Hazard Ratio Research Articles

Long-Term Intake of Red Meat in Relation to Dementia Risk and Cognitive Function in US Adults.

Previous studies have shown inconsistent associations between red meat intake and cognitive health. Our objective was to examine the association between red meat intake and multiple cognitive outcomes. In this prospective cohort study, we included participants free of dementia at baseline from 2 nationwide cohort studies in the United States: the Nurses' Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS). Diets were assessed using a validated semiquantitative food frequency questionnaire. We ascertained incident dementia cases from both NHS participants (1980-2023) and HPFS participants (1986-2023). Objective cognitive function was assessed using the Telephone Interview for Cognitive Status (1995-2008) among a subset of NHS participants. Subjective cognitive decline (SCD) was self-reported by NHS participants (2012, 2014) and HPFS participants (2012, 2016). Cox proportional hazards models, general linear regression, and Poisson regression models were applied to assess the associations between red meat intake and different cognitive outcomes. The dementia analysis included 133,771 participants (65.4% female) with a mean baseline age of 48.9 years, the objective cognitive function analysis included 17,458 female participants with a mean baseline age of 74.3 years, and SCD analysis included 43,966 participants (77.1% female) with a mean baseline age of 77.9 years. Participants with processed red meat intake ≥0.25 serving per day, compared with <0.10 serving per day, had a 13% higher risk of dementia (hazard ratio [HR] 1.13; 95% CI 1.08-1.19; plinearity < 0.001) and a 14% higher risk of SCD (relative risk [RR] 1.14; 95% CI 1.04-1.25; plinearity = 0.004). Higher processed red meat intake was associated with accelerated aging in global cognition (1.61 years per 1 serving per day increment [95% CI 0.20-3.03]) and in verbal memory (1.69 years per 1 serving per day increment [95% CI 0.13-3.25], both plinearity = 0.03). Unprocessed red meat intake of ≥1.00 serving per day, compared with <0.50 serving per day, was associated with a 16% higher risk of SCD (RR 1.16; 95% CI 1.03-1.30; plinearity = 0.04). Replacing 1 serving per day of nuts and legumes for processed red meat was associated with a 19% lower risk of dementia (HR 0.81, 95% CI 0.75-0.86), 1.37 fewer years of cognitive aging (95% CI -2.49 to -0.25), and a 21% lower risk of SCD (RR 0.79, 95% CI 0.68-0.92). Higher intake of red meat, particularly processed red meat, was associated with a higher risk of developing dementia and worse cognition. Reducing red meat consumption could be included in dietary guidelines to promote cognitive health. Further research is needed to assess the generalizability of these findings to populations with diverse ethnic backgrounds.

Long-Term Effect of Intensive vs Standard Blood Pressure Control on Mild Cognitive Impairment and Probable Dementia in SPRINT.

The Systolic Blood Pressure Intervention Trial suggested that intensive lowering of systolic blood pressure (SBP) decreases the risk of developing dementia. However, an insufficient number of probable dementia cases stemming from the trial's early termination made results inconclusive. The goal of this study was to estimate the effect of intensive vs standard SBP lowering on the longer term incidence of cognitive impairment leveraging extended follow-up for cognitive status. This is a prespecified secondary analysis of a randomized clinical trial. Between 2010 and 2013, patients aged 50 years and older with hypertension and increased cardiovascular risk excluding those with diabetes mellitus or history of stroke were recruited from 102 clinics in the United States and Puerto Rico. Participants were randomized to a SBP goal of <120 mm Hg (intensive treatment) or <140 mm Hg (standard treatment) and received treatment for 3.3 years. In-person cognitive assessment follow-up occurred through July 2018. Continued ascertainment of cognitive status by telephone began in December 2019 for participants who had not withdrawn consent or been previously adjudicated with probable dementia, but provided consent for future research. Data were analyzed using survival analyses. Of 9,361 randomized participants, 7,221 (77%) were eligible to be re-contacted. Cognitive status of 4,232 (59%) was ascertained (mean age 67 years, 36% female). We accrued a total of 216 new cases of probable dementia, less than our target of 326. Over a median follow-up of 7 years, 248 participants of the intensive treatment group (8.5 per 1,000 person-years) were adjudicated with probable dementia, compared with 293 participants (10.2 per 1,000 person-years) in the standard treatment group (hazard ratio [HR], 0.86; 95% CI, 0.72-1.02). Consistent with earlier results from the trial, the rate of both mild cognitive impairment (MCI; HR, 0.87 95% CI, 0.76-1.00) and a composite of MCI or probable dementia was lower with intensive treatment (HR, 0.89; 95% CI, 0.79, 0.99). Among ambulatory adults with hypertension and high cardiovascular risk, intensive treatment vs standard treatment of SBP for 3.3 years resulted in a lower risk of MCI and cognitive impairment including MCI or probable dementia, but not for probable dementia alone. This study provides Class II evidence that intensively reducing SBP (target <120 mm Hg) decreases the risk of cognitive impairment in individuals aged 50 years and older with hypertension. Clinical trial number NCT01206062.

Reverse Time-to-Death as Time-Scale in Time-to-Event Analysis for Studies of Advanced Illness and Palliative Care.

Incidence of adverse outcome events rises as patients with advanced illness approach end-of-life. Exposures that tend to occur near end-of-life, for example, use of wheelchair, oxygen therapy and palliative care, may therefore be found associated with the incidence of the adverse outcomes. We propose a concept of reverse time-to-death (rTTD) and its use for the time-scale in time-to-event analysis based on partial likelihood to mitigate the time-varying confounding. We used data on community-based palliative care uptake (exposure) and emergency department visits (outcome) among patients with advanced cancer in Singapore to illustrate. We compare the results against that of the common practice of using time-on-study (TOS) as time-scale. Graphical analysis demonstrated that cancer patients receiving palliative care had higher rate of emergency department visits than non-recipients mainly because they were closer to end-of-life, and that rTTD analysis made comparison between patients at the same time-to-death. In analysis of a decedent cohort, emergency department visits in relation to palliative care using TOS time-scale showed significant increase in hazard ratio estimate when observed time-varying covariates were omitted from statistical adjustment (% change-in-estimate = 16.2%; 95% CI 6.4% to 25.6%). There was no such change in otherwise the same analysis using rTTD (% change-in-estimate = 3.1%; 95% CI -1.0% to 8.5%), demonstrating the ability of rTTD time-scale to mitigate confounding that intensifies in relation to time-to-death. A similar pattern was found in the full cohort. Simulations demonstrated that the proposed method had smaller relative bias and root mean square error than TOS-based analysis. In conclusion, use of rTTD as time-scale in time-to-event analysis provides a simple and robust approach to control time-varying confounding in studies of advanced illness, even if the confounders are unmeasured.

Nutritional assessment using subjective global assessment identifies energy malnutrition and predicts mortality in patients with liver cirrhosis

Abstract This study aimed to evaluate whether the subjective global assessment (SGA) could effectively predict energy malnutrition, as assessed by indirect calorimetry, and mortality in hospitalized patients with cirrhosis. Energy malnutrition was defined by a nonprotein respiratory quotient (npRQ) &lt; 0.85 using an indirect calorimetry. The usefulness of the SGA in identifying energy malnutrition and predicting mortality was assessed by the logistic regression and Cox proportional hazards models, respectively. Out of the 230 patients analyzed, 43% were found to have energy malnutrition. The distribution of SGA classifications was 54% for SGA-A, 32% for SGA-B, and 14% for SGA-C. Multivariable analysis indicated that both SGA-B (odds ratio, 3.59; 95% confidence interval [CI], 1.59–8.10) and SGA-C (odds ratio, 19.70; 95% CI, 3.46–112.00), along with free fatty acids (FFA), were independently linked to energy malnutrition. Regarding mortality, 125 patients (54%) died over a median follow-up period of 2.8 years. After adjustment, SGA-B (hazard ratio, 1.81; 95% CI, 1.08–3.03) and SGA-C (hazard ratio, 3.35; 95% CI, 1.28–8.76) were predictors of mortality in cirrhosis patients, while energy malnutrition and FFA were not. The SGA is a valuable tool for identifying energy malnutrition and predicting mortality in patients with cirrhosis.

Second-line anti-CD38 monoclonal antibody therapy mitigates the negative impact of functional high-risk status in myeloma patients.

In multiple myeloma, functional high risk (FHR) is a predictor of poor outcomes. It is defined as M protein reduction to ≤ 50% of normal, suboptimal response (SR), or progressive disease (PD) within 12months (i.e., early PD). The clinical significance of anti-CD38 monoclonal antibody (MoAb) as second-line treatment for FHR myeloma remains unclear. We retrospectively investigated the efficacy of anti-CD38 MoAb as second-line treatment for FHR myeloma. We included 332 patients who were newly diagnosed with myeloma and received proteasome inhibitors and/or immunomodulatory drugs as first-line therapy. Their median age was 70years, and 29.4% were FHR. At a median follow-up of 48.5months, the overall survival (OS) in the FHR group was significantly shorter (hazard ratio [HR], 2.086; P < 0.001). However, the OS in the SR without early-PD group was comparable to that in the non-FHR group (HR, 1.659; P = 0.330). The OS in patients with FHR who received anti-CD38 MoAb as second-line treatment was similar to that in the non-FHR group (HR, 1.157; P = 0.660). Anti-CD38 MoAb as second-line treatment improved the outcome in our patients with FHR although FHR predicted a poor prognosis.

Diabetic retinopathy further increases risk of cardiovascular disease mortality in a high-risk cohort

Abstract Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and is strongly linked with systemic vascular comorbidities. This study investigated if DR predicts risk of cardiovascular disease (CVD) mortality in a high CVD risk cohort. This was a prospective cohort study of 1582 adult participants who presented to a tertiary Australian hospital for evaluation of acute coronary syndrome by coronary angiography. Participants were concurrently examined for DR from mydriatic fundus photographs which were mask-graded according to International Clinical Classification categories of no DR, mild non-proliferative DR, moderate-to-severe NPDR, and proliferative DR. Coronary artery disease was graded from coronary angiograms using the Gensini score. CVD mortality follow-up was assessed 9 years after baseline examination using linkage with the Australian National Death Index. At baseline, 355 (22.4%) participants had any DR. There were 181 (11.4%) fatal CVD events after 9-years follow-up. After controlling for age, sex, BMI, diabetes, total cholesterol, smoking status, hypertension, previous myocardial infarction and stroke, any DR was associated with 1.8-fold higher risk of CVD mortality (Hazard Ratio [HR] 1.84, 95% Confidence Interval [95% CI: 1.30–2.61]). Mild non-proliferative DR (1.85 [1.26–2.72]) and proliferative DR (5.27 [2.32–12.00]) were associated with greater CVD mortality risk. Further adjustment for coronary artery disease using Gensini scores and excluding patients without diabetes had minimal impact on the association. The increased risk of CVD mortality was significant in both men (2.25 [1.60–3.19]) and women (2.38 [1.24–4.58]) with any DR. In individuals with high CVD risk, presence of DR independently predicts increased CVD mortality. This likely reflects additional contribution of microvascular disease to CVD mortality. Individuals with DR may benefit from a comprehensive cardiovascular risk assessment, lifestyle changes, more intensive cardiovascular management and follow-up to minimise risk of death from CVD events.

Impact of magnetic resonance imaging-defined sarcopenia on prognosis in patients with locally advanced nasopharyngeal carcinoma.

To investigate the impact of sarcopenia assessed by pretherapy magnetic resonance imaging (MRI) of the third cervical vertebra (C3) on the survival of patients with locally advanced nasopharyngeal carcinoma (LANPC). We analyzed the clinical information of 478 patients with LANPC who underwent radiotherapy between July 2016 and June 2019. Sarcopenia was evaluated using the skeletal muscle mass index, which was determined based on an MRI of the C3. The cutoff values for sarcopenia were determined using receiver operating characteristic curves. The thresholds were < 12.83 cm2/m2 for male and < 11.15 cm2/m2 for female. Comparisons between patients with and without sarcopenia were conducted using the chi-squared test. The Kaplan-Meier method was applied to plot survival curves, which were then assessed using the log-rank test. Survival factors were identified using univariate and multivariate analyses. The 5-year overall survival (OS) rate was 75.3%, with a median follow-up period of 59months. Patients with sarcopenia (181/478) had a lower OS than those without sarcopenia (70.7% vs 78.1%, hazard ratio = 1.87, 95% confidence interval: 1.26-2.77, P < 0.01). Sarcopenia was elevated in patients with advanced T-stage tumors and a low body mass index. Univariate and multivariate analyses showed that sarcopenia, age, sex, T stage, and N stage were significant variables that affected the OS of patients with LANPC (P < 0.05). MRI-based sarcopenia is significantly correlated with the OS of patients with LANPC. This finding highlights the importance of evaluating sarcopenia before treatment, as it can guide personalized treatment programs, thereby enhancing patient prognosis.

Acetylsalicylic acid and subarachnoid haemorrhage in the Nurses' Health Study.

Acetylsalicylic acid (aspirin) is known to increase the risk of bleeding throughout the body. However, there is also evidence to suggest that acetylsalicylic acid may have a protective role in the formation and rupture of intracranial aneurysms. Previous studies investigating acetylsalicylic acid and subarachnoid haemorrhage (SAH) have so far provided conflicting results. The aim of this study was to analyse the Nurse's Health Study (NHS) using serial assessments to evaluate differences in rates of SAH in those participants taking acetylsalicylic acid and those not taking acetylsalicylic acid while considering dose, frequency, and duration as well as different types of SAH. The Nurse's Health Study (NHS) is a prospective population-based cohort study of female nurses. Information on acetylsalicylic acid was first reported in 1980 until 2016 and included acetylsalicylic acid use, dose, frequency and duration. All stroke cases were classified by physicians. Cox proportional-hazards regression models were used to estimate the hazard ratio (HR) associated with acetylsalicylic acid use. A total of 117,648 NHS participants were eligible for analysis with 357 cases of SAH observed over 4,091,239 years of follow up. There was no association between acetylsalicylic acid use and SAH (HR 1.02 [0.82, 1.28], p=0.85), aneurysmal SAH (1.04 [0.78, 1.39], p=0.78), or idiopathic SAH (HR 0.94 [0.65, 1.34], p=0.72). The number of acetylsalicylic acid tablets per week was associated with SAH (HR 1.03 [1.00, 1.06], p=0.02), specifically fatal SAH (HR 1.04 [1.00, 1.08], p=0.03). There was no association between frequency and SAH (HR 1.06 [0.99, 1.13], p=0.07). There was no evidence to support a protective association between acetylsalicylic acid and either SAH or aneurysmal SAH in female participants. In fact, there was some evidence to suggest increased SAH risk with increased acetylsalicylic acid dose in some but not all analyses. Data are available by request from the Brigham and Women's Hospital, Harvard Medical School, and Harvard T.H. Chan School of Public Health.

Prevalence and prognostic value of different iron deficiency definitions in light chain cardiac amyloidosis patients.

Research on iron deficiency (ID) in patients with light chain cardiac amyloidosis (AL-CM) has been limited in previous studies. The purpose of this study was to investigate the prevalence and its association with prognosis of ID based on different definitions in patients with AL-CM. Three different ID definitions were applied: (1) serum ferritin concentration of <100ng/mL, or 100-299ng/mL with transferrin saturation (TSAT)<20% (according to guidelines on heart failure), (2) TSAT<20% and (3) serum iron <13μmol/L. The primary outcome measure was all-cause mortality. Prevalence and outcomes of various ID definitions were evaluated among patients diagnosed with AL-CM at Heart Failure Center, Fuwai Hospital between September 2017 and October 2023. Overall, 149 patients were included with a mean age of 60.71±10.11years, of whom 60 (40.3%) patients were female, 127 (85.2%) patients were in New York Heart Association (NYHA) class III-IV and 136 (91.3%) patients were in the revised Mayo 2012 stage III-IV. Assessments of iron biomarkers revealed the following results: median ferritin levels were 183.68ng/mL (interquartile range [IQR] 95.48, 339.01), median TSAT was 21.80% (IQR 16.34, 29.48), and median serum iron was 10.87μmol/L (IQR 7.38, 13.71). Serum iron were highly correlated with TSAT (r=0.85, P<0.0001). Depending on the definition used, 63 (42.3%) patients, 61 (40.9%) patients and 105 (70.5%) patients were defined as ID, respectively (P<0.0001). ID defined by TSAT and serum iron was associated with the primary outcome [hazard ratio (HR) 2.14, 95% confidence interval (CI) 1.36-3.37, P<0.001, and HR 2.16, 95% CI (1.23-3.80), P<0.01], but the same association was not seen with the guideline definition of ID [HR 1.39, 95% CI (0.88-2.18), P=0.158]. In the multivariable model adjusting for age, gender, haemoglobin, and revised 2012 Mayo staging, the predictive value of TSAT<20% [adjusted HR 2.49, 95% CI (1.54-4.05), P<0.001] and serum iron<13μmol/L [adjusted HR 2.24, 95% CI (1.23-4.09), P<0.01] remained. Different definitions of ID yield inconsistent results in terms of prevalence and prognosis. ID, as defined by TSAT<20% or serum iron<13μmol/L, rather than the guideline definition, emerged as an independent predictor of all-cause mortality in patients with AL-CM.

Associations between degree of food processing and colorectal cancer risk in a large-scale European cohort.

Industrial food processing has been linked to various health outcomes including cancer. To examine associations between the degree of food processing and risk of colorectal cancer (CRC) and its sub-sites, data from the European Prospective Investigation into Cancer (EPIC) including 6155 incident CRC cases (n = 450,111 participants), were analyzed. Dietary intakes were assessed using baseline food frequency questionnaires. Foods were classified into culinary ingredients, unprocessed, processed (PFs), and ultra-processed foods (UPFs) according to the Nova classification. Cox proportional hazards models, adjusted for established CRC risk factors, were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) associated with a 10% increase in proportion of consumption (%g/d) of each Nova group. Substitution analysis examined the effect of replacing UPFs and PFs with unprocessed foods on CRC risk. A 10% increase in proportion of UPFs was associated with 6% higher CRC risk (95% CI:1.02-1.10). A positive association was also found between PFs and CRC risk (HR per 10% increase: 1.10 [95% CI, 1.05-1.15]). Conversely, unprocessed food consumption was inversely associated with CRC risk (HR per 10% increase: 0.93[95% CI, 0.90-0.95]). Substitution of 10% of the overall proportion of the diet comprising UPFs or PFs with 10% unprocessed foods was associated with a decreased risk of CRC (HRUPFs: 0.94 [95% CI, 0.90-0.97]; HRPFs: 0.90 [95% CI, 0.86-0.94]). In conclusion, UPF was positively associated with CRC risk while diets richer in unprocessed foods were associated with lower CRC risk. Further studies are needed to understand the mechanisms by which food processing affects CRC risk.

Mortality risk stratification based on comorbidity status among cervical cancer patients in Lagos, Nigeria.

Comorbidity amplifies mortality risk by approximately sixfold in cancer patients and affects about 26% of cervical cancer (CC) patients in Nigeria. However, its impact on CC outcomes has yet to be fully explored. We analysed data from the Lagos University Teaching Hospital and the NSIA-LUTH Cancer Center in Lagos, Nigeria, between January 2015 and December 2021. Based on the hypertension-augmented Charlson comorbidity index (hCCI), the hazard ratios (HRs) associated with CC mortality were estimated using Cox proportional hazards model. Our results showed a mortality rate of 30.1/100 women-years with a mean age at death of 59.8years. Women with hCCI 2-6 had a significant increase in mortality risk in unadjusted (HR 1.68 [95% confidence interval {CI} 1.10 to 2.57]) and age-adjusted models (adjusted HR 1.57 [95% CI 1.02 to 2.42]) compared with those with hCCI 0. When CC stage was considered, the mortality risk gradient by hCCI was pronounced for late-metastatic CC with hCCI 2-6 (HR 2.32 [95% CI 1.23 to 4.39], increasing to 4.15 (95% CI 1.69 to 10.18) in the adjusted model compared with hCCI 0. Cervical cancer mortality risk increases with an increasing comorbidity score. Routine incorporation of comorbidity scoring in the clinical assessment of CC patients as well as the use of multidisciplinary cancer care teams may positively impact their clinical and psychosocial management.

Prognostic impact of late gadolinium enhancement granularity in non-ischemic dilated cardiomyopathy.

We aimed to assess the additional prognostic value of the concept of "late gadolinium enhancement (LGE) granularity" in non-ischemic dilated cardiomyopathy (DCM) patients to predict all-cause death. Between 2008 and 2021, we conducted a bicentric retrospective study including all consecutive DCM patients referred for Cardiovascular Magnetic Resonance (CMR). The primary outcome was all-cause death. Cox regressions were performed to determine the prognostic value of LGE findings. Of 1668 DCM patients recruited (age 52 ± 8 years, 54% male), 268 (16%) died after a median (interquartile range) follow-up of 9 (7-12) years. In DCM patients with LGE (N = 472), the LGE extent, the septal location, and its presence in multiple areas were independently associated with death after adjustment for all prognostic variables (adjusted hazard ratio (HR): 4.27, 95% CI: 2.22-8.22; HR: 5.74, 95% CI: 3.35-9.85; and HR: 4.38, 95% CI: 2.08-9.22 respectively; all p < 0.001). The LGE granularity model combining all these LGE features showed the best improvement in model discrimination and reclassification over traditional prognostic variables, including the left ventricular ejection fraction (LVEF) value (C-statistic improvement: 0.14; net reclassification improvement = 64.3%; integrative discrimination index = 29.0%; all p < 0.05). In a large cohort of DCM patients, a LGE granularity model combining LGE extent, location and multiple areas had additional prognostic value above traditional prognostic variables including the LVEF value to predict all-cause death. Question Assessment of late gadolinium enhancement (LGE) is recommended in non-ischemic dilated. cardiomyopathy (DCM) patients to stratify the risk of death, but other LGE characteristics are not currently considered. Findings The concept of "LGE granularity," including the extent, location, and number of areas, provides additional prognostic value, especially in predicting all-cause mortality. Clinical relevance "LGE granularity" could play a crucial role not only in guiding the decision to implant a defibrillator in DCM patients but also in providing more personalized management, such as enhanced cardioprotective treatments, for those with high-risk LGE characteristics.

Outcomes and Disease Management in Patients With Atrial Fibrillation ≥80 Years: Data From a Consecutive 11-Year Real-World Registry.

As the population ages, atrial fibrillation (AF) prevalence increases, but data on optimal oral anticoagulation (OAC) in patients ≥80 years remain limited. This study tested whether direct OACs offer comparable benefits to vitamin K antagonists in patients ≥80 years with AF presenting to the emergency department. This single-center retrospective all-comer study used data from the Heidelberg Registry of Atrial Fibrillation, including patients with AF presenting to the emergency department of the University Hospital of Heidelberg from June 2009 until March 2020. Data were analyzed by age for outcomes and risk factors for predefined end points. Patients ≥80 years comprised 32.2% of AF cases. Hazard ratios (HRs) for the primary end point (all-cause mortality, stroke, or myocardial infarction) and secondary end point (including major bleeding) were 3.09 (95% CI, 2.73-3.21) and 2.96 (95% CI, 2.73-3.21) for patients ≥80 years, compared with younger patients. Anticoagulation rates were slightly lower in patients ≥80 years (67.9% versus 70.5%, P=0.0070). OAC use, particularly the use of direct OACs, increased over time. Patients ≥80 years without OACs had higher HRs for primary (3.48 [95% CI, 3.07-3.94]) and secondary end points (3.23 [95% CI, 2.86-3.64]) compared with those with OACs. Vitamin K antagonist use was linked to higher HR for stroke or major bleeding events (HR, 1.25 [95% CI, 1.05-1.50]), rising to 1.64 (95% CI, 1.34-2.01) after excluding reduced direct OAC doses. Our data highlight patients ≥80 years as an important and vulnerable subpopulation of patients with AF, where evidence for optimal OAC therapy remains conflicting. URL: https://www.clinicaltrials.gov; Unique identifier: NCT05995561.

Association Between Age at Diagnosis of Atrial Fibrillation and Subsequent Risk of Ischemic Stroke.

Atrial fibrillation (AF) significantly increases the ischemic stroke risk. However, the relationship between age at diagnosis of AF and subsequent stroke risk remains poorly understood. We analyzed data from 5 prospective cohorts: ARIC (Atherosclerosis Risk in Communities) study, CHS (Cardiovascular Health Study), CARDIA (Coronary Artery Risk Development in Young Adults), MESA (Multi-Ethnic Study of Atherosclerosis), and Framingham Heart Study (including Offspring cohort and the Third-Generation cohorts). Cox regression models and competing risk survival analyses were used to assess incidence rates and hazard ratios (HRs) for ischemic stroke stratified by age groups. Among 47 239 participants (median follow-up: 21.1 years), 6689 (14.2%) developed AF, and 536 (8.0%) subsequently experienced ischemic stroke. Younger age at AF diagnosis was significantly associated with a higher ischemic stroke risk. Fully adjusted HRs for ischemic stroke were 5.35 (95% CI, 3.56-8.03), 2.99 (95% CI, 2.32-3.86), 2.13 (95% CI, 1.75-2.58), and 1.93 (95% CI, 1.59-2.34) for AF diagnosed at ages 55, 65, 75, and 85, respectively. Compared with participants without AF at age 55, HRs for ischemic stroke were 7.30 (95% CI, 3.27-16.31) for AF diagnosed >10 years earlier, 4.98 (95% CI, 2.99-8.29) for 6 to 10 years earlier, and 4.60 (95% CI, 1.48-14.34) for ≤5 years earlier (P-trend <0.001). The presence of AF yielded a 13.9 years earlier occurrence of ischemic stroke among those with AF diagnosis at 55 years compared with 1.5 years earlier at age 85. Younger age at AF diagnosis was associated with a higher risk of subsequent ischemic stroke.

Association Between Inflammatory Arthritis, Genetic Risk, and the Long-Term Risk of Degenerative Aortic Stenosis: A Prospective Cohort Study.

Inflammatory arthritis is recognized to increase cardiovascular disease risk, but its association with degenerative aortic stenosis is not well understood. This prospective cohort study used participants from the UK Biobank, focusing on 4 major types of inflammatory arthritis, including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and gout. The primary outcome was the incidence of degenerative aortic stenosis. The primary analysis used Cox proportional hazards models to evaluate the association between inflammatory arthritis and the long-term risk of degenerative aortic stenosis, as well as to explore potential effect modifiers. Genetic risk was evaluated using polygenic risk scores and self-reported family history of cardiovascular diseases. The study included 497 567 participants, with 271 129 women (54.5%) and 468 015 White individuals (94.1%). The median age was 58 years. Over a median follow-up of 12.58 years, 4571 cases (0.9%) of degenerative aortic stenosis were identified. Compared with the control group, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and gout were associated with increased risks of degenerative aortic stenosis by 54% (hazard ratio [HR], 1.54 [95% CI, 1.28-1.85]), 72% (HR, 1.72 [95% CI, 1.19-2.50]), 176% (HR, 2.76 [95% CI, 1.43-5.32]), and 36% (HR, 1.36 [95% CI, 1.20-1.54]), respectively. These associations were independent of genetic risk (P for interaction>0.05). Additionally, we identified significant interactions between sex (P for interaction=0.036), age (P for interaction<0.001), and socioeconomic status (P for interaction=0.014) with rheumatoid arthritis, ankylosing spondylitis, and gout on the incidence of degenerative aortic stenosis, respectively. Inflammatory arthritis is significantly associated with an increased long-term risk of degenerative aortic stenosis, underscoring the need for enhanced risk assessment for degenerative aortic stenosis in these populations.

Dual-energy CT extracellular volume fraction predicts tumor collagen ratio and possibly survival for inoperable pancreatic cancer patients.

Tumor collagen is vital in chemotherapy resistance of pancreatic cancer (PC), but its non-invasive evaluation remains challenging. This study aims to investigate the association of variables derived from dual-energy CT with the collagen ratio (CR) of PC and to determine the prognostic value of CR in unresectable diseases. A total of 83 patients with resected PC and 71 patients with unresectable PC were enrolled. In the resected group, the correlation between the tumor CR and variables of dual-energy CT was analyzed. In the unresectable group, Cox regression analyses were conducted to investigate the prognostic value of dual-energy CT-predicted CR and other clinicoradiological indicators. The patients with resected PC were divided into low and high-CR sets with a threshold of 55%. In the resected group, the extracellular volume fraction calculated by the iodine concentration (ECV_IC) was the only predictor of tumor CR according to univariate and multivariate analysis (hazard ratio [HR] (95% confidence interval [CI]):1.19 [1.03-1.37]). The correlation coefficient r was 0.26 (p = 0.02) between ECV_IC and specific CR values. In the training set of unresectable PC group, ECV_IC (HR (95% CI): 0.94 (0.89-0.99), p = 0.03) and contrast-enhanced pattern (CEP) (HR (95% CI): 3.20 (1.41-7.27), p = 0.01) were independent prognostic factors for overall survival. The nomogram model was constructed and showed a good performance. The ECV_IC is a non-invasive indicator of tumor CR in PC. The ECV_IC and CEP have the potential to predict the prognosis of unresectable PC. Question Non-invasive evaluation of tumor collagen, a vital determinant of chemotherapy resistance of pancreatic cancer, remains challenging. Findings Tumor collagen ratio can be noninvasively predicted by extracellular volume fraction based on iodine concentration. Clinical relevance The nomogram model composed of extracellular volume fraction and contrast-enhanced pattern can serve as an effective and convenient tool for stratifying the prognosis of patients with unresectable pancreatic cancer.

Silent Myocardial Infarction and Risk of Stroke Recurrence: A Post Hoc Analysis of the IRIS Trial.

Unrecognized or silent myocardial infarction (MI) detected on an ECG is associated with first-ever stroke, but the impact on stroke recurrence is unknown. We aimed to determine the association of silent MI with stroke recurrence in patients with a recent ischemic stroke. Subjects from the IRIS (Insulin Resistance Intervention After Stroke) trial with an available ECG were included. Clinical MI was defined as a history of hospitalization for MI. Silent MI was defined as ECG evidence of MI in the absence of clinical MI. The primary outcome was recurrent stroke. Ischemic stroke and subtype were assessed as secondary outcomes. Multivariable Cox regression analysis adjusted for demographics, pioglitazone, and vascular risk factors was used to examine the association between MI and stroke recurrence. A total of 2282 participants met the inclusion criteria. Clinical and silent MI were identified in 161 (7.1%) and 94 (4.1%) subjects, respectively. Over the study period, 209 recurrent strokes occurred, with 191 classified as ischemic. In the fully adjusted model, silent MI was significantly associated with any stroke (hazard ratio [HR], 2.29 [95% CI, 1.34-3.90]) and ischemic stroke (HR, 2.09 [95% CI, 1.18-3.70]) recurrence. Clinical MI was associated with stroke recurrence in the unadjusted analysis but not in the fully adjusted model (HR, 1.31 [95% CI, 0.81-2.11]). Silent MI was not associated with potential cardioembolic subtypes (HR, 1.50 [95% CI, 0.70-3.22]). Among patients with a recent ischemic stroke, silent MI was associated with stroke recurrence. Tailored prevention strategies in this population warrant future investigation. URL: https://clinicaltrials.gov. Unique Identifier: NCT00091949.

Loneliness as a risk factor for time to care home entry for older adults receiving community care

Abstract Background and Objectives International efforts to contain long-term care costs have prioritised personal care. However, reductions in services aimed at addressing loneliness or promoting social participation may affect demand for long-term care facilities. Research on the impact of loneliness on entry to residential or nursing care is based on survey data, which under-represents those with highest needs. Administrative records include such individuals and, unlike surveys, contain continuous data on service receipt, enabling accurate modelling of time to care home entry. Research Design and Methods We use administrative data for 1,101 individuals receiving care in a London local authority. We extract loneliness from free text notes using a large language model and model its impact on care home entry five years after assessment, controlling for needs and demographics. We use logistic regression and a competing risks survival model to measure time until care home entry. Results The odds ratio for care home entry associated with loneliness is 1.45 with logistic regression (95% CI 1.04 – 2.01). The hazard ratio is 1.32 (95% CI 1.01 – 1.72) with a cause-specific model, and 1.39 (95% CI 1.08 - 1.79) using the Fine &amp; Gray method. Among those most likely to enter a care home, the median time to entry is 9 months (95% CI 228 - 328 days) earlier for those who are lonely. Discussion and Implications The hazard ratio of loneliness on care home entry is around the magnitude associated with gender, ethnicity or living alone. However, loneliness is modifiable. Reductions to services for social participation, such as day centres, are likely to cause an increase in loneliness. We demonstrate that for those with the highest needs, loneliness is a significant risk factor for time until care home entry. Policymakers seeking to delay care home entry should consider the impact of services for loneliness.

Preoperative prediction of IDH genotypes and prognosis in adult-type diffuse gliomas: intratumor heterogeneity habitat analysis using dynamic contrast-enhanced MRI and diffusion-weighted imaging

BackgroundIntratumor heterogeneity (ITH) is a key biological characteristic of gliomas. This study aimed to characterize ITH in adult-type diffuse gliomas and assess the feasibility of using habitat imaging based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) to preoperatively predict isocitrate dehydrogenase (IDH) genotypes and prognosis.MethodsSixty-three adult-type diffuse gliomas with known IDH genotypes were enrolled. Volume transfer constant (Ktrans) and apparent diffusion coefficient (ADC) maps were acquired from DCE-MRI and DWI, respectively. After tumor segmentation, the k-means algorithm clustered Ktrans and ADC image voxels to generate spatial habitats and extract quantitative image features. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were used to evaluate IDH predictive performance. Multivariable logistic regression models were constructed and validated using leave-one-out cross-validation, and the contrast-enhanced subgroup was analyzed independently. Kaplan-Meier and Cox proportional hazards regression analyses were used to investigate the relationship between tumor habitats and progression-free survival (PFS) in the two IDH groups.ResultsThree habitats were identified: Habitat 1 (hypo-vasopermeability and hyper-cellularity), Habitat 2 (hypo-vasopermeability and hypo-cellularity), and Habitat 3 (hyper-vasopermeability). Compared to the IDH wild-type group, the IDH mutant group exhibited lower mean Ktrans values in Habitats 1 and 2 (both P < 0.001), higher volume (P < 0.05) and volume percentage (pVol, P < 0.01) of Habitat 2, and lower volume and pVol of Habitat 3 (both P < 0.001). The optimal logistic regression model for IDH prediction yielded an AUC of 0.940 (95% confidence interval [CI]: 0.880–1.000), which improved to 0.948 (95% CI: 0.890–1.000) after cross-validation. Habitat 2 contributed the most to the model, consistent with the findings in the contrast-enhanced subgroup. In IDH wild-type group, pVol of Habitat 2 was identified as a significant risk factor for PFS (high- vs. low-pVol subgroup, hazard ratio = 2.204, 95% CI: 1.061–4.580, P = 0.034), with a value below 0.26 indicating a 5-month median survival benefit.ConclusionsHabitat imaging employing DCE-MRI and DWI may facilitate the characterization of ITH in adult-type diffuse gliomas and serve as a valuable adjunct in the preoperative prediction of IDH genotypes and prognosis.Clinical trial numberNot applicable.

Joint effect of sleep patterns and secondhand smoke exposure with mortality among non-smoking adults.

Unhealthy sleep and secondhand smoke (SHS) exposure are independent risk factors for death. Their joint association with all-cause and cardiovascular disease (CVD) mortality (ACDM) deserves to be investigated in a nationally representative population. Data from 15175 adults from the National Health and Nutrition Examination Survey database (2005-2014) were analyzed. The study endpoints were all-cause and CVD mortality. Sleep patterns (healthy, intermediate, and poor) were classified based on self-reported questionnaires, including sleep duration, self-reported trouble sleeping and doctor-diagnosed sleep disorders. SHS exposure among nonsmokers was defined according to cotinine levels in serum. Multivariate Cox hazards regression models were conducted to assess the association between sleep patterns and SHS exposure, alone and in combination, with ACDM. During 15 years of follow-up, 2016 all-cause deaths and 678 CVD deaths were recorded. In multivariable models, poor sleep was independently associated with higher risk of all-cause (hazard ratio [HR] 1.32; 95% confidence interval [CI] 1.15-1.51) and CVD mortality (HR= 1.31; 95% CI: 1.02-1.68). Exposure to SHS was associated with higher risk of all-cause (HR, 1.21; 95% CI, 1.08-1.36) and CVD mortality (HR, 1.25; 95% CI, 1.04-1.50). In the joint analyses, participants with both unhealthy sleep patterns (intermediate and poor) and SHS exposure had a significantly higher risk of all-cause (HR, 1.48; 95% CI: 1.26-1.74) and CVD mortality (HR, 1.51; 95% CI, 1.15-1.97) than those with neither risk factor. The coexistence of SHS exposure and unhealthy sleep patterns was associated with an increased risk of death from all causes and CVD. The findings of this study indicate that both poor sleep patterns and exposure to SHS are independently associated with a higher risk of all-cause and CVD mortality. Furthermore, the coexistence of SHS exposure and unhealthy sleep patterns further increases the risk of mortality from all causes and CVD. Since both sleep patterns and SHS exposure are modifiable factors, interventions aimed at reducing SHS exposure and improving sleep quality could have significant implications in reducing these adverse effects and lowering mortality risk.