Efficacy of naltrexone and acamprosate for alcoholism treatment: a meta-analysis.

BACKGROUND: Renewed interest in medications to prevent relapse in alcoholics (i.e., antidipsotropics) resulted in approval by the Food and Drug Administration of naltrexone to treat alcohol dependence. Acamprosate, although not approved in the United States, is used in alcoholism treatment in many other parts of the world. In the absence of studies that compare the effects of these medications, we used a meta-analytic approach to the literature to compare their efficacy in alcoholism treatment. METHODS: All published placebo-controlled trials of naltrexone or acamprosate for alcohol dependence were examined, and, when suitable, data were extracted for calculation of a mean effect size. A sample of studies of selective serotonin reuptake inhibitors for treatment of major depression conducted over the last two decades served as a comparator for the antidipsotropics. RESULTS: Both antidipsotropics exerted significant, but modest, effects on treatment retention and/or drinking outcomes. There was significant variability among the studies for the measure on which the largest effect was exerted by each of these medications. Based on limited comparisons of the two medications, there appears to be no statistical difference in their efficacy in the treatment of alcohol dependence. In contrast, there was a consistent effect of selective serotonin reuptake inhibitors on depressive symptoms in major depression, which was significantly greater than the effects observed for the antidipsotropics. CONCLUSIONS: Both naltrexone and acamprosate are efficacious in reducing alcohol consumption in alcoholics. However, their specific role in alcoholism treatment remains to be more clearly defined. New approaches to the use of these medications and development of new medications are needed if pharmacotherapy is to play a substantial role in the treatment of alcoholism.

Impact of smoking cessation on ambulatory blood pressure and heart rate in postmenopausal women.

BACKGROUND: Smoking and hypertension interact to increase the incidence of cardiovascular disease; however, little is known about the effects of smoking cessation on blood pressure (BP) control. We prospectively evaluated the impact of smoking cessation on clinic and ambulatory BP and heart rate (HR) in stage 1 hypertensive and normotensive postmenopausal women. METHODS: A total of 66 women were randomly assigned using a 3:1 randomization scheme to immediate smoking cessation or to a wait list control group. Clinic and ambulatory BP and HR, and 24-h urinary catecholamine concentrations were obtained at baseline and again at 6 weeks. Carbon monoxide levels and self-report were used to assess compliance with smoking cessation. RESULTS: Ambulatory monitoring showed that the awake SBP decreased by 3.6+/-1.9 mm Hg in the treated subjects who quit smoking (n=19), whereas in the control group (n=15) there was an increase of 1.7+/-2.4 mm Hg (P=.045). Awake HR decreased after smoking cessation by 7+/-1 beats/min and did not change (0+/-1 beat/min) in the control group (P=.001). Blood pressure and HR did not significantly change during sleep after smoking cessation. Changes in the awake HR correlated with changes in urinary epinephrine concentrations (r= 0.58, P=.001), and norepinephrine concentrations (r= 0.45, P=.001), There was no significant change in clinic systolic BP, diastolic BP, or HR between groups. CONCLUSIONS: Smoking cessation reduces systolic BP and HR during the daytime, when patients typically smoke. These hemodynamic changes are due in part to reductions in sympathetic nervous system activity.

Adverse effects of oral naltrexone: analysis of data from two clinical trials.

RATIONALE: Naltrexone treatment of alcohol dependence is associated with adverse events that may limit its effectiveness. Consequently, understanding the impact of adverse events on medication compliance and treatment retention may enhance naltrexone therapy of alcoholism. OBJECTIVES: To examine the relations among adverse events, drinking behavior, medication compliance and study retention in alcoholics receiving naltrexone for relapse prevention. METHODS: The current report is based on analysis of data from 92 subjects who participated in two previously published studies. Moderate or severe adverse effects were monitored weekly and categorized as either neuropsychiatric (NP) or gastrointestinal (GI). Medication compliance was determined by weekly urinary riboflavin testing. Study retention was determined by the proportion of study weeks completed by the subject. The causal relations among adverse events, medication compliance and study retention were analyzed separately for NP and GI adverse events using regression-based recursive path models. RESULTS: Both the NP and GI models fit the data well [NP model: chi 2(4) = 0.59, P = 0.96; GI model: chi 2(4) = 2.81, P = 0.59]. NP adverse events exerted little influence on medication compliance (beta = -0.17, P = 0.071), but directly decreased the length of study retention (beta = -0.35, P < 0.001). In contrast, there was a significant impact of GI adverse events on medication compliance (beta = -0.29, P = 0.002), but not directly on study retention (beta = -0.14, P = 0.081). CONCLUSION: Future studies aimed at enhancing the effectiveness of naltrexone should examine ways of reducing both NP and GI adverse events, in order to enhance both medication compliance and treatment retention.

Sweet taste preference as a risk factor for alcohol dependence.

OBJECTIVE: Previous research has found that alcoholics have a greater preference for sweet solutions than comparison subjects. This study tested the hypothesis that preference for sweet solutions is a marker for alcoholism risk. METHOD: A total of 122 nonalcoholic subjects (59 men) participated. Fifty-eight subjects had a paternal history of alcoholism, and 64 did not. Each subject rated a series of sucrose solutions for intensity of sweetness and degree of preference. RESULTS: Subjects were able to rate accurately the relative intensity of sweetness in the sucrose solutions. Both subjects with and those without a paternal history of alcoholism preferred a 0.42-M sucrose solution, irrespective of gender. CONCLUSIONS: This study failed to support the hypothesis that sweet preference is a marker of alcoholism risk. The sweet preference observed previously among alcoholics may be a consequence of chronic alcohol consumption or other factors associated with heavy drinking.

The Werner syndrome gene and global sequence variation.

We have identified a dense set of markers useful in association studies involving the Werner syndrome (WRN) gene. The homozygotic disruption of the WRN gene is the cause of Werner disease. In addition, this gene is likely to be involved in many complex traits, such as aging, or at least some of the traits and diseases related to age. To investigate the genetic variation associated with the WRN gene, a sample of 93 individuals representing all the continents was analyzed by denaturing high-performance liquid chromatography. A systematic survey of all 35 exons and flanking regions identified 58 single-nucleotide polymorphisms, 15 of which fall in the coding region and cause 11 missense mutations. The resulting global nucleotide diversity was 5.226 x 10(-4), with a slight difference between coding and noncoding regions.

Naltrexone vs. nefazodone for treatment of alcohol dependence. A placebo-controlled trial.

This study compared the effects of nefazodone, a serotonergic antidepressant, with the opioid antagonist naltrexone, and an inactive placebo in 183 alcohol-dependent subjects receiving weekly relapse prevention psychotherapy. Following a single-blind, placebo lead-in period, subjects were randomly assigned to receive study medication, which they took under double-blind conditions for 11 weeks. Naltrexone treatment was associated with significantly more adverse neuropsychiatric and gastrointestinal effects, poorer compliance, and a greater rate of treatment attrition. There were no reliable between-group differences in drinking behavior. These results indicate that nefazodone is not efficacious for treatment of alcohol dependence. Furthermore, the clinical utility of naltrexone seems to be limited by its adverse effects, a finding that has important implications for efforts to develop medications to treat alcohol dependence.

Refining the measurement of physician job satisfaction: results from the Physician Worklife Survey. SGIM Career Satisfaction Study Group. Society of General Internal Medicine.

BACKGROUND: Physician job satisfaction has been linked to various patient care and health system outcomes. A survey instrument that concisely measures physicians' satisfaction with various job facets can help diverse stake-holders to better understand and manage these outcomes. OBJECTIVE: To document the development and validation of a multidimensional physician job satisfaction measure and separate global satisfaction measures. DESIGN: Self-administered questionnaire: Physician Worklife Survey (PWS). SUBJECTS: A pilot study employed a national American Medical Association Masterfile sample of US primary care physicians and random samples from four states. Responses (n = 835; 55% return rate) were randomly assigned to developmental (n = 560) or cross-validation (n = 275) samples. A national sample (n = 2,325; 52% response rate) of physicians was used in a subsequent validation study. RESULTS: A 38-item, 10-facet satisfaction measure resulting from factor and reliability analyses of 70 pilot items was further reduced to 36 items. Reliabilities of the 10 facets ranged from .65 to .77. Three scales measuring global job, career, and specialty satisfaction were also constructed with reliabilities from .84 to .88. Results supported face, content, convergent, and discriminant validity of the measures. CONCLUSIONS: Physician job satisfaction is a complex phenomenon that can be measured using the PWS.

Measuring physician job satisfaction in a changing workplace and a challenging environment. SGIM Career Satisfaction Study Group. Society of General Internal Medicine.

BACKGROUND: Changes in the demographic, specialty, and employment sector composition of medicine have altered physicians' jobs, limiting autonomy and reducing morale. Because physician job satisfaction has been linked to clinical variables, better measurement might help to ameliorate conditions linked to medical disaffection, possibly improving health care. OBJECTIVE: To document conceptual development, item construction, and use of content experts in designing multidimensional measures of physician job satisfaction and global satisfaction scales for assessing physicians' job perceptions across settings and specialties. DESIGN: Using previous research, physician focus groups, secondary analysis of survey data, interviews with physician informants, and a multispecialty physician expert panel, distinct job facets and statements representing those facets were developed. RESULTS: Facets from previously validated instruments included autonomy, relationships with colleagues, relationships with patients, relationships with staff, pay, resources, and status. New facets included intrinsic satisfaction, free time away from work, administrative support, and community involvement. Physician status items were reconfigured into relationships with peers, patients, staff, and community, yielding 10 hypothetical facets. Global scales and items were developed representing satisfaction with job, career, and specialty. CONCLUSIONS: A comprehensive approach to assessing physician job satisfaction yielded 10 facets, some of which had not been previously identified, and generated a matching pool of items for subsequent use in field tests.

The validity of self-reported cocaine use in two groups of cocaine abusers.

To evaluate the validity of 2 self-report methods for estimating cocaine use, Timeline Follow-Back (TLFB) and weekly calendar reports from 65 patients with a cocaine use disorder were compared with urine drug test results. The TLFB showed fair to moderate validity, and the weekly calendar showed moderate to high validity in measuring the frequency of cocaine use. Similar results were obtained when the self-report measures were used to time specific cocaine use episodes. In addition to evidence for superiority of the weekly calendar, the validity of self-reports was inversely related to the percentage of positive urine test results. Furthermore, there was some evidence that validity increased as the time window over which the comparisons were drawn increased. Given the central role of self-reports in the clinical and research evaluation of drug use, factors affecting their validity warrant further investigation.

Naltrexone treatment of comorbid alcohol and cocaine use disorders.

Naltrexone (NTX) has been shown to be efficacious for the treatment of alcohol dependence. Since alcohol and cocaine use disorders commonly co-occur, we conducted a randomized, double-blind, placebo-controlled trial of NTX 50 mg/day in 64 subjects with comorbid alcohol and cocaine use disorders. Although subjects in both groups reduced their consumption of both alcohol and cocaine during the 8-week trial, there was no consistent advantage to NTX over placebo treatment. We conclude that, due to behavioral, neurochemical, or other factors, individuals with both alcohol and cocaine use disorders are distinct from those dependent on alcohol alone, and that NTX at a dosage of 50 mg/day is not efficacious in this patient population. Several factors, including medication dosage, length of treatment, sample size and attrition rate, limit the interpretation of these findings. Consequently, we recommend that subsequent trials of NTX to reduce the risk of relapse in patients with comorbid alcohol and cocaine use disorders take these issues into account.

Physician job satisfaction: developing a model using qualitative data. SGIM Career Satisfaction Study Group.

The purpose of this study was to develop a current and comprehensive model of physician job satisfaction. Information was gathered by (1) analysis of open-ended responses from a large group practice physician survey in 1988, and (2) analysis of focus group data of diverse physician subgroups from 1995. Participants were 302 physicians from large-group practices and 26 participants in six focus groups of HMO, women, minority, and inner-city physicians. Data were used to develop a comprehensive model of physician job satisfaction. The large group practice survey data supported the key importance of day-to-day practice environment and relationships with patients and physician peers. Future concerns focused on the effect of managed care on the physician-patient relationship and the ability of physicians to provide quality care. Focus groups provided contemporary data on physician job satisfaction, reinforcing the centrality of relationships as well as special issues for diverse physician subgroups of practicing physicians. New variables that relate to physician job satisfaction have emerged from economic and organizational changes in medicine and from increasing heterogeneity of physicians with respect to gender, ethnicity, and type of practice. A more comprehensive model of physician job satisfaction may enable individual physicians and health care organizations to better understand and improve physician work life.

Physician job satisfaction : Developing a model using qualitative data.

The purpose of this study was to develop a current and comprehensive model of physician job satisfaction. Information was gathered by (1) analysis of open-ended responses from a large group practice physician survey in 1988, and (2) analysis of focus group data of diverse physician subgroups from 1995. Participants were 302 physicians from large-group practices and 26 participants in six focus groups of HMO, women, minority, and inner-city physicians. Data were used to develop a comprehensive model of physician job satisfaction. The large group practice survey data supported the key importance of day-to-day practice environment and relationships with patients and physician peers. Future concerns focused on the effect of managed care on the physician-patient relationship and the ability of physicians to provide quality care. Focus groups provided contemporary data on physician job satisfaction, reinforcing the centrality of relationships as well as special issues for diverse physician subgroups of practicing physicians. New variables that relate to physician job satisfaction have emerged from economic and organizational changes in medicine and from increasing heterogeneity of physicians with respect to gender, ethnicity, and type of practice. A more comprehensive model of physician job satisfaction may enable individual physicians and health care organizations to better understand and improve physician work life.

Strategies for managing uncertainty and complexity.

OBJECTIVES: To identify strategies involved in the diagnosis and treatment plans of primary care problems that are uncertain and complex. METHODS: In this exploratory study we observed primary care physicians encountering standardized patients who portrayed typical primary care problems involving uncertainty and complexity. First, we analyzed 10 tapes of nine physicians with a range of clinical experience (first-year residents through faculty physicians) interacting with four standardized patient cases (headache, back pain, hypertension, and abdominal pain). We analyzed the 10 tapes to determine the regular occurrence of physician behavior patterns that we later described as strategies. Then, using a written questionnaire, 19 general internal medicine faculty physicians from our hospital and from an affiliated hospital rated the perceived importance of these strategies for clinical practice in general. Finally, we checked the incidence of the strategies: (1) across a range of six cases (headache, back pain, hypertension, abdominal pain, fatigue, and well-adult care) using six first-year residents (a total of 19 encounters), and (2) across different levels of clinical experience using the standardized patient case of headache involving eight physicians (first-year residents through faculty physicians). RESULTS: Nine strategies were identified, and each was rated as important to primary care clinical practice. The strategies were: (1) defines the context of the diagnosis and explains the signs and symptoms as part of the expected spectrum of the disease; (2) eliminates alternative diagnoses by dealing with patient fears, giving reasons in the context of the patient's belief system; (3) describes the prognosis in terms of the likely course of the disease and expectations of treatment; (4) negotiates key problems or issues that are important to both patient and physician; (5) negotiates the plan and ensures patient understands, and is willing and able to comply, given his/her particular context; (6) keeps diagnostic options open by making provisional diagnoses while keeping alternatives in mind; (7) is circumspect and takes action to minimize the possibility of missing other critical diagnoses; (8) plays for time by allowing signs and symptoms to develop to help clarify the diagnosis; and (9) plans for contingencies by providing appropriate if/then statements concerning situations requiring further action. The strategies were used in each of the six cases, and by physicians with all levels of clinical experience. CONCLUSIONS: The nine strategies led to the generation of a construct we termed "strategic medical management," which refers to the management (diagnosis and proposed treatment) of uncertain and complex medical problems in primary care. The construct provides a more elaborated framework in which to view clinical decision making and integrates recent ideas concerning doctor-patient communication into this process. Strategic medical management appears to be based on tacit knowledge that is seldom explicity articulated or taught. It has potential implications for enhancing instruction and assessment in medical education.

Evaluation of resident performance in an outpatient internal medicine clinic using standardized patients.

OBJECTIVE: To observe and evaluate the performance of primary care internal medicine residents within the outpatient clinic milieu. DESIGN: Longitudinal descriptive study. PATIENTS/PARTICIPANTS: 48 internal medicine resident encounters with two standardized patients at the University of Wisconsin General Internal Medicine Clinics. INTERVENTION: Residents were rated by the standardized patients with a medical skills checklist and an interpersonal skills checklist, and by the staffing physician with a clinical reasoning skills checklist. The investigators reviewed audiotapes of the standardized patient encounters for strategic management skills. MAIN RESULTS: Resident performance on these scales was examined for improvement with years of training; when considered separately, no such effect was seen for either standardized patient case. When the cases were grouped together, however, there was significant improvement on the Clinical Reasoning Instrument. The grouped standardized patient data were compared with data from inpatient faculty evaluations of the residents. Faculty evaluations correlated with standardized patient evaluations of resident performance only on the medical checklist. Finally, comparison of the four assessment scales demonstrated a significant correlation between interpersonal skills, as assessed by the patient, and strategic management skills. CONCLUSION: Resident outpatient performance, measured in a blinded setting, does not improve with year of training. Faculty inpatient assessments of residents correlate with medical "thoroughness" as measured by a medical skills checklist, and interpersonal skills as rated by standardized patients correlate with resident use of strategic medical management.

A study of 'routine' gonorrhea cultures in a family practice.

A varying, but significant, incidence of "asymptomatic" gonorrhea in women has been reported by numerous investigators and is one rationale for collecting specimens during pelvic examinations for screening gonorrhea cultures. There is a lack of research evidence, however, to document the value of such cultures in all settings. In this retrospective study of gonorrhea cultures in a family practice, all of the cultures performed in one year were reviewed. Of the 219 clinically asymptomatic women who had screening cultures ordered, only two (0.9 percent) had culture-positive results, and both were known to be recent contacts of men with confirmed gonorrhea and hence would have had a screening culture ordered anyway. This finding opens to serious question the value of routinely screening women for gonorrhea by culturing vaginal specimens in all circumstances and suggests that thorough history and examination alone, supplemented by cultures only when clinically indicated, would suffice in certain settings.

Evaluation of influenza virus mutants for possible use in a live virus vaccine.

Two approaches to the attenuation of influenza A2 virus were studied: adaptation to a sub-optimum growth temperature and the production of temperature-sensitive mutants.A strain of A2/Hong Kong/68 virus was adapted to growth at 25 degrees C in calf kidney tissue culture, and a virus suspension was prepared for administration to volunteers after cloning by 2 terminal dilution purifications. The results indicated that the low-temperature-adapted strain had reduced infectivity for man, but was not attenuated since illness occurred when sufficient virus was administered to infect all volunteers.More encouraging results were obtained with 2 temperature-sensitive mutants of influenza A2/1965 virus. One of these mutants was unable to form plaques in calf kidney tissue culture at temperatures above 36 degrees C; the other showed restriction of plaque formation only at 38 degrees C and above. Both mutants were able to infect hamsters, but compared with the wild-type virus there was marked restriction of replication in the lungs. Prior infection of hamsters or mice with either mutant induced significant resistance to subsequent challenge with wild-type influenza A2 virus.