A secondary analysis of SPRINT, a trial involving patients with hypertension and high cardiovascular risk in which intensive therapy resulted in lower rates of cardiovascular events than standard ...therapy, showed that patient-reported outcomes were similar in the two groups.
Abstract
Background
The accumulation of deficits model for frailty has been used to develop an electronic health record (EHR) frailty index (eFI) that has been incorporated into British guidelines ...for frailty management. However, there have been limited applications of EHR-based approaches in the United States.
Methods
We constructed an adapted eFI for patients in our Medicare Accountable Care Organization (ACO, N = 12,798) using encounter, diagnosis code, laboratory, medication, and Medicare Annual Wellness Visit (AWV) data from the EHR. We examined the association of the eFI with mortality, health care utilization, and injurious falls.
Results
The overall cohort was 55.7% female, 85.7% white, with a mean age of 74.9 (SD = 7.3) years. In the prior 2 years, 32.1% had AWV data. The eFI could be calculated for 9,013 (70.4%) ACO patients. Of these, 46.5% were classified as prefrail (0.10 < eFI ≤ 0.21) and 40.1% frail (eFI > 0.21). Accounting for age, comorbidity, and prior health care utilization, the eFI independently predicted all-cause mortality, inpatient hospitalizations, emergency department visits, and injurious falls (all p < .001). Having at least one functional deficit captured from the AWV was independently associated with an increased risk of hospitalizations and injurious falls, controlling for other components of the eFI.
Conclusions
Construction of an eFI from the EHR, within the context of a managed care population, is feasible and can help to identify vulnerable older adults. Future work is needed to integrate the eFI with claims-based approaches and test whether it can be used to effectively target interventions tailored to the health needs of frail patients.
Despite rapid advances in genomic technology, our ability to account for phenotypic variation using genetic information remains limited for many traits. This has unfortunately resulted in limited ...application of genetic data towards preventive and personalized medicine, one of the primary impetuses of genome-wide association studies. Recently, a large proportion of the "missing heritability" for human height was statistically explained by modeling thousands of single nucleotide polymorphisms concurrently. However, it is currently unclear how gains in explained genetic variance will translate to the prediction of yet-to-be observed phenotypes. Using data from the Framingham Heart Study, we explore the genomic prediction of human height in training and validation samples while varying the statistical approach used, the number of SNPs included in the model, the validation scheme, and the number of subjects used to train the model. In our training datasets, we are able to explain a large proportion of the variation in height (h(2) up to 0.83, R(2) up to 0.96). However, the proportion of variance accounted for in validation samples is much smaller (ranging from 0.15 to 0.36 depending on the degree of familial information used in the training dataset). While such R(2) values vastly exceed what has been previously reported using a reduced number of pre-selected markers (<0.10), given the heritability of the trait (∼ 0.80), substantial room for improvement remains.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Systolic Blood Pressure Intervention Trial (SPRINT) is testing whether a lower systolic blood pressure (BP) target of 120 mm Hg leads to a reduction in cardiovascular morbidity and mortality ...among hypertensive, nondiabetic adults. Because there may be detrimental effects of intensive BP control, particularly in older, frail adults, we sought to characterize frailty within SPRINT to address ongoing questions about the ability of large-scale trials to enroll representative samples of noninstitutionalized, community-dwelling, older adults.
We constructed a 36-item frailty index (FI) in 9,306 SPRINT participants, classifying participants as fit (FI ≤ 0.10), less fit (0.10 < FI ≤ 0.21), or frail (FI > 0.21). Recurrent event models were used to evaluate the association of the FI with the incidence of self-reported falls, injurious falls, and all-cause hospitalizations.
The distribution of the FI was comparable with what has been observed in population studies, with 2,570 (27.6%) participants classified as frail. The median FI was 0.18 (interquartile range = 0.14 to 0.24) in participants aged 80 years and older (N = 1,159), similar to the median FI of 0.17 reported for participants in the Hypertension in the Very Elderly Trial. In multivariable analyses, a 1% increase in the FI was associated with increased risk for self-reported falls (hazard ratio HR = 1.030), injurious falls (HR = 1.035), and all-cause hospitalizations (HR = 1.038) (all p values < .0001).
Large clinical trials assessing treatments to reduce cardiovascular disease risk, such as SPRINT, can enroll heterogeneous populations of older adults, including the frail elderly, comparable with general population cohorts.
Anthropometric-based classification schemes for excess adiposity do not include direct assessment of obesity-related comorbidity and functional status and thus have limited clinical utility. We ...examined the ability of the Edmonton obesity staging system, a 5-point ordinal classification system that considers comorbidity and functional status, in predicting mortality in a nationally representative US sample.
We analyzed data from the National Health and Human Nutrition Examination Surveys (NHANES) III (1988-1994) and the NHANES 1999-2004, with mortality follow-up through to the end of 2006. Adults (age ≥ 20 yr) with overweight or obesity who had been randomized to the morning session at the mobile examination centre were scored according to the Edmonton obesity staging system. We examined the relationship between staging system scores and mortality, and Cox proportional hazards models were adjusted for the presence of the metabolic syndrome or hypertriglyceridemic waist.
Over 75% of the cohort with overweight or obesity were given scores of 1 or 2. Scores of 4 could not be reliably assigned because specific data elements were lacking. Survival curves clearly diverged when stratified by scores of 0-3, but not when stratified by obesity class alone. Within the data from the NHANES 1988-1994, scores of 2 (hazard ratio HR 1.57; 95% confidence interval CI 1.16 to 2.13) and 3 (HR 2.69; 95% CI 1.98 to 3.67) were associated with increased mortality compared with scores of 0 or 1, even after adjustment for body mass index and the metabolic syndrome. We found similar results after adjusting for hypertriglyceridemic waist (i.e., waist circumference ≥ 90 cm and a triglyceride level ≥ 2 mmol/L for men; the corresponding values for women were ≥ 85 cm and ≥ 1.5 mmol/L), as well as in a cohort eligible for bariatric surgery.
The Edmonton obesity staging system independently predicted increased mortality even after adjustment for contemporary methods of classifying adiposity. The Edmonton obesity staging system may offer improved clinical utility in assessing obesity-related risk and prioritizing treatment.
IMPORTANCE: The appropriate treatment target for systolic blood pressure (SBP) in older patients with hypertension remains uncertain. OBJECTIVE: To evaluate the effects of intensive (<120 mm Hg) ...compared with standard (<140 mm Hg) SBP targets in persons aged 75 years or older with hypertension but without diabetes. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized clinical trial of patients aged 75 years or older who participated in the Systolic Blood Pressure Intervention Trial (SPRINT). Recruitment began on October 20, 2010, and follow-up ended on August 20, 2015. INTERVENTIONS: Participants were randomized to an SBP target of less than 120 mm Hg (intensive treatment group, n = 1317) or an SBP target of less than 140 mm Hg (standard treatment group, n = 1319). MAIN OUTCOMES AND MEASURES: The primary cardiovascular disease outcome was a composite of nonfatal myocardial infarction, acute coronary syndrome not resulting in a myocardial infarction, nonfatal stroke, nonfatal acute decompensated heart failure, and death from cardiovascular causes. All-cause mortality was a secondary outcome. RESULTS: Among 2636 participants (mean age, 79.9 years; 37.9% women), 2510 (95.2%) provided complete follow-up data. At a median follow-up of 3.14 years, there was a significantly lower rate of the primary composite outcome (102 events in the intensive treatment group vs 148 events in the standard treatment group; hazard ratio HR, 0.66 95% CI, 0.51-0.85) and all-cause mortality (73 deaths vs 107 deaths, respectively; HR, 0.67 95% CI, 0.49-0.91). The overall rate of serious adverse events was not different between treatment groups (48.4% in the intensive treatment group vs 48.3% in the standard treatment group; HR, 0.99 95% CI, 0.89-1.11). Absolute rates of hypotension were 2.4% in the intensive treatment group vs 1.4% in the standard treatment group (HR, 1.71 95% CI, 0.97-3.09), 3.0% vs 2.4%, respectively, for syncope (HR, 1.23 95% CI, 0.76-2.00), 4.0% vs 2.7% for electrolyte abnormalities (HR, 1.51 95% CI, 0.99-2.33), 5.5% vs 4.0% for acute kidney injury (HR, 1.41 95% CI, 0.98-2.04), and 4.9% vs 5.5% for injurious falls (HR, 0.91 95% CI, 0.65-1.29). CONCLUSIONS AND RELEVANCE: Among ambulatory adults aged 75 years or older, treating to an SBP target of less than 120 mm Hg compared with an SBP target of less than 140 mm Hg resulted in significantly lower rates of fatal and nonfatal major cardiovascular events and death from any cause. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01206062
Abstract
Background
Type 2 diabetes and obesity increase the accumulation of health deficits and may accelerate biological aging. Multidomain lifestyle interventions may mitigate against this.
...Methods
Within a large, randomized clinical trial of intensive lifestyle intervention including caloric restriction, increased physical activity, dietary counseling, and risk factor monitoring compared with diabetes support and education, we examined the accumulation of health deficits across 8 years. We used two complementary frailty indices (FIs) based on deficit accumulation, one modeled on work in the Systolic Blood Pressure Intervention Trial and the other including additional deficits related to obesity and type 2 diabetes mellitus. Differences between intervention groups and their consistency among subgroups were assessed with re-randomization tests.
Results
Data from 4,859 adults (45–76 years at baseline, 59% female) were analyzed. Random assignment to intensive lifestyle intervention was associated with lower FI scores throughout follow-up as captured by areas under curves traced by longitudinal means (p ≤ .001), over which time mean (SE) differences between intervention groups averaged 5.8% (0.9%) and 5.4% (0.9%) for the two indices. At year 8, the percentage of participants classified as frail (FI > 0.21) was lower among intensive lifestyle intervention (39.8% and 54.5%) compared with diabetes support and education (42.7% and 60.9%) for both FIs (both p < .001). Intervention benefits were relatively greater for participants who were older, not obese, and without history of cardiovascular disease at baseline.
Conclusions
Eight years of multidomain lifestyle intervention create a buffer against the accumulation of age-related health deficits in overweight or obese adults with type 2 diabetes.
ClinicalTrials.gov Identifier: NCT00017953
There has been considerable progress in the prevention and treatment of cardiovascular disease, reducing the population burden of cardiovascular morbidity and mortality. Recently, some randomized ...trials, including the SPRINT (Systolic Blood Pressure Intervention Trial), have suggested that improvements in cardiovascular risk factors may also slow cognitive decline and reduce the eventual development of dementia. Unfortunately, the randomized trial template that has been used repeatedly to successfully demonstrate reductions in major adverse cardiac events faces several design and analytic obstacles when applied in the context of cognitive decline and dementia. Here, we review these obstacles, motivated by SPRINT and the context of selecting an appropriate cognitive end point for future preventive randomized trials. A few options are available, spanning neuropsychological test scores or composites reflecting specific domains of cognitive function, adjudicated cognitive impairment, or potentially physiological biomarkers. This choice entails considerations around statistical power, modes of ascertainment, the clinical relevance of treatment effects, a myriad of statistical issues (interval censoring, missing data, the competing risk of death, practice effects, etc), as well as ethical considerations around equipoise. Collectively, these considerations indicate that trials aiming to mitigate the cardiovascular contribution to cognitive decline and dementia will generally need to be large, inclusive of a wide age range of older adults, and with multiple years of follow-up.
IMPORTANCE: Advance care planning (ACP), especially among vulnerable older adults, remains underused in primary care. Additionally, many ACP initiatives fail to integrate directly into the electronic ...health record (EHR), resulting in infrequent and disorganized documentation. OBJECTIVE: To determine whether a nurse navigator–led ACP pathway combined with a health care professional–facing EHR interface improves the occurrence of ACP discussions and their documentation within the EHR. DESIGN, SETTING, AND PARTICIPANTS: This was a randomized effectiveness trial using the Zelen design, in which patients are randomized prior to informed consent, with only those randomized to the intervention subsequently approached to provide informed consent. Randomization began November 1, 2018, and follow-up concluded November 1, 2019. The study population included patients 65 years or older with multimorbidity combined with either cognitive or physical impairments, and/or frailty, assessed from 8 primary care practices in North Carolina. INTERVENTIONS: Participants were randomized to either a nurse navigator–led ACP pathway (n = 379) or usual care (n = 380). MAIN OUTCOMES AND MEASURES: The primary outcome was documentation of a new ACP discussion within the EHR. Secondary outcomes included the usage of ACP billing codes, designation of a surrogate decision maker, and ACP legal form documentation. Exploratory outcomes included incident health care use. RESULTS: Among 759 randomized patients (mean age 77.7 years, 455 women 59.9%), the nurse navigator–led ACP pathway resulted in a higher rate of ACP documentation (42.2% vs 3.7%, P < .001) as compared with usual care. The ACP billing codes were used more frequently for patients randomized to the nurse navigator–led ACP pathway (25.3% vs 1.3%, P < .001). Patients randomized to the nurse navigator–led ACP pathway more frequently designated a surrogate decision maker (64% vs 35%, P < .001) and completed ACP legal forms (24.3% vs 10.0%, P < .001). During follow-up, the incidence of emergency department visits and inpatient hospitalizations was similar between the randomized groups (hazard ratio, 1.17; 95% CI, 0.92-1.50). CONCLUSIONS AND RELEVANCE: A nurse navigator–led ACP pathway integrated with a health care professional–facing EHR interface increased the frequency of ACP discussions and their documentation. Additional research will be required to evaluate whether increased EHR documentation leads to improvements in goal-concordant care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03609658
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