prevention Initiative Generation Study 1 (<span><span>NCT02565511</span><svg><path></path></svg></span>). Eligible individuals were cognitively unimpaired (Mini-Mental State Exam total score ≥24), aged 60–75 years, and psychologically pre-screened for readiness (by measures of depressive symptoms and anxiety) to receive their <em>APOE</em> genotype from a health-care provider. Participants were assessed before disclosure, and 2–7 days, 6 weeks, 6 months, and 12 months after disclosure. Multivariable linear and ordinal logistic regressions were used to compare changes in genetic disease knowledge, anxiety, depression, and distress by <em>APOE4</em> genotype status, adjusting for key covariates, with a focus on 2–7 days after disclosure. Multiple imputation by chained equations methods was used to account for missing outcome data.</div></div><div><h3>Findings</h3><div>The trial took place between Nov 30, 2015, and Sept 23, 2019. In total, 9496 participants (including 790 <em>APOE4</em> homozygotes, 4869 heterozygotes, and 3837 non-carriers) learned their <em>APOE</em> genotype from a health-care provider as part of Generation Study 1 screening. 4038 (42·5%) participants were in the 65–69-year age group, 5790 (61·0%) were female, 3706 (39·0%) were male, and 8862 (93·3%) self-identified as White. Increase in genetic disease knowledge 2–7 days after disclosure was greater in <em>APOE4</em> homozygotes (mean 1·19 [SD 3·95]) than in heterozygotes (0·78 [3·95], p=0·042) and non-carriers (0·29 [3·96], p=0·0002). Disease-specific distress 2–7 days after disclosure increased more in homozygotes (2·25 [6·42]) than in heterozygotes (0·53 [5·08], p<0·0001) and non-carriers (0·79 [4·95], p<0·0001). Levels of anxiety 2–7 days after disclosure increased in homozygotes (0·17 [2·95]) but decreased in heterozygotes (–0·67 [2·68], p<0·0001) and non-carriers (–0·66 [2·67], p<0·0001). There were no significant changes in depressive symptoms following disclosure for any <em>APOE4</em> group. Notably, for all <em>APOE4</em> groups, increases in distress and anxiety were small and did not reach predefined levels of clinical concern.</div></div><div><h3>Interpretation</h3><div>In cognitively unimpaired, psychologically pre-screened adults, <em>APOE</em> disclosure by a trained health-care provider was generally safe an","PeriodicalId":34394,"journal":{"name":"Lancet Healthy Longevity","volume":"6 11","pages":"Article 100778"},"PeriodicalIF":14.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145649473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.lanhl.2025.100775
Anne Suffel PhD , Fariyo Abdullahi MSc , Eleanor Barry PhD , Jemma Walker PhD , Prof Nick Andrews PhD , Zahin Amin-Chowdhury MSc , Prof Shamez N Ladhani PhD , Daniel Grint PhD , Helen I McDonald PhD , Prof Ian Douglas PhD , Prof Kathryn E Mansfield PhD , Edward P K Parker PhD
Background
Invasive pneumococcal disease (IPD) is associated with increased long-term mortality, but it is unclear if this is explained by pre-existing comorbidities. We aimed to estimate the long-term survival following IPD in comparison with the general population, adjusting for potential confounders such as underlying comorbidities.
Methods
We conducted a matched cohort study comparing long-term survival (>120 days after infection) in individuals with IPD and comparators without IPD. Cases were individuals aged 65 years or older with laboratory-confirmed IPD (2012–19) identified through enhanced national surveillance. Comparators matched on age, sex, and calendar date of laboratory-confirmed diagnosis were drawn from primary care electronic health records in Clinical Practice Research Datalink GOLD. We used Cox regression, stratified by matched set, to compare mortality in people with and without IPD, adjusting for relevant comorbidities, socioeconomic deprivation, and ethnicity.
Findings
We included 13 401 IPD cases and 67 005 comparators without IPD. There were 5038 (53·5%) female and 4380 (46·5%) male IPD cases and 19 927 (53·5%) female and 17 351 (46·5%) male comparators without IPD. After adjusting for comorbidities, socioeconomic deprivation, and ethnicity, we found increased all-cause mortality in IPD cases compared with comparators without IPD (hazard ratio 3·74 [95% CI 3·50–3·99]). The predicted median survival was 4·7 years (IQR 2·9–7·4) for IPD cases and more than 11·9 years (IQR 8·7 to >11·9) for comparators without IPD. This increased mortality was consistent across subgroups defined by age, vaccination history, and comorbidity status (including diabetes, chronic respiratory disease, and chronic heart disease).
Interpretation
IPD was associated with increased mortality at least 5 years after infection. These findings emphasise the value of IPD prevention and the need for more research into the clinical management of people who have had IPD. Long-term mortality should be incorporated in cost-effectiveness analyses for pneumococcal vaccines.
Funding
National Institute for Health and Care Research (NIHR) Health Protection Research Unit in Vaccines and Immunisation (NIHR200929).
{"title":"Long-term survival after invasive pneumococcal disease: a matched cohort study using electronic health records in England","authors":"Anne Suffel PhD , Fariyo Abdullahi MSc , Eleanor Barry PhD , Jemma Walker PhD , Prof Nick Andrews PhD , Zahin Amin-Chowdhury MSc , Prof Shamez N Ladhani PhD , Daniel Grint PhD , Helen I McDonald PhD , Prof Ian Douglas PhD , Prof Kathryn E Mansfield PhD , Edward P K Parker PhD","doi":"10.1016/j.lanhl.2025.100775","DOIUrl":"10.1016/j.lanhl.2025.100775","url":null,"abstract":"<div><h3>Background</h3><div>Invasive pneumococcal disease (IPD) is associated with increased long-term mortality, but it is unclear if this is explained by pre-existing comorbidities. We aimed to estimate the long-term survival following IPD in comparison with the general population, adjusting for potential confounders such as underlying comorbidities.</div></div><div><h3>Methods</h3><div>We conducted a matched cohort study comparing long-term survival (>120 days after infection) in individuals with IPD and comparators without IPD. Cases were individuals aged 65 years or older with laboratory-confirmed IPD (2012–19) identified through enhanced national surveillance. Comparators matched on age, sex, and calendar date of laboratory-confirmed diagnosis were drawn from primary care electronic health records in Clinical Practice Research Datalink GOLD. We used Cox regression, stratified by matched set, to compare mortality in people with and without IPD, adjusting for relevant comorbidities, socioeconomic deprivation, and ethnicity.</div></div><div><h3>Findings</h3><div>We included 13 401 IPD cases and 67 005 comparators without IPD. There were 5038 (53·5%) female and 4380 (46·5%) male IPD cases and 19 927 (53·5%) female and 17 351 (46·5%) male comparators without IPD. After adjusting for comorbidities, socioeconomic deprivation, and ethnicity, we found increased all-cause mortality in IPD cases compared with comparators without IPD (hazard ratio 3·74 [95% CI 3·50–3·99]). The predicted median survival was 4·7 years (IQR 2·9–7·4) for IPD cases and more than 11·9 years (IQR 8·7 to >11·9) for comparators without IPD. This increased mortality was consistent across subgroups defined by age, vaccination history, and comorbidity status (including diabetes, chronic respiratory disease, and chronic heart disease).</div></div><div><h3>Interpretation</h3><div>IPD was associated with increased mortality at least 5 years after infection. These findings emphasise the value of IPD prevention and the need for more research into the clinical management of people who have had IPD. Long-term mortality should be incorporated in cost-effectiveness analyses for pneumococcal vaccines.</div></div><div><h3>Funding</h3><div>National Institute for Health and Care Research (NIHR) Health Protection Research Unit in Vaccines and Immunisation (NIHR200929).</div></div>","PeriodicalId":34394,"journal":{"name":"Lancet Healthy Longevity","volume":"6 11","pages":"Article 100775"},"PeriodicalIF":14.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145597879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.lanhl.2025.100789
Prof Duminda N Wijeysundera PhD , Prof Shabbir M H Alibhai MD , Prof Martine T E Puts PhD , Keying Xu MSc , Julian F Daza PhD , Calvin Diep MD , Karim S Ladha MD , Tyler R Chesney MD , Prof C David Mazer MD , Alice C Wei MD , Sahar Ehtesham MSc , Emily Hladkowicz PhD , Janneth Pazmino-Canizares MSc , Stephen Choi MD , Melinda Davis MBBS , Prof Derek Dillane MD , Emmanuelle Duceppe PhD , Prof Eric Jacobsohn MBChB , Gianni R Lorello MD , David B MacDonald MD , J Wu
Background
Older adults aged 65 years and older considering major surgery often prioritise functional and cognitive outcomes over survival. Therefore, we conducted a prospective cohort study that aimed to characterise the incidence, effect, and predictors of new postoperative disability in older adults.
Methods
The Functional Improvement Trajectories After Surgery multicentre prospective cohort study enrolled older adults (ie, those aged ≥65 years) undergoing major elective non-cardiac surgery at 17 hospitals across Canada. Endovascular, joint replacement, intra-cranial, and palliative procedures were excluded. The WHO Disability Assessment Schedule was used to assess disability preoperatively and at 1, 3, 6, 9, and 12 months postoperatively. The primary outcome was 6-month significant new disability or death. The secondary outcome was this composite outcome at 12 months. Multivariable logistic regression models were used to estimate associations of baseline characteristics with outcomes.
Findings
Between Dec 16, 2019, and April 26, 2023, we enrolled 2007 patients (median age 72 years [IQR 68–76]; 853 [42·5%] were female), of whom 1988 (99·1%) lived at home and 868 (43·3%) lived with frailty. By 6 months after surgery, 16·5% patients had significant new disability and death, increasing to 20·7% by 1 year. Patients with new disability at 6 months had higher risks of concurrent depression (risk difference 36·7%, 95% CI 31·9–41·6) and decisional regret (9·9%, 5·1–14·7). At 12 months, the higher risks of depression (33·6%, 28·2–39·0) and decisional regret (12·9%, 7·9–17·8) persisted. Multivariable modelling identified baseline frailty, cognitive impairment, mobility aids, open surgery, smoking, and possibly unmet social supports as associated with increased risks of postoperative new disability or death.
Interpretation
One in six older adults in this cohort experienced new disability or death at 6 months following major surgery, increasing to one in five patients by 1 year. Preoperative assessment of frailty, cognitive status, and social supports could enhance shared decision making, care planning, and functional recovery.
Funding
Canadian Institutes of Health Research, PSI Foundation, Ontario Ministry of Health Innovation Fund, and the Elizabeth A and Richard J Currie, OC Chair in Translational Anesthesia Research at St Michael’s Hospital and the University of Toronto.
{"title":"Significant new disability after major non-cardiac surgery in older adults aged 65 years and older in Canada: a multicentre prospective cohort study","authors":"Prof Duminda N Wijeysundera PhD , Prof Shabbir M H Alibhai MD , Prof Martine T E Puts PhD , Keying Xu MSc , Julian F Daza PhD , Calvin Diep MD , Karim S Ladha MD , Tyler R Chesney MD , Prof C David Mazer MD , Alice C Wei MD , Sahar Ehtesham MSc , Emily Hladkowicz PhD , Janneth Pazmino-Canizares MSc , Stephen Choi MD , Melinda Davis MBBS , Prof Derek Dillane MD , Emmanuelle Duceppe PhD , Prof Eric Jacobsohn MBChB , Gianni R Lorello MD , David B MacDonald MD , J Wu","doi":"10.1016/j.lanhl.2025.100789","DOIUrl":"10.1016/j.lanhl.2025.100789","url":null,"abstract":"<div><h3>Background</h3><div>Older adults aged 65 years and older considering major surgery often prioritise functional and cognitive outcomes over survival. Therefore, we conducted a prospective cohort study that aimed to characterise the incidence, effect, and predictors of new postoperative disability in older adults.</div></div><div><h3>Methods</h3><div>The Functional Improvement Trajectories After Surgery multicentre prospective cohort study enrolled older adults (ie, those aged ≥65 years) undergoing major elective non-cardiac surgery at 17 hospitals across Canada. Endovascular, joint replacement, intra-cranial, and palliative procedures were excluded. The WHO Disability Assessment Schedule was used to assess disability preoperatively and at 1, 3, 6, 9, and 12 months postoperatively. The primary outcome was 6-month significant new disability or death. The secondary outcome was this composite outcome at 12 months. Multivariable logistic regression models were used to estimate associations of baseline characteristics with outcomes.</div></div><div><h3>Findings</h3><div>Between Dec 16, 2019, and April 26, 2023, we enrolled 2007 patients (median age 72 years [IQR 68–76]; 853 [42·5%] were female), of whom 1988 (99·1%) lived at home and 868 (43·3%) lived with frailty. By 6 months after surgery, 16·5% patients had significant new disability and death, increasing to 20·7% by 1 year. Patients with new disability at 6 months had higher risks of concurrent depression (risk difference 36·7%, 95% CI 31·9–41·6) and decisional regret (9·9%, 5·1–14·7). At 12 months, the higher risks of depression (33·6%, 28·2–39·0) and decisional regret (12·9%, 7·9–17·8) persisted. Multivariable modelling identified baseline frailty, cognitive impairment, mobility aids, open surgery, smoking, and possibly unmet social supports as associated with increased risks of postoperative new disability or death.</div></div><div><h3>Interpretation</h3><div>One in six older adults in this cohort experienced new disability or death at 6 months following major surgery, increasing to one in five patients by 1 year. Preoperative assessment of frailty, cognitive status, and social supports could enhance shared decision making, care planning, and functional recovery.</div></div><div><h3>Funding</h3><div>Canadian Institutes of Health Research, PSI Foundation, Ontario Ministry of Health Innovation Fund, and the Elizabeth A and Richard J Currie, OC Chair in Translational Anesthesia Research at St Michael’s Hospital and the University of Toronto.</div></div>","PeriodicalId":34394,"journal":{"name":"Lancet Healthy Longevity","volume":"6 11","pages":"Article 100789"},"PeriodicalIF":14.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145640753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.lanhl.2025.100793
Philippa K Harris
{"title":"Highlights of the EuGMS congress 2025","authors":"Philippa K Harris","doi":"10.1016/j.lanhl.2025.100793","DOIUrl":"10.1016/j.lanhl.2025.100793","url":null,"abstract":"","PeriodicalId":34394,"journal":{"name":"Lancet Healthy Longevity","volume":"6 11","pages":"Article 100793"},"PeriodicalIF":14.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.lanhl.2025.100795
Carolyn E Schwartz
{"title":"A pragmatic application with clear personal impact","authors":"Carolyn E Schwartz","doi":"10.1016/j.lanhl.2025.100795","DOIUrl":"10.1016/j.lanhl.2025.100795","url":null,"abstract":"","PeriodicalId":34394,"journal":{"name":"Lancet Healthy Longevity","volume":"6 11","pages":"Article 100795"},"PeriodicalIF":14.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145640782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.lanhl.2025.100796
Changyuan Yang MD , Hanneke Joosten MD PhD , Lynne Chepulis PhD , Fabiana Rossi Varallo PhD , Peter van Dijk MD PhD , Deidra C Crews MD , Priya Vart PhD
Chronic kidney disease (CKD) is common among older adults, with more than a third of individuals older than 65 years having moderate to severe CKD globally. Management of CKD in older adults is often complex because of multiple comorbidities, polypharmacy, and frailty. However, older adults remain under-represented in clinical trials for both type 2 diabetes (T2D), which is the leading risk factor for CKD, and CKD itself. Recent analyses show consistent low representation of older adults in T2D trials. Similarly, participants of dialysis trials tend to be younger, healthier, and have a lower mortality rate than individuals in the real-world dialysis population, and even greater age disparities are reported in trials for non-dialysis-dependent CKD. This under-representation limits the evidence base for treating older adults and often compels clinicians to extrapolate findings from younger populations or rely on observational data. Consequently, both undertreatment and overtreatment of T2D and CKD might occur. Excluding older adults from trial participation leads to society bearing the costs of avoidable harms from preventable adverse events, inappropriate medication use, and missed opportunities to improve functional outcomes in an ageing population. Addressing this age gap in trial population and target treatment population is crucial to ensure evidence-based, equitable care for older adults. In this Personal View, we explore the barriers of under-representation of older adults and propose strategies to enhance their inclusion in future trials for T2D and CKD.
{"title":"Bridging the age gap: improving representation of older adults in clinical trials for type 2 diabetes and chronic kidney disease","authors":"Changyuan Yang MD , Hanneke Joosten MD PhD , Lynne Chepulis PhD , Fabiana Rossi Varallo PhD , Peter van Dijk MD PhD , Deidra C Crews MD , Priya Vart PhD","doi":"10.1016/j.lanhl.2025.100796","DOIUrl":"10.1016/j.lanhl.2025.100796","url":null,"abstract":"<div><div>Chronic kidney disease (CKD) is common among older adults, with more than a third of individuals older than 65 years having moderate to severe CKD globally. Management of CKD in older adults is often complex because of multiple comorbidities, polypharmacy, and frailty. However, older adults remain under-represented in clinical trials for both type 2 diabetes (T2D), which is the leading risk factor for CKD, and CKD itself. Recent analyses show consistent low representation of older adults in T2D trials. Similarly, participants of dialysis trials tend to be younger, healthier, and have a lower mortality rate than individuals in the real-world dialysis population, and even greater age disparities are reported in trials for non-dialysis-dependent CKD. This under-representation limits the evidence base for treating older adults and often compels clinicians to extrapolate findings from younger populations or rely on observational data. Consequently, both undertreatment and overtreatment of T2D and CKD might occur. Excluding older adults from trial participation leads to society bearing the costs of avoidable harms from preventable adverse events, inappropriate medication use, and missed opportunities to improve functional outcomes in an ageing population. Addressing this age gap in trial population and target treatment population is crucial to ensure evidence-based, equitable care for older adults. In this Personal View, we explore the barriers of under-representation of older adults and propose strategies to enhance their inclusion in future trials for T2D and CKD.</div></div>","PeriodicalId":34394,"journal":{"name":"Lancet Healthy Longevity","volume":"6 11","pages":"Article 100796"},"PeriodicalIF":14.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145606714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}