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.

Tissue irritation, as evidenced by phlebitis, associated with Optiva (Johnson & Johnson Medical) and Insyte (Becton Dickinson) polyurethane cannulae was studied. The integrity of the cannulae on removal, the incidence of infection at the cannula site and the factors which influence phlebitis were also examined. One thousand and eight patients had a polyurethane cannula placed for induction of anaesthesia for cardiac surgery. After surgery, the cannula was examined every 24 hours. If evidence of phlebitis occurred, the cannula was removed and sent for culture. All remaining cannulae were removed at 72 hours and the site examined daily for a further three days. There were 503 Optiva and 505 Insyte cannulae studied. The distributions between the two cannulae with respect to patient characteristics, gauge of cannula, number of attempts and difficulty of insertion, cannula site and anaesthetist inserting were similar. The early removal rate for both groups was 47%. Overall phlebitis rate with Optiva was 31% and Insyte 33%. This difference is not statistically significant. The cumulative phlebitis rate increased with time but did not differ between the two types of cannulae. Minor tip distortion or shaft kinking of the cannulae occurred in 16.2% of Optiva and 23.5% of Insyte. This difference is statistically significant and may relate to the slightly more acute taper at the Optiva cannula tip. Both cannulae were similar in clinical performance.

To study local structures in proteins, we previously developed an autoassociative artificial neural network (autoANN) and clustering tool to discover intrinsic features of macromolecular structures. The hidden unit activations computed by the trained autoANN are a convenient low-dimensional encoding of the local protein backbone structure. Clustering these activation vectors results in a unique classification of protein local structural features called Structural Building Blocks (SBBs). Here we describe application of this method to a larger database of proteins, verification of the applicability of this method to structure classification, and subsequent analysis of amino acid frequencies and several commonly occurring patterns of SBBs. The SBB classification method has several interesting properties: 1) it identifies the regular secondary structures, alpha helix and beta strand; 2) it consistently identifies other local structure features (e.g., helix caps and strand caps); 3) strong amino acid preferences are revealed at some positions in some SBBs; and 4) distinct patterns of SBBs occur in the 'random coil' regions of proteins. Analysis of these patterns identifies interesting structural motifs in the protein backbone structure, indicating that SBBs can be used as 'building blocks' in the analysis of protein structure. This type of pattern analysis should increase our understanding of the relationship between protein sequence and local structure, especially in the prediction of protein structures

A major AIDS meeting ended here today with the hope that some of the experimental drugs reported on will ultimately ease the burden of patients who must adhere to difficult regimens when they take the drugs that are now available. Speakers at the meeting, which drew more than 2,300 AIDS experts and other scientists, said they had been astonished by the favorable turn of events since last year's AIDS conference, when combination drug therapies were first shown to be able to suppress H.I.V., the virus that causes AIDS, below the limits of detection. The combination therapies use older drugs like AZT and a new class of drugs, protease inhibitors. Many participants said they had come to believe that when a therapy failed in a patient, any newly prescribed regimen should include at least two drugs that the patient had never taken. However, that strategy cannot work for the many patients who have taken virtually every licensed and experimental drug and who desperately need new drugs, Dr. Harvey J. Makadon, an AIDS expert at Beth Israel Hospital in Boston, said in an interview

A major AIDS meeting ended here yesterday with the hope that some of the experimental drugs reported on will ultimately ease the burden of patients who must adhere to difficult regimens when they take the drugs that are now available. Speakers at the meeting, which drew more than 2,300 AIDS experts and other scientists, said they had been astonished by the favorable turn of events since last year's AIDS conference, when combination drug therapies were first shown to be able to suppress HIV, the virus that causes AIDS, below the limits of detection. The combination therapies use older drugs like AZT and a new class of drugs, protease inhibitors

When [Paul E. Tsongas] ran unsuccessfully for the Democratic nomination in the 1992 presidential campaign, he made an issue of his survival from a form of cancer known as non-Hodgkin's lymphoma. But Tsongas and his doctors at the Dana-Farber Cancer Institute in Boston, Ronald W. Takvorian and George P. Canellos, repeatedly said he had been cancer-free when he had not. In so doing, they implied that the cancer was cured when indeed it was not curable. Tsongas' death Jan. 18 from pneumonia at age 55 came two days shy of what would have been a full term. The pneumonia was the final, fatal complication of many complications for treatment for non-Hodgkin's lymphoma that he had battled since 1983. In his fight, Tsongas underwent two bone marrow transplants, in 1986 and last May. PHOTO 1 PHOTO 2; Caption: Ex-Sen. Paul E. Tsongas appears at a medical conference in November, less than two months before his death. Handicap: If Paul E. Tsongas, shown campaigning for president in Baltimore, had won, he might have have been forced by his illness to resign, been unable to run again or have died in office.; Credit: ASSOCIATED PRESS ASSOCIATED PRESS: 1992

For the first time since the AIDS epidemic was recognized in 1981, deaths from the disease in New York City dropped sharply last year, declining by 30 percent, a city Health Department official said Friday. Dr. Mary Ann Chiasson, assistant commissioner for disease intervention research, said that the number of people who died from the disease fell to 4,944 in 1996 from 7,046 in 1995, and that the decline occurred in all ethnic groups and in both sexes. For unknown reasons, the drop was greater among men than women

For the first time since the AIDS epidemic was recognized in 1981, deaths from the disease in New York City dropped sharply last year, declining by 30 percent, a City Health Department official said today. ''It's great news, and we haven't had a lot of that in the AIDS epidemic,'' Dr. Harold W. Jaffe, an AIDS expert at the Federal Centers for Disease Control and Prevention in Atlanta, said at a news conference on the New York City report. Dr. Lars O. Kallings of Stockholm, a leader in international AIDS research, said ''the data were very impressive and will have global importance because widespread publicity has focused attention on New York City's epidemic.'' He said that because so many of New York's AIDS cases are among the poor, the new statistics would offer hope to poor nations with intractable AIDS problems

Dr. David Ho, a leading AIDS scientist, said here today that he had pushed back by up to a year his plans to do crucial tests to determine whether infection with the AIDS virus can be cured in some people. Then Dr. Ho's team at the Aaron Diamond AIDS Research Center in Manhattan would test the individual repeatedly to determine if H.I.V. could be detected again. Today, Dr. Ho said that ''we have never popped the question with our patients'' to stop therapy to test the theory that AIDS might be curable. He spoke at a news conference before opening an AIDS meeting here tonight with a talk entitled: ''Can H.I.V. Be Eradicated From an Infected Person?''