Individualized Absolute Risk Calculations for Persons with Multiple Chronic Conditions: Embracing Heterogeneity, Causality, and Competing Events

Approximately 75% of adults over the age of 65 years are affected by two or more chronic medical conditions. We provide a conceptual justification for individualized absolute risk calculators for competing patient-centered outcomes (PCO) (i.e. outcomes deemed important by patients) and patient reported outcomes (PRO) (i.e. outcomes patients report instead of physiologic test results). The absolute risk of an outcome is the probability that a person receiving a given treatment will experience that outcome within a pre-defined interval of time, during which they are simultaneously at risk for other competing outcomes. This allows for determination of the likelihood of a given outcome with and without a treatment. We posit that there are heterogeneity of treatment effects among patients with multiple chronic conditions (MCC) largely depends on those coexisting conditions. We outline the development of an individualized absolute risk calculator for competing outcomes using propensity score methods that strengthen causal inference for specific treatments. Innovations include the key concept that any given outcome may or may not concur with any other outcome and that these competing outcomes do not necessarily preclude other outcomes. Patient characteristics and MCC will be the primary explanatory factors used in estimating the heterogeneity of treatment effects on PCO and PRO. This innovative method may have wide-spread application for determining individualized absolute risk calculations for competing outcomes. Knowing the probabilities of outcomes in absolute terms may help the burgeoning population of patients with MCC who face complex treatment decisions

Accounting for the Hierarchical Structure in Veterans Health Administration Data: Differences in Healthcare Utilization between Men and Women Veterans

Women currently constitute 15% of active United States of America military service personnel, and this proportion is expected to double in the next 5 years. Previous research has shown that healthcare utilization and costs differ in women US Veterans Health Administration (VA) patients compared to men. However, none have accounted for the potential effects of clustering on their estimates of healthcare utilization. US Women Veterans are more likely to serve in specific military branches (e.g. Army), components (e.g. National Guard), and ranks (e.g. officer) than men. These factors may confer different risk and protection that can affect subsequent healthcare needs. Our study investigates the effects of accounting for the hierarchical structure of data on estimates of the association between gender and VA healthcare utilization. The sample consisted of data on 406,406 Veterans obtained from VA's Operation Enduring Freedom/ Operation Iraqi Freedom roster provided by Defense Manpower Data Center - Contingency Tracking System Deployment File. We compared three statistical models, ordinary, fixed and random effects hierarchical logistic regression, in order to assess the association of gender with healthcare utilization, controlling for branch of service, component, rank, age, race, and marital status. Gender was associated with utilization in ordinary logistic and, but not in fixed effects hierarchical logistic or random effects hierarchical logistic regression models. This points out that incomplete inference could be drawn by ignoring the military structure that may influence combat exposure and subsequent healthcare needs. Researchers should consider modeling VA data using methods that account for the potential clustering effect of hierarchy

Longitudinal Patterns of Potentially Inappropriate Medication Use Following Incident Dementia Diagnosis

Introduction: Potentially inappropriate medication (PIM) use in older adults with dementia is an understudied area. We assessed longitudinal changes in PIM exposure by dementia type following dementia diagnosis. Methods: We followed 2448 participants aged ≥ 65 years (52% women, 85.5% Caucasian, mean age 80.9 ± 7.5 years) diagnosed with dementia after enrollment in the National Alzheimer\u27s Coordinating Center (2005-2014). We estimated the association between dementia type and PIM annually for 2 years after diagnosis, using Generalized Estimating Equations. Results:Participants with Lewy body dementia had more PIM use, and participants with frontotemporal dementia had less PIM use than participants with Alzheimer\u27s disease. In the first year following diagnosis, total number of medications increased, on average, by 10% for Alzheimer\u27s disease and 15% for Lewy body dementia (P \u3c .05 for both). Discussion: A tailored approach aimed at optimizing drug therapy is needed to mitigate PIM exposure to improve medical care for individuals with dementia

Associations between home deaths and end-of-life nursing care trajectories for community-dwelling people: a population-based registry study

Background: Few studies have estimated planned home deaths compared to actual place of death in a general population or the longitudinal course of home nursing services and associations with place of death. We aimed to investigate trajectories of nursing services, potentially planned home deaths regardless of place of death; and associations of place of death with potentially planned home deaths and nursing service trajectories, by analyzing data from the last 90 days of life. Methods: A retrospective longitudinal study with data from the Norwegian Cause of Death Registry and National registry for statistics on municipal healthcare services included all community-dwelling people who died in Norway 2012–2013 (n = 53,396). We used a group-based trajectory model to identify joint trajectories of home nursing (hours per week) and probability of a skilled nursing facility (SNF) stay, each of the 13 weeks leading up to death. An algorithm estimated potentially planned home deaths. We used a multinomial logistic regression model to estimate associations of place of death with potentially planned home deaths, trajectories of home nursing and short-term SNF. Results: We identified four home nursing service trajectories: no (46.5%), accelerating (7.6%), decreasing (22.1%), and high (23.5%) home nursing; and four trajectories of the probability of a SNF stay: low (69.0%), intermediate (6.7%), escalating (15.9%), and increasing (8.4%) SNF. An estimated 24.0% of all deaths were potentially planned home deaths, of which a third occurred at home. Only high home nursing was associated with increased likelihood of a home death (adjusted relative risk ratio (aRRR) 1.29; CI 1.21–1.38). Following any trajectory with elevated probability of a SNF stay reduced the likelihood of a home death. Conclusions: We estimated few potentially planned home deaths. Trajectories of home nursing hours and probability of SNF stays indicated possible effective palliative home nursing for some, but also missed opportunities of staying at home longer at the end-of-life. Continuity of care seems to be an important factor in palliative home care and home death.publishedVersio

The Method of Randomization for Cluster-Randomized Trials: Challenges of Including Patients with Multiple Chronic Conditions

Cluster-randomized clinical trials (CRT) are trials in which the unit of randomization is not a participant but a group (e.g. healthcare systems or community centers). They are suitable when the intervention applies naturally to the cluster (e.g. healthcare policy); when lack of independence among participants may occur (e.g. nursing home hygiene); or when it is most ethical to apply an intervention to all within a group (e.g. school-level immunization). Because participants in the same cluster receive the same intervention, CRT may approximate clinical practice, and may produce generalizable findings. However, when not properly designed or interpreted, CRT may induce biased results. CRT designs have features that add complexity to statistical estimation and inference. Chief among these is the cluster-level correlation in response measurements induced by the randomization. A critical consideration is the experimental unit of inference; often it is desirable to consider intervention effects at the level of the individual rather than the cluster. Finally, given that the number of clusters available may be limited, simple forms of randomization may not achieve balance between intervention and control arms at either the cluster- or participant-level. In non-clustered clinical trials, balance of key factors may be easier to achieve because the sample can be homogenous by exclusion of participants with multiple chronic conditions (MCC). CRTs, which are often pragmatic, may eschew such restrictions. Failure to account for imbalance may induce bias and reducing validity. This article focuses on the complexities of randomization in the design of CRTs, such as the inclusion of patients with MCC, and imbalances in covariate factors across clusters

Sequence Analysis of Cardiometabolic Multimorbidity and Association with Subsequent Dementia

Sequence analysis is used in the social sciences to examine patterns of events occurring across the life course, but there are few examples of its use in multimorbidity research among older adults. We used sequence analysis to identify longitudinal patterns of cardiometabolic multimorbidity over a five-year period among participants in the National Health and Aging Trends Study (N=5,218). Multimorbidity sequences were constructed using self-reported diagnosis of diabetes, heart disease, stroke, and myocardial infarction (MI) assessed annually. Death was included as an absorbing state, yielding a total of 281 distinct sequences. We calculated sequence dissimilarity using optimal matching then used hierarchical clustering to identify seven distinct sequence clusters. The largest cluster (46.2%) was characterized by no baseline cardiometabolic disease and minimal incident disease across the 5-year period. Three clusters were characterized by stable sequences: diabetes (13.1%), heart disease (7.5%), and MI or stroke (7.3%) across the 5-year period. Two clusters exhibited a high rate of incident cardiometabolic disease during the 5-year period, one among persons with no baseline disease (9.6%) and one with rapid accumulation of cardiometabolic multimorbidity (5.3%). Finally, one cluster largely contained persons who died during the study period (11.0%). Compared to those with no baseline and minimal incident cardiometabolic disease, the odds of subsequent dementia were significantly higher among the cluster without prior disease who developed incident cardiometabolic disease (OR= 1.61, 95% CI:1.07,2.43) and the cluster with high cardiometabolic multimorbidity (OR=2.77, 95% CI:1.84,4.18). These findings contribute to our understanding of the impact of cardiometabolic multimorbidity on cognitive health

Impact of Anticholinergic Burden on Cognitive Performance: A Cohort Study of Community-Dwelling Older Adults

Older people are susceptible to the adverse effects of anticholinergic medications, including cognitive impairment. A systematic review of observational studies reported mixed associations between high anticholinergic burden, a cumulative measure of anticholinergic medications, and cognitive performance in older people. Observational studies may have biased estimates of the impact of exposures, as the exposed and unexposed may systematically differ in covariates associated with the outcomes

Multimorbidity and Associated Informal Care Receiving Characteristics for US Older Adults: a Latent Class Analysis

Older adults with varying patterns of multimorbidity may require distinct types of care and rely on informal caregiving to meet their care needs. This study aims to identify groups of older adults with distinct, empirically-determined multimorbidity patterns and compare characteristics of informal care received among estimated classes. Methods Data are from the 2011 National Health and Aging Trends Study (NHATS). Ten chronic conditions were included to estimate multimorbidity patterns among 7532 individuals using latent class analysis. Multinomial logistic regression model was estimated to examine the association between sociodemographic characteristics, health status and lifestyle variables, care-receiving characteristics and latent class membership. Results A four-class solution identified the following multimorbidity groups: some somatic conditions with moderate cognitive impairment (30%), cardiometabolic (25%), musculoskeletal (24%), and multisystem (21%). Compared with those who reported receiving no help, care recipients who received help with household activities only (OR = 1.44, 95% CI 1.05–1.98), mobility but not self-care (OR = 1.63, 95% CI 1.05–2.53), or self-care but not mobility (OR = 2.07, 95% CI 1.29–3.31) had greater likelihood of being in the multisystem group versus the some-somatic group. Having more caregivers was associated with higher odds of being in the multisystem group compared with the some-somatic group (OR = 1.09, 95% CI 1.00-1.18), whereas receiving help from paid helpers was associated with lower odds of being in the multisystem group (OR = 0.36, 95% CI 0.19–0.77). Conclusions Results highlighted different care needs among persons with distinct combinations of multimorbidity, in particular the wide range of informal needs among older adults with multisystem multimorbidity. Policies and interventions should recognize the differential care needs associated with multimorbidity patterns to better provide person-centered care

Pain, Complex Chronic Conditions and Potential Inappropriate Medication in People with Dementia. Lessons Learnt for Pain Treatment Plans Utilizing Data from the Veteran Health Administration

Alzheimer’s disease and related dementias (ADRD), pain and chronic complex conditions (CCC) often co-occur leading to polypharmacy and with potential inappropriate medications (PIMs) use, are important risk factors for adverse drug reactions and hospitalizations in older adults. Many US veterans are at high risk for persistent pain due to age, injury or medical illness. Concerns about inadequate treatment of pain—accompanied by evidence about the analgesic efficacy of opioids—has led to an increase in the use of opioid medications to treat chronic pain in the Veterans Health Administration (VHA) and other healthcare systems. This study aims to investigate the relationship between receipt of pain medications and centrally (CNS) acting PIMs among veterans diagnosed with dementia, pain intensity, and CCC 90-days prior to hospitalization. The final analytic sample included 96,224 (81.7%) eligible older veterans from outpatient visits between October 2012–30 September 2013. We hypothesized that veterans with ADRD, and severe pain intensity may receive inappropriate pain management and CNS-acting PIMs. Seventy percent of the veterans, and especially people with ADRD, reported severe pain intensity. One in three veterans with ADRD and severe pain intensity have an increased likelihood for CNS-acting PIMs, and/or opioids. Regular assessment and re-assessment of pain among older persons with CCC, patient-centered tapering or discontinuation of opioids, alternatives to CNS-acting PIMs, and use of non-pharmacological approaches should be considered.publishedVersio