Faculty Bibliography

BACKGROUND: Poor adherence to antituberculosis treatment is the most important obstacle to tuberculosis control. PURPOSE: To identify and analyze predictors and consequences of nonadherence to antituberculosis treatment. PATIENTS AND METHODS: Retrospective study of a citywide cohort of 184 patients with tuberculosis in New York City, newly diagnosed by culture in April 1991-before the strengthening of its control program-and followed up through 1994. Follow-up information was collected through the New York City tuberculosis registry. Nonadherence was defined as treatment default for at least 2 months. RESULTS: Eighty-eight of the 184 (48%) patients were nonadherent. Greater nonadherence was noted among blacks (unadjusted relative risk [RR] 3.0, 95% confidence interval [CI] 1.1 to 8.6, compared with whites), injection drug users (RR 1.5, 95% CI 1.1 to 2.0), homeless (RR 1.4, 95% CI 1.0 to 1.8), alcoholics (RR 1.4, 95% CI 1.0 to 1.9), and HIV-infected patients (RR 1.4, 95% CI 1.1 to 1.9); also, census-derived estimates of household income were lower among nonadherent patients (P = 0.018). In multivariate analysis, only injection drug use and homelessness predicted nonadherence, yet 46 (39%) of 117 patients who were neither homeless nor drug users were nonadherent. Nonadherent patients took longer to convert to negative culture (254 versus 64 days, P < 0.001), were more likely to acquire drug resistance (RR 5.6, 95% CI 0.7 to 44.2), required longer treatment regimens (560 versus 324 days, P < 0.0001), and were less likely to complete treatment (RR 0.5, 95% CI 0.4 to 0.7). There was no association between treatment adherence and all-cause mortality. CONCLUSIONS: In the absence of public health intervention, half the patients defaulted treatment for 2 months or longer. Although common among the homeless and injection drug users, the problem occurred frequently and unpredictably in other patients. Nonadherence may contribute to the spread of tuberculosis and the emergence of drug resistance, and may increase the cost of treatment. These data lend support to directly observed therapy in tuberculosis.

Thousands of articles on "noncompliance" have appeared since 1975. Yet the term has been criticized as paternalistic--as wrongly implying that patients should necessarily follow doctors' orders. This paper, which reviews how noncompliance has been constructed historically, argues that the problem with noncompliance is more than just one of terminology. Changing social and cultural factors during the 20th century have influenced the way in which uncooperative patients have been described. For example, resentment of poor immigrants in the early 1900s led doctors to describe tuberculosis patients who did not follow advice as "ignorant" and "vicious." Following World War II, patients who balked at taking new curative antibiotics for tuberculosis were called "recalcitrant." The term "noncompliance," popularized by Sackett and Haynes in the 1970s, reflected their early role in the field of research now termed "evidence-based medicine." While Sackett and Haynes had hoped that the new term would eschew earlier value judgments, noncompliance, through its association with the positivistic ethos of evidence-based medicine, has been conceptualized as a "tragic" problem potentially solvable by clinical research. Hence, noncompliant patients are still seen as deviant. With the growth of managed care in the United States, there is increasing pressure to get patients to follow medical recommendations. History suggests that labels such as "noncompliant" are invariably judgmental. Rather than seeing the provider's role as trying to get noncompliant patients to comply, we should emphasize the importance of negotiation and accommodation within the provider-patient relationship.

Shigella pathogenesis involves bacterial invasion of colonic epithelial cells and movement of bacteria through the cytoplasm and into adjacent cells by means of actin-based motility. The Shigella protein IcsA (VirG) is unipolar on the bacterial surface and is both necessary and sufficient for actin-based motility. IcsA is inserted into the outer membrane as a 120-kDa polypeptide that is subsequently slowly cleaved, thereby releasing the 95-kDa amino-terminal portion into the culture supernatant. IcsP, the major Shigella protease that cleaves IcsA, was identified and cloned. It has significant sequence similarity to the E. coli serine proteases, OmpP and OmpT. Disruption of icsP in serotype 2a S. flexneri leads to a marked reduction in IcsA cleavage, increased amounts of IcsA associated with the bacterium and altered distribution of IcsA on the bacterial surface. The icsP mutant displays significantly increased rates of actin-based motility, with a mean speed 27% faster than the wild-type strain; moreover, a significantly greater percentage of the icsP mutant moves in the cytoplasm. Yet, plaque formation on epithelial monolayers by the mutant was not altered detectably. These data suggest that IcsA, and not a host protein, is limiting in the rate of actin-based motility of wild-type serotype 2a S. flexneri.

OBJECTIVES: This study evaluated the efficacy of radiographic screening for tuberculosis in correctional facilities. METHODS: Inmates at an admission facility in New York, NY, were screened for tuberculosis by registry cross-match, symptom interviews, tuberculin testing, and chest radiography. RESULTS: Thirty-two cases of tuberculosis were detected among 4172 inmate admissions (767 cases per 100,000). Twenty-five inmates (78%) were previously diagnosed but incompletely treated; all were identified by registry cross-match. Seven inmates (22%) were newly diagnosed, of whom four (57%) were asymptomatic, had negative skin tests, and were detected only by their abnormal radiographs. CONCLUSIONS: Screening strategies that limit radiographic testing to inmates with either positive skin tests or symptoms may result in missed opportunities for diagnosing active tuberculosis.

OBJECTIVES: To describe the changes in psychoactive drug use in nursing homes after implementation of physical restraint reduction interventions and mandates of the Omnibus Budget Reconciliation Act of 1987 (OBRA '87). METHODS: A secondary analysis was conducted using data from a controlled clinical trial that took place in three nursing homes: a control home, one that received an educational intervention, and one that received an educational/consultation intervention. All three homes were influenced by the OBRA mandates. Complete pre- and 6 months' post-intervention data on use of psychoactive drugs and physical restraints were available for 446 resident subjects. Changes were first analyzed with the resident subjects as the unit of analysis and then using the nursing home ward (n = 16) as the unit of analysis. RESULTS: While physical restraint use declined in the home that received the educational/consultation intervention, neither neuroleptic nor benzodiazepine use increased in any of the homes after the interventions. The percentage of residents taking neuroleptics declined in the control home (18.6% to 11.3%, P = .014). Benzodiazepine use, which was more prevalent than described previously in the literature, declined in all three homes (P < .001). Of those residents whose physical restraints were discontinued, only 2% were started on neuroleptics. When the effect of OBRA mandates on appropriateness of neuroleptic use was examined, the percentage of residents on neuroleptics who lacked an OBRA-approved indication declined from 21.3% to 14.6% in the total sample, and from 39.9% to 8% in the control home. CONCLUSIONS: Interventions to reduce physical restraint did not lead to an increase in psychoactive drug use; further, reduction in both can occur simultaneously. OBRA mandates regarding psychoactive drug use were not uniformly effective, but appear, at minimum, to have increased awareness of the indications for neuroleptics.

Men who have more orgasms seem to live longer, a statistical study of Welsh villagers in The British Medical Journal has found. It is one of the rare studies of sex and death, and the authors lightheartedly suggested in the article that the findings might result in new kinds of promotional campaigns for healthy living. Before then, further studies of both sexes are needed to confirm their findings, the authors said. Two other scientists added a few drops of cold water, cautioning that because of its design, the epidemiological study might not have been able to identify a number of factors that could have inadvertently influenced the findings. One possibility is that the link could be reversed - ill people may be less likely to have sex, according to the critics who commented in the same issue. [George Davey-Smith]'s team assessed the existence of heart disease in the men when they entered the study from 1979 to 1983. After explaining the purpose of their question, they asked the men about the frequency of sexual activity. The answers were put into categories ranging from 'never' to 'daily.'

Large-cell change of hepatocytes (LCC), also called liver cell dysplasia of large-cell type, is a set of cytologic changes comprising nuclear and cytoplasmic enlargement, nuclear pleomorphism, and multinucleation. This entity is encountered frequently on histologic or cytologic examination of specimens obtained from livers with a variety of chronic diseases and originally was thought to have a premalignant nature. Accumulating evidence, however, now suggests that LCC is merely a reactive change. Having often observed LCC in liver specimens with chronic biliary tract disease, that is, in livers where cholestasis preceded hepatocyte injury, we surmised that LCC may be a result of prolonged cholestasis. To determine whether there was any association between LCC and cholestasis, we examined microscopically a series of 400 nodules from 40 consecutive adult cirrhotic livers, resected on transplantation, and graded LCC and cholestasis semiquantitatively. LCC was present diffusely in cirrhotic nodules of 25 specimens (62.5%). Nine additional specimens (22.5%) had focal mild LCC. Usually, LCC and cholestasis occurred together, in the same cirrhotic nodules and in the same areas of nodules. There was a statistically significant association between the presence and grade of LCC and those of cholestasis (p < 0.0001; chi-square test). Within etiological categories of cirrhosis (chronic hepatitis; n = 28; alcoholic liver disease; n = 6; biliary disease: n = 6), the significance was maintained. We conclude that, in cirrhosis of different etiologies, LCC may represent a reactive change that results from prolonged cytoplasmic cholestasis

Twenty-six patients with Grade III acromioclavicular joint separations were evaluated to determine the outcomes of nonoperative and operative management. Evaluation consisted of a detailed functional questionnaire, physical examination, and comprehensive isokinetic strength assessment. The patients were divided into two groups: operative (n = 16) and nonoperative (n = 10). Operative management consisted of coracoclavicular stabilization with heavy suture material and with nine of the sixteen patients treatment also consisted of coracoacromial ligament transfer and lateral clavicle resection. Nonoperative management consisted of short-term immobilization with early range of motion and rehabilitation. The two groups were similar in all characteristics except mean age: 30.7 years for the operative group and 49.6 years for the nonoperative group. Follow-up evaluation was performed an average of 32.9 months after either injury (nonoperative group) or surgery. Our results indicated that nonoperative management was superior to operative management with respect to time to return to work (0.8 months vs. 2.6 months), time to return to athletics (3.5 months vs. 6.4 months) and time of immobilization (2.7 weeks vs. 6.2 weeks). However, operative management was superior to nonoperative management in the following parameters: time to attain completely pain-free status, the patient's subjective impression of pain, range of motion, functional limitations, cosmesis, and long-term satisfaction. There were no significant differences between the two groups with respect to shoulder range of motion, manual muscle testing, or neurovascular findings. Isokinetic strength testing of the involved shoulder, expressed as a percentage of the uninvolved shoulder, showed no significant differences in peak torque, total work, or total power between the operative and nonoperative groups. However, comparison of the involved to the uninvolved extremity within each group did reveal a trend toward decreased peak torque, work, and power for abduction in the involved extremity regardless of the treatment used. These findings reached statistical significance only for power at the slower testing speed (60 degrees/sec). There was also a significant decrease in power in the involved extremity for external rotation at the faster speed (120 degrees/sec) in the nonoperative group. Finally, the absolute values for peak torque, work, and power were significantly greater for all motions tested in the operative group as compared to the nonoperative group. This may reflect the difference in age between the two groups. Based upon the patients studied, there are benefits to both nonoperative and operative methods of treatment of Grade III acromioclavicular separations. Recovery of strength did not differ between the two groups and therefore should be viewed as a less important factor in patient selection for operative versus nonoperative management. Careful patient selection should remain an important aspect of treatment for this controversial injury