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A study was conducted to test the hypothesis that vaccination against varicellazoster virus (VZV) would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. The result showed that the zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.

The Short-Term Persistence Substudy (STPS) of the Shingles Prevention Study (SPS) assessed persistence of zoster vaccine efficacy. Vaccine efficacy was lower in the STPS than in SPS, but there was evidence of persistence of vaccine efficacy for at least 5 years.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. [ABSTRACT FROM AUTHOR]

Study Objective: To determine whether current therapies are useful in preventing postherpetic neuralgia (PHN) by analysis of study designs and pooled results.Design: Meta-analysis of all controlled studies investigating PHN prevention in the immunocompetent host. Articles were identified through MEDLINE, Index Medicus and bibliographic reviews of major texts and review articles. Studies meeting eligibility criteria were independently assessed using explicit methodologic criteria for validity and generalizability in clinical trials. Pooled analysis was also performed where appropriate.Measurements and Main Results: Twenty-one investigations met eligibility criteria and primarily addressed the use of antiviral agents and corticosteroids. Among studies with strong designs, no evidence of benefit was found for acyclovir or corticosteroids. Pooled results showed no significant effect of acyclovir on the prevention of PHN (odds ratio 0.81, 95% confidence interval 0.56, 1.11). The strongest studies that found potential efficacy in PHN prevention involved adenosine monophosphate and idoxuridine in dimethyl sulfoxide, but problems with clinical application limit the use of these compounds. Outcome definition, compliance assessment, power estimation, and method of randomization were infrequently addressed aspects of design.Conclusion: Currently there is no proven useful therapy for the prevention of PHN. The benefits of acyclovir and corticosteroids are limited but key questions remain regarding these medications. A clear consensus definition of PHN is needed to improve future investigations. [ABSTRACT FROM AUTHOR]

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.

The authors investigated whether postmenopausal estrogen use helps to maintain cognitive function; a brief screen, the Short Portable Mental Status Questionnaire (SPMSQ), was used. Information was gathered from a stratified, random sample of 1,907 African-American and White women (aged 65-100 years) participating in the longitudinal Duke Established Populations for Epidemiologic Studies of the Elderly project carried out in five urban and rural counties of North Carolina. All women were cognitively unimpaired in 1986-1987 and were evaluated 3 and 6 years later. Decline in cognitive function was measured as an increase of two or more errors on the SPMSQ and crossing of an SPMSQ threshold indicative of cognitive impairment. Recency and continuity of estrogen use were measured. Univariate analyses indicated that recent (crude odds ratio = 0.42, 95% confidence interval: 0.21, 0.86) and continuous (crude odds ratio = 0.32, 95% confidence interval: 0.13, 0.81) estrogen use reduced the risk of cognitive decline but not of cognitive impairment. After adjustment for demographic and health characteristics, protective effects became nonsignificant. While postmenopausal use of estrogen may be protective for Alzheimer's disease, current findings based on a brief cognitive screen suggest that it is not protective for cognitive decline related to aging.

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.

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.

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.

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.

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.

Objective: To test the reliability of drug utilization evaluation (DUE) applied to medications commonly used by the ambulatory elderly., Methods: A DUE model was developed for four domains: (1) justification for use, (2) critical process indicators, (3) complications, and (4) clinical outcomes. DUE criteria specific to use in the elderly were developed for angiotensin-converting enzyme (ACE) inhibitors and histamine2 (H2)-antagonists, and consensus was reached by an external expert panel. After pilot testing, two clinical pharmacists independently evaluated these medications, applying the DUE criteria and rating each item as appropriate or inappropriate. Interrater and intrarater reliability was assessed by using kappa statistics., Results: In a sample of 208 ambulatory elderly veterans, 42 (20.2%) were taking an ACE inhibitor and 56 (26.9%) an H2-antagonist. The interrater agreement for individual domains, represented by kappa statistics, were 0.10-0.58 and 0-0.83 for ACE inhibitors and H2-antagonists, respectively. The kappa statistic for overall agreement, which considered ratings from all criteria across all domains, was 0.24 for ACE inhibitors and 0.18 for H2-antagonists. Intrarater reliability was assessed 3 months later, and kappa statistics were 0.61-0.65 (0.49 overall) and 0-0.96 (0.81 overall) for ACE inhibitors and H2-antagonists, respectively., Conclusions: Intrarater reliability for DUE was good to excellent. However, interrater reliability exhibited only marginal reproducibility, particularly where evaluators were required to use subjective judgement (i.e., complications, clinical outcomes). DUE may not be a suitable standard for assessing medication appropriateness in ambulatory elderly patients.

Objective: To determine the relationship of inappropriate prescribing in the elderly to health outcomes., Setting: General Medical Clinic of the Durham Veterans Affairs Medical Center., Patients: A total of 208 veterans more than 65 years old who were each taking five or more drugs and participated in a pharmacist intervention trial., Measurements: Prescribing appropriateness was assessed by a clinical pharmacist using the medication appropriateness index (MAI). A summed MAI score was calculated, with higher scores indicating less appropriate prescribing. The health outcomes were hospitalization, unscheduled ambulatory or emergency care visits, and blood pressure control., Results: Bivariate analyses revealed that mean MAI scores at baseline were higher for those with hospital admissions (18.9 vs. 16.9, p = 0.07) and unscheduled ambulatory or emergency care visits (18.8 vs. 16.3, p = 0.05) over the subsequent 12 months than for those without admissions and emergency care visits. MAI scores for antihypertensive medications were higher for patients with inadequate blood pressure control (> 160/90 mm Hg) than for those whose blood pressure was controlled (4.7 vs. 3.1, p = 0.02)., Conclusions: Inappropriate prescribing appeared to be associated with adverse health outcomes. This findings needs to be confirmed in future studies that have larger samples and control for potential confounders.

Objective: To evaluate the reliability of a medication appropriateness index (MAI) modified for elderly outpatients in a non-Veterans Affairs setting., Design: Reliability study., Setting: General community., Participants: Ten community-dwelling elderly (> 65 y) taking five or more regularly scheduled medications and participating in a university-based health service intervention study., Main Outcome Measures: Interrater reliability of MAI ratings of 65 medications made by two clinical pharmacists for individual items and for an overall summed score was calculated by use of kappa statistics and intraclass correlation coefficient., Results: The interrater agreement for each of the individual MAI items was high for both appropriate and inappropriate ratings and ranged from 80% to 100% (overall kappa = 0.64). Overall agreement for the summed score was good (intraclass correlation = 0.80)., Conclusions: The modified MAI is a reliable instrument for evaluation of medication appropriateness in a non-Veterans Affairs, ambulatory, elderly population and may provide pharmacists with a practical and standard method to evaluate patients' drug regimens and identify some potential drug-related problems.

To determine whether medication use differs by cognitive status among community dwelling elderly, a survey was made of a stratified random sample of 4110 black and white participants, aged 65 or older from the Duke Established Populations for Epidemiologic Studies of the Elderly in five adjacent urban and rural counties in the Piedmont area of North Carolina. Main outcome measures were usage of prescription medications, non-prescription medications, and medicines within therapeutic classes in the previous 2 weeks as determined during an in-home interview; and total number of prescription and non-prescription medicines used in the previous 2 weeks. Multivariate analyses, using weighted data adjusted for sampling design, were conducted to assess the association between drug use patterns and cognitive status, as assessed by the Short Portable Mental Status Questionnaire, while adjusting for demographic, health status, and access to health care factors. Participants with cognitive impairment (13.7% of sample) were less likely to use any prescription medications (Adjusted OR = 0.66, 95% CI = 0.48-0.90) or any non-prescription medications (Adjusted OR = 0. 71, 95% CI = 0.56-0.89) than cognitively intact subjects. Both groups took a similar number of prescription and non-prescription medications. Those who were cognitively impaired were less likely to take analgesics (Adjusted OR = 0.66, 95% CI = 0.52-0.83), but were more likely to take central nervous drugs (Adjusted OR = 1.55, 95% CI 1.18-2.04) than those who were cognitively intact. We conclude that drug use patterns by community-dwelling elderly people differ with cognitive status. Future research needs to examine medication use by specific causes of cognitive impairment.

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.

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.

An important target tissue for murine cytomegalovirus (CMV) infection is the submaxillary salivary gland. Submaxillary salivary gland biopsy specimens from BALB/c mice latently infected with murine CMV were examined for murine CMV DNA by in vitro enzymatic amplification using the polymerase chain reaction preceding oligonucleotide hybridization. The amplified sequence was a 152-base pair segment from within the immediate early gene of murine CMV. Biopsy and whole gland specimens from acutely infected BALB/c mice and latently infected, immunosuppressed BALB/c mice were compared for active murine CMV infection. After acute infection with murine CMV, virus was recovered in all cultures of both biopsy and whole salivary gland specimens but from none of the latently infected animals. Reactivated virus was detected by culture of both biopsy (90%) and whole salivary gland specimens (100%) from latently infected mice that received antithymocyte serum. Viral nucleic acid was detected in 90% of biopsy specimens from latently infected animals. Hence, active murine CMV infection can be detected in biopsy specimens from mice with acute and reactivated infection and murine CMV DNA can be amplified and detected in salivary gland biopsy specimens from latently infected animals. Biopsy of this or other target tissues can be useful for obtaining tissue for viral studies where the survival of the animal is important and it is useful to distinguish latent from acute or reactivated infection.

The ability of the Epstein-Barr virus (EBV) to cause latent lifelong infection in the host and its capabilities of transformation may have important implications for the elderly host. Reports in the literature and hospital records were reviewed to determine the activity of EBV in the elderly. Seroepidemiologic surveys demonstrated that 90%-97% of adults more than 60 years old were seropositive for EBV. Geometric mean antibody titers and the percentage of individuals with high antibody titers to EBV increased with age--changes that were not associated with clinical illness. Only 29 cases of infectious mononucleosis have been reported in adults more than 60 years old. The elderly with infectious mononucleosis had significantly fewer occurrences of pharyngitis, lymphadenopathy, and splenomegaly when compared with young adults. The cases of two patients with illnesses that did not meet full criteria for infectious mononucleosis but may still have represented clinical manifestations of EBV infection are presented. Other EBV-associated diseases reported in the elderly include nasopharyngeal carcinoma and possibly B cell lymphoproliferative disease but not a chronic mononucleosis-like syndrome.

Study Objective: To determine whether current therapies are useful in preventing postherpetic neuralgia (PHN) by analysis of study designs and pooled results., Design: Meta-analysis of all controlled studies investigating PHN prevention in the immunocompetent host. Articles were identified through MEDLINE, Index Medicus and bibliographic reviews of major texts and review articles. Studies meeting eligibility criteria were independently assessed using explicit methodologic criteria for validity and generalizability in clinical trials. Pooled analysis was also performed where appropriate., Measurements and Main Results: Twenty-one investigations met eligibility criteria and primarily addressed the use of antiviral agents and corticosteroids. Among studies with strong designs, no evidence of benefit was found for acyclovir or corticosteroids. Pooled results showed no significant effect of acyclovir on the prevention of PHN (odds ratio 0.81, 95% confidence interval 0.56, 1.11). The strongest studies that found potential efficacy in PHN prevention involved adenosine monophosphate and idoxuridine in dimethyl sulfoxide, but problems with clinical application limit the use of these compounds. Outcome definition, compliance assessment, power estimation, and method of randomization were infrequently addressed aspects of design., Conclusion: Currently there is no proven useful therapy for the prevention of PHN. The benefits of acyclovir and corticosteroids are limited but key questions remain regarding these medications. A clear consensus definition of PHN is needed to improve future investigations.