Restriction of Pharmacoepidemiologic Cohorts to Initiators of Medications in Unrelated Preventive Drug Classes to Reduce Confounding by Frailty in Older Adults

Abstract Nonexperimental studies of the effectiveness of seasonal influenza vaccine in older adults have found 40%–60% reductions in all-cause mortality associated with vaccination, potentially due to confounding by frailty. We restricted our cohort to initiators of medications in preventive drug classes (statins, antiglaucoma drugs, and β blockers) as an approach to reducing confounding by frailty by excluding frail older adults who would not initiate use of these drugs. Using a random 20% sample of US Medicare beneficiaries, we framed our study as a series of nonrandomized “trials” comparing vaccinated beneficiaries with unvaccinated beneficiaries who had an outpatient health-care visit during the 5 influenza seasons occurring in 2010–2015. We pooled data across trials and used standardized-mortality-ratio–weighted Cox proportional hazards models to estimate the association between influenza vaccination and all-cause mortality before influenza season, expecting a null association. Weighted hazard ratios among preventive drug initiators were generally closer to the null than those in the nonrestricted cohort. Restriction of the study population to statin initiators with an uncensored approach resulted in a weighted hazard ratio of 1.00 (95% confidence interval: 0.84, 1.19), and several other hazard ratios were above 0.95. Restricting the cohort to initiators of medications in preventive drug classes can reduce confounding by frailty in this setting, but further work is required to determine the most appropriate criteria to use.

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Alcohol-related mortality and all-cause mortality following bereavement in two successive generations

PLoS ONE ◽

10.1371/journal.pone.0243290 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0243290

Author(s):

David Teye Doku ◽

Subas Neupane ◽

Henrik Dobewall ◽

Arja Rimpelä

Keyword(s):

Alcohol Abuse ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Conclusive Evidence ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

Risk Of Mortality ◽

All Cause Mortality ◽

Successive Generations ◽

Related Mortality

Background and aim Bereavement affects the health of the bereaved both emotionally and physically. Bereavement resulting from alcohol-related death of the previous generation (parents-first generation) may increase the risk of alcohol abuse and consequently alcohol-related mortality as well as all-cause mortality in the next generation (offspring-second generation). Furthermore, these associations can be bi-directional. However, there is no conclusive evidence of these effects, and studies exploring these intergenerational effects are rare. This study investigates these associations. Methods A longitudinal data were constructed by linking participants from the Adolescent Health and Lifestyle Surveys (AHLS) from 1979 to 1997 with census and registry-based data from Statistics Finland containing the socioeconomic status of the survey participants and their parents (N = 78610) to investigate these associations. Multivariate Cox proportional hazards models were used to calculate hazard ratios with 95% confidence intervals to determine the effect of bereavement with alcohol-related mortality and all-cause mortality. Results The findings suggest that bereavement following the death of an offspring increases the risk of both alcohol-related and all-cause mortality among both parents. The magnitude of the risk of mortality following the death of an offspring is higher for mothers than for fathers. There were no clear associations of a parent’s death with an offspring’s alcohol-related or all-cause mortality. However, generally, a father’s death seems to be protective of the risk of mortality among the offspring while a mother’s alcohol-related death slightly increased the risk of alcohol-related mortality among their offspring. Conclusions These findings emphasise the role of bereavement, particularly resulting from the death of an offspring, on alcohol-related and all-cause mortality and therefore inequalities in mortality. Furthermore, the findings highlighting the need for alcohol abuse intervention and emotional support for bereaved persons following the death of an offspring.

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Cardiorespiratory Fitness without Exercise Testing Can Predict All-Cause Mortality Risk in a Representative Sample of Korean Older Adults

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16091633 ◽

2019 ◽

Vol 16 (9) ◽

pp. 1633 ◽

Cited By ~ 2

Author(s):

Moongu Song ◽

Inhwan Lee ◽

Hyunsik Kang

Keyword(s):

Older Adults ◽

Cardiorespiratory Fitness ◽

Exercise Testing ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Geriatric Population ◽

Hazard Ratios ◽

All Cause Mortality ◽

Using Data

This study examined the association between cardiorespiratory fitness (CRF) without exercise testing and all-cause mortality in Korean older adults. The present study was carried out using data from the 2008 and 2011 Living Profiles of Older People Survey. A total of 14,122 participants aged 60 years and older (57% women) completed the 2008 baseline and 2011 follow-up assessments (i.e., socioeconomic status, health behaviors and conditions, and prevalence of chronic diseases), and they were included for the final analyses. CRF was estimated (eCRF) with sex-specific algorithms and classified as lower (lowest 25%), middle (middle 50%), and upper (highest 25%). Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) across eCRF categories. In total, multivariable-adjusted HRs and 95% CIs were 1 for the upper eCRF group (referent), 1.059 (0.814~1.378) for the middle eCRF group, and 1.714 (1.304~2.253) for the lower eCRF group. In men, multivariable-adjusted HRs and 95% CIs were 1 for the upper eCRF group (referent), 1.011 (0.716~1.427) for the middle eCRF group, and 1.566 (1.098~2.234) for the lower eCRF group. In women, multivariable-adjusted HRs and 95% CIs were 1 for the upper eCRF group (referent), 1.064 (0.707~1.602) for the middle eCRF group, and 1.599 (1.032~2.478) for the lower eCRF group. The current findings suggest that eCRF may have an independent predictor of all-cause mortality, underscoring the importance of promoting physical activity to maintain a healthful level of CRF in Korean geriatric population.

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Changes in Metabolic Syndrome Status and Breast Cancer Risk: A Nationwide Cohort Study

Cancers ◽

10.3390/cancers13051177 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1177

Author(s):

In Young Choi ◽

Sohyun Chun ◽

Dong Wook Shin ◽

Kyungdo Han ◽

Keun Hye Jeon ◽

...

Keyword(s):

Breast Cancer ◽

Metabolic Syndrome ◽

Proportional Hazards ◽

Screening Program ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

Increased Risk ◽

Health Screening Program ◽

Design And Methods

Objective: To our knowledge, no studies have yet looked at how the risk of developing breast cancer (BC) varies with changes in metabolic syndrome (MetS) status. This study aimed to investigate the association between changes in MetS and subsequent BC occurrence. Research Design and Methods: We enrolled 930,055 postmenopausal women aged 40–74 years who participated in a biennial National Health Screening Program in 2009–2010 and 2011–2012. Participants were categorized into four groups according to change in MetS status during the two-year interval screening: sustained non-MetS, transition to MetS, transition to non-MetS, and sustained MetS. We calculated multivariable-adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for BC incidence using the Cox proportional hazards models. Results: At baseline, MetS was associated with a significantly increased risk of BC (aHR 1.11, 95% CI 1.06–1.17) and so were all of its components. The risk of BC increased as the number of the components increased (aHR 1.46, 95% CI 1.26–1.61 for women with all five components). Compared to the sustained non-MetS group, the aHR (95% CI) for BC was 1.11 (1.04–1.19) in the transition to MetS group, 1.05 (0.96–1.14) in the transition to non-MetS group, and 1.18 (1.12–1.25) in the sustained MetS group. Conclusions: Significantly increased BC risk was observed in the sustained MetS and transition to MetS groups. These findings are clinically meaningful in that efforts to recover from MetS may lead to reduced risk of BC.

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Association Between Informant-Reported Sleep Disturbance and Incident Dementia: An Analysis of the National Alzheimer’s Coordinating Center Uniform Data Set

Journal of Applied Gerontology ◽

10.1177/0733464820967202 ◽

2020 ◽

pp. 073346482096720

Author(s):

Woojung Lee ◽

Shelly L. Gray ◽

Douglas Barthold ◽

Donovan T. Maust ◽

Zachary A. Marcum

Keyword(s):

Older Adults ◽

Sleep Disturbance ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Cognitive Screening ◽

Cognitive Level ◽

Data Set ◽

Cox Proportional Hazards Models ◽

Incident Dementia ◽

Normal Cognition

Informants’ reports can be useful in screening patients for future risk of dementia. We aimed to determine whether informant-reported sleep disturbance is associated with incident dementia, whether this association varies by baseline cognitive level and whether the severity of informant-reported sleep disturbance is associated with incident dementia among those with sleep disturbance. A longitudinal retrospective cohort study was conducted using the uniform data set collected by the National Alzheimer’s Coordinating Center. Older adults without dementia at baseline living with informants were included in analysis. Cox proportional hazards models showed that participants with an informant-reported sleep disturbance were more likely to develop dementia, although this association may be specific for older adults with normal cognition. In addition, older adults with more severe sleep disturbance had a higher risk of incident dementia than those with mild sleep disturbance. Informant-reported information on sleep quality may be useful for prompting cognitive screening.

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Effects of antiarrhythmic drugs on atrioventricular conduction in patients with preexisting bundle branch block

European Heart Journal ◽

10.1093/ehjci/ehaa946.3358 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

S Kochav ◽

R.C Chen ◽

J.M.D Dizon ◽

J.A.R Reiffel

Keyword(s):

Proportional Hazards ◽

Cox Proportional Hazards ◽

Class I ◽

Class Iii ◽

Bundle Branch Block ◽

Kaplan Meier ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

History Of ◽

Propensity Score Stratification

Abstract Background Theoretical concern exists regarding AV block (AVB) with class I antiarrhythmics (AADs) when bundle branch block (BBB) is present. Whether this is substantiated in real-world populations is unknown. Purpose To determine the relationship between type of AAD and incidence of AVB in patients with preexisting BBB. Methods We retrospectively studied all patients with BBB who received class I and III AADs between 1997–2019 to compare incidence of AVB. We defined index time as first exposure to either drug class and excluded patients with prior AVB or exposed to both classes. Time-at-risk window ended at first outcome occurrence or when patients were no longer observed in the database. We estimated hazard ratios for incident AVB using Cox proportional hazards models with propensity score stratification, adjusting for over 32,000 covariates from the electronic health record. Kaplan-Meier methods were used to determine treatment effects over time. Results Of 40,120 individuals with BBB, 148 were exposed to a class I AAD and 2401 to a class III AAD. Over nearly 4,200 person-years of follow up, there were 22 and 620 outcome events in the class I and class III cohorts, respectively (Figure). In adjusted analyses, AVB risk was markedly lower in patients exposed to class I AADs compared with class III (HR 0.48 [95% CI 0.30–0.75]). Conclusion Among patients with BBB, exposure to class III AADs was strongly associated with greater risk of incident AVB. This likely reflects differences in natural history of patients receiving class I vs class III AADs rather than adverse class III effects, however, the lack of worse outcomes acutely with class I AADs suggests that they may be safer in BBB than suspected. Funding Acknowledgement Type of funding source: None

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Adverse Effect of Older Age on the Recurrence of Soft Tissue Sarcoma of the Extremities and Trunk

Journal of Clinical Oncology ◽

10.1200/jco.2010.34.0711 ◽

2011 ◽

Vol 29 (30) ◽

pp. 4029-4035 ◽

Cited By ~ 32

Author(s):

David J. Biau ◽

Peter C. Ferguson ◽

Robert E. Turcotte ◽

Peter Chung ◽

Marc H. Isler ◽

...

Keyword(s):

Soft Tissue ◽

Local Recurrence ◽

Soft Tissue Sarcoma ◽

Older Patients ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

Age At Surgery ◽

Effect Of Age

Purpose To examine the effect of age on the recurrence of soft tissue sarcoma in the extremities and trunk. Patients and Methods This was a multicenter study that included 2,385 patients with median age at surgery of 57 years. The end points considered were local recurrence and metastasis. Cox proportional hazards models were used to estimate hazard ratios across the age ranges with and without adjustment for known confounding factors. Results Older patients presented with tumors that were larger (P < .001) and of higher grade (P < .001). The proportion of positive margins increased significantly as patients age (P < .001), but radiation therapy was relatively underused in patients older than age 60 years. The 5-year cumulative incidences of local recurrence were 7.2% (95% CI, 4% to 11.7%) for patients age 30 years or younger and 12.9% (95% CI, 9.1% to 17.5%) for patients age 75 years or older. The corresponding 5-year cumulative incidences of metastasis were 17.5% (95% CI, 12.1% to 23.7%) and 33.9% (95% CI, 28.1% to 39.8%) for the same groups. Regression models showed that age was significantly associated with local recurrence (P < .001) and metastasis (P < .001) in nonadjusted models. After adjusting for imbalance in presentation and treatment variables, age remained significantly associated with local recurrence (P = .031) and metastasis (P = .019). Conclusion Older patients have worse outcomes because they tend to present with worse tumors and are treated less aggressively. However, there remained a significant increase in the risk of both local and systemic recurrence associated with increasing age that could not be explained by tumor or treatment characteristics.

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Dietary Omega-3 Fatty Acid Intake and Mortality in CKD Population: A 1999–2014 NHANES Analysis

American Journal of Nephrology ◽

10.1159/000520027 ◽

2021 ◽

pp. 1-10

Author(s):

Wei-Lan Li ◽

Nan-Hui Zhang ◽

Shu-Wang Ge ◽

Gang Xu

Keyword(s):

Cardiovascular Disease ◽

Fatty Acid ◽

Proportional Hazards ◽

Early Death ◽

Cox Proportional Hazards ◽

Omega 3 ◽

Pufa Intake ◽

Dietary Recall ◽

Cox Proportional Hazards Models ◽

All Cause Mortality

Introduction: High risk of early death, especially contributed to cardiovascular disease, exists in patients who have chronic kidney disease (CKD). And the burden of cardiovascular disease is able to be lightened by an increase in omega-3 polyunsaturated fatty acid (omega-3 PUFA). A diet high in omega-3 PUFA in the general population is protective, although it is inconclusive about its beneficial role in the CKD population. Methods: From the 1999 to 2014 National Health and Nutrition Examination Surveys (NHANES), we can collect 2,990 participants who suffered from CKD, who were classified into 4 groups: <0.86, 0.87–1.30, 1.31–1.92, and 1.93–9.65 g/day based on NHANES 24-h dietary recall questionnaire dietary omega-3 PUFA. Moreover, their mortality details were available to be obtained by linking NHANES to the National Death Index. The associations between dietary omega-3 PUFA and mortality were evaluated by constructing multivariable Cox proportional hazards models. Results: Over 8 years of a median follow-up, 864 deaths were recorded. The adjusted hazard ratios (95% confidence interval) for all-cause mortality of the diseased people with CKD in the 2nd (0.87–1.30 g/day), 3rd (0.87–1.30 g/day), and 4th (1.93–9.65 g/day) quartiles of dietary omega-3 PUFA were 0.94 (0.72, 1.23), 0.74 (0.54, 1.02), and 0.67 (0.48, 0.93), respectively, versus those with the lowest quartile of dietary omega-3 PUFA intake (<0.86 g/day) (p for trend = 0.011). Conclusion: There may be a inverse relation of dietary omega-3 PUFA intake and all-cause mortality in patients with CKD. Therefore, an increase of dietary omega-3 PUFA may be encouraged to be used clinically in patients with CKD.

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NHSR 155: Comparative Analysis of the National Health and Nutrition Examination Survey Public-Use and Restricted-Use Linked Mortality Files - Production Schedule

10.15620/cdc:104774 ◽

2021 ◽

Author(s):

Lisa Mirel

Keyword(s):

Comparative Analysis ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

The Public ◽

Health And Nutrition ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

Specific Mortality ◽

Standard Set ◽

Restricted Use

This report describes a comparative analysis of the public-use and restricted-use NHANES LMFs. Cox proportional hazards models were used to estimate relative hazard ratios for a standard set of sociodemographic covariates for all-cause as well as cause-specific mortality, using the public-use and restricted-use NHANES LMFs.

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Suicide risk within one year of cognitive impairment diagnosis in older adults: a nationwide retrospective cohort study

10.21203/rs.2.19129/v1 ◽

2019 ◽

Author(s):

Jae Woo Choi ◽

Kang Soo Lee ◽

Euna Han

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mental Disorders ◽

Suicide Risk ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

One Year

Abstract Background This study aims to investigate suicide risk within one year of receiving a diagnosis of cognitive impairment in older adults without mental disorders. Methods This study used National Health Insurance Service-Senior Cohort data on older adults with newly diagnosed cognitive impairment including Alzheimer’s disease, vascular dementia, other/unspecified dementia, and mild cognitive impairment from 2004 to 2012. We selected 41,195 older adults without cognitive impairment through 1:1 propensity score matching using age, gender, Charlson Comorbidity Index, and index year, with follow-up throughout 2013. We eliminated subjects with mental disorders and estimated adjusted hazard ratios (AHR) of suicide deaths within one year after diagnosis using the Cox proportional hazards models. Results We identified 49 suicide deaths during the first year after cognitive impairment diagnosis. The proportion of observed suicide deaths was the highest within one year after cognitive impairment diagnosis (48.5% of total); older adults with cognitive impairment were at a higher suicide risk than those without cognitive impairment (AHR, 1.89; 95% confidence interval [CI], 1.18–3.04). Subjects with Alzheimer’s disease and other/unspecified dementia were at greater suicide risk than those without cognitive impairment (AHR, 1.94, 1.94; 95% CI, 1.12–3.38, 1.05–3.58). Suicide risk in female and young-old adults (60–74 years) with cognitive impairment was higher than in the comparison group (AHR, 2.61, 5.13; 95% CI, 1.29–5.28, 1.48–17.82). Conclusions Older patients with cognitive impairment were at increased suicide risk within one year of diagnosis. Early intervention for suicide prevention should be provided to older adults with cognitive impairment.

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AUTOMATED MEASUREMENT OF MUSCLE DENSITY ON COMPUTED TOMOGRAPHY (CT) PREDICTS ALL-CAUSE MORTALITY IN OLDER ADULTS

Innovation in Aging ◽

10.1093/geroni/igz038.3234 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S883-S883

Author(s):

Leon Lenchik ◽

Ryan Barnard ◽

Robert D Boutin ◽

Stephen B Kritchevsky ◽

Ashley A Weaver ◽

...

Keyword(s):

Proportional Hazards ◽

Learning Algorithm ◽

Cox Proportional Hazards ◽

Muscle Density ◽

National Lung Screening Trial ◽

Cox Proportional Hazards Models ◽

All Cause Mortality ◽

Automated Machine Learning ◽

Lung Screening ◽

Paraspinous Muscle

Abstract The purpose was to examine the association of paraspinous muscle density (CT surrogate of myosteatosis) with all-cause mortality in 6803 men and 4558 women, age 60-69 years (mean age 63.6) in the National Lung Screening Trial. Our fully-automated machine learning algorithm: 1) selected the appropriate CT series, 2) chose a single CT image at the level of T12 vertebra, 3) segmented the left paraspinous muscle, and 4) recorded the muscle density in Hounsfield Units (HU). Association between baseline muscle density and all-cause mortality was determined using Cox proportional hazards models, adjusted for age, race, body mass index, pack years of smoking, and presence of diabetes, lung disease, cardiovascular disease, and cancer at enrollment. After a mean 6.44 ± 1.06 years of follow-up, 635 (9.33%) men and 265 (5.81%) women died. In men, lower muscle density on baseline CT examinations was associated with increased all-cause mortality (HR per SD = 0.90; CI = 0.83, 0.99; p=0.03). Each standard deviation (7.8 HU) decrease in muscle density was associated with a 10% increase in mortality. In women, the association did not reach significance.

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