Advancement of pharmacokinetic models of iohexol in patients aged 70 years or older with impaired kidney function
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ABSTRACT:
SUBMITTER: Taubert M
PROVIDER: S-EPMC8608910 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeFollowing the demonstrated efficacy and safety of eribulin mesylate in heavily pretreated patients with metastatic breast cancer, an exploratory analysis was performed to investigate the effect of age in these patients.MethodsData were pooled from two single-arm phase II studies and one open-label randomized phase III study in which patients received eribulin mesylate at 1.4 mg/m(2) as 2- to 5-minute intravenous infusions on days 1 and 8 of a 21-day cycle. The effect of age on median overall survival (OS), progression-free survival (PFS), overall response rate (ORR), clinical benefit rate (CBR), and incidence of adverse events (AEs) was calculated for four age groups (<50 years, 50-59 years, 60-69 years, ≥ 70 years). RESULTS. Overall, 827 patients were included in the analysis (<50 years, n = 253; 50-59 years, n = 289; 60-69 years, n = 206; ≥ 70 years, n = 79). Age had no significant impact on OS (11.8 months, 12.3 months, 11.7 months, and 12.5 months, respectively; p = .82), PFS (3.5 months, 2.9 months, 3.8 months, and 4.0 months, respectively; p = .42), ORR (12.7%, 12.5%, 6.3%, and 10.1%, respectively), or CBR (20.2%, 20.8%, 20.4%, and 21.5%, respectively). Although some AEs had higher incidence in either the youngest or the oldest subgroup, there was no overall effect of age on the incidence of AEs (including neuropathy, neutropenia, and leukopenia).ConclusionEribulin monotherapy in these selected older patients with good baseline performance status led to OS, PFS, ORR, CBR, and tolerability similar to those of younger patients with metastatic breast cancer. The benefits and risks of eribulin appear to be similar across age groups.
| S-EPMC3983814 | biostudies-literature
Project description:BackgroundPeople with HIV (PWH) are aging. Frailty is an age-related condition predictive of hospitalization and mortality. Here, we assessed the frequency and factors associated with frailty transitions at 1-year follow-up in elderly PWH.MethodsFive hundred eight PWH aged 70 years or older who were on antiretroviral treatment were included in the French multicenter SEPTAVIH study in 2019-2020. Participants were classified as robust, prefrail, or frail according to Fried frailty phenotype at baseline and at 1 year. Logistic regression models were used to evaluate socioeconomic and medical factors associated with transition between frailty states. Models were adjusted for gender, age at baseline, education, and period of HIV diagnosis (before vs after 1996).ResultsSeventeen PWH died during the 1-year follow-up. Of the remaining 491 PWH (median age, 73 years), frailty status worsened for 18% of participants and improved for 14% at 1 year. Advanced age, baseline CD4+ T-cell count <350 cells/mm3, and type 2 diabetes were associated with transition from prefrailty to frailty (adjusted odds ratio [aOR], 1.10 per 1-year positive difference; 95% CI, 1.01-1.20; aOR, 3.05; 95% CI, 1.14-8.18; and aOR, 2.63; 95% CI, 1.05-6.57; respectively). Being female was associated with more frequent improvement from prefrailty to robustness (aOR, 2.50; 95% CI, 1.09-5.55).ConclusionsPreventing frailty in elderly PWH is a long-term problem, beginning with the early diagnosis of HIV infection and the management of comorbidities.
| S-EPMC11222971 | biostudies-literature
Project description:INTRODUCTION:Tobacco use remains a leading modifiable cause of cancer incidence and premature mortality in the U.S. and globally. Despite increasing life expectancy worldwide, less is known about the effects of cigarette smoking on older populations. This study sought to determine the effects of smoking on mortality in older age. METHODS:Associations of mortality with self-reported age at smoking cessation, age at smoking initiation, and amount smoked after age 70 years were examined in 160,113 participants of the NIH-AARP Diet and Health Study aged >70 years. Participants completed a questionnaire detailing their smoking use in 2004-2005, and were followed for mortality through December 31, 2011. Analyses were conducted between 2014 and 2016. RESULTS:Relative to never smokers, current smokers were more likely to die during follow-up (hazard ratio, 3.18; 95% CI=3.04, 3.31). Furthermore, former smokers had lower risks than current smokers (hazard ratios for quitting between ages 30-39, 40-49, 50-59, and 60-69 years were 0.41 [95% CI=0.39, 0.43], 0.51 [95% CI=0.49, 0.54], 0.64 [95% CI=0.61, 0.67], and 0.77 [95% CI=0.73, 0.81], respectively). Among current smokers, mortality was inversely associated with age at initiation, but directly associated with the number of cigarettes smoked per day at age >70 years. CONCLUSIONS:As among younger people, lifetime cigarette smoking history is a key determinant of mortality after age 70 years.
| S-EPMC5318256 | biostudies-literature
Project description:BackgroundSurvival in elderly patients undergoing sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) has not been specifically analyzed. This study aimed to explore the association between different types of axillary lymph node (ALN) evaluations and survival of elderly breast cancer patients.MethodsA retrospective cohort study was conducted of invasive ductal breast cancer patients 70 years and older in the Surveillance, Epidemiology, and End Results database (2004-2016). Analyses were performed to compare the characteristics and survival outcomes of patients who received surgical lymph node dissection and those who did not. Breast cancer specific survival (BCSS) and overall survival were compared by using Cox proportional hazards regression analysis and propensity score matching (PSM) methods to account for selection bias from covariate imbalance.ResultsOf the 75,950 patients analyzed, patients without ALN evaluation had a significantly worse prognosis, while there was no significant difference for BCSS between using a sentinel lymph node biopsy (SLNB) and an axillary lymph node dissection (ALND) after adjustment for known covariates [adjusted hazard ratio (HR) = 0.991, 95% confidence interval (CI) = 0.925-1.062, p = 0.800]. In the stratification analyses after PSM, the ALND did not show a significant BCSS advantage compared with SLNB in any subgroups except for the pN1 stage or above. Furthermore, after PSM of the pN1 stage patients, SLNB was associated with a significantly worse BCSS in hormone receptor negative (HR-) patients (HR = 1.536, 95%CI = 1.213-1.946, p < 0.001), but not in the hormone receptor positive (HR+) group (HR = 1.150, 95%CI = 0.986-1.340, p = 0.075).ConclusionIn our study, ALND does not yield superior survival compared with SLNB for elderly patients with pN1 stage HR+ breast cancer. Although our findings are limited by the bias associated with retrospective study design, we believe that in the absence of results from randomized clinical trials, our findings should be considered when recommending the omission of ALND for elderly breast cancer patients.
| S-EPMC7877252 | biostudies-literature
Project description:In this study, we evaluated trends and outcomes of allogeneic hematopoietic cell transplantation (HCT) in adults ≥70 years with hematologic malignancies across the United States. Adults ≥70 years with a hematologic malignancy undergoing first allogeneic HCT in the United States between 2000 and 2013 and reported to the Center for International Blood and Marrow Transplant Research were eligible. Transplant utilization and transplant outcomes, including overall survival (OS), progression-free survival (PFS), and transplant-related mortality (TRM) were studied. One thousand one hundred and six patients ≥70 years underwent HCT across 103 transplant centers. The number and proportion of allografts performed in this population rose markedly over the past decade, accounting for 0.1% of transplants in 2000 to 3.85% (N = 298) in 2013. Acute myeloid leukemia and myelodysplastic syndromes represented the most common disease indications. Two-year OS and PFS significantly improved over time (OS: 26% [95% confidence interval (CI), 21% to 33%] in 2000-2007 to 39% [95% CI, 35% to 42%] in 2008-2013, P < .001; PFS: 22% [16% to 28%] in 2000-2007 to 32% [95% CI, 29% to 36%] in 2008-2013, P = .003). Two-year TRM ranged from 33% to 35% and was unchanged over time (P = .54). Multivariable analysis of OS in the modern era of 2008-2013 revealed higher comorbidity by HCT comorbidity index ≥3 (hazard ratio [HR], 1.27; P = .006), umbilical cord blood graft (HR, 1.97; P = .0002), and myeloablative conditioning (HR, 1.61; P = .0002) as adverse factors. Over the past decade, utilization and survival after allogeneic transplant have increased in patients ≥70 years. Select adults ≥70 years with hematologic malignancies should be considered for transplant.
| S-EPMC5580273 | biostudies-literature
Project description:BackgroundThe use of a polygenic risk score (PRS) to improve risk prediction of coronary heart disease (CHD) events has been demonstrated to have clinical utility in the general adult population. However, the prognostic value of a PRS for CHD has not been examined specifically in older populations of individuals aged ≥70 years, who comprise a distinct high-risk subgroup. The objective of this study was to evaluate the predictive value of a PRS for incident CHD events in a prospective cohort of older individuals without a history of cardiovascular events.MethodsWe used data from 12 792 genotyped, healthy older individuals enrolled into the ASPREE trial (Aspirin in Reducing Events in the Elderly), a randomized double-blind placebo-controlled clinical trial investigating the effect of daily 100 mg aspirin on disability-free survival. Participants had no previous history of diagnosed atherothrombotic cardiovascular events, dementia, or persistent physical disability at enrollment. We calculated a PRS (meta-genomic risk score) consisting of 1.7 million genetic variants. The primary outcome was a composite of incident myocardial infarction or CHD death over 5 years.ResultsAt baseline, the median population age was 73.9 years, and 54.9% were female. In total, 254 incident CHD events occurred. When the PRS was added to conventional risk factors, it was independently associated with CHD (hazard ratio, 1.24 [95% CI, 1.08-1.42], P=0.002). The area under the curve of the conventional model was 70.53 (95% CI, 67.00-74.06), and after inclusion of the PRS increased to 71.78 (95% CI, 68.32-75.24, P=0.019), demonstrating improved prediction. Reclassification was also improved, as the continuous net reclassification index after adding PRS to the conventional model was 0.25 (95% CI, 0.15-0.28).ConclusionA PRS for CHD performs well in older people and improves prediction over conventional cardiovascular risk factors. Our study provides evidence that genomic risk prediction for CHD has clinical utility in individuals aged 70 years and older. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01038583.
| S-EPMC8847323 | biostudies-literature
Project description:The risk of atherosclerotic cardiovascular disease rises with age and remains the leading cause of death in older adults. Evidence for the use of statins for primary prevention in older adults is limited, despite the possibility that this population may derive significant clinical benefit given its increased cardiovascular risk. Until publication of the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the Management of Blood Cholesterol, and the 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease, guidelines for statin prescription in older adults remained unchanged despite new evidence of possible benefit in older adults. In this review, we present key updates in the 2018 and 2019 guidelines and the evidence informing these updates. We compare the discordant recommendations of the seven major North American and European guidelines on cholesterol management released in the past 5 years and highlight gaps in the literature regarding primary prevention of cardiovascular disease in older adults. As most cardiovascular events in older adults are nonfatal, we ask how clinicians should weigh the risks and benefits of continuing a statin for primary prevention in older adults. We also reframe the concept of deprescribing of statins in the older population, using the Geriatrics 5Ms framework: Mind, Mobility, Medications, Multi-complexity, and what Matters Most to older adults. A recent call from the National Institute on Aging for a statin trial focusing on older adults extends from similar concerns.
| S-EPMC7245614 | biostudies-literature
Project description:Several features differentiate aged cells from young cells, many of which are due to changes in gene expression during the aging process. The mechanisms of altered gene expression in aging cells remain incompletely understood, and we hypothesized that long non-coding (lnc) RNAs mediate at least some of these changes. To determine candidate lncRNAs which are associated with aging process, we screened for alterations in lncRNA expression with aging in skin fibroblasts. Twenty-eight lncRNAs were found to be expressed more than 2-fold in aged fibroblasts, and thirty-five lncRNAs expressed less than 0.5-fold.
2018-07-24 | GSE117545 | GEO
Project description:BackgroundMale breast cancer constitutes a minority of breast cancer diagnoses, yet its incidence has been on the rise in recent decades. However, elderly male breast cancer patients have been inadequately represented in clinical trials, posing challenges in treatment decisions. This study seeks to clarify the efficacy of chemotherapy in this demographic and identify the population most likely to benefit from such intervention.MethodsWe conducted a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database, encompassing a total of 1900 male breast cancer patients aged 70 years or older. Among them, 1652 were categorized in the no-chemotherapy group, while 248 were in the chemotherapy group. A multifactorial logistic regression model was employed to investigate the determinants influencing the administration of chemotherapy in elderly male breast cancer patients. Additionally, the multivariate Cox proportional hazards regression model was applied to identify factors associated with outcomes, with overall survival (OS) as the primary endpoint.ResultsMultivariate logistic regression analysis revealed that grade, tumor size, and nodal status were robust predictors for elderly male breast cancer patients receiving chemotherapy. Furthermore, the multivariate analysis demonstrated that chemotherapy conferred benefits compared to the no-chemotherapy group (HR = 0.822, 95% CI: 0.682-0.991, p = 0.040). Stratified analyses indicated that individuals with N+, poorly/undifferentiated grade, and stage II/III disease could derive benefits from chemotherapy. Upon further investigation of progesterone receptor (PR) positive patients, it was found that only stage III patients experienced significant benefits from chemotherapy (HR = 0.571, 95% CI: 0.372-0.875, p = 0.010). Conversely, in PR negative patients, both stage II (HR = 0.201, 95% CI: 0.051-0.792, p = 0.022) and stage III patients (HR = 0.242, 95% CI: 0.060-0.972, p = 0.046) derived benefits from chemotherapy.ConclusionAdjuvant chemotherapy may benefit certain elderly male breast cancer patients, specifically those with positive lymph node status, poorly/undifferentiated grade, and PR-positive in stage III, as well as PR-negative expression in stage II/III. Given favorable physical tolerance, it is advisable not to hastily dismiss chemotherapy for these elderly male breast cancer patients.
| S-EPMC10964698 | biostudies-literature
Project description:Aims and objectives:This study aimed to evaluate Tai Chi group training among patients with chronic heart failure (CHF) aged 70 years and older. Background:Physical activity is recommended for CHF treatment. Tai Chi is found to be beneficial to different patient groups, although few studies focus on older patients with CHF. Design:A mixed methods study. Participants were randomly assigned to Tai Chi training twice a week for 16 weeks (N = 25) or control (N = 20). Quantitative data were collected at baseline, at the end of the training period and 6 months after training, assessing self-rated fatigue and quality of life, natriuretic peptides and physical performance. Individual qualitative interviews were conducted with participants (N = 10) in the Tai Chi training group. Results:No statistical differences between the Tai Chi training group and the control group in quality of life or natriuretic peptides was found. After 16 weeks, the training group tended to rate more reduced activity and the control group rated more mental fatigue. Participants in the training group rated increased general fatigue at follow-up compared with baseline. Qualitative interviews showed that Tai Chi training was experienced as a new, feasible and meaningful activity. The importance of the leader and the group was emphasized. Improvements in balance were mentioned and there was no physical discomfort. Conclusion:Tai Chi was experienced as a feasible and meaningful form of physical exercise for patients with CHF aged over 70 years despite lack of achieved health improvement. Further investigations, using feasibility and meaningfulness as outcome variables seems to be useful.
| S-EPMC5867290 | biostudies-literature