Functional status after lung transplantation in older adults in the post-allocation score era.

This manuscript describes the functional status trajectory of older (age 65 or older) and younger (age 18-64) adults after lung transplantation (LT). After the implementation of the lung allocation score (LAS) in 2005, older adults became the fastest growing subgroup of recipients. Yet the impact of LT on physical function, a main determinant of quality of life in older adults, is unknown. We conducted a retrospective cohort study using United Network for Organ Sharing data on 4805 adults who received a LT during 2005-2009. We divided them into older (≥65; n = 774) and younger (18-64; n = 4031) cohorts. Functional status was measured by Karnofsky performance score (KPS). Mixed models estimated the impact of age group on the rate of functional decline starting at 1 year posttransplantation. We controlled for KPS at transplantation, gender, race, diagnosis, LAS and LT type. Age group was not associated with different rates of decline in KPS over time. On average, recipients who were older, received a single LT, or had a low KPS at transplantation had worse functional status posttransplantation when compared to their counterparts, but rarely reached disability at 48 months. Overall, LT had a positive and durable effect on physical function for both older and younger recipients.

Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease.

Gene dosage of the apolipoprotein E (APOE) epsilon 4 allele is a major risk factor for familial Alzheimer disease (AD) of late onset (after age 60). Here we studied a large series of 115 AD case subjects and 243 controls as well as 150 affected and 197 unaffected members of 66 AD families. Our data demonstrate a protective effect of the epsilon 2 allele, in addition to the dose effect of the epsilon 4 allele in sporadic AD. Although a substantial proportion (65%) of AD is attributable to the presence of epsilon 4 alleles, risk of AD is lowest in subjects with the epsilon 2/epsilon 3 genotype, with an additional 23% of AD attributable to the absence of an epsilon 2 allele. The opposite actions of the epsilon 2 and epsilon 4 alleles further support the direct involvement of APOE in the pathogenesis of AD.

Persistence of the efficacy of zoster vaccine in the shingles prevention study and the short-term persistence substudy.

BACKGROUND: The Shingles Prevention Study (SPS; Department of Veterans Affairs Cooperative Study 403) demonstrated that zoster vaccine was efficacious through 4 years after vaccination. The Short-Term Persistence Substudy (STPS) was initiated after the SPS to further assess the persistence of vaccine efficacy. METHODS: The STPS re-enrolled 7320 vaccine and 6950 placebo recipients from the 38 546-subject SPS population. Methods of surveillance, case determination, and follow-up were analogous to those in the SPS. Vaccine efficacy for herpes zoster (HZ) burden of illness, incidence of postherpetic neuralgia (PHN), and incidence of HZ were assessed for the STPS population, for the combined SPS and STPS populations, and for each year through year 7 after vaccination. RESULTS: In the STPS as compared to the SPS, vaccine efficacy for HZ burden of illness decreased from 61.1% to 50.1%, vaccine efficacy for the incidence of PHN decreased from 66.5% to 60.1%, and vaccine efficacy for the incidence of HZ decreased from 51.3% to 39.6%, although the differences were not statistically significant. Analysis of vaccine efficacy in each year after vaccination for all 3 outcomes showed a decrease in vaccine efficacy after year 1, with a further decline thereafter. Vaccine efficacy was statistically significant for the incidence of HZ and the HZ burden of illness through year 5. CONCLUSIONS: Vaccine efficacy for each study outcome was lower in the STPS than in the SPS. There is evidence of the persistence of vaccine efficacy through year 5 after vaccination but, vaccine efficacy is uncertain beyond that point.

Solid-organ transplantation in older adults: current status and future research.

An increasing number of patients older than 65 years are referred for and have access to organ transplantation, and an increasing number of older adults are donating organs. Although short-term outcomes are similar in older versus younger transplant recipients, older donor or recipient age is associated with inferior long-term outcomes. However, age is often a proxy for other factors that might predict poor outcomes more strongly and better identify patients at risk for adverse events. Approaches to transplantation in older adults vary across programs, but despite recent gains in access and the increased use of marginal organs, older patients remain less likely than other groups to receive a transplant, and those who do are highly selected. Moreover, few studies have addressed geriatric issues in transplant patient selection or management, or the implications on health span and disability when patients age to late life with a transplanted organ. This paper summarizes a recent trans-disciplinary workshop held by ASP, in collaboration with NHLBI, NIA, NIAID, NIDDK and AGS, to address issues related to kidney, liver, lung, or heart transplantation in older adults and to propose a research agenda in these areas.

A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

BACKGROUND: The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. METHODS: We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. RESULTS: More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. CONCLUSIONS: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.

Adverse events after discontinuing medications in elderly outpatients.

BACKGROUND: Discontinuation of drug therapy is an important intervention in elderly outpatients receiving multiple medications, but it may be associated with adverse drug withdrawal events (ADWEs). OBJECTIVE: To determine the frequency, types, timing, severity, and factors associated with ADWEs after discontinuing medications in elderly outpatients. PATIENTS: One hundred twenty-four ambulatory elderly participants in 1-year health service intervention trial at the Durham Veterans Affairs General Medicine Clinic in Durham, NC, who stopped taking medications. METHODS: A geriatrician retrospectively reviewed computerized medication records and clinical charts to determine medications no longer being taken and adverse events in the subsequent 4-month period. Possible ADWEs, determined by using the Naranjo causality algorithm, were categorized by therapeutic class, organ system, and severity. RESULTS: Of 238 drugs stopped, 62 (26%) resulted in 72 ADWEs among 38 patients. Cardiovascular (42%) and central nervous system (18%) drug classes were most frequently associated with ADWEs. The ADWEs most commonly involved the circulatory (51%) and central nervous (13%) systems, and 88% were attributed to exacerbations of underlying disease. Twenty-six ADWEs (36%) resulted in hospitalization or an emergency department or urgent care clinic visit. Only the number of medications stopped was associated with ADWE occurrence (adjusted odds ratio, 1.89; 95% confidence interval, 1.33-2.67). CONCLUSIONS: Most medications can be stopped in elderly outpatients without an ADWE occurrence. However, when ADWEs occur they resulted in substantial health care utilization. Practitioners should strive to discontinue drug therapy in the elderly but be vigilant for disease recurrence.

Benzodiazepine use and cognitive function among community-dwelling elderly.

OBJECTIVE: To evaluate the relation between benzodiazepine use and cognitive function among community-dwelling elderly. METHODS: This prospective cohort study included 2765 self-reporting subjects from the Duke Established Populations for Epidemiologic Studies of the Elderly. The subjects were cognitively intact at baseline (1986-1987) and alive at follow-up data collection 3 years later. Cognitive function was assessed with the Short Portable Mental Status Questionnaire (unimpaired versus impaired and change in score) and on the basis of the number of errors on the individual domains of the Orientation-Memory-Concentration Test. Benzodiazepine use was determined during in-home interviews and classified by dose, half-life, and duration. Covariates included demographic characteristics, health status, and health behaviors. RESULTS: After control for covariates, current users of benzodiazepine made more errors on the memory test (beta coefficient, 0.35; 95% confidence interval [CI], 0.10 to 0.61) than nonusers. Further assessment of the negative effects on memory among current users suggested a dose response in which users taking the recommended or higher dose made more errors (beta coefficient, 0.57; 95% CI, 0.26 to 0.88) and a duration response in which long-term users made more errors (beta coefficient, 0.39; 95% CI, 0.05 to 0.73) than nonusers. Users of agents with long half-lives and users of agents with short half-lives both had increased memory impairment (beta coefficient, 0.32; 95% CI, 0.01 to 0.64 and beta coefficient, 0.38; 95% CI, 0.02 to 0.75, respectively) relative to nonusers. Previous benzodiazepine use was unrelated to memory problems, and current and previous benzodiazepine use was unrelated to level of cognitive functioning as measured with the other 4 tests. CONCLUSIONS: The results suggested that current benzodiazepine use, especially in recommended or higher doses, is associated with worse memory among community-dwelling elderly.

Apolipoprotein E, survival in Alzheimer's disease patients, and the competing risks of death and Alzheimer's disease.

The apolipoprotein E (APOE) epsilon 4 allele carries an increased risk of a patient developing Alzheimer's disease (AD) while the epsilon 2 allele carries a decreased risk. We compared survival from the onset of AD in subjects with different numbers of epsilon 4 alleles and evaluated changes in genotypic frequencies with age. Two subject groups were investigated: unrelated AD case and control subjects, and affected and unaffected members from 74 multiplex AD families. In both subject groups, survival from onset decreased with increasing onset age, was longer in women, and was unrelated to epsilon 4 gene dose. The epsilon 2/epsilon 3 genotype became more common with age (p = 0.004). The epsilon 4 allele decreased in frequency with age in all patient groups but, unexpectedly, remained unchanged in control subjects. We conclude that the progression of AD is not strongly related to epsilon 4 gene dose, that the higher prevalence of AD in women may involve the longer survival of affected women, and that AD and death are competing risks involving APOE that change over time.

A randomized, controlled trial of a clinical pharmacist intervention to improve inappropriate prescribing in elderly outpatients with polypharmacy.

PURPOSE: To evaluate the effect of sustained clinical pharmacist interventions involving elderly outpatients with polypharmacy and their primary physicians. PATIENTS AND METHODS: Randomized, controlled trial of 208 patients aged 65 years or older with polypharmacy (> or = 5 chronic medications) from a general medicine clinic of a Veterans Affairs Medical Center. A clinical pharmacist met with intervention group patients during all scheduled visits to evaluate their drug regimens and make recommendations to them and their physicians. Outcome measures were prescribing appropriateness, health-related quality of life, adverse drug events, medication compliance and knowledge, number of medications, patient satisfaction, and physician receptivity. RESULTS: Inappropriate prescribing scores declined significantly more in the intervention group than in the control group by 3 months (decrease 24% versus 6%, respectively; P = 0.0006) and was sustained at 12 months (decrease 28% versus 5%, respectively; P = 0.0002). There was no difference between groups at closeout in health-related quality of life (P = 0.99). Fewer intervention than control patients (30.2%) versus 40.0%; P = 0.19) experienced adverse drug events. Measures for most other outcomes remained unchanged in both groups. Physicians were receptive to the intervention and enacted changes recommended by the clinical pharmacist more frequently than they enacted changes independently for control patients (55.1% versus 19.8%; P <0.001). CONCLUSIONS: This study demonstrates that a clinical pharmacist providing pharmaceutical care for elderly primary care patients can reduce inappropriate prescribing and possibly adverse drug effects without adversely affecting health-related quality of life.

Relation of prescription nonsteroidal antiinflammatory drug use to cognitive function among community-dwelling elderly.

PURPOSE: To evaluate the relationship of nonsteroidal antiinflammatory drug (NSAID) use to level of cognitive function in community-dwelling elderly persons. METHODS: The prospective cohort study included 2765 nonproxy subjects from the Duke University Established Populations for Epidemiologic Studies of the Elderly who were cognitively intact at baseline (1986-1987) and alive at follow-up three year later. Cognitive function was assessed by the Short Portable Mental Status Questionnaire (i.e., intact vs. impaired and change in score) and by the individual domains of the Orientation-Memory-Concentration Test (i.e., number of errors). NSAID use, determined from in-home interviews, was coded for chronicity, dose, frequency of use, and prescription status. RESULTS: After controlling for demographic factors as well as health status and behavior, continuous, regularly-scheduled, prescription use of NSAID was associated with preservation of one aspect of cognitive functioning: concentration (beta coefficient, 0.29; 95% confidence interval [CI] -0.54 to -0.04, indicating fewer errors). However, no consistent dose-response relationship was found. Current and prior NSAID use was unrelated to level of cognitive functioning across all five measures; among current users, those taking moderate or high doses (beta coefficient, 0.41; 95% CI, 0.08 to 0.74) made more errors on the memory test compared with those taking low doses (beta coefficient 0.03; 95% CI, -.85 to 0.91). CONCLUSIONS: These results suggest no substantial or consistent protective effect of prescription NSAID use on cognitive function in community-dwelling elderly. However, recent use at higher doses may be associated with memory deterioration in this population.

A method for assessing drug therapy appropriateness.

This study evaluated the reliability of a new medication appropriateness index. Using the index, independent assessments were made of chronic medications taken by 10 ambulatory, elderly male patients by a clinical pharmacist and an internist-geriatrician. Their overall inter-rater agreement for medication appropriateness (ppos) was 0.88, and for medication inappropriateness (pneg) was 0.95; the overall kappa was 0.83. Their intra-rater agreement for ppos was 0.94 overall, for pneg was 0.98 overall while the overall kappa was 0.92. The chronic medications taken by 10 different ambulatory elderly male patients were independently evaluated by two different clinical pharmacists. Their overall inter-rater agreement for ppos was 0.76, and for pneg was 0.93, while the overall kappa was 0.59. This new index provides a reliable method to assess drug therapy appropriateness. Its use may be applicable as a quality of care outcome measure in health services research and in institutional quality assurance programs.

The prevalence and 3-year incidence of dementia in older Black and White community residents.

OBJECTIVE: To determine the prevalence and 3-year incidence of dementia in Blacks and Whites age 65 and older in a five-county Piedmont area of North Carolina. DESIGN: Stratified random sample of members of the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE) (baseline n = 4,136; 55% Black; weighted n = 28,000). Prevalence study members were differentially selected on the basis of score on the Short Portable Mental Status Questionnaire at the second in-person Duke EPESE wave. Incidence study members included all persons with obvious cognitive decline over a 3-year period, and a 10% sample of the remainder. MEASUREMENTS: Self- and informant report on health history, functional status, and memory. Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Neuropsychology Battery administered to all subjects, and CERAD Clinical Battery to those with impaired memory. Clinical consensus to determine presence and type of dementia. RESULTS: Prevalence of dementia for persons > or =68 years old was 0.070 (95% confidence interval = 0.021-0.119) for Blacks and 0.072 (0.022-0.122) for Whites. Rates for Black men (0.078, 0.001-0.155) exceeded those for Black women (0.066, 0.003-0.129), but gender rates for Whites were reversed (men: 0.044, 0.000-0.103), (women: 0.087, 0.015-0.160). Neither race nor gender differences were significant. Prevalence of dementia increased through age 84 and tapered off thereafter. Three-year incidence of dementia was 0.058 (0.026-0.090) for Blacks and 0.062 (0.027-0.097) for Whites. Neither race nor gender differences were significant. Incidence increased through age 84, but moderated thereafter for all but Black men. The proportional representation of different types of dementia varied little by race. CONCLUSION: Prevalence, 3-year incidence, and types of dementia are comparable in Black and White elderly in the Piedmont area of North Carolina.

A summated score for the medication appropriateness index: development and assessment of clinimetric properties including content validity.

Inappropriate medication prescribing is an important problem in the elderly, but is difficult to measure. As part of a randomized controlled trial to evaluate the effectiveness of a pharmacist intervention among elderly veterans using many medications, we developed the Medication Appropriateness Index (MAI), which uses implicit criteria to measure elements of appropriate prescribing. This paper describes the development and validation of a weighting scheme used to produce a single summated MAI score per medication. Using this weighting scheme, two clinical pharmacists rated 105 medications prescribed to 10 elderly veterans from a general medicine clinic. The summated score demonstrated acceptable reliability (intraclass correlation co-efficient = 0.74). In addition, the summated MAI adequately reflected the putative heterogeneity in prescribing appropriateness among 1644 medications prescribed to 208 elderly veterans in the same general medicine clinic. These data support the content validity of the summated MAI. The MAI appears to be a relatively reliable, valid measure of prescribing appropriateness and may be useful for research studies, quality improvement programs, and patient care.

Assessment of pain in herpes zoster: lessons learned from antiviral trials.

Pain typically accompanies acute herpes zoster and, in a proportion of patients, it persists well beyond rash healing. Pain must therefore be analyzed in trials of antiviral agents in herpes zoster, but different methods have been used to analyze pain in recent published trials. These reports are reviewed and their methodological strengths and weaknesses examined. Based on this review, recommendations for the design and analysis of future trials of antiviral agents in herpes zoster are proposed. The principal recommendation is that antiviral efficacy should be evaluated both by distinguishing post-herpetic neuralgia from acute pain and by considering pain as a continuum. The primary endpoint should address both the prevalence and duration of post-herpetic neuralgia and should be examined in those patients who have post-herpetic neuralgia. Adopting the proposed recommendations in design and analysis of future trials should facilitate comparison across trials of the efficacy of antiviral agents in the treatment of herpes zoster.

Suboptimal prescribing in older inpatients and outpatients.

Investigators searched Medline and HealthSTAR databases from January 1, 1985 through June 30, 1999 to identify articles on suboptimal prescribing in those age 65 years and older. A manual search of the reference lists from identified articles and the authors' article files, book chapters, and recent reviews was conducted to identify additional articles. The definitions for various types of suboptimal prescribing (polypharmacy, inappropriate, and underutilization) are numerous, and measurement varies from study to study. The literature suggests that suboptimal prescribing is common in older outpatients and inpatients. Moreover, there is significant morbidity and mortality associated with suboptimal prescribing for these older patients. Evidence from well-controlled studies suggests that multidisciplinary teams and clinical pharmacy interventions can modify suboptimal drug use in older people. Future research is necessary to measure and test other methods for tackling this major public health problem facing older people.

Adverse drug events in high risk older outpatients.

OBJECTIVE: To describe the prevalence, types, and consequences of adverse drug events (ADEs) in older outpatients with polypharmacy. DESIGN: A cohort study. SETTING: General Medicine Clinic at the Durham Veterans Affairs Medical Center. PATIENTS: A total of 167 high risk (taking > or = 5 scheduled medications) ambulatory older veterans who participated in a year long health service intervention trial. MEASUREMENTS: Potential ADEs were identified by asking patients during closeout interviews whether, in the past year, they had experienced any side effects, unwanted reactions, or other problems from any medication. All reported medications and corresponding adverse experiences were assessed for plausibility by a research clinical pharmacist using two standard pharmacological textbooks and categorized by predictability, therapeutic class, and organ system. RESULTS: Eighty self-reported ADEs involving 72 medications taken by 58 (35%) of 167 patients were textbook confirmed. Seventy-six of 80 (95%) ADEs were classified as Type A (predictable) reactions. Cardiovascular (33.3%) and central nervous system (27.8%) medication classes were most commonly implicated. Gastrointestinal (30%) and central nervous system (28.8%) ADE symptoms were common. Sixty-three percent of patients with ADEs required physician contacts, 10% emergency room visits, and 11% hospitalization. Twenty percent of medications implicated with ADEs required dosage adjustments, and 48% of ADE-related medications were discontinued. No significant differences (P > .05) were observed when ADE reporters (n = 58) and nonreporters (n = 109) were compared. CONCLUSION: Predictable ADEs are common in high risk older outpatients, resulting in considerable medication modification and substantial healthcare utilization.

Inappropriate drug use among community-dwelling elderly.

This study examined inappropriate drug use defined by updated criteria among respondents in the second and third in-person waves of the Duke Established Populations for Epidemiologic Studies of the Elderly. Information about sociodemographics, health status, access to health care, and drug use was determined by in-home interviews. Drug use was coded for therapeutic class and appropriateness by applying explicit criteria. Among participants, 27% of the second and 22.5% of the third in-person wave took one or more inappropriate agents. Of these drugs, the most common therapeutic classes were central nervous system and cardiovascular. Longitudinal multivariate analyses found that persons taking several prescription drugs, those having continuity of care, those who previously took inappropriate drugs, and those with many health visits were most likely (p<0.05) to use inappropriate drugs. We conclude that inappropriate drug use is common among community-dwelling elderly.

The cost-effectiveness of a clinical pharmacist intervention among elderly outpatients.

We estimated the cost and cost-effectiveness of a clinical pharmacist intervention known to improve the appropriateness of drug prescribing. Elderly veteran outpatients prescribed at least five drugs were randomized to an intervention (105 patients) or control (103) group and followed for 1 year. The intervention pharmacist provided advice to patients and their physicians during all general medicine visits. Mean fixed and variable costs/intervention patient were $36 and $84, respectively Health services use and costs were comparable between groups. Intervention costs ranged from $7.50-30/patient/unit change in drug appropriateness. The cost to improve the appropriateness of drug prescribing is thus relatively low.