Opioids versus antidepressants in postherpetic neuralgia: a randomized, placebo-controlled trial.

BACKGROUND: Tricyclic antidepressants (TCA) provide less than satisfactory pain relief for postherpetic neuralgia (PHN), and the role of opioids is controversial. OBJECTIVE: To compare the analgesic and cognitive effects of opioids with those of TCA and placebo in the treatment of PHN. METHODS: Seventy-six patients with PHN were randomized in a double-blind, placebo-controlled, crossover trial. Each subject was scheduled to undergo three treatment periods (opioid, TCA, and placebo), approximately 8 weeks' duration each. Doses were titrated to maximal relief or intolerable side effects. The primary outcome measures were pain intensity (0 to 10 scale), pain relief (0 to 100%), and cognitive function. Analyses included patients who provided any pain ratings after having received at least a single dose of a study medication. RESULTS: Fifty patients completed two periods, and 44 patients completed all three. Mean daily maintenance doses were morphine 91 mg or methadone 15 mg and nortriptyline 89 mg or desipramine 63 mg. Opioids and TCA reduced pain (1.9 and 1.4) more than placebo (0.2; p < 0.001), with no appreciable effect on any cognitive measure. The trend favoring opioids over TCA fell short of significance (p = 0.06), and reduction in pain with opioids did not correlate with that following TCA. Treatment with opioids and TCA resulted in greater pain relief (38 and 32%) compared with placebo (11%; p < 0.001). More patients completing all three treatments preferred opioids (54%) than TCA (30%; p = 0.02). CONCLUSIONS: Opioids effectively treat PHN without impairing cognition. Opioids and TCA act via independent mechanisms and with varied individual effect.

Cognitive changes 5 years after coronary artery bypass grafting: is there evidence of late decline?

OBJECTIVE: To determine the long-term (preoperative to 5 years postoperative) and late (1-5 years postoperative) changes in cognitive test performance in patients after coronary artery bypass grafting. SETTING: The departments of surgery and neurology at The Johns Hopkins University School of Medicine, Baltimore, Md. PATIENTS: A group of 102 patients who completed preoperative and follow-up cognitive testing up to 5 years after coronary artery bypass grafting. MAIN OUTCOME MEASURES: A battery of neuropsychological tests, assessing 8 cognitive domains (attention, language, verbal and visual memory, visuoconstruction, executive function, and psychomotor and motor speed), was administered preoperatively and at 1 month, 1 year, and 5 years postoperatively. RESULTS: Significant changes in neuropsychological test scores from baseline to 5 years were observed in only 3 of the 8 domains: there were declines in visuoconstruction and psychomotor speed and an improvement in executive function. When the period from baseline to 5 years was divided into 2 intervals, we found that cognitive test scores generally improved from baseline to 1 year. By contrast, between 1 and 5 years, there was significant decline in all cognitive domains except for attention and executive function. Some potential explanatory covariates (demographic, medical history, and surgery variables) were associated with changes from baseline to 5 years in some cognitive domains, but few covariates were statistically significant in more than 1 cognitive domain. CONCLUSIONS: The change in cognitive test performance between baseline and 5 years is likely related to several factors, including low baseline performance and practice effects. The significant decline in performance between 1 and 5 years, however, raises the possibility that a late cognitive decline may be occurring in this population. Additional studies, with the use of a nonsurgical control group, are needed to determine if the observed cognitive decline is related to bypass surgery itself, normal aging in a population with cardiovascular risk factors, or some combination of these and other factors.

Effects of pathway and neuronal aging on the specificity of motor axon regeneration.

Youth is a strong predictor of functional recovery after peripheral nerve repair, while adulthood is commonly associated with poor outcome. Identification of the factors responsible for this difference could form the basis for strategies to improve regeneration in adults. Preferential reinnervation of motor pathways by motor axons (PMR) occurs strongly in young rats, but is often absent in older animals, and thus parallels the overall trend for superior results in young individuals. These experiments evaluate the individual contributions of peripheral nerve age and motoneuron age to the decline in regeneration specificity (PMR) which accompanies the aging process. The femoral nerves of young and old Lewis rats were removed as inverted "Y" grafts from the femoral trunk proximally to the terminal muscle and cutaneous branches distally. These grafts were transferred from (1) old to young, (2) young to old, (3) old to old, and (4) young to young bilaterally in 10 individuals per group. After 8 weeks of regeneration, reinnervation of cutaneous and muscle branches was assessed by dual labeling with HRP and Fluoro-Gold. Motor neuron regeneration was random in old to old (mean muscle branch (M) = 159, mean cutaneous branch (C) = 168), but PMR was seen when young pathways were used in old animals (M = 163, C = 116). PMR was vigorous when either type of graft was used in young animals (young graft, M = 218, C = 134; old graft, M = 204, C = 127). In this model, motoneuron age appears to be the primary determinant of specificity. However, the pathway also makes significant contributions, as shown by the ability of young pathways to generate specificity in old animals. Manipulation of graft Schwann cell behavior might therefore be an appropriate strategy to improve outcome in older individuals.

Contributions of pathway and neuron to preferential motor reinnervation.

Motor axons regenerating after transection of mixed nerve preferentially reinnervate distal muscle branches, a process termed preferential motor reinnervation (PMR). Motor axon collaterals appear to enter both cutaneous and muscle Schwann cell tubes on a random basis. Double-labeling studies suggest that PMR is generated by pruning collaterals from cutaneous pathways while maintaining those in motor pathways (the "pruning hypothesis"). If all collaterals projecting to muscle are saved, then stimulation of regenerative sprouting should increase specificity by increasing the number of motoneurons with at least one collateral in a muscle pathway. In the current experiments, collateral sprouting is stimulated by crushing the nerve proximal to the repair site before suture, a maneuver that also conditions the neuron and predegenerates the distal pathway. Control experiments are performed to separate these effects from those of collateral generation. Experiments were performed on the rat femoral nerve and evaluated by exposing its terminal cutaneous and muscle branches to HRP or Fluoro-Gold. Crush proximal to the repair site increased motor axon collaterals at least fivefold and significantly increased the percentage of correctly projecting motoneurons, consistent with the pruning hypothesis. Conditioning the nerve with distal crushes before repair had no effect on specificity. A graft model was used to separate the effects of collateral generation and distal stump predegeneration. Previous crush of the proximal femoral nerve significantly increased the specificity of fresh graft reinnervation. Stimulation of regenerative collateral sprouting thus increased PMR, confirming the pruning hypothesis. However, this effect was overshadowed by the dramatic specificity with which predegenerated grafts were reinnervated by fresh uncrushed proximal axons. These unexpected effects of predegeneration on specificity could involve a variety of possible mechanisms and warrant further study because of their mechanistic and clinical implications.

Racial differences in the cause-specific prevalence of blindness in east Baltimore.

BACKGROUND: Bilateral blindness unrelated to simple refractive error is twice as prevalent among blacks as among whites, although the difference narrows among the elderly. The reasons for this race- and age-related pattern are uncertain. METHODS AND RESULTS: A randomly selected, stratified, multistage cluster sample of 2395 blacks and 2913 whites 40 years of age and older in East Baltimore underwent detailed ophthalmic examinations by a single team. We identified 64 subjects who were blind in both eyes. The leading causes of blindness were unoperated senile cataract (accounting for blindness in 27 of the total of 128 eyes), primary open-angle glaucoma (17 eyes), and age-related macular degeneration (16 eyes). Together, these three disorders accounted for 47 percent of all blindness in this sample. Unoperated cataract accounted for 27 percent of all blindness among blacks, among whom it was four times more common than among whites; whites were almost 50 percent more likely than blacks to have undergone cataract extraction before the age of 80 (P less than 0.002). Primary open-angle glaucoma accounted for 19 percent of all blindness among blacks; it was six times as frequent among blacks as among whites and began 10 years earlier, on average. By contrast, age-related macular degeneration resulting in blindness was limited to whites, among whom it was the leading cause of blindness (prevalence, 2.7 per 1000; 95 percent confidence interval, 1.2 to 5.4); it affected 3 percent of all white subjects 80 years of age or older. CONCLUSIONS: The pattern of blindness in urban Baltimore appears to be different among blacks and whites. Whites are far more likely to have age-related macular degeneration, and blacks to have primary open-angle glaucoma. The high rate of unoperated cataracts among younger blacks and among elderly subjects of both races suggests that health services are underused. Half of all blindness in this urban population is probably preventable or reversible.

Racial variations in the prevalence of primary open-angle glaucoma. The Baltimore Eye Survey.

OBJECTIVE: --To compare the prevalence of primary open-angle glaucoma between black and white Americans. DESIGN, SETTING, AND PARTICIPANTS: --The design was a population-based prevalence survey of a noninstitutionalized black and white population aged 40 years or older from the eastern and southeastern health districts of Baltimore, Md. A multistage random sampling strategy was used to identify 7104 eligible participants, of whom 5308 (2395 blacks, 2913 whites) received an ophthalmologic screening examination. Those with abnormalities were referred for definitive diagnostic evaluation. MAIN OUTCOME MEASURE: --Primary open-angle glaucoma was defined based on evidence of glaucomatous optic nerve damage, including abnormal visual fields and/or severe optic disc cupping, and was independent of intraocular pressure. MAIN RESULTS: --Age-adjusted prevalence rates for primary open-angle glaucoma were four to five times higher in blacks as compared with whites. Rates among blacks ranged from 1.23% in those aged 40 through 49 years to 11.26% in those 80 years or older, whereas rates for whites ranged from 0.92% to 2.16%, respectively. There was no difference in rates of primary open-angle glaucoma between men and women for either blacks or whites in this population. Based on these data, an estimated 1.6 million persons aged 40 years or older in the United States have primary open-angle glaucoma. CONCLUSIONS: --Black Americans are at higher risk of primary open-angle glaucoma than their white neighbors. This may reflect an underlying genetic susceptibility to this disease and indicates that additional efforts are needed to identify and treat this sight-threatening disorder in high-risk communities.

Blindness and visual impairment in an American urban population. The Baltimore Eye Survey.

Data on the prevalence of blindness and visual impairment in multiracial urban populations of the United States are not readily available. The Baltimore Eye Survey was designed to address this lack of information and provide estimates of prevalence in age-race subgroups that had not been well studied in the past. A population-based sample of 5300 blacks and whites from east Baltimore, Md, received an ophthalmologic screening examination that included detailed visual acuity measurements. Blacks had, on average, a twofold excess prevalence of blindness and visual impairment than whites, irrespective of definition. Rates rose dramatically with age for all definitions of vision loss, but there was no difference in prevalence by sex. More than 50% of subjects improved their presenting vision after refractive correction, with 7.5% improving three or more lines. Rates in Baltimore are as high or higher than those reported from previous studies. National projections indicate that greater than 3 million persons are visually impaired, 890,000 of whom are bilaterally blind by US definitions.

Health and mental health problems of homeless men and women in Baltimore.

A study of homeless people in Baltimore, Md, focused on their health and other characteristics, with special emphasis on their needs for services. In the first stage, 298 men and 230 women were randomly selected from the missions, shelters, and jail in Baltimore to respond to a baseline interview that provided extensive sociodemographic and health-related data. In the second stage, a subsample of 203 subjects was randomly selected from the baseline survey respondents to have systematic psychiatric and physical examinations. Data are presented from both stages. Data from the first stage demonstrate, among other things, the high levels of disaffiliation of this population and their heavy involvement in substance abuse. Data from the clinical examinations demonstrate the high prevalence of mental illnesses and other psychiatric disorders and of a wide range of physical disorders and confirm the high prevalence of alcohol abuse disorders. The high rates of comorbidity of these conditions is demonstrated and data are provided on the subjects' needs for mental health and substance abuse services.

Heparin-associated thrombocytopenia: a comparison of three heparin preparations.

We performed a prospective, double-blind study of the incidence of thrombocytopenia in 149 patients randomly assigned to treatment with one of three heparin preparations--from bovine lung from intestinal-mucosa A, or from intestinal-mucosa O. Thrombocytopenia developed in 21 patients (platelets, < 100 x 10(9) per liter): 13 of the 50 receiving bovine lung heparin, four of 45 receiving intestinal-mucosa-A heparin, and four of 54 receiving intestinal-musoca-O heparin (P < 0.005). There was a significantly increased incidence of thrombocytopenia in the bovine-lung group (P < 0.002); estimated incidence rates after nine days of treatment were 24 per cent in this group and 7 per cent in the combined intestinal-mucosa A and O groups. Thrombocytopenia appeared in the bovine-lung group on days 3 to 16, in the intestinal-mucosa-A groups on Days 4 to 12, and in the intestinal-mucosa-O group on Days 3 to 7; it disappeared in all groups three to eight days after discontinuation of heparin. A total of 121 patients were subsequently given warfarin for four to six months, and thrombocytopenia was not observed.

Prediction models in small area estimation.

Finite population estimation problems are formulated as prediction problems under superpopulation models. For linear regression models, a general theorem on optimal linear estimation is presented. The theorem is applied to simple cross-classification models to generate and analyze various statistics for estimating small area totals. These statistics include the synthetic and composite estimators, as well as some interesting alternatives.