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Biomedical subjects

K Schmader

Publications and source records attributed to K Schmader.

At least 19 recordsLinked to original sources

Herpes zoster in older adults.

Herpes zoster (HZ) strikes millions of older adults annually worldwide and disables a substantial number of them via postherpetic neuralgia (PHN). Key age-related clinical, epidemiological, and treatment features of zoster and PHN are reviewed. HZ is caused by renewed replication and spread of varicella-zoster virus (VZV) in sensory ganglia and afferent peripheral nerves in the setting of age-related, disease-related, and drug-related decline in cellular immunity to VZV. VZV-induced neuronal destruction and inflammation causes the principal problems of pain, interference with activities of daily living, and reduced quality of life in elderly patients. Recently, attempts to reduce or eliminate HZ pain have been bolstered by the findings of clinical trials that antiviral agents and corticosteroids are effective treatment for HZ and that tricyclic antidepressants, topical lidocaine, gabapentin, and opiates are effective treatment for PHN. Although these advances have helped, PHN remains a difficult condition to prevent and treat in many elderly patients.

Adult↗

Reducing medication regimen complexity: a controlled trial.

OBJECTIVE: To determine if a visual intervention (medication grid) delivered to physicians can reduce medication regimen complexity. DESIGN: Nonrandomized, controlled trial. SETTING: Veterans Affairs medical center. PATIENTS/PARTICIPANTS: Eight hundred thirty-six patients taking at least 5 medications at the time of admission and the 48 teams of physicians and students on the general medicine inpatient service. INTERVENTION: For intervention patients, a medication grid was created that displayed all of the patients' medicines and the times of administration for 1 week. This grid was delivered to the admitting resident soon after admission. MEASUREMENTS AND MAIN RESULTS: For the patients of each team of physicians, we calculated the change in the average number of medications and doses from admission to discharge. The number of medications in the intervention group decreased by 0.92 per patient, and increased by 1.65 in the control group (P <.001). The mean number of doses per day in the intervention group decreased by 2.47 per patient and increased by 3.83 in the control group (P <.001). CONCLUSIONS: This simple intervention had a significant impact on medication regimen complexity in this population. Apparently, physicians were able to address polypharmacy when the issue was brought to their attention.

Adult↗

Enhanced green fluorescent protein as a marker for localizing murine cytomegalovirus in acute and latent infection.

A recombinant murine cytomegalovirus (mCMV) that expresses enhanced green fluorescent protein (EGFP) under control of the native immediate-early 1/3 promoter was constructed to detect directly sites of viral activity in latent and reactivated infections. The recombinant virus had acute and latent infection characteristics similar to those of wild-type mCMV. Rare green-fluorescing foci were observed in paraffin sections from lungs and spleens infected latently. Positive immunoperoxidase staining for EGFP in sections of the same lung tissues suggests that these cells may be sites of restricted viral gene expression. EGFP was detected easily in tissue explants reactivating from latent infection in vitro. Morphology and adhesion characteristics of fluorescing cells suggest that viral reactivation occurs in tissue macrophages in explant cultures. The observations presented in this study demonstrate the usefulness of EGFP-expressing recombinants as tools for direct tracking of mCMV activity in vivo and in vitro.

Acute Disease↗

Staphylococcus aureus bacteremia among elderly vs younger adult patients: comparison of clinical features and mortality.

BACKGROUND: Previous studies give conflicting results regarding the effect of age on outcomes in Staphylococcus aureus bacteremia (SAB). These studies have been limited by retrospective design or small sample size. METHODS: We conducted a prospective cohort study of 385 patients with SAB aged 18 to 90 years. The setting was a large academic medical center. We observed patients from diagnosis of SAB to discharge or death. Discharged patients were contacted 12 weeks after their first positive culture findings. Data were collected on demographics, comorbid conditions, focus of infection, length of stay, and outcome. Primary outcomes were total mortality and death due to SAB. RESULTS: Comparisons were made between 145 patients, aged 66 to 90 years, and 240 patients, aged 18 to 60 years. Forty-three (29.7%) of the elderly patients and 36 (15%) of the younger patients died. Death directly attributable to SAB occurred in 21 (14.5%) older and 15 (6.3%) younger patients. After adjusting for confounding variables, older patients continued to have higher total mortality (odds ratio, 2.21; 95% confidence interval, 1.32-3.70), and higher mortality from SAB (odds ratio, 2.30; 95% confidence interval, 1.13-4.69). Infection with methicillin-resistant S aureus was associated with higher total mortality in the elderly (odds ratio, 2.59; 95% confidence interval, 1.23-5.43). CONCLUSIONS: Staphylococcus aureus bacteremia among the elderly is associated with high mortality. Both total mortality and mortality directly attributable to SAB are more than twice as likely in older patients. Infection with methicillin-resistant S aureus carries a worse prognosis than infection with methicillin-sensitive S aureus in the elderly.

Adult↗

Herpes zoster in the elderly: issues related to geriatrics.

This article reviews specific clinical and research issues of herpes zoster related to geriatric medicine. Salient epidemiological and clinical issues include the increasing probability of zoster and postherpetic neuralgia with aging, age-related decline in immunity to varicella-zoster virus, the functional and psychosocial impact of zoster on the quality of life of the elderly, illness behavior in elderly patients with zoster, and varicella-zoster virus transmission and control in the nursing home. The role of antiviral therapy, corticosteroids, and analgesics; the measurement and analysis of pain, health-related quality of life, and functional status; and development of the varicella vaccine in the management of zoster in the elderly are also emphasized. Fertile research opportunities exist within these areas for investigators interested in infectious diseases, geriatrics, and other zoster-related disciplines.

Aged↗

Postherpetic neuralgia in immunocompetent elderly people.

The most menacing complication of herpes zoster in immunocompetent elderly people is chronic pain or postherpetic neuralgia (PHN). The cardinal epidemiological feature of PHN is its striking relationship to aging. Among zoster patients over 60 years old, estimates of the occurrence of PHN, defined as pain 1 month after rash onset, vary from 27 to 68%. The pathogenesis of PHN is incompletely understood but seems to involve varicella-zoster virus (VZV)-induced damage of peripheral afferent neurons and resultant changes in central afferent neurons and efferent pain-modulating neurons. PHN improves over time in many elderly patients, but an unfortunate subset experience of debilitating pain lasts for years. They experience constant and/or intermittent spontaneous pain and stimulus-evoked pain such as allodynia or hyperpathia. The outcomes of this pain include fatigue, sleep disturbance, anorexia, depression, social withdrawal, impaired activities of daily living and profound lowering of quality of life. The management of PHN is hampered by two problems: (1) a uniformly effective treatment for PHN is not available (although tricyclic antidepressants, local or regional anaesthetics, capsaicin, opiates, anticonvulsants and physical therapies are sometimes useful); and (2) early antiviral therapy of zoster may be ineffective in preventing PHN, partly related to the fact that days of VZV replication and neuronal destruction have occurred by the time the patient reaches the doctor. A potential solution to the problem of PHN is the vaccination of elderly persons with the varicella vaccine to prevent or attenuate zoster or PHN.

Aged↗

Racial and psychosocial risk factors for herpes zoster in the elderly.

The effects of black race and psychologic stress on the risk of acquiring herpes zoster in late life were examined. Subjects were participants of a stratified probability sample of community-dwelling persons > or = 65 years old. A comprehensive health survey was administered in 1986-1987 (P1), 1989-1990 (P2), and 1992-1994 (P3). Incident cases of zoster between P1 and P2 and P2 and P3 served as the dependent variables. Hypothesis-testing variables included race, negative life events, and measures of social support. Control variables included age, sex, education, cancer, other chronic diseases, hospitalization, activities of daily living, self-rated health, depression, and cigarette smoking. From P1 to P2, 1.4% of black and 3.4% of white subjects developed zoster (P < .001). From P2 to P3, 2.9% of black and 7.5% of white subjects developed zoster (P < .001). After controlling for variables, black subjects were significantly less likely to develop zoster than were white subjects (adjusted odds ratio, 0.37; 95% confidence interval, 0.26, 0.53; P = .0001). Most measures of stress were not significantly related to zoster; however, study limitations preclude definitive conclusions.

Black or African American↗

Race and stress in the incidence of herpes zoster in older adults.

OBJECTIVES: To examine the effect of black race and acute (negative life events) and chronic (lack of social support) psychological stress on the risk of herpes zoster in late life. DESIGN: A population-based, prospective cohort study. SETTING: Central North Carolina. PARTICIPANTS: Duke Established Populations for Epidemiological Studies of the Elderly, a stratified probability sample of community-dwelling persons more than 65 years of age. MEASUREMENTS: Interviewers administered a comprehensive health survey to the participants in 1986-1987 (P1, n = 4162), 1989-1990 (P2, n = 3336), and 1992-1994 (P3, n = 2568). Incident cases of zoster between P1 and P2 and P2 and P3 served as the dependent variable. Hypothesis-testing variables included race, negative life events, and five measures of social support. Control variables included age, sex, education, cancer, chronic diseases, basic ADLs, instrumental ADLs, depression, self-rated health, hospitalization, and cigarette smoking. Statistical analyses employed chi-square tests and proportional hazards model. RESULTS: At baseline, the sample had a mean age of 73.6 years and was 55% black, 45% white, and 65% female. There were 65 cases of zoster between P1 and P2 and 102 cases of zoster between P2 and P3. From P1 to P2, 1.4% of blacks and 3.4% of whites developed zoster (P < .001). From P2 to P3, 2.9% of blacks and 7.5% of whites developed zoster (P < .001). After controlling for the above variables, blacks were significantly less likely to develop zoster (adjusted risk ratio = 0.35; 95% confidence interval (CI), 0.24-0.51; P < .001). Negative life events increased the risk of zoster, but the result was borderline for statistical significance (adjusted RR = 1.38, 95% CI 0.96-1.97; P = .078). No measures of social support were significantly associated with zoster. CONCLUSION: Black race decreased the risk of zoster in late life significantly. Measures of stress were not significantly related to zoster, but study limitations preclude definitive conclusions. Future research should focus on these factors in larger samples and different populations.

Black or African American↗

The association of weight change in Alzheimer's disease with severity of disease and mortality: a longitudinal analysis.

OBJECTIVE: To describe weight loss in relation to the severity of Alzheimer's disease (AD), to identify confounders that might account for weight loss, and to investigate the association of weight change with mortality. METHODS: This study included 666 subjects with AD from the Consortium to Establish a Registry for Alzheimer's Disease, a longitudinal study of subjects with AD studied for < or = 6 years. Body weight was measured on entry and at annual follow-up examinations as part of standardized clinical assessments. Hierarchical linear models were used to estimate weight change per change in stage of AD, as measured by the Clinical Dementia Rating scale, and to assess the impact of possible confounders on the tendency for weight loss. Linear correlation of the trajectories of weight and CDR over time were used to determine the association between weight change and stage change. The association between weight change and mortality was modeled using the Cox proportional hazards model. RESULTS: Each change in stage of AD was associated with an estimated average weight loss of nearly 2 lb (P = .0001). The correlation between change in stage of AD and weight change was statistically significant (r = -0.09, P = .005), which indicates a greater tendency toward weight loss with progression of AD. Weight loss of > or = 5% in any year before death was a significant predictor of mortality. When weight loss in the year before death or censoring was analyzed as a continuous variable, it was a significant predictor of mortality. Additionally, the relative risk of death increased as weight loss increased. In contrast, weight gain decreased the risk of mortality. CONCLUSION: The risk of weight loss tends to increase with severity and progression of AD. Weight loss is a predictor of mortality among subjects with AD, whereas weight gain appears to have a protective effect.

Aged↗

Attitudes of elderly patients and their families toward physician-assisted suicide.

OBJECTIVES: To examine and compare attitudes of elderly outpatients and their families toward physician-assisted suicide (PAS), explore sociodemographic and health correlates of these attitudes, assess family members' ability to predict patients' attitudes toward PAS, and determine family members' ability to agree on these predictions. SUBJECTS AND METHODS: Elderly patients with medical and psychiatric problems (n = 168; mean age, 75.8 years) who were attending a geriatrics specialty clinic, along with accompanying family members (n = 146), were systematically surveyed on their attitudes toward PAS in case of terminal illness, chronic illness, and mental incompetence. Relatives were also asked to predict patients' responses to items on the questionnaire. Patients and relatives were blinded to each others' responses. RESULTS: Favorable attitudes toward PAS were reported by 39.9% of the patients and 59.3% of the relatives (P < .001) in case of terminal illness, 18.2% and 25.3%, respectively, in case of chronic illness, 13.5% and 15.4%, respectively, in case of mental incompetence, and 34.0% and 55.6% (P < .001), respectively, for legalization of PAS. Family members showed a marginal ability to predict patients' attitudes toward PAS with kappa values of agreement that ranged from 0.09 to 0.41. Family members also had difficulty agreeing with each other on how they thought patients would respond (range of kappa values, 0.18-0.47). Patients who opposed PAS were women, black individuals, and those with less education, low incomes, and dementia or cognitive impairment. CONCLUSIONS: While many frail elderly patients favored PAS in cases of terminal illness, the proportion that opposed it was significantly higher than that among relatives; relatives, in turn, displayed only a marginal ability either to predict patients' attitudes or to agree among themselves. Patients who oppose PAS represent a particularly vulnerable element of society (elderly persons, women, black individuals, and poor, uneducated, and demented persons), and such patients may warrant special protection.

Aged↗

Weight change in Alzheimer's disease.

PURPOSE: To determine the natural history of weight change and the occurrence of clinically significant weight loss in subjects with Alzheimer's disease (AD). PATIENTS AND METHODS: Subjects with AD and cognitively normal older controls were recruited from 21 U.S. university medical centers that were participating in the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Annual assessments were performed. Subjects with AD (n = 362) and controls (n = 317) with two or more weight measurements taken a year or more apart were included in this analysis. The average period of follow-up was > 2 years for both subjects with AD and controls. Four variables describing different aspects of weight change were defined: >/= 5% weigh loss, percent weight change/year, maximum percent weight loss over 1 year, and standard deviation of measurements/subject. RESULTS: Nearly twice as many subjects with AD experienced a weight loss of 5% or more when compared with controls (men P = .003 women P = .001). Surprisingly, a weight gain of 5% or more was also more common among AD cases. Overall, there was a tendency toward weight loss for both subjects with AD and controls, as measured by percent weight change/year. When other possible causes of weight loss were controlled using a multivariate model, a diagnosis of AD remained a significant predictor of >/= 5% weigh loss (P << .001), maximum percent weight loss over 1 year (P << .001), and standard deviation of measurements/subject (P << .001). A trend toward significance was noted for percent weight change/year (P = .07). Other than AD, very few of the possible confounders of this association remained significant predictors of weight change. In bivariate analysis, the severity of AD at entry correlated with percent weight change/year and standard deviation of measurements/subject. Additionally, the functional status of subjects with AD correlated with all four measures of weight change. CONCLUSION: Clinically important weight loss occurs more frequently among patients with AD than among cognitively normal control subjects. Instances of weight gain, periods of acute weight loss, and greater fluctuations in weight suggest that the natural history of weight change in AD may be characterized by dysfunction in body weight regulation. Further analysis is warranted regarding the relationship of severity of dementia, functional status, and other specific aspects of AD to weight change.

Activities of Daily Living↗

Racial differences in the occurrence of herpes zoster.

The purpose of this study was to determine if there are racial differences in the occurrence of herpes zoster (shingles). The study population was the Duke Established Populations for Epidemiologic Studies of the Elderly, a probability sample of community-dwelling persons > 64 years old in North Carolina. Interviewers administered a comprehensive health survey to the participants that included questions about lifetime occurrence of shingles. Of the 3206 subjects, 316 (9.9%) had had zoster: 81 (4.5%) of 1754 blacks and 235 (16.1%) of 1452 whites had had shingles (P < .0001). After controlling for age, cancer, and demographic factors, blacks remained one-fourth as likely as whites (adjusted odds ratio 0.25, 95% confidence interval 0.18-0.35; P = .0001) to have experienced zoster. In summary, blacks had a significantly lower risk of developing herpes zoster than whites, a new finding in herpes zoster epidemiology.

Age Factors↗

Mouse cytomegalovirus reactivation in severe combined immune deficient mice after implantation of latently infected salivary gland.

The hypothesis that replication-competent mouse cytomegalovirus (MCMV) is detectable in severe combined immunodeficient (scid) mice after implantation of latently infected tissue was examined. Sections of latently infected salivary gland from 5 BALB/c mice were implanted into 20 C.B-17 scid mice. Recipient scid mice were sacrificed weekly for 5 weeks, and MCMV infection was detected in target organs using culture and DNA polymerase chain reaction (PCR). All donors were negative by standard culture but positive by DNA PCR. Replicating MCMV was recovered from 9 of 15 recipient scid mouse salivary gland, lung, liver, or spleen samples at postoperative weeks 2-5. No virus was recovered from recipient scid mice at weeks 1 or 12. Transplantation of latently infected tissues into scid mice resulted in rapid reactivation and dissemination of the virus. Further study of this model promises insight into the mechanisms of CMV latency and reactivation.

Animals↗

The accuracy of self-report of herpes zoster.

The accuracy of self-report of herpes zoster was investigated in the Duke Established Populations for Epidemiological Studies of the Elderly, a longitudinal study of 4162 community-dwelling elderly persons residing in North Carolina, 1986-1993. The authors compared self-reports of zoster with physician diagnosis of zoster and with a zoster verification questionnaire (ZVQ). Compared to physician diagnosis, 3.2% (95% confidence interval 0-61%) of self-reports of zoster (n = 31) were false-positive and no denials of zoster (n = 63) were false-negative. The agreement of self-reports to physician diagnosis was 98.9%, the sensitivity and negative predictive value were 100%, the specificity was 98.4% and the positive predictive value was 96.7%. The ZVQ comparisons were similarly high. These data suggest that the frequency of false-positive and false-negative reports of zoster is low in this elderly population. Zoster self-reports appear to be accurate and suitable for epidemiological investigations.

Aged↗

Appropriateness of medication prescribing in ambulatory elderly patients.

OBJECTIVE: To assess the quality of medication prescribing in ambulatory elderly patients on multiple medications using the Medication Appropriateness Index (MAI). DESIGN: Cross-sectional study. SETTING: General Medical Clinic of the Durham VA Medical Center. PATIENTS: 208 elderly outpatients on five or more regularly scheduled medications. MEASUREMENTS: Medication prescribing appropriateness was measured with the MAI, a reliable method that employs 10 implicit criteria. A weighted MAI score (range 0-18 per drug) served as a summary measure of appropriateness. RESULTS: There were 1644 medications evaluated; 26% received no inappropriate ratings, 37% had one, 19% had two, and 18% had three or more. Of 16,440 ratings, 2295 (14%) were evaluated as inappropriate. The percentage of inappropriate ratings varied across prescribing dimensions: drug-drug interactions, 0%; drug-disease interactions, 1.4%; medication effectiveness, 4.7%; therapeutic duplication, 5.7%; indication, 11.5%; duration of treatment, 16.5%; dosage, 17.3%; practical directions, 20.3%; cost, 29.7%; and correct directions, 32.4%. The mean MAI score for all medications was 2.2 +/- 2.1 (range 0-10) and varied by therapeutic class. MAI scores were significantly lower for medications with a high potential for adverse effects compared with those with a low potential (MAI score of 1.8 vs 2.9, P < 0.001). Regression analysis revealed that no patient characteristics were associated with a higher likelihood of inappropriate prescribing. CONCLUSIONS: Medication prescribing for elderly outpatients taking multiple medications was substantially appropriate. Prescribing dimensions with the most room for improvement were more exact directions, less expensive drugs, and practical directions. Drugs at high risk for adverse effects were prescribed more appropriately than those at low risk.

Age Factors↗

Assessing health-related quality of life in elderly outpatients: telephone versus face-to-face administration.

OBJECTIVE: While health-related quality of life (HRQOL) is increasingly being used as an outcome in clinical trials, it is unknown whether HRQOL assessments are influenced by the method of administration. Within the context of a randomized, controlled trial evaluating a pharmacist intervention for elderly outpatients prescribed at least five medications, we compared telephone and face-to-face administration of the SF-36, a widely used HRQOL measure. DESIGN: Survey. SETTING: General Medicine Clinic, Veterans Affairs Medical Center. PATIENTS: At entry, participants in the randomized trial received continuous care from a general medicine clinic physician, were > or = 65 years of age, and were prescribed > or = 5 regularly scheduled medications. Patients were excluded if they were cognitively impaired and had no caregiver available to participate in the study as a proxy or if they resided in a nursing home. MEASUREMENTS: Subjects completed the SF-36 by telephone at closeout and face-to-face at clinic visits within 1 month (mean = 16.7 days). MAIN RESULTS: Telephone administration required significantly less time than face-to-face interviews (10.2 vs 14.0 minutes, P < 0.001). Although systematic differences between modes of administration were generally small, there were substantial nonsystematic discrepancies for all eight SF-36 scales (mean absolute difference scores ranged from 10.8 to 30.1). Discrepancies were greatest for emotional role functioning, physical role functioning, social functioning, and bodily pain; these four scales also demonstrated low to moderate correlations (.33 to .58). CONCLUSIONS: The two modes of administration may not produce interchangeable results. Researchers should be cautious when mixing modes of administration to elderly patients.

Activities of Daily Living↗

Apolipoprotein E epsilon 4 allele distributions in late-onset Alzheimer's disease and in other amyloid-forming diseases.

The frequency of the allele for apolipoprotein E type 4 (epsilon 4) is increased in late-onset familial and sporadic Alzheimer's disease (AD). We have examined epsilon 4 frequencies in four distinct, normal, elderly control groups and, most importantly, in patients with amyloid-forming diseases whose epsilon 4 distributions were not previously known (Creutzfeldt-Jakob disease, familial amyloidotic polyneuropathy, Down's syndrome). There were no differences between any of these controls and published control series, cementing the relevance of epsilon 4 for late-onset AD. The increase in late-onset AD was confirmed in two new series.

Age Factors↗