Alzheimer's disease medication and risk of all-cause mortality and all-cause hospitalization: A retrospective cohort study.
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ABSTRACT: Introduction
Identifying Alzheimer's disease (AD) pharmacologic treatment options that effectively reduce the risk of mortality and hospitalization in real-world settings is critical.Methods
We compared donepezil, galantamine, memantine, oral rivastigmine, and transdermal rivastigmine with regard to all-cause mortality and all-cause hospitalization risk among fee-for-service Medicare beneficiaries with AD (aged ? 65 years) using a retrospective cohort study design. Our primary analysis was based on intention to treat (ITT), but we also present as-treated analysis.Results
In our final study sample (N = 21,558), significant difference in survival among index AD medication groups were observed with donepezil being associated with better survival than memantine, and oral and transdermal forms of rivastigmine for both ITT and as-treated analysis. Difference in hazards of all-cause hospitalization among index AD medication groups was observed in ITT analysis but not in as-treated analysis.Discussion
Significant differences exist in terms of mortality and hospitalization risk with different AD medication initiation in real-world setting.
SUBMITTER: Bhattacharjee S
PROVIDER: S-EPMC6626065 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
Publications
Alzheimer's disease medication and risk of all-cause mortality and all-cause hospitalization: A retrospective cohort study.
Bhattacharjee Sandipan S Patanwala Asad E AE Lo-Ciganic Wei-Hsuan WH Malone Daniel C DC Lee Jeannie K JK Knapp Shannon M SM Warholak Terri T Burke William J WJ
Alzheimer's & dementia (New York, N. Y.) 20190710
<h4>Introduction</h4>Identifying Alzheimer's disease (AD) pharmacologic treatment options that effectively reduce the risk of mortality and hospitalization in real-world settings is critical.<h4>Methods</h4>We compared donepezil, galantamine, memantine, oral rivastigmine, and transdermal rivastigmine with regard to all-cause mortality and all-cause hospitalization risk among fee-for-service Medicare beneficiaries with AD (aged ≥ 65 years) using a retrospective cohort study design. Our primary an ...[more]
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Project description:ObjectivesThis study is aimed at determining the association between metabolic syndrome and risk of cardiovascular disease (CVD) mortality and all-cause mortality among Malaysian adults.DesignRetrospective cohort study.SettingThe Malaysian Non-Communicable Disease Surveillance (MyNCDS-1) 2005/2006.ParticipantsA total of 2525 adults (1013 men and 1512 women), aged 24-64 years, who participated in the MyNCDS-1 2005/2006.MethodsParticipants' anthropometric indices, blood pressure, fasting lipid profile and fasting blood glucose levels were evaluated to determine the prevalence of metabolic syndrome by the Harmonized criteria. Participants' mortality status were followed up for 13 years from 2006 to 2018. Mortality data were obtained via record linkage with the Malaysian National Registration Department. The Cox proportional hazards regression model was applied to determine association between metabolic syndrome (MetS) and risk of CVD mortality and all-cause mortality with adjustment for selected sociodemographic and lifestyle behavioural factors.ResultsThe overall point prevalence of MetS was 30.6% (95% CI: 28.0 to 33.3). Total follow-up time was 31 668 person-years with 213 deaths (111 (11.3%) in MetS subjects and 102 (6.1%) in non-MetS subjects) from all-causes, and 50 deaths (33 (2.9%) in MetS group and 17 (1.2%) in non-MetS group) from CVD. Metabolic syndrome was associated with a significantly increased hazard of CVD mortality (adjusted HR: 2.18 (95% CI: 1.03 to 4.61), p=0.041) and all-cause mortality (adjusted HR: 1.47 (95% CI: 1.00 to 2.14), p=0.048). These associations remained significant after excluding mortalities in the first 2 years.ConclusionsOur study shows that individuals with MetS have a higher hazard of death from all-causes and CVD compared with those without MetS. It is thus imperative to prescribe individuals with MetS, a lifestyle intervention along with pharmacological intervention to improve the individual components of MetS and reduce this risk.
| S-EPMC8375738 | biostudies-literature
Project description:BackgroundNumerous interventions are available to boost medication adherence, but the targeting of these interventions often relies on crude measures of poor adherence. Group-based trajectory models identify individuals with similar longitudinal prescription filling patterns. Identifying distinct adherence trajectories may be more useful for targeting interventions, although the association between adherence trajectories and clinical outcomes is unknown.ObjectiveTo examine the association between adherence trajectories for oral hypoglycemics and subsequent hospitalizations among diabetes patients.DesignRetrospective cohort study.PatientsA total of 16,256 Pennsylvania Medicaid enrollees, non-dually eligible for Medicare, initiating oral hypoglycemics between 2007 and 2009.Main measuresWe used group-based trajectory models to identify trajectories of oral hypoglycemics in the 12 months post-treatment initiation, using monthly proportion of days covered (PDC) as the adherence measure. Multivariable Cox proportional hazard models were used to examine the association between trajectories and time to first diabetes-related hospitalization/emergency department (ED) visits in the following year. We used the C-index to compare prediction performance between adherence trajectories and dichotomous cutpoints (annual PDC <80 vs. ?80 %).ResultsThe mean annual PDC was 0.58 (SD 0.32). Seven trajectories were identified: perfect adherers (9 % of the cohort), nearly perfect adherers (31.4 %), moderate adherers (21.0 %), low adherers (11.0 %), late discontinuers (6.8 %), early discontinuers (9.7 %), and non-adherers with only one fill (11.1 %). Compared to perfect adherers, trajectories of moderate adherers (HR = 1.48, 95 % CI 1.25, 1.75), low adherers (HR = 1.51, 95 % CI 1.25, 1.83), and non-adherers with only one fill (HR = 1.35, 95 % CI 1.09, 1.67) had greater risk of diabetes-related hospitalizations/ED visits. Predictive accuracy was improved using trajectories compared to dichotomized cutpoints (C-index = 0.714 vs. 0.652).ConclusionsOral hypoglycemic treatment trajectories were highly variable in this large Medicaid cohort. Low and moderate adherers and those filling only one prescription had a modestly higher risk of hospitalizations/ED visits compared to perfect adherers. Trajectory models may be valuable in identifying specific non-adherence patterns for targeting interventions.
| S-EPMC4978686 | biostudies-literature
Project description:IntroductionCognitive reserve predicts delayed diagnosis of Alzheimer's disease (AD) and faster postdiagnosis decline. The net impact of cognitive reserve, combining both prediagnosis and postdiagnosis risk, on adverse AD-related outcomes is unknown. We adopted a novel approach, using AD genetic risk scores (AD-GRS), to evaluate this.MethodsUsing 242,959 UK Biobank participants age 56+ years, we evaluated whether cognitive reserve (operationalized as education) modified associations between AD-GRS and mortality or hospitalization (total count, fall-related, and urinary tract infection-related).ResultsAD-GRS predicted mortality and hospitalization outcomes. Education did not modify AD-GRS effects on mortality, but had a nonsignificantly (interaction P = .10) worse effect on hospitalizations due to urinary tract infection or falls among low education (OR = 1.07 [95% CI: 1.02, 1.12]) than high education (OR = 1.01 [0.95, 1.07]) individuals.DiscussionEducation did not convey differential survival advantages to individuals with higher genetic risk of AD, but may reduce hospitalization risk associated with AD genetic risk.
| S-EPMC7049165 | biostudies-literature
Project description:Polypharmacy is a growing and major public health issue, particularly in the geriatric population. This study aimed to examine the association between polypharmacy and the risk of hospitalization and mortality. We included 3,007,620 elderly individuals aged ≥ 65 years who had at least one routinely-prescribed medication but had no prior hospitalization within a year. The primary exposures of interest were number of daily prescribed medications (1-2, 3-4, 5-6, 7-8, 9-10, and ≥ 11) and presence of polypharmacy (≥ 5 prescription drugs per day). The corresponding comparators were the lowest number of medications (1-2) and absence of polypharmacy. The study outcomes were hospitalization and all-cause death. The median age of participants was 72 years and 39.5% were men. Approximately, 46.6% of participants experienced polypharmacy. Over a median follow-up of 5.0 years, 2,028,062 (67.4%) hospitalizations and 459,076 (15.3%) all-cause deaths were observed. An incrementally higher number of daily prescribed medications was found to be associated with increasingly higher risk for hospitalization and mortality. These associations were consistent across subgroups of age, sex, residential area, and comorbidities. Furthermore, polypharmacy was associated with greater risk of hospitalization and death: adjusted HRs (95% CIs) were 1.18 (1.18-1.19) and 1.25 (1.24-1.25) in the overall and 1.16 (1.16-1.17) and 1.25 (1.24-1.25) in the matched cohorts, respectively. Hence, polypharmacy was associated with a higher risk of hospitalization and all-cause death among elderly individuals.
| S-EPMC7609640 | biostudies-literature
Project description:BACKGROUND: Evidence is lacking about outcomes associated with the cumulative use of anticholinergic and sedative drugs in people with Alzheimer's disease (AD). This retrospective cohort study investigated the relationship between cumulative exposure to anticholinergic and sedative drugs and hospitalization and mortality in people with and without AD in Finland. METHODS: Community-dwelling people aged 65 years and over, with AD on December 31(st) 2005 (n?=?16,603) and individually matched (n?=?16,603) comparison persons (age, sex, region of residence) were identified by the Social Insurance Institution of Finland. Drug utilization data were extracted from the Finnish National Prescription Register. Exposure to anticholinergic and sedative drugs was defined using the Drug Burden Index (DBI). Hospitalization and mortality data were extracted from national registers. Cox and zero-inflated negative binomial analyses were used to investigate the relationship between DBI and hospitalization and mortality over a one-year follow-up. RESULTS: In total, 5.8% of people with AD and 3.7% without AD died during 2006. For every unit increase in DBI, the adjusted hazard ratio for mortality was 1.21 (95% confidence intervals [CI]: 1.09-1.33) among people with AD, and 1.37 (95%CI: 1.20-1.56) among people without AD. Overall, 44.3% of people with AD and 33.4% without AD were hospitalized. When using no DBI exposure as the reference group, the adjusted incidence rate ratio for length of hospital stay among high DBI group (?1) in people with AD was 1.15 (95%CI: 1.05-1.26) and 1.63 (95%CI: 1.41-1.88) in people without AD. CONCLUSION: There is a dose-response relationship between cumulative anticholinergic and sedative drug use and hospitalization and mortality in people with and without AD.
| S-EPMC3890276 | biostudies-literature
Project description:Although recent short-term cross-sectional studies have revealed that chronic periodontitis (CP) may be a risk factor for increased cognitive impairment in patients with Alzheimer's disease (AD), systematic reviews and long-term longitudinal studies have provided less clear evidence regarding the relationship between CP and AD. Therefore, we conducted a retrospective cohort study using the National Health Insurance Research Database (NHIRD) of Taiwan to determine whether patients with CP are at increased risk of developing AD.We conducted a retrospective matched-cohort study using the NHIRD of Taiwan. We identified 9291 patients newly diagnosed with CP between 1997 and 2004. A total of 18,672 patients without CP were matched to the patient cohort according to sex, age, index year, co-morbidity and urbanisation level. Cox proportional hazards regression analyses were performed to evaluate the subsequent risk of AD.Patients with CP had a higher prevalence of hyperlipidaemia, depression, traumatic brain injury and co-morbidities, as well as higher urbanisation levels, than those in the unexposed cohort (all p < 0.01). At the final follow-up, totals of 115 (1.24%) and 208 (1.11%) individuals in the CP exposed and unexposed groups, respectively, had developed AD. Patients with 10 years of CP exposure exhibited a higher risk of developing AD than unexposed groups (adjusted HR 1.707, 95% CI 1.152-2.528, p = 0.0077).Our findings demonstrate that 10-year CP exposure was associated with a 1.707-fold increase in the risk of developing AD. These findings highlight the need to prevent progression of periodontal disease and promote healthcare service at the national level.
| S-EPMC5547465 | biostudies-other
Project description:BackgroundMortality during and after incarceration is poorly understood in low- and middle-income countries (LMICs). The need to address this knowledge gap is especially urgent in South America, which has the fastest growing prison population in the world. In Brazil, insufficient data have precluded our understanding of all-cause and cause-specific mortality during and after incarceration.Methods and findingsWe linked incarceration and mortality databases for the Brazilian state of Mato Grosso do Sul to obtain a retrospective cohort of 114,751 individuals with recent incarceration. Between January 1, 2009 and December 31, 2018, we identified 3,127 deaths of individuals with recent incarceration (705 in detention and 2,422 following release). We analyzed age-standardized, all-cause, and cause-specific mortality rates among individuals detained in different facility types and following release, compared to non-incarcerated residents. We additionally modeled mortality rates over time during and after incarceration for all causes of death, violence, or suicide. Deaths in custody were 2.2 times the number reported by the national prison administration (n = 317). Incarcerated men and boys experienced elevated mortality, compared with the non-incarcerated population, due to increased risk of death from violence, suicide, and communicable diseases, with the highest standardized incidence rate ratio (IRR) in semi-open prisons (2.4; 95% confidence interval [CI]: 2.0 to 2.8), police stations (3.1; 95% CI: 2.5 to 3.9), and youth detention (8.1; 95% CI: 5.9 to 10.8). Incarcerated women experienced increased mortality from suicide (IRR = 6.0, 95% CI: 1.2 to 17.7) and communicable diseases (IRR = 2.5, 95% CI: 1.1 to 5.0). Following release from prison, mortality was markedly elevated for men (IRR = 3.0; 95% CI: 2.8 to 3.1) and women (IRR = 2.4; 95% CI: 2.1 to 2.9). The risk of violent death and suicide was highest immediately post-release and declined over time; however, all-cause mortality remained elevated 8 years post-release. The limitations of this study include inability to establish causality, uncertain reliability of data during incarceration, and underestimation of mortality rates due to imperfect database linkage.ConclusionsIncarcerated individuals in Brazil experienced increased mortality from violence, suicide, and communicable diseases. Mortality was heightened following release for all leading causes of death, with particularly high risk of early violent death and elevated all-cause mortality up to 8 years post-release. These disparities may have been underrecognized in Brazil due to underreporting and insufficient data.
| S-EPMC8486113 | biostudies-literature
Project description:Introduction: MicroRNAs (miRNAs) are small, non-coding RNA molecules involved in post-transcriptional gene regulation and have recently been shown to play a role in cancer metastasis. In solid tumors, especially breast cancer, alterations in miRNA expression contribute to cancer pathogenesis, including metastasis. Considering the emerging role of miRNAs in metastasis, the identification of predictive markers is necessary to further understanding of stage-specific breast cancer development. This is a retrospective analysis that aimed to identify molecular biomarkers related to distant breast cancer metastasis development.<br><br>Methods: A retrospective case cohort study was performed in 64 breast cancer patients treated during the period from 1998-2001. The case group (n=29) consisted of patients with a poor prognosis who presented with breast cancer recurrence or metastasis during follow up. The control group (n=35) consisted of a random sample of patients with a good prognosis who did not develop breast cancer recurrence or metastasis. These patient groups were stratified according to TNM clinical stage (CS) I, II and III, and the main clinical features of the patients were homogeneous. miRNA profiling was performed using formalin-fixed, paraffin-embedded tumors. Biomarkers related to metastatic potential were identified independent of clinical stage, and a cutoff point was selected based on the optimal sensitivity and specificity (ROC curve). Finally, a hazard risk analysis of these biomarkers was performed to evaluate their relation to metastatic potential. <br><br>Results: miRNA expression profiling identified several miRNAs that were either specific and shared across all clinical stages (p?0.05). Among these, we identified miRNAs previously associated with cell motility (let-7 family), cell proliferation and invasion (hsa-miR-16 and has-miR-205) and distant metastasis (hsa-miR-21). In addition, hsa-miR-494 and hsa-miR-21 were up-regulated in metastatic cases of CSI and II. Furthermore, the combination of the 3 miRNAs identified for CSII (hsa-miR-494, hsa-miR-183 and hsa-miR-21) was significant and were a more effective risk marker compared to the single miRNAs. <br><br>Conclusions: Women with metastatic breast cancer, especially CSII, presented up-regulated levels of miR-183, miR-494 and miR-21, which were associated with a poor prognosis. These miRNAs therefore represent new risk biomarkers of breast cancer metastasis and may be useful for future targeted therapies.
2013-08-07 | E-MEXP-3947 | biostudies-arrayexpress
Project description:Objectives To evaluate the risk of all cause mortality associated with initiating compared with not initiating benzodiazepines in adults, and to address potential treatment barriers and confounding related to the use of a non-active comparator group.Design Retrospective cohort study.Setting Large de-identified US commercial healthcare database (Optum Clinformatics Datamart).Participants 1:1 high dimensional propensity score matched cohort of benzodiazepine initiators, and randomly selected benzodiazepine non-initiators with a medical visit within 14 days of the start of benzodiazepine treatment (n=1?252?988), between July 2004 and December 2013. To address treatment barriers and confounding, patients were required to have filled one or more prescriptions for any medication in the 90 days and 91-180 days before the index date (ie, the date of starting benzodiazepine treatment for initiators and the date of the selected medical visit for benzodiazepine non-initiators) and the high dimensional propensity score was estimated on the basis of more than 300 covariates.Main outcome measure All cause mortality, determined by linkage with the Social Security Administration Death Master File.Results Over a six month follow-up period, 5061 and 4691 deaths occurred among high dimensional propensity score matched benzodiazepine initiators versus non-initiators (9.3 v 9.4 events per 1000 person years; hazard ratio 1.00, 95% confidence interval 0.96 to 1.04). A 4% (95% confidence interval 1% to 8%) to 9% (2% to 7%) increase in mortality risk was observed associated with the start of benzodiazepine treatment for follow-ups of 12 and 48 months and in subgroups of younger patients and patients initiating short acting agents. In secondary analyses comparing 1:1 high dimensional propensity score matched patients initiating benzodiazepines with an active comparator, ie, patients starting treatment with selective serotonin reuptake inhibitor antidepressants, benzodiazepine use was associated with a 9% (95% confidence interval 3% to 16%) increased risk.Conclusions This large population based cohort study suggests either no increase or at most a minor increase in risk of all cause mortality associated with benzodiazepine initiation. If a detrimental effect exists, it is likely to be much smaller than previously stated and to have uncertain clinical relevance. Residual confounding likely explains at least part of the small increase in mortality risk observed in selected analyses.
| S-EPMC5499256 | biostudies-literature
Project description:This study determined the effects of anti-diabetic medication adherence on the long-term all-cause mortality and hospitalization for cerebrovascular disease and myocardial infarction among newly diagnosed patients. The study used retrospective cohort from the National Health Insurance Service. Study participants were 65,076 newly diagnosed type 2 diabetes mellitus patients aged ?40 years. The medication adherence was evaluated from the proportion of days covered (PDC) between 2006 and 2007. Outcome variables were mortality, newly diagnosed cerebrovascular disease (CVD) and myocardial infarction (MI) in 2008-2017. Cox-proportional hazard regression analysis was performed. After adjusting for sex, age, monthly contribution, insurance type, medical institution type, Charlson comorbidity index score, disability, hypertension, and active ingredients of oral hypoglycemic agents, the adjusted hazard ratio (aHR) for all-cause-mortality of the lowest PDC group (<0.20) was 1.45 (95% confidence interval [CI]?=?1.36-1.54) as compared to the highest PDC (?0.8). The aHR for all-cause-mortality associated with PDC levels of 0.60-0.79, 0.40-0.59, and 0.20-0.39 were 1.19, 1.26, and 1.34, respectively (Ptrend?<?0.001). Compared to the highest PDC group, diabetic patients with the lowest PDC had elevated risk for CVD (aHR?=?1.41; 95% CI?=?1.30-1.52; Ptrend?<?0.001). Improving anti-diabetic medication adherence among newly diagnosed type 2 diabetes mellitus patients is essential to the reduce risk for cardiovascular disease and long-term all-cause mortality.
| S-EPMC6093904 | biostudies-other