Effect of Bicarbonate on Net Acid Excretion, Blood Pressure, and Metabolism in Patients With and Without CKD: The Acid Base Compensation in CKD Study.

RATIONALE & OBJECTIVE: Patients with CKD are at elevated risk of metabolic acidosis due to impaired net acid excretion (NAE). Identifying early markers of acidosis may guide prevention in chronic kidney disease (CKD). This study compared NAE in participants with and without CKD, as well as the NAE, blood pressure (BP), and metabolomic response to bicarbonate supplementation. STUDY DESIGN: Randomized order, cross-over study with controlled feeding. SETTING & PARTICIPANTS: Participants consisted of 8 patients with CKD (estimated glomerular filtration rate 30-59mL/min/1.73m2 or 60-70mL/min/1.73m2 with albuminuria) and 6 patients without CKD. All participants had baseline serum bicarbonate concentrations between 20 and 28 mEq/L; they did not have diabetes mellitus and did not use alkali supplements at baseline. INTERVENTION: Participants were fed a fixed-acid-load diet with bicarbonate supplementation (7 days) and with sodium chloride control (7 days) in a randomized order, cross-over fashion. OUTCOMES: Urine NAE, 24-hour ambulatory BP, and 24-hour urine and plasma metabolomic profiles were measured after each period. RESULTS: During the control period, mean NAE was 28.3±10.2 mEq/d overall without differences across groups (P=0.5). Urine pH, ammonium, and citrate were significantly lower in CKD than in non-CKD (P<0.05 for each). Bicarbonate supplementation reduced NAE and urine ammonium in the CKD group, increased urine pH in both groups (but more in patients with CKD than in those without), and increased; urine citrate in the CKD group (P< 0.2 for interaction for each). Metabolomic analysis revealed several urine organic anions were increased with bicarbonate in CKD, including 3-indoleacetate, citrate/isocitrate, and glutarate. BP was not significantly changed. LIMITATIONS: Small sample size and short feeding duration. CONCLUSIONS: Compared to patients without CKD, those with CKD had lower acid excretion in the form of ammonium but also lower base excretion such as citrate and other organic anions, a potential compensation to preserve acid-base homeostasis. In CKD, acid excretion decreased further, but base excretion (eg, citrate) increased in response to alkali. Urine citrate should be evaluated as an early and responsive marker of impaired acid-base homeostasis. FUNDING: National Institute of Diabetes and Digestive and Kidney Diseases and the Duke O'Brien Center for Kidney Research. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT02427594.

Association of Sustained Blood Pressure Control with Lower Risk for High-Cost Multimorbidities Among Medicare Beneficiaries in ALLHAT.

BACKGROUND: Clustering of chronic conditions is associated with high healthcare costs. Sustaining blood pressure (BP) control could be a strategy to prevent high-cost multimorbidity clusters. OBJECTIVE: To determine the association between sustained systolic BP (SBP) control and incident multimorbidity cluster dyads and triads. DESIGN: Cohort study of Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) linked to Medicare claims. PARTICIPANTS: ALLHAT included adults with hypertension and ≥1 coronary heart disease risk factor. This analysis was restricted to 5234 participants with ≥ 8 SBP measurements during a 48-month BP assessment period. MAIN MEASURES: SBP control was defined as <140 mm Hg at <50%, 50 to <75%, 75 to <100%, and 100% of study visits during the BP assessment period. High-cost multimorbidity clusters included dyads (stroke/chronic kidney disease [CKD], stroke/chronic obstructive pulmonary disease [COPD], stroke/heart failure [HF], stroke/asthma, COPD/CKD) and triads (stroke/CKD/asthma, stroke/CKD/COPD, stroke/CKD/depression, stroke/CKD/HF, stroke/HF/asthma) identified during follow-up. KEY RESULTS: Incident dyads occurred in 1334 (26%) participants and triads occurred in 481 (9%) participants over a median follow-up of 9.2 years. Among participants with SBP control at <50%, 50 to <75%, 75 to <100%, and 100% of visits, 32%, 23%, 23%, and 19% of participants developed high-cost dyads, respectively, and 13%, 9%, 8%, and 5% of participants developed high-cost triads, respectively. Compared to those with sustained BP control at <50% of visits, adjusted HRs (95% CI) for incident dyads were 0.66 (0.57, 0.75), 0.67 (0.59, 0.77), and 0.51 (0.42, 0.62) for SBP control at 50 to <75%, 75 to <100%, and 100% of visits, respectively. The corresponding HRs (95% CI) for incident triads were 0.69 (0.55, 0.85), 0.56 (0.44, 0.71), and 0.32 (0.22, 0.47). CONCLUSIONS: Among Medicare beneficiaries in ALLHAT, sustained SBP was associated with a lower risk of developing high-cost multimorbidity dyads and triads.

Predictors of Net Acid Excretion in the Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: Higher urine net acid excretion (NAE) is associated with slower chronic kidney disease progression, particularly in patients with diabetes mellitus. To better understand potential mechanisms and assess modifiable components, we explored independent predictors of NAE in the CRIC (Chronic Renal Insufficiency Cohort) Study. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: A randomly selected subcohort of adults with chronic kidney disease enrolled in the CRIC Study with NAE measurements. PREDICTORS: A comprehensive set of variables across prespecified domains including demographics, comorbid conditions, medications, laboratory values, diet, physical activity, and body composition. OUTCOME: 24-hour urine NAE. ANALYTICAL APPROACH: NAE was defined as the sum of urine ammonium and calculated titratable acidity in a subset of CRIC participants. 22 individuals were excluded for urine pH < 4 (n = 1) or ≥7.4 (n = 19) or extreme outliers of NAE values (n = 2). From an analytic sample of 978, we identified the association of individual variables with NAE in the selected domains using linear regression. We estimated the percent variance explained by each domain using the adjusted R2 from a domain-specific model. RESULTS: Mean NAE was 33.2 ± 17.4 (SD) mEq/d. Multiple variables were associated with NAE in models adjusted for age, sex, estimated glomerular filtration rate (eGFR), race/ethnicity, and body surface area, including insulin resistance, dietary potential renal acid load, and a variety of metabolically active medications (eg, metformin, allopurinol, and nonstatin lipid agents). Body size, as indicated by body surface area, body mass index, or fat-free mass; race/ethnicity; and eGFR also were independently associated with NAE. By domains, more variance was explained by demographics, body composition, and laboratory values, which included eGFR and serum bicarbonate level. LIMITATIONS: Cross-sectional; use of stored biological samples. CONCLUSIONS: NAE relates to several clinical domains including body composition, kidney function, and diet, but also to metabolic factors such as insulin resistance and the use of metabolically active medications.

Efficacy and Safety of Massage for Osteoarthritis of the Knee: a Randomized Clinical Trial.

BACKGROUND: Current treatment options for knee osteoarthritis have limited effectiveness and potentially adverse side effects. Massage may offer a safe and effective complement to the management of knee osteoarthritis. OBJECTIVE: Examine effects of whole-body massage on knee osteoarthritis, compared to active control (light-touch) and usual care. DESIGN: Multisite RCT assessing the efficacy of massage compared to light-touch and usual care in adults with knee osteoarthritis, with assessments at baseline and weeks 8, 16, 24, 36, and 52. Subjects in massage or light-touch groups received eight weekly treatments, then were randomized to biweekly intervention or usual care to week 52. The original usual care group continued to week 24. Analysis was performed on an intention-to-treat basis. PARTICIPANTS: Five hundred fifty-one screened for eligibility, 222 adults with knee osteoarthritis enrolled, 200 completed 8-week assessments, and 175 completed 52-week assessments. INTERVENTION: Sixty minutes of protocolized full-body massage or light-touch. MAIN MEASURES: Primary: Western Ontario and McMaster Universities Arthritis Index. Secondary: visual analog pain scale, PROMIS Pain Interference, knee range of motion, and timed 50-ft walk. KEY RESULTS: At 8 weeks, massage significantly improved WOMAC Global scores compared to light-touch (- 8.16, 95% CI = - 13.50 to - 2.81) and usual care (- 9.55, 95% CI = - 14.66 to - 4.45). Additionally, massage improved pain, stiffness, and physical function WOMAC subscale scores compared to light-touch (p < 0.001; p = 0.04; p = 0.02, respectively) and usual care (p < 0.001; p = 0.002; p = 0.002; respectively). At 52 weeks, the omnibus test of any group difference in the change in WOMAC Global from baseline to 52 weeks was not significant (p = 0.707, df = 3), indicating no significant difference in change across groups. Adverse events were minimal. CONCLUSIONS: Efficacy of symptom relief and safety of weekly massage make it an attractive short-term treatment option for knee osteoarthritis. Longer-term biweekly dose maintained improvement, but did not provide additional benefit beyond usual care post 8-week treatment. TRIAL REGISTRATION: clinicaltrials.gov NCT01537484.

Association of Kidney Disease Quality of Life (KDQOL-36) with mortality and hospitalization in older adults receiving hemodialysis.

BACKGROUND: For older adults receiving dialysis, health-related quality of life is not often considered in prognostication of death or future hospitalizations. To determine if routine health-related quality of life measures may be useful for prognostication, the objective of this study is to determine the extent of association of Kidney Disease Quality of Life (KDQOL-36) subscales with adverse outcomes in older adults receiving dialysis. METHODS: This is a longitudinal study of 3500 adults aged ≥75 years receiving dialysis in the United States in 2012 and 2013. We used Cox and Fine and Gray models to evaluate the association of KDQOL-36 subscales with risk of death and hospitalization. We adjusted for sociodemographic variables, hemodialysis access type, laboratory values, and Charlson index. RESULTS: Three thousand one hundred thirty-two hemodialysis patients completed the KDQOL-36. From KDQOL-36 completion date in 2012, 880 (28.1%) died and 2023 (64.6%) had at least one hospitalization over a median follow-up of 512 and 203 days, respectively. Cohort members with a SF-12 physical component summary (PCS) in the lowest quintile had an increased adjusted risk of death [hazard ratio (HR), 1.55, 95% confidence interval (CI) 1.19-2.03] and hospitalization (HR, 1.29, 95% CI 1.09-1.54) compared with those with scores in the highest quintile. Cohort members with a SF-12 mental component summary in the lowest quintile had an increased risk of hospitalization (HR, 1.39, 95% CI 1.17-1.65) compared with those in the highest quintile. In adjusted analyses, there was no association between the symptoms of kidney disease, effects of kidney disease, and burden of kidney disease subscales with time to death or first hospitalization. Competing risk models showed similar HRs. CONCLUSIONS: Among the KDQOL-36 subscales, the SF-12 PCS demonstrates the strongest association with both death and future hospitalizations in older adults receiving hemodialysis Further research is needed to assess the value this subscale may add to prognostication.

Barriers and Facilitators to Sustainment of an Evidence-Based Supported Employment Program.

Large-scale initiatives to expand evidence-based practices are often poorly implemented and rarely endure. The purpose of this study was to identify the perceived barriers and facilitators to sustainment of an evidence-based supported employment program, Individual Placement and Support (IPS). Within a 2-year prospective study of sustainment among 129 IPS programs in 13 states participating in a national learning community, we interviewed IPS team leaders and coded their responses to semi-structured interviews using a conceptual framework adapted from another large-scale implementation study. Leaders in 122 agencies (95%) that sustained their IPS programs identified funding, prioritization, and workforce characteristics as both key facilitators and barriers. Additional key factors were lack of local community supports as a barrier and leadership and structured workflow as facilitators. Within the IPS learning community, team leaders attributed the sustainment of their program to funding, prioritization, workforce, agency leadership, and structured workflow. The actions of the learning community's leadership, state governments, and local programs together may have contributed to the high sustainment rate.

Addressing distress in patients with head and neck cancers: a mental health quality improvement project.

This study sought to improve mental health care for patients with head and neck cancers (HNCs) through the implementation of an evidence-based process for identifying and managing psychological distress. This process in an HNC medical oncology clinic was assessed and redesigned using quality improvement (QI) methods from November 2010 through April 2012. The redesign, starting in January 2011, involved a 2-component QI intervention: the validated NCCN Distress Thermometer and an evidence-based treatment decision algorithm. Screening processes were improved through Plan-Do-Study-Act (PDSA) cycles. Before January 2011, distress identification was based on a provider's clinical assessment. Cause-effect diagramming suggested that lack of a formalized process for distress assessment contributed to missed diagnoses. Providers were also unfamiliar with mental health resources. After implementing process changes, biweekly distress screening rates rose from 0% to 38% between January and July 2011. Furthermore, with additional PDSA cycles, these rates increased to 74% between October 2011 and April 2012. Similar to proposed benchmarks, 84% (n=47) of newly diagnosed patients (n=56) were screened. Improvement in screening was attributed to process changes and involvement of senior leadership. QI principles can be applied to the cancer setting in order to create systems of care which more reliably identify and address the needs of patients with psychological distress.

A qualitative study of career exploration among young adult men with psychosis and co-occurring substance use disorder.

OBJECTIVE: This article explores the meaning and importance of career exploration and career development in the context of integrated treatment for young adults with early psychosis and substance use disorders (i.e., co-occurring disorders). METHODS: Twelve young adult men (aged 18 to 35 years) with co-occurring disorders recruited from an integrated treatment center completed a series of three semi-structured in-depth qualitative interviews. Data were transcribed verbatim and analyzed using thematic analysis. Purposive sampling ensured participants represented a range of substance abuse treatment stages. RESULTS: Participants had a mean age of 26 (SD = 3) and identified as White. Two-thirds of participants (n = 8, 67%) had diagnosed schizophrenia-spectrum disorders, three (25%) had bipolar disorder, and one (8%) had major depression; four (33%) also had a co-occurring anxiety disorder. The most common substance use disorders involved cannabis (n = 8, 67%), cocaine (n = 5, 42%), and alcohol (n = 5, 42%). These young adult men with co-occurring disorders described past jobs that did not align with future goals as frustrating and disempowering, rather than confidence-building. Most young adult participants began actively developing their careers in treatment through future-oriented work or school placements. They pursued ambitious career goals despite sporadic employment and education histories. Treatment engagement and satisfaction appeared to be linked with career advancement prospects. CONCLUSIONS: Integrating career planning into psychosocial treatment is a critical task for providers who serve young adults with co-occurring disorders. Whether integrating career planning within early intervention treatment planning will improve clinical, functional, or economic outcomes is a promising area of inquiry for rehabilitation researchers and clinicians.

Long-term sobriety strategies for men with co-occurring disorders.

OBJECTIVE: Roughly half of people with severe mental disorders also experience a co-occurring substance use disorder, and recovery from both is a critical objective for health care services. While understanding of abstinence initiation has grown, the strategies people with co-occurring disorders use to maintain sobriety are largely unknown. This article reports strategies for relapse prevention as described by men with co-occurring disorders who achieved one or more years of sobriety. METHODS: We analyzed semi-structured interviews conducted with a sample of 12 men with co-occurring psychosis and substance use disorder who achieved and maintained sobriety for at least one year, supplemented with demographic and diagnostic clinical record data. These men were participating in residential or outpatient treatment at a private, nonprofit integrated treatment clinic. RESULTS: The 12 men were primarily Caucasian (91.7%) and unmarried (100%), and their ages ranged from 23 to 42 years. The two most common psychiatric disorders were schizoaffective disorder (n = 4, 33.3%) and bipolar disorder (n = 4, 33.3%), while the two most commonly misused substances were alcohol and cannabis. Qualitative analyses showed that participants maintained sobriety for at least one year by building a supportive community, engaging in productive activities, and carefully monitoring their own attitudes toward substances, mental health, and responsibility. Alcoholics Anonymous might act as a catalyst for building skills. CONCLUSIONS: People with co-occurring disorders who achieve sobriety use a variety of self-management strategies to prevent relapse-seeking support, activities, and a healthy mindset. The findings suggest a relapse prevention model that focuses on social networks, role functioning, and self-monitoring and conceptualizes self-care as critical to extending periods of wellness.

Is high fidelity to supported employment equally attainable in small and large communities?

Individual Placement and Support (IPS) is an evidence-based model to help people with serious mental illness achieve employment. This study examined variation in model adherence in small and large communities. We compared program-level ratings on a standardized 25-item IPS fidelity scale (range = 25-125) for 79 sites in eight states categorized by local community size. Programs in large and small communities achieved comparable fidelity scores (mean = 100 and 104, respectively). Fidelity-outcome correlations within the two groups were both of moderate size. As a practical guide, the IPS fidelity scale is suitable for use in both small and large communities.

Longitudinal fragility phenotyping contributes to the prediction of lifespan and age-associated morbidity in C57BL/6 and Diversity Outbred mice.

Aging studies in mammalian models often depend on natural lifespan data as a primary outcome. Tools for lifespan prediction could accelerate these studies and reduce the need for veterinary intervention. Here, we leveraged large-scale longitudinal frailty and lifespan data on two genetically distinct mouse cohorts to evaluate noninvasive strategies to predict life expectancy in mice. We applied a modified frailty assessment, the Fragility Index, derived from existing frailty indices with additional deficits selected by veterinarians. We developed an ensemble machine learning classifier to predict imminent mortality (95% proportion of life lived [95PLL]). Our algorithm represented improvement over previous predictive criteria but fell short of the level of reliability that would be needed to make advanced prediction of lifespan and thus accelerate lifespan studies. Highly sensitive and specific frailty-based predictive endpoint criteria for aged mice remain elusive. While frailty-based prediction falls short as a surrogate for lifespan, it did demonstrate significant predictive power and as such must contain information that could be used to inform the conclusion of aging experiments. We propose a frailty-based measure of healthspan as an alternative target for aging research and demonstrate that lifespan and healthspan criteria reveal distinct aspects of aging in mice.

Longitudinal Fragility Phenotyping Predicts Lifespan and Age-Associated Morbidity in C57BL/6 and Diversity Outbred Mice.

Aging studies in mammalian models often depend on natural lifespan data as a primary outcome. Tools for lifespan prediction could accelerate these studies and reduce the need for veterinary intervention. Here, we leveraged large-scale longitudinal frailty and lifespan data on two genetically distinct mouse cohorts to evaluate noninvasive strategies to predict life expectancy in mice. We applied a modified frailty assessment, the Fragility Index, derived from existing frailty indices with additional deficits selected by veterinarians. We developed an ensemble machine learning classifier to predict imminent mortality (95% proportion of life lived [95PLL]). Our algorithm represented improvement over previous predictive criteria but fell short of the level of reliability that would be needed to make advanced prediction of lifespan and thus accelerate lifespan studies. Highly sensitive and specific frailty-based predictive endpoint criteria for aged mice remain elusive. While frailty-based prediction falls short as a surrogate for lifespan, it did demonstrate significant predictive power and as such must contain information that could be used to inform the conclusion of aging experiments. We propose a frailty-based measure of healthspan as an alternative target for aging research and demonstrate that lifespan and healthspan criteria reveal distinct aspects of aging in mice.

The Sickle Cell Disease Functional Assessment (SCD-FA) tool: a feasibility pilot study.

BACKGROUND: The life expectancy for individuals with sickle cell disease (SCD) has greatly increased over the last 50 years. Adults with SCD experience multiple complications such as cardiopulmonary disease, strokes, and avascular necrosis that lead to limitations that geriatric populations often experience. There are no dedicated instruments to measure functional decline and functional age to determine risk of future adverse outcomes in older adults with SCD. The objective of this study was to assess the feasibility of performing the Sickle Cell Disease Functional Assessment (SCD-FA). METHODS: We enrolled 40 adults with SCD (20 younger adults aged 18-49 years as a comparison group and 20 older adults aged 50 years and older) in a single-center prospective cohort study. Participants were recruited from a comprehensive sickle cell clinic in an academic center in the southeastern United States. We included measures validated in an oncology geriatric assessment enriched with additional physical performance measures: usual gait speed, seated grip strength, Timed Up and Go, six-minute walk test, and 30-second chair stand. We also included an additional cognitive measure, which was the Montreal Cognitive Assessment, and additional patient-reported measures at the intersection of sickle cell disease and geriatrics. The primary outcome was the proportion completing the assessment. Secondary outcomes were the proportion consenting, duration of the assessment, acceptability, and adverse events. RESULTS: Eighty percent (44/55) of individuals approached consented, 91% (40/44) completed the SCD-FA in its entirety, and the median duration was 89 min (IQR 80-98). There were no identified adverse events. On the acceptability survey, 95% (38/40) reported the length as appropriate, 2.5% (1/40) reported a question as upsetting, and 5% (2/40) reported portions as difficult. Exploratory analyses of physical function showed 63% (25/40) had a slow usual gait speed (< 1.2 m/s). CONCLUSION: The SCD-FA is feasible, acceptable, and safe and physical performance tests identified functional impairments in adults with SCD. These findings will inform the next phase of the study where we will assess the validity of the SCD-FA to predict patient-important outcomes in a larger sample of adults with SCD.

Sustained SBP control and long-term nursing home admission among Medicare beneficiaries.

OBJECTIVES: Sustaining SBP control reduces the risk for cardiovascular events that impair function but its association with nursing home admission has not been well studied. METHODS: We conducted an analysis of sustained SBP control and long-term nursing home admissions using data from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) linked to Medicare claims restricted to participants with fee-for-service coverage, at least eight study visits with SBP measurements, who were not living in a nursing home during a 48-month baseline BP assessment period (n = 6557). Sustained SBP control was defined as less than 140 mmHg at less than 50%, 50% to less than 75%, 75% to less than 100%, and 100% of visits. Nursing home admissions were identified using the Medicare Long Term Care Minimum Data Set. RESULTS: The mean age of participants was 73.8 years and 44.3% were men. Over a median follow-up of 9.2 years, 844 participants (12.8%) had a nursing home admission. Rates of nursing home admission per 100 person-years were 16.3 for participants with SBP control at less than 50%, 14.1 at 50% to less than 75%, 7.8 at 75% to less than 100%, and 5.3 at 100% of visits. Compared with those with sustained SBP control at less than 50% of visits, hazard ratios (95% confidence intervals) for nursing home admission were 0.79 (0.66-0.93), 0.70 (0.58-0.84), and 0.57 (0.44-0.74) among participants with SBP control at 50% to less than 75%, 75% to less than 100%, and 100% of visits, respectively. CONCLUSION: Among Medicare beneficiaries in ALLHAT, sustained SBP control was associated with a lower risk of long-term nursing home admission.

Geriatric assessment for older adults with sickle cell disease: protocol for a prospective cohort pilot study.

BACKGROUND: The life expectancy for people with sickle cell disease (SCD) has improved tremendously over the last 50 years. This population experiences hemolysis and vaso-occlusion in multiple organs that lead to complications such as cardiopulmonary disease, strokes, and avascular necrosis. These complications can limit mobility and aerobic endurance, similar to limitations that often occur in geriatric populations. These sickle-cell and age-related events lead to frequent hospitalization, which further increases the risk of functional decline. We have few tools to measure functional decline in people with SCD. The purpose of this paper is to describe a protocol to evaluate the feasibility of sickle cell disease geriatric assessment (SCD-GA). METHODS/DESIGN: We will enroll 40 adults with SCD (20 age 18-49.99 years and 20 age ≥ 50 years) in a prospective cohort study to assess the feasibility of SCD-GA. The SCD-GA includes validated measures from the oncology geriatric assessment enriched with additional physical and cognitive measures. The SCD-GA will be performed at the first study visit, at 10 to 20 days after hospitalization, and at 12 months (exit visit). With input from a multidisciplinary team of sickle cell specialists, geriatricians, and experts in physical function and physical activity, we selected assessments across 7 domains: functional status (11 measures), comorbid medical conditions (1 measure), psychological state (1 measure), social support (2 measures), weight status (2 measures), cognition (3 measures), and medications (1 measure). We will measure the proportion completing the assessment with feasibility as the primary outcome. Secondary outcomes include the proportion consenting and completing all study visits, duration of the assessment, acceptability, and adverse events. DISCUSSION: We present the protocol and rationale for selection of the measures included in SCD-GA. We also outline the methods to determine feasibility and subsequently to optimize the SCD-GA in preparation for a larger multicenter validation study of the SCD-GA.

Physical Function Assessment in Older Hemodialysis Patients.

RATIONALE & OBJECTIVE: Physical function is not routinely measured in older adults receiving dialysis. We evaluated the appropriateness of repeated measurements of physical function, including Short Physical Performance Battery (SPPB), handgrip strength, and activities of daily living (ADLs), in older adults receiving dialysis. STUDY DESIGN: Prospective study. SETTING & PARTICIPANTS: 37 community-dwelling adults 65 years and older receiving in-center hemodialysis at 5 dialysis units located in North Carolina. EXPOSURES: SPPB (an assessment of standing balance, chair stands, and gait speed), handgrip strength, and Katz and Lawton ADLs at baseline and subsequent 3-month intervals up to 6 months. OUTCOMES: Completion rate, presence of floor or ceiling effects, and presence of clinically meaningful change in physical function measurements. RESULTS: Of 55 potential participants, we enrolled 37 (67%) older adults receiving hemodialysis. Among 35 enrolled participants who completed baseline assessment in a dialysis unit, mean age was 70.1 (SD, 5) years, 46% (n = 16) were women, 77% (n = 27) were African American, and median time receiving dialysis was 2.7 (IQR, 0.6-5.0) years. There were 3 deaths within the observation period, and study retention at 3 and 6 months was 83% (n = 29) and 74% (n = 26), respectively. Participants tolerated measurements; only 2 participants did not attempt 1 of the performance-based tests at a study visit. Baseline median SPPB score, grip strength, and gait speed were 6 (IQR, 4-9), 55 (IQR, 42-70) kg, and 0.76 (IQR, 0.46-0.86) m/s, respectively. Baseline median for Katz and Lawton ADLs were 6 (IQR, 6-6) and 7 (IQR, 4-8), respectively; ceiling effects were observed for both measures. For some participants, clinically meaningful changes (improvement or decline) in SPPB score, grip strength, and gait speed occurred at each 3-month interval. LIMITATIONS: Limited geographic and ethnic variation. CONCLUSIONS: SPPB, handgrip strength, and gait speed alone are appropriate measures for interval physical function assessment in community-dwelling older adults receiving in-center hemodialysis.

Association of Sustained Blood Pressure Control with Multimorbidity Progression Among Older Adults.

BACKGROUND/OBJECTIVES: Due to the high costs and excess mortality associated with multimorbidity, there is a need to develop approaches for delaying its progression. High blood pressure (BP) is a common chronic condition and a risk factor for many additional chronic conditions, making it an ideal target for intervention. The purpose of this analysis was to determine the association between the level of sustained BP control and the progression of multimorbidity. DESIGN: Retrospective cohort study. SETTING: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) linked to Medicare claims. PARTICIPANTS: A total of 6,591 ALLHAT participants with Medicare who had systolic BP (SBP) measurements at eight or more study visits. MEASUREMENTS: SBP control was categorized as lower than 140 mm Hg at less than 50%, 50% to less than 75%, 75% to less than 100%, and 100% of visits. Multimorbidity progression was defined by the number of incident chronic conditions, including arthritis, asthma, atrial fibrillation, cancer, chronic kidney disease, chronic obstructive pulmonary disease, coronary heart disease, dementia, depression, diabetes mellitus, heart failure, hyperlipidemia, osteoporosis, and stroke. Recurrent event survival analysis was used to calculate rate ratios (RRs) for the association of sustained SBP control with progression of multimorbidity. RESULTS: Rates of incident conditions per 10 person-years (95% CIs) were 5.2 (5.1-5.4), 4.7 (4.5-4.8), 4.4 (4.2-4.5), and 4.0 (3.8-4.2) for participants with SBP control at less than 50%, 50% to less than 75%, 75% to less than 100%, and 100% of visits, respectively, over a median follow-up of 9.0 years. Compared with participants with SBP control at less than 50% of visits, adjusted RRs (95% CIs) for multimorbidity progression were 0.90 (0.86-0.95), 0.85 (0.81-0.89), and 0.77 (0.72-0.82) for those with SBP control at 50% to less than 75%, 75% to less than 100%, and 100% of visits, respectively. CONCLUSIONS: Sustaining BP control may be an effective approach to slow multimorbidity progression and may reduce the population burden of multimorbidity.

Self-reported Physical Function Decline and Mortality in Older Adults Receiving Hemodialysis.

RATIONALE & OBJECTIVE: Timely recognition of functional decline in older adults receiving dialysis will allow clinicians to pursue interventions to prevent further disability and/or lead patient-centered goals of care discussions. Annual change in the 12-Item Short Form Health Survey (SF-12) physical component score (PCS) could identify patients with functional decline. Our objectives were to assess SF-12 PCS change over a year, risk factors associated with SF-12 PCS change, and the association of SF-12 PCS change with mortality in a survivor cohort of older adults receiving dialysis. STUDY DESIGN: Retrospective study. SETTING & PARTICIPANTS: 1,371 adults 65 years or older receiving hemodialysis for 6 or more months who completed SF-12 PCSs 300 or more days apart from 2012 to 2013. EXPOSURES: Serum albumin level; hemodialysis access type; SF-12 PCS change (for mortality analyses). OUTCOMES: SF-12 PCS change and mortality. ANALYTICAL APPROACH: Multivariable-adjusted linear regression model; Cox proportional hazards model. RESULTS: We excluded 24% (n = 801) of our cohort for death before the second SF-12 PCS. Among the 1,371 with sufficient SF-12 PCS data, mean age was 79.9 ± 4.5 years. Average SF-12 PCS change in 1 year was minimal (-0.9 ± 9.6), but 39.3% (n = 539) and 32.2% (n = 442) had clinically relevant SF-12 PCS decline and improvement, respectively. Albumin level and access type were not statistically associated with SF-12 PCS change. SF-12 PCS change was not associated with mortality (adjusted HR, 0.98; 95% CI, 0.96-1.00). LIMITATIONS: 2 time points to assess SF-12 PCS change; covariate assessment only at baseline; survivor bias. CONCLUSIONS: In this cohort of older adults receiving hemodialysis, nearly one-fourth died, while among survivors, it was more common for SF-12 PCS to decline than improve in a year. Annual SF-12 PCS change was not associated with traditional risk factors for functional impairment or mortality risk. Additional research is needed to identify appropriate measures and frequency of assessment for functional decline.

Sustained blood pressure control and coronary heart disease, stroke, heart failure, and mortality: An observational analysis of ALLHAT.

Achieving blood pressure (BP) control is associated with lower cardiovascular disease (CVD) risk, but less is known about CVD risk associated with sustained BP control over time. This observational analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was restricted to participants with four to seven visits with systolic BP (SBP) measurements during a 22-month period (n = 24 309). The authors categorized participants as having sustained BP control (SBP < 140 mm Hg) at 100%, 75% to <100%, 50% to <75%, and <50% of visits during this period. Outcomes included fatal coronary heart disease (CHD)/nonfatal myocardial infarction (MI), stroke, heart failure (HF), a composite CVD outcome (fatal CHD/nonfatal MI, stroke, or HF), and mortality. Hazard ratios (HRs) for the association of category of sustained BP control for each outcome were obtained using proportional hazards models. SBP control was present among 20.0% of participants at 100%, 16.4% at 75% to less than 100%, 27.0% at 50% to less than 75%, and 36.6% at less than 50% of visits. Compared to those with SBP control at 100% visits, adjusted HR (95% CI) among those with SBP control at <50% of visits was 1.16 (0.93-1.44) for fatal CHD/nonfatal MI, 1.71 (1.26-2.32) for stroke, 1.63 (1.30-2.06) for HF, 1.39 (1.20-1.62) for the composite CVD outcome, and 1.14 (0.99-1.30) for mortality. Sustained SBP control may be beneficial for preventing stroke, HF, and CVD outcomes in adults taking antihypertensive medication.

Combined Inflammation and Metabolism Biomarker Indices of Robust and Impaired Physical Function in Older Adults.

OBJECTIVES: To determine whether combinations of inflammatory markers are related to physical function. DESIGN AND SUBJECTS: secondary analysis of baseline of three observational studies of community-dwelling older adults MEASUREMENTS: The baseline data from 3 cohorts of older adults with different health and disease status were employed. Twenty markers of inflammation and metabolism were individually assessed for correlation with usual gait speed and were separated into robust and impairment quartiles. For the robustness and impairment indices, individual markers were selected using step-wise regression over bootstrapping iterations, and regression coefficients were estimated for the markers individually and collectively as an additive score. RESULTS: We developed a robustness index involving 6 markers and an impairment index involving 8 markers corresponding positively and negatively with gait speed. Two markers, glycine and tumor necrosis factor receptor 1 (TNFR1), appeared only in the robustness index, and TNFR2; regulated on activation, normal T-cell expressed and secreted; the amino acid factor; and matrix metallopeptidase 3; appeared only in the impairment index. CONCLUSION: Indices of biomarkers were associated with robust and impaired physical performance but differ, in composition suggesting potential biological differences that may contribute to robustness and impairment.