A circular organization chart promotes a hospital-wide focus on teams.

Our Lady of the Way Hospital, like most hospitals in the late 1980s and early 1990s, exemplified the bureaucratic organization represented by the traditional "line and box organization chart." Additionally, as in most small hospitals, the CEO of Our Lady of the Way Hospital--a 39-bed, JCAHO accredited, general, acute care hospital in Martin, Kentucky--had direct management responsibility for several functional departments. In 1992, administration replaced the traditional, hierarchical organization chart with a circular structure that reflected its increased reliance on team processes throughout the organization. The new structure also significantly reduced the number of reporting assignments to the CEO. This article describes the hospital's transition to a team-based organization, illustrates the application of a circular organization chart, and assesses its value and limitations.

A comparison of two regimens for the treatment of Mycobacterium avium complex bacteremia in AIDS: rifabutin, ethambutol, and clarithromycin versus rifampin, ethambutol, clofazimine, and ciprofloxacin. Canadian HIV Trials Network Protocol 010 Study Group.

BACKGROUND: Bacteremia with the Mycobacterium avium complex is common in patients with the acquired immunodeficiency syndrome (AIDS), but the most effective treatment for this infection remains unclear. METHODS: We randomly assigned 229 patients with AIDS and M. avium complex bacteremia to receive either rifampin (600 mg daily), ethambutol (approximately 15 mg per kilogram of body weight daily), clofazimine (100 mg daily), and ciprofloxacin (750 mg twice daily) (the four-drug group) or rifabutin (600 mg daily), ethambutol (as above), and clarithromycin (1000 mg twice daily) (the three-drug group). In the three-drug group the dose of rifabutin was reduced by half after 125 patients were randomized, because 24 of 63 patients had uveitis. RESULTS: Among 187 patients who could be evaluated, blood cultures became negative more often in the three-drug group than in the four-drug group (69 percent vs. 29 percent, P<0.001). Among patients treated for at least four weeks, the bacteremia resolved more frequently in the three-drug group (78 percent vs. 40 percent, P<0.001). In the three-drug group, bacteremia resolved more often with the 600-mg dose of rifabutin than with the 300-mg dose (P=0.025), but the latter regimen was more effective than the four-drug regimen (P<0.05). The median survival was 8.6 months in the three-drug group and 5.2 months in the four-drug group (P = 0.001). The median Karnofsky performance score was higher in the three-drug group than in the four-drug group from week 2 to week 16 (P<0.05). Mild uveitis developed in 3 of the 53 patients receiving the 300-mg dose of rifabutin, an incidence about one quarter that observed with the 600-mg dose (P<0.001). CONCLUSIONS: In patients with AIDS and M. avium complex bacteremia, treatment with the three-drug regimen of rifabutin, ethambutol, and clarithromycin leads to resolution of the bacteremia more frequently and more rapidly than treatment with rifampin, ethambutol, clofazimine, and ciprofloxacin, and survival rates are better.

Ongoing high-risk sexual behaviors in relation recreational drug use in sexual encounters. Analysis of 5 years of data from the Toronto Sexual Contact Study.

The current study investigated the association between the use of recreational drugs at the time of sexual activity and high-risk sexual behavior in a Toronto cohort of 249 homosexual and bisexual men over a 5-year period commencing in 1984 to 1985 and concluding in 1989 to 1990. The main analysis was based on a total of 2536 visits. Univariate and multivariate Liang-Zeger regression models were used to relate the log of the sexual activity score (SARS) to the independent variables over the 20 follow-up visits while controlling for intercorrelations between variables from the same respondent. We found that there was a significant decline, over time, in the sexual activities that pose a higher risk of infection with human immunodeficiency virus. Recreational drugs still appear to be playing an important role in the continuation of higher-risk sexual activities. The use of poppers in conjunction with sex is a strong predictor of high-risk activity, as is use of alcohol and marijuana in conjunction with sex. Also, simultaneously strongly associated with higher-risk score is the Centers for Disease Control classification II. More emphasis needs to be placed on educating the population about the potential risks of combining reactional drugs with sexual activity.

Zidovudine toxicity. Clinical features and management.

Zidovudine is a dideoxynucleoside analogue of thymidine. It acts by interfering with viral reverse transcriptase, thereby inhibiting human immunodeficiency virus (HIV) replication. Zidovudine has been shown in clinical trials to prolong survival of patients with acquired immune deficiency syndrome (AIDS) and advanced AIDS-related complex (ARC), and to delay progression to ARC or AIDS in patients with earlier disease. At the present time it is suggested that zidovudine be initiated when the CD4 lymphocyte count is less than 500 cells/mm3. Recent studies have suggested a delay in the development of AIDS in patients with CD4 counts over 500 cells/mm3, but ongoing studies will require confirmation. The adverse reactions associated with zidovudine have been well described. It appears that haematological toxicity is associated with both the dose and stage of disease. Anaemia may present more often within the first 3 months of therapy, whereas neutropenia can occur early or late. Mild headache and gastrointestinal intolerance may occur early and in some cases limit tolerance to the drug. A number of neurological adverse reactions have been reported rarely including seizures and dose-reduction encephalopathy. The most significant late adverse reaction is that of myopathy, which occurs in patients receiving zidovudine for more than 6 months. With careful monitoring, the adverse reactions of zidovudine are manageable and patient tolerance of the medication is acceptable.

Using serial observations to identify predictors of progression to AIDS in the Toronto Sexual Contact Study.

The Toronto Sexual Contact Study comprises a cohort of 249 male sexual contacts of men with HIV disease which has been followed every 3 months for almost 5 years. On enrollment 143 were seropositive and 16 seroconverted during the follow-up period. By 31 December 1989, 41 of the 159 seropositive cohort members had developed AIDS. Using Cox relative risk regression models, we investigated the association of a number of laboratory and clinical variables and progression to AIDS. Fixed covariate models examined laboratory variables from the enrollment visit of cohort members, with time calculated from this date. In models assessing time dependent covariates, time was calculated from the estimated date of HIV infection. In the univariate models of either fixed or time dependent covariates, many variables were significantly associated with risk of progression to AIDS (T4 cell count, T4/T8 ratio, blastogenic responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen, serum IgA, appearance of p24 antigen, and the development of oral hairy leukoplakia, thrush, or herpes zoster). Appearance of persistent generalized lymphadenopathy was not associated with increased risk of progression. In the multivariate model which evaluated fixed laboratory covariates, T4/T8 ratio, IgA level, and PHA response at enrollment were significantly associated with elevated risk.(ABSTRACT TRUNCATED AT 250 WORDS)

The probability of progression to AIDS in a cohort of male sexual contacts of men with HIV disease.

In a cohort of 249 male sexual contacts of men with AIDS or an AIDS-related condition (ARC), 143 cohort members were seropositive on enrollment and 16 seroconverted during follow-up. A logistic Weibull mixture model was used to estimate the probability of progression to AIDS after HIV infection when infection was assumed to occur during the period of sexual contact with the primary case. Forty cohort members developed AIDS while under study. It appears that at least 50% of men with HIV disease will progress to AIDS and that the best estimate of this probability lies anywhere in the interval 70% to 100%.

Sexual behaviour changes in a cohort of male sexual contacts of men with HIV disease: a three-year overview.

We describe the sexual behaviour reported by 240 seronegative and seropositive homosexual men over a 3-year period. Sexual partners of men with HIV disease were recruited into a prospective study between July 1984 and July 1985 and were monitored every 3 months thereafter. Data on sexual activities were collected through interviewer-administered questionnaires. The cohort experienced a reduction in both the number of sexual partners and the volume of sexual activity. Reductions in the number of partners were early and dramatic. Changes in sexual activities were gradual and consistent in trend. The greatest reduction occurred in high risk activities (receptive and insertive anal intercourse). After 3 years of follow-up, only 10% of the men continue to be exposed to semen through unprotected receptive anal intercourse and 18% through unprotected receptive oral-genital sex. The proportion of men engaging in oral-genital contact and masturbation remained stable over the 3 years. Once informed of their serostatus, both seropositive and seronegative men reduced their high risk behaviour. The decline in rates of STDs and seroconversion confirmed that this cohort had indeed reduced their high risk behaviour.

Comparison of three HIV antigen detection kits in sequential sera from a cohort of homosexual men.

HIV antigen detection kits are available from a number of commercial sources. Abbott, Coulter, and Du Pont antigen kits were used to test 661 sera collected sequentially from 65 members of the Toronto Sexual Contact Study (TSCS). The sera had been collected at 3-month intervals over 4 years from nine persistently HIV-seronegative men, 14 seroconverters, and 42 seroprevalent participants. Antigen was not detected in any seronegative men. Two of 14 seroconverters were antigen positive in the specimen immediately preceding seroconversion (by all kits). Antigen was detected in 22 of 56 seropositive participants; of these, 16 of 22 demonstrated the emergence of antigen during observation. Discrepancies were noted in the time of detection of antigen (ranging from 3 months to more than 3 years) in nine participants. Although overall concordance among all kits for all specimens appears high (95.4%), when the bias introduced by testing multiple specimens from the same patient is removed, the lower bound of concordance among all three kits is estimated to be 80%. Similarly, after correction, the upper and lower bound of estimates of sensitivity are Abbott 96, 92%; Coulter 88, 63%; and Du Pont 88, 58%. There are significant differences in the performance characteristics of these commercial products for the detection of HIV antigen in serum.

Cofactors of progression to acquired immunodeficiency syndrome in a cohort of male sexual contacts of men with human immunodeficiency virus disease.

In a cohort of 249 male sexual contacts of men with acquired immunodeficiency syndrome (AIDS) or an AIDS-related condition in Toronto, Ontario, Canada, 143 cohort members were seropositive on enrollment and 16 seroconverted between initial recruitment in July 1984 to July 1985 and December 1988. Data on age, smoking and drinking status, recreational drug use, and history of sexually transmitted diseases and other diseases were obtained from interviews at induction and during follow-up on the cohort members every 3 months. Cox relative risk regression models, in which time was calculated from estimated date of human immunodeficiency virus (HIV) infection for seroprevalent cohort members and from 90 days prior to the first positive test for seroconverters, examined the potential effect of use of a variety of recreational drugs and the occurrence of selected infections on the risk of development of AIDS. Thirty-five cohort members developed AIDS while under study. No significant association with risk of progression to AIDS was noted for use of various recreational drugs (singly or in combination), history of specific infections, age at enrollment, or smoking and drinking status at enrollment. Only estimated duration of HIV infection appeared to be associated with increasing risk of development of AIDS.

Foscarnet therapy of cytomegalovirus retinitis in AIDS.

Cytomegalovirus (CMV) retinitis is the most common cause of blindness in AIDS. Twenty patients were treated with a 21-day course of foscarnet therapy by continuous infusion. Response to therapy was good in eight (47%) of 17 evaluable patients; partial arrest of progression was observed in eight (47%); and no response was obtained in one (6%). Foscarnet therapy did not lead to suppression of urinary excretion of CMV in four of 12 patients who nonetheless had improvement in retinal lesions. Toxic effects, especially reversible renal failure, were common, with blood creatinine increase in 50% and dialysis in two patients. Renal toxicity occurred primarily during the third week of therapy. Anemia (hemoglobin less than 80 g/L) occurred in 10 patients after a mean of 14.5 +/- 5.1 days of therapy and required transfusion. Review of this study and of data from a previous case series, however, was inconclusive regarding the additional benefit of a third week of therapy. Maintenance therapy was given to seven patients. Four had recurrence of CMV retinitis at a mean interval of 62 +/- 52 days. Only one patient has maintained prolonged remission on maintenance (greater than 24 weeks). Toxicity on the maintenance protocol included anemia (two of seven patients) and increased creatinine blood levels (one of seven patients). Zidovudine therapy in six patients did not contribute to increased toxicity of induction or maintenance therapy. Drug levels during continuous infusion were stable for individual patients but showed wide inter-patient variability. Peak levels of post-maintenance infusion varied both within and between patients.

Kaposi's sarcoma and AIDS: a variable spectrum.

A cohort of 61 patients with Kaposi's sarcoma (KS) and AIDS was seen in the Oncology Unit of the Toronto General Hospital between 1982 and 1986. In an attempt to identify prognostic variables, laboratory and clinical parameters were examined using Kaplan-Meier estimates and the Cox Regression Model. All patients were male, median age 36 years (range 23-52). In 49 patients KS was diagnosed before any AIDS-associated opportunistic infection (OI). Three patients had concurrent KS and OI, and nine patients developed KS one or more months after an OI. Only 11 patients had stage I or II disease, 34 stage III, and 15 stage IV. Only 18 patients (30%) were asymptomatic. Twenty-six percent had fever, night sweats, or weight loss, 11% had minor opportunistic infections, and 33% had both symptom complexes. The median overall survival was 10.5 months. The survival of patients who received chemotherapy for their KS was not significantly different from the survival of non-treated patients (p = 0.7). Although significant differences in survival could not be seen between stages, patients with both systemic symptoms and minor opportunistic infections had significantly shorter survival (p = 0.03). Survival from the onset of KS was significantly shorter for patients who had experienced a previous OI, but their overall survival from the date of diagnosis of AIDS was not significantly different from those patients presenting with KS alone. When analyzed separately the laboratory parameters of hemoglobin (p less than 0.0001), absolute lymphocyte count (p = 0.03), platelet count (p = 0.04), and T4 level (p = 0.05) demonstrated a significant relationship with survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Validity of sexual histories in a prospective study of male sexual contacts of men with AIDS or an AIDS-related condition.

As part of a prospective study in Toronto, Canada of male sexual contacts of men with either acquired immunodeficiency syndrome (AIDS) or an AIDS-related condition (primary cases), separate interviews were conducted in 1984-1985 with primary cases and their corresponding sexual contacts. Seventy-five primary cases and their corresponding sexual contacts were asked details concerning the sexual activities involved in their sexual encounters. Spearman correlation coefficients were calculated for the responses regarding frequency of various sexual activities between the primary case and his corresponding contact. Comparison of responses revealed good to excellent correlations for the majority of the sexual activities. Regression analysis of responses (dependent variable = contact's response; independent variable = primary's response) revealed the tendency for primary cases to report greater numbers of various activities than sexual contacts, as illustrated by regression coefficients that were consistently less than unity. Agreement between primary responses and sexual contact responses appeared to be affected by the time lapsed from the last sexual encounter with the contact and the date of the primary case's interview. No effect on agreement was observed when primary case diagnosis and the total number of other sexual partners of primary cases were considered. The authors conclude that such data can be captured with sufficient reliability and validity for use in epidemiologic investigations to assess the risk of acquisition of human immunodeficiency virus for the more common forms of sexual activity. However, some caution may be necessary in interpreting the results for some activities (anal digit insertion, anilingus) since agreement is less satisfactory for these activities.

Risk factors for HIV infection in male sexual contacts of men with AIDS or an AIDS-related condition.

A total of 246 healthy male sexual contacts of men with either acquired immunodeficiency syndrome (AIDS) or an AIDS-related condition were recruited into a prospective study in Toronto, Canada between July 1984 and July 1985. At induction, data were collected on the sexual relationship between the contact and his primary case, sexual activities with other men, history of sexually transmitted diseases and other diseases, and use of recreational drugs. At recruitment, 144 sexual contacts had antibodies to human immunodeficiency virus (HIV); 102 of the contacts were seronegative at induction and at three months following recruitment. No association between HIV seropositivity and total number of sexual partners could be demonstrated. In univariate and multivariate analyses, receptive and insertive anal intercourse with the primary cases, and activities which either indicated or potentially caused anorectal mucosal injury (rectal douching, perianal bleeding, receipt of objects in ano, and receptive fisting) were strongly associated with HIV seropositivity. In the final multiple logistic regression model, two significant interaction effects were observed: the interaction between receptive anal intercourse and insertive anal intercourse and that between receptive anal intercourse and the anorectal mucosal injury index. These two interaction terms had negative regression coefficients which suggested that change in one sexual activity would not decrementally reduce risk of HIV infection without a comparable modification in the other activity. No association could be demonstrated between oral-genital and oral-anal sexual contact and odds ratios for these sexual activities declined to levels below 1.0 when adjusted for frequency of receptive anal intercourse.

Combination chemotherapy and alpha-interferon in the treatment of Kaposi's sarcoma associated with acquired immune deficiency syndrome.

Thirteen men with a median age of 37 (range 28 to 46) years who had extensive Kaposi's sarcoma associated with acquired immune deficiency syndrome (AIDS) were treated with combination chemotherapy and alpha-interferon. Four patients had stage III disease and nine had stage IV disease (one with pulmonary and eight with gastrointestinal involvement). Treatment consisted of monthly courses of actinomycin D, 1 mg/m2, and vinblastine sulfate, 6 mg/m2, given intravenously on day 1, bleomycin, 10 mg/m2 given intravenously on days 1 and 8, and human lymphoblastoid (alpha-) interferon, 10 million U/m2 given subcutaneously three times a week for six doses starting on day 14. Forty-one treatment cycles (median 3, range 1 to 12) were administered. The median granulocyte and platelet counts on day 14 before the start of interferon therapy were 600 X 10(9)/L and 134 X 10(9)/L respectively; the counts did not fall further during interferon therapy. There was no difference in T-cell subsets, 2',5'-oligoadenylate synthetase level or results of blastogenesis studies after interferon therapy. Four patients required admission to hospital for neutropenia-associated fever. A complete response (of 24 weeks' duration) was seen in one patient and a partial response (of 14 to 44 weeks' duration) in four. One patient had a mixed response, with regression of skin involvement but progression of pulmonary disease. The median length of survival was 48 (range 4 to 143) weeks. Eleven patients died of progressive Kaposi's sarcoma, one of lymphoma and one of Pneumocystis carinii pneumonia. The results suggest that this form of therapy is not appropriate for patients with Kaposi's sarcoma associated with AIDS.

Assessment of generalized lymphadenopathy in AIDS research: the degree of clinical agreement.

The degree of clinical agreement amongst different physicians on the presence or absence of generalized lymphadenopathy was assessed in 32 randomly selected participants from a prospective study of male sexual contacts of men with AIDS or an AIDS-related condition (ARC). Three physicians completed the same standard examination that was developed for the main project and conducted the examination of the anatomic regions in the same order on each person, at approximately the same time, and in random order. One physician (Doctor A) was the physician responsible for conducting examinations on the main cohort from which these participants were selected. Intra-observer agreement was assessed by comparing Doctor A's examinations on these participants with those he had recently conducted within a one and a half month period in the main study. Acceptable levels of intra-observer agreement (kappa = 0.72) and interobserver agreement (kappa = 0.66) were demonstrated for the presence or absence of generalized lymphadenopathy for Doctor A and Doctor B, a physician who periodically replaced Doctor A in the main project. Agreement between Doctors A, B, and C, was less satisfactory (kappa of 0.45 and 0.39, respectively). Doctor C was the least experienced with the standardized examination. However, during the progress of this study, agreement between the three doctors improved (kappa values for the latter 16 participants ranged from 0.60 to 0.86) suggesting that experience with the criteria and the standardization of the examination may enhance agreement.(ABSTRACT TRUNCATED AT 250 WORDS)

Lack of biological significance of in vitro Brugia malayi microfilarial cytotoxicity mediated by Propionibacterium acnes ("Corynebacterium parvum")-and Mycobacterium bovis BCG-activated macrophages.

The effect of nonspecific activation of host macrophages by Propionibacterium acnes ("Corynebacterium parvum") or Mycobacterium bovis BCG on Brugia malayi microfilariae was determined by in vitro and in vivo studies. Intraperitoneal injection of C. parvum or BCG stimulated peritoneal exudate cells, which were toxic to microfilariae. Microfilariae were equally susceptible to damage by C57BL/6J or BALB/cJ peritoneal exudate cells. Furthermore, inhibitors of oxidative metabolism and arginine supplementation did not prevent this toxicity, suggesting that the mechanism of microfilarial damage differs from that seen with another multicellular helminth, Schistosoma mansoni. In vivo studies with both BCG and C parvum, however, did not confirm the importance of nonspecific immunity in resistance to B. malayi microfilaremia. Despite the lack of biologic relevance of this phenomenon, in vitro studies may yield important knowledge about the mechanisms of microfilarial damage.