Cynthia R. Gross

Long-term consequences of kidney donation.

BACKGROUND The long-term renal consequences of kidney donation by a living donor are attracting increased appropriate interest. The overall evidence suggests that living kidney donors have survival similar to that of nondonors and that their risk of end-stage renal disease (ESRD) is not increased. Previous studies have included relatively small numbers of donors and a brief follow-up period. METHODS We ascertained the vital status and lifetime risk of ESRD in 3698 kidney donors who donated kidneys during the period from 1963 through 2007; from 2003 through 2007, we also measured the glomerular filtration rate (GFR) and urinary albumin excretion and assessed the prevalence of hypertension, general health status, and quality of life in 255 donors. RESULTS The survival of kidney donors was similar to that of controls who were matched for age, sex, and race or ethnic group. ESRD developed in 11 donors, a rate of 180 cases per million persons per year, as compared with a rate of 268 per million per year in the general population. At a mean (+/-SD) of 12.2+/-9.2 years after donation, 85.5% of the subgroup of 255 donors had a GFR of 60 ml per minute per 1.73 m(2) of body-surface area or higher, 32.1% had hypertension, and 12.7% had albuminuria. Older age and higher body-mass index, but not a longer time since donation, were associated with both a GFR that was lower than 60 ml per minute per 1.73 m(2) and hypertension. A longer time since donation, however, was independently associated with albuminuria. Most donors had quality-of-life scores that were better than population norms, and the prevalence of coexisting conditions was similar to that among controls from the National Health and Nutrition Examination Survey (NHANES) who were matched for age, sex, race or ethnic group, and body-mass index. CONCLUSIONS Survival and the risk of ESRD in carefully screened kidney donors appear to be similar to those in the general population. Most donors who were studied had a preserved GFR, normal albumin excretion, and an excellent quality of life.

The pilot Stroke Data Bank: definition, design, and data.

Four university centers collaborated to contribute 1158 patients with acute episodes of cerebrovascular disease to the pilot Stroke Data Bank, initiated by NINCDS in 1978. During the pilot project a standard set of data collection forms were developed and used at each of the collaborating centers. Data on clinical course, laboratory findings, therapy and outcome were gathered prospectivcly throughout the patients hospitalization and at specified follow-up intervals. Using operational definitions of stroke sub-types, consecutive cases were systematically allocated to specific categories of brain and vascular pathology. The definitions were based on clinical criteria as well as on laboratory data, including computer- ized tomography (CT), and angiography findings. This paper describes the pilot Stroke Data Bank and presents the distribution of cases by diagnostic and demographic categories. It represents one of the largest series of prospectively collected stroke cases studied by CT (90% of the cases) and angiography (42%). Based upon the methods and processes of this pilot study, a main phase of the Stroke Data Bank has been established to address a number of questions pertaining to stroke classification, evolution, diagnosis, and prognosis. Stroke Vol 15, No 4, 1984

Screening for depression in stroke patients: the reliability and validity of the Center for Epidemiologic Studies Depression Scale.

This study examined the inter-observer reliability and validity of the Center for Epidemiologic Studies Depression Scale (CES-D) as a measure of depressive symptomatology in stroke patients, and its utility as a screening tool for depression in this population. The CES-D Scale is a brief questionnaire originally designed for use in community surveys. Twenty-seven non-aphasic patients enrolled in the Stroke Data Bank at the University of Maryland were interviewed by a research nurse using the CES-D. On the same day, each patient was independently evaluated by a research assistant using a psychiatric battery for depression and measures of cognitive, physical, and social functioning. Forty-one percent (11/27) of the patients were depressed according to clinical criteria for major or minor depression. With a cutpoint corresponding to the upper (most severe) 20% in community surveys, the CES-D Scale picked up 73% (8/11) of the depressed patients. In this sample no nondepressed patient scored over 16 on the CES-D (no false positives). The CES-D Scale scores correlated significantly with the other depression measures (r = .57 to r = .82, p less than .002) and did not correlate with the measures of cognitive, physical, or social functioning. Based on 24 patients who received a CES-D Scale score from both the nurse and the research assistant, inter-rater reliability was high (r = .76, p less than .001). Thus, the CES-D was found to be reliable and valid as a screening tool for assessing depression in stroke patients.

Use of inappropriate prescription drugs by older people

OBJECTIVES To determine the prevalence and predictors of inappropriate drug prescribing defined by expert national consensus panel drug utilization review criteria for community-dwelling older people. DESIGN Survey. SETTING Five adjacent urban and rural counties in the Piedmont area of North Carolina. PARTICIPANTS A stratified random sample of participants from the fourth (n = 3,234) and seventh (n = 2,508) waves of the Duke Established Populations for Epidemiological Studies of the Elderly. MEASUREMENTS The prescribing appropriateness for digoxin, calcium channel blockers, angiotensin-converting enzyme inhibitors, histamine(2) receptor antagonists, nonsteroidal antiinflammatory drugs (NSAIDs), benzodiazepines, antipsychotics, and antidepressants as determined by explicit criteria (through Health Care Financing Administration expert consensus panel drug utilization review criteria for dosage, duplication, drug-drug interactions and duration, and U.S. and Canadian expert consensus panel criteria for drug-disease interactions). Multivariable analyses, using weighted data adjusted for sampling design, were conducted to assess the association between inappropriate prescribing and demographic, health-status, and access-to-healthcare factors cross-sectionally and longitudinally. RESULTS We found that 21.0 of the fourth wave and 19.2 of the seventh wave participants who used one or more agents from the eight drug classes had one or more elements identified as inappropriate. The therapeutic classes with the most problems were benzodiazepines and NSAIDs. The most common problems were with drug-disease interactions and duration of use. Longitudinal multivariable analyses found that participants who were white (adjusted odds ratio (AOR) = 1.67, 95 confidence interval (CI) = 1.28-2.17), were married (AOR = 1.40, 95% CI = 1.01-1.93), had arthritis (AOR = 1.74, 95% CI = 1.27-2.38), had one or more physical function disabilities (AOR = 1.42, 95% CI = 1.02-1.96), and had inappropriate drugs prescribed at wave 4 (AOR = 6.87, 95% CI = 5.11-9.22) were more likely to have inappropriate prescribing at wave 7. CONCLUSION These results indicate that inappropriate prescribing is common among community-dwelling older people and persists over time. Longitudinal studies in older people are needed to examine the impact of inappropriate drug prescribing on health-related outcomes.

Clinical indicators of dehydration severity in elderly patients

STUDY OBJECTIVE To determine which of the signs and symptoms of dehydration obtainable from patient history and physical examination in the emergency department are most useful in assessing the severity of dehydration in elderly patients. DESIGN Prospective, correlational study. SETTING Two university teaching hospitals. PATIENTS Fifty-five patients aged 60 or older presenting to the emergency department with suspected dehydration were studied. MEASUREMENTS AND MAIN RESULTS In the emergency department, patients were evaluated by a standardized history and physical examination that included assessment of 38 signs and symptoms commonly attributed to dehydration. The relationships between the presence and intensity of these putative dehydration indicators and an independent rating of dehydration severity based on a comprehensive review of the medical record were evaluated. Also evaluated were the relationships between these dehydration indicators and patient age. Indicators that correlated best with dehydration severity but were unrelated to patient age included: tongue dryness (P less than 0.001), longitudinal tongue furrows (P less than 0.001), dryness of the mucous membranes of the mouth (P less than 0.001), upper body muscle weakness (P less than 0.001), confusion (P less than 0.001), speech difficulty (P less than 0.01), and sunkenness of eyes (P less than 0.01). Other indicators had only weak associations with dehydration severity or were also related to age. Patient thirst was unrelated to dehydration severity. CONCLUSIONS A set of signs and symptoms related to dehydration severity in elderly patients has been identified. These indicators may be more useful for evaluation of dehydration severity in the emergency department than other commonly used indicators.

Impact of inappropriate drug use on mortality and functional status in representative community dwelling elders

Background. The predictive validity of Drug Utilization Review (DUR) and drugs‐to‐avoid criteria in elders is unknown. Objectives. To evaluate the relationship between use of inappropriate drugs as determined by these explicit criteria and mortality and decline in functional status in community dwelling elders. Research Design. Cohort study. Subjects. The fourth wave (3234 participants) of the Duke Established Populations for Epidemiologic Studies of the Elderly. Measures. Two sets of inappropriate drug‐use criteria: (1) DUR with respect to dosage, duplication, drug‐drug interactions, duration, and drug‐disease interactions; and (2) Beers‐modified criteria regarding drugs‐to‐avoid were applied to drug use reported in an in‐home interview. Death was identified from the National Death Index; change in four functional status measures (basic self‐care, intermediate self‐care, complex self‐management, physical function) was determined during the following 3 years. Results. Use of inappropriate drugs identified by either set of criteria was not significantly associated with mortality. The drugs‐to‐avoid criteria identified no significant associations between use of these drugs and decline in functional status. With DUR criteria, however, the association between use of inappropriate drugs and basic self‐care was significant and pronounced among those with drug‐drug or drug‐disease interaction problems (Adj. OR 2.04; 95% CI 1.32‐3.16). Conclusions. Identifying the impact of inappropriate drug use may depend on the criteria applied. Further studies are needed that measure additional outcomes and use alternate measures of inappropriate drug use.

Intensive care unit drug use and subsequent quality of life in acute lung injury patients

ObjectiveTo examine the relationship between the use of sedative and neuromuscular blocking agents during a patient’s intensive care unit (ICU) stay and subsequent measures of health-related quality of life. DesignCross-sectional mail survey and retrospective medical record abstraction of a prospectively identified cohort of lung injury patients. SettingICUs in three teaching hospitals in a major metropolitan area. PatientsPatients with acute lung injury (n = 24). InterventionsNone—observational study. Measurements and Main ResultsPatients’ charts were reviewed for those patients returning postdischarge quality-of-life questionnaires. Duration, daily dose, and route of administration for sedatives and neuromuscular blocking agents were abstracted from ICU flow sheets. Relationships among ICU variables (days of sedation, days of neuromuscular blockade, and severity of illness as measured by Acute Physiology and Chronic Health Evaluation III score) and outcomes (symptoms of depression and symptoms of posttraumatic stress disorder) were assessed. Depressive symptoms at follow-up were correlated with days of sedation (p = .007), but not with days of neuromuscular blockade or initial severity of illness. The composite posttraumatic stress disorder symptom impact score was correlated with days of sedation (p = .006) and days of neuromuscular blockade (p = .035), but not with initial severity of illness. There were no significant differences between the frequency of patients reporting a specific posttraumatic stress disorder symptom in the high sedation group and the low sedation group, and there were no significant differences in specific posttraumatic stress disorder symptoms between the group that had received neuromuscular blockade and those who had not. ConclusionsThe use of sedatives and neuromuscular blocking agents in the ICU is positively associated with subsequent measures of depression and posttraumatic stress disorder symptoms 6–41 months after ICU treatment for acute lung injury.

Concentration-controlled compared with conventional antiretroviral therapy for Hiv infection

Objectives To demonstrate the feasibility of a concentration-controlled approach to combination antiretroviral therapy, and to compare the virological responses and safety of this strategy versus conventional fixed-dose therapy. Design A prospective, randomized, 52 week, open-label trial of concentration-controlled compared with conventional dose zidovudine, lamivudine, and indinavir therapy conduced in a university-based general clinical research center in the United States. Patients Forty antiretroviral-naive individuals with plasma HIV-RNA levels > 5000 copies/ml. Interventions Zidovudine, lamivudine, and indinavir plasma concentrations were measured in all participants. Doses were adjusted in those assigned to concentration-controlled therapy to achieve levels equal to or greater than target values. Main outcome measures The proportion of patients who achieved the desired drug concentrations, the proportion of patients with HIV-RNA levels < 50 copies/ml at week 52, and safety and tolerance in the concentration-controlled versus conventional therapy arms. Results Significantly more concentration-controlled recipients achieved the desired concentration targets for all three drugs: 15 of 16 concentration-controlled recipients compared with nine of 17 conventional recipients (P = 0.017) had HIV-RNA levels < 50 copies/ml at week 52. No difference was observed in the occurrence of drug-related clinical events or laboratory abnormalities between the two treatment arms. Conclusion Concentration-controlled therapy implemented simultaneously for three antiretroviral agents was feasible, as well tolerated as conventional therapy, and resulted in a greater proportion of recipients with HIV-RNA levels < 50 copies/ml after 52 weeks. These findings provide a scientific basis to challenge the accepted practice of administering the same dose of antiretroviral agents to all adults, ignoring the concentrations actually achieved.

Mindfulness-Based Stress Reduction Versus Pharmacotherapy for Chronic Primary Insomnia: A Randomized Controlled Clinical Trial

OBJECTIVE The aim of this study was to investigate the potential of mindfulness-based stress reduction (MBSR) as a treatment for chronic primary insomnia. DESIGN A randomized controlled trial was conducted. SETTING The study was conducted at a university health center. PATIENTS Thirty adults with primary chronic insomnia based on criteria of the Diagnostic and Statistical Manual of Mental Disorders, Text Revision, 4th Edition were randomized 2:1 to MBSR or pharmacotherapy (PCT). INTERVENTIONS Mindfulness-based stress reduction, a program of mindfulness meditation training consisting of eight weekly 2.5 hour classes and a daylong retreat, was provided, with ongoing home meditation practice expectations during three-month follow-up; PCT, consisting of three milligrams of eszopiclone (LUNESTA) nightly for eight weeks, followed by three months of use as needed. A 10-minute sleep hygiene presentation was included in both interventions. MAIN OUTCOMES The Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), sleep diaries, and wrist actigraphy were collected pretreatment, posttreatment (eight weeks), and at five months (self-reports only). RESULTS Between baseline and eight weeks, sleep onset latency (SOL) measured by actigraphy decreased 8.9 minutes in the MBSR arm (P < .05). Large, significant improvements were found on the ISI, PSQI, and diary-measured total sleep time, SOL, and sleep efficiency (P < .01, all) from baseline to five-month follow-up in the MBSR arm. Changes of comparable magnitude were found in the PCT arm. Twenty-seven of 30 patients completed their assigned treatment. This study provides initial evidence for the efficacy of MBSR as a viable treatment for chronic insomnia as measured by sleep diary, actigraphy, well-validated sleep scales, and measures of remission and clinical recovery.

Changes in the Body Image and Relationship Scale following a one-year strength training trial for breast cancer survivors with or at risk for lymphedema

The aim of this study was to evaluate the impact of a twice-weekly strength training intervention on perceptions of body image in 234 breast cancer survivors (112 with lymphedema) who participated in the Physical Activity and Lymphedema (PAL) trial. The study population included two hundred and thirty-four women randomly assigned to twice-weekly strength training or control group that completed the 32-item Body Image and Relationships Scale (BIRS) at baseline and 12 months. Percent change in baseline to 12-month BIRS total and subscale scores, upper and lower body strength, and general quality of life (QOL) were compared by intervention status. A series of multiple linear regression models including indicator variables for subgroups based on age, marital status, race, education, BMI, and strength change were used to examine differential intervention impact by subgroup. Strength and QOL variables were assessed as mediators of the intervention effect on BIRS. Results: Baseline BIRS scores were similar across intervention and lymphedema status. Significantly greater improvement in BIRS total score was observed from baseline to 12 months in treatment vs. control participants (12.0 vs. 2.0%; P < 0.0001). A differential impact of the intervention on the Strength and Health subscale was observed for older women (>50 years old) in the treatment group (P = 0.03). Significantly greater improvement was observed in bench and leg press among treatment group when compared to control group participants, regardless of lymphedema. Observed intervention effects were independent of observed strength and QOL changes. Twice-weekly strength training positively impacted self-perceptions of appearance, health, physical strength, sexuality, relationships, and social functioning. Evidence suggests the intervention was beneficial regardless of prior diagnosis of lymphedema. Strength and QOL improvements did not mediate the observed intervention effects.