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Biomedical subjects

M T Schechter

Publications and source records attributed to M T Schechter.

At least 91 records · Page 5Linked to original sources
PubMed1997

Patterns of geographic mobility of persons with AIDS in Canada from time of AIDS index diagnosis to death.

OBJECTIVE: To characterize migration patterns of persons with AIDS in Canada during the period from AIDS diagnosis to death. DESIGN: Descriptive, population-based study. SETTING: Canada. PATIENTS: Canada's AIDS Case Reporting Surveillance System (ACRSS) was linked to deaths in the Canadian Mortality Data Base (CMDB). Probabilistic linkage was based on initials, date of birth, date of death, birthplace, and location at diagnosis and at death. Analysis was restricted to AIDS cases reported from Jan. 1, 1982, to Sept. 30, 1994, and to deaths reported from Jan. 1, 1982, to Dec. 31, 1992. MAIN OUTCOME MEASURES: Change in usual place of residence; migration rates by region and community size. RESULTS: A total of 5755 AIDS cases recorded in the ACRSS were linked to deaths in the CMDB. Of these linked cases, 5366 (93%) included information on province or territory of usual residence or community size. A total of 160 (3.0%) persons with AIDS changed their province or territory of residence between the time of their AIDS diagnosis and death. Multivariate analysis indicated that those who changed residences between AIDS index diagnosis and death were more likely than other persons with AIDS to live in provinces other than British Columbia, Ontario and Quebec (p < 0.001), to be diagnosed earlier (p = 0.004), to be younger (p < 0.001) and to be gay or bisexual (p = 0.042). CONCLUSIONS: Our analysis revealed that only a small proportion of persons changed their residence between AIDS diagnosis and death. Geographic mobility was the greatest among persons with AIDS residing outside of the regions where the overwhelming majority of persons with AIDS in this country reside.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Adherence to clinical guidelines for the therapeutic management of HIV disease.

OBJECTIVE: To determine the knowledge of HIV-disease management and the adherence to contemporary guidelines among British Columbia physicians whose practices focused on HIV/AIDS. DESIGN: Self-administered mail survey. PARTICIPANTS: All 659 physicians registered in a province-wide HIV/AIDS drug treatment program. OUTCOME MEASURES: Data on demographic and personal characteristics of respondents, level of HIV-related experience, use of preventive vaccinations and tests, and preferred approaches to the prophylaxis and treatment of common opportunistic infections. Knowledge scores in 4 areas of patient care, as well as an overall score, were computed by comparing respondents' answers with the therapeutic strategies recommended at the time of the survey. Associations between physician characteristics and knowledge scores were identified by linear regression analysis. RESULTS: Of the 659 physicians surveyed, 65% returned responses: only 38% returned completed surveys while a further 27% returned a follow-up survey that asked nonrespondents about their demographic characteristics and HIV-related experience. Scores for specific areas of patient management ranged from 29% for the treatment of opportunistic infections to 62% for preventive measures, with a mean overall score of 47%. Physician knowledge in all areas of patient care was associated with the number of HIV-positive patients in the practice (p = 0.003 to p < 0.001). Physicians who were younger were more knowledgeable regarding preventive measures (p = 0.001); those whose practice location was in Vancouver had a greater knowledge of prophylaxis (p = 0.047); and those who had medical specialty training were more knowledgeable about the treatment of opportunistic infections (p = 0.009). CONCLUSIONS: There is substantial disparity in how physicians approach the management of HIV and related conditions. Deviations from therapeutic guidelines are common and may be associated with physician characteristics, particularly lack of experience in managing HIV.

AIDS-Related Opportunistic Infections↗
PubMed1997

Social determinants predict needle-sharing behaviour among injection drug users in Vancouver, Canada.

Despite the fact that needle exchange was introduced in Vancouver as early as 1988, needle sharing remains common. An analysis was conducted to identify determinants of borrowing used needles among subjects participating in a case-control study. IDUs had a documented HIV seroconversion after 1 January, 1994 (n = 89), or repeatedly tested HIV-seronegative after this date (n = 192). Interviewer-administered questionnaires focused on drug use, sexual behaviours, source of needles and depression. Subjects were asked if they had "ever been forced to have sex" as a child, youth or adult. Logistic regression identified determinants of borrowing needles. After controlling for HIV serostatus, factors independently associated with borrowing were injecting > 4 times/day, polydrug use, and ever experiencing non-consensual sex (AOR = 3.4, 95% CI: 1.8, 6.5). Depression was associated with borrowing, although not independently so. Homosexual activity was independently associated with borrowing among males, whereas living with a sexual partner was an independent predictor for females. Access or barriers to clean needle use were not associated with borrowing. Social determinants, particularly a history of sexual abuse, are among the most significant predictors of needle borrowing among Vancouver's IDUs. Early identification of these factors should be a component of HIV prevention programmes.

Adult↗
PubMed1996

Should we embrace new drugs with open arms? Experience from a community-based, open-arm, randomized clinical trial of combination antiretroviral therapy in advanced HIV disease.

The effect of an open arm in the enrollment to a randomized clinical trial comparing zidovudine (ZDV) plus didanosine (ddI) versus ZDV plus zalcitabine (ddC) was assessed. HIV-infected individuals were eligible to participate in this protocol if they were ddI and ddC naive, had CD4 counts of 50-350/mm3, and were residents of the province of British Columbia. Participating individuals could choose between open-label ZDV/ddI, ZDV/ddC, or randomization to open-label ZDV/ddI or ZDV/ ddC. Study drugs were made available free of charge for all participants through a centralized drug distribution system. There is no other source of these drugs in the province. Primary care physicians were required to renew the patient's prescription every 2 months. Enrollment was initiated in November 1992 and was closed in March 1994 when the randomized arm of the protocol met the predetermined target sample size of 120 evaluable participants. A total of 582 patients received combination therapy in the province through this protocol: 138 (28%) enrolled in the randomized arm and 444 (76%) in the open arm. In the latter group, 320 (72%) were initially prescribed ZDV/ddI and 124 (28%) were prescribed ZDV/ddC. The enrollment rate was strikingly higher in the open arm, with 168 patients enrolled in the first 2 months compared with 138 patients enrolled in the randomized arm over 17 months. Of the 78 study physicians, 69 enrolled patients in the open arm and 23 enrolled patients in the randomized arm of the study. Experienced physicians were more likely to refer patients for randomization (p = 0.025). No statistically significant differences were observed between patients enrolled in either study arm. Our results illustrate the challenge posed to recruitment into clinical trials by the coexistence of an open arm. This is despite the noncoercive, open-label and community-based nature of our randomized protocol and the high priority given to it by a variety of local and national organizations. It is clear that an increased commitment by all interested parties will be required if randomized clinical trials are to be carried out with coexistent open arms.

Adult↗
PubMed1996

The XI International Conference on AIDS: at the crossroads of hope and urgency.

This month Canada will host the largest conference ever held on the worldwide epidemic of AIDS. More than 12,000 participants from over 130 countries are expected to convene in Vancouver from July 7 to 12 for the XI International Conference on AIDS. As at previous conferences, the program will be organized along four tracks: basic science, clinical science, epidemiology and public health, and social and behavioural science. The author notes that although in each of these areas there is reason to take heart, we must not become complacent in the fight against HIV infection and AIDS. The pandemic is still growing at an alarming rate, and governments need to be reminded that a failure to commit funding and resources to the extension of programs for AIDS research, prevention and care is both cynical and unwise. Now is the time to redouble our efforts, not to abandon them.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Double-blind placebo-controlled pilot trial of acemannan in advanced human immunodeficiency virus disease.

SUMMARY: We assessed the safety and surrogate markers' effect of acemannan as an adjunctive to antiretroviral therapy among patients with advanced HIV disease receiving zidovudine (ZDV) or didanosine (ddI) in a randomized, double-blind, placebo-controlled trial of acemannan (400 mg orally four times daily). Eligible patients of either sex had CD4 counts of 50-300/microl twice within 1 month of study entry and had received 26 months of antiretroviral treatment (ZDV or ddI) at a stable dose for the month before entry. CD4 counts were made every 4 weeks for 48 weeks. P24 antigen was measured at entry and every 12 weeks thereafter. Sequential quantitative lymphocyte cultures for HIV and ZDV pharmacokinetics were performed in a subset of patients. Sixty-three patients were randomized. All were males (mean age 39 years). The mean baseline CD4 counts were 165 and 147/microl in the placebo and acemannan groups, respectively; 90 percent of the patients were receiving ZDV at entry. Six patients in the acemannan group and five in the placebo group developed AIDS-defining illnesses. There was no statistically significant difference between the groups at 48 weeks with regard to the absolute change or rate of decline at CD4 count. Among ZDV-treated patients, the median rates of CD4 change (ACD4) in the initial 16 weeks were - 121 and - 120 cells per year in the placebo and acemannan groups, respectively ( p = 0.45), ACD4 from week 16 to 48 was 0 and - 61 cells per year in the acemannan and placebo groups (p = .11), respectively. There was no statistical difference between groups with regard to adverse events, p24 antigen, quantitative virology, or pharmacokinetics. Twenty-four patients, 11 receiving placebo and 13 receiving acemannan, discontinued study therapy prematurely, none due to serious adverse reactions. Our results demonstrate that acemannan at an oral daily dose of 1600 mg does not prevent the decline in CD4 count characteristic of progressive HIV disease. Acemannan showed no significant effect on p24 antigen and quantitative virology. Acemannan was well tolerated and showed no significant pharmacokinetic interaction with ZDV.

Administration, Oral↗
PubMed1996

Impact of missing data due to dropouts on estimates of the treatment effect in a randomized trial of antiretroviral therapy for HIV-infected individuals. Canadian HIV Trials Network A002 Study Group.

PURPOSE: To evaluate the impact of missing data due to nonrandom dropout on estimates of the effect of treatment on the CD4 count in a clinical trial of antiretroviral therapy for HIV infected individuals. METHODS: The effect of treatment on CD4 counts in a recent study of continued ZDV versus ddI in HIV-infected individuals was estimated from the observed data and after imputing missing CD4 counts for patients who dropped out of the study. Imputation methods studied were (a) carrying forward the last observed CD4 count, (b) predicting missing CD4 counts from regression models, and (c) assuming that CD4 counts of patients who dropped out declined at a rate of 100 cells per year. RESULTS: Of the 245 patients enrolled in the study, 52% completed the planned 48 weeks of follow-up. Patients with lower CD4 counts were more likely to drop out of the study (RR = 1.77; p = 0.0001). Patients receiving ZDV had a greater tendency to drop out than patients receiving ddI (p = 0.07). Mean CD4 counts calculated after imputing missing data were lower than those obtained from the observed data at all follow-up times for both treatment groups. Imputing CD4 counts with regression models yielded higher estimates of the effect of treatment than were obtained using the observed data. CONCLUSION: Missing outcome data due to dropouts can result in an underestimation of the treatment effect and overly optimistic statements about the outcome of participants on both treatment arms due to the selective dropout of participants with lower or decreasing CD4 counts. When there are significant dropout rates in randomized trials, imputation is a useful technique to assess the range of plausible values of the treatment effect.

Antiviral Agents↗
PubMed1996

Pattern of utilization of rifabutin for prophylaxis of Mycobacterium avium complex among patients with advanced human immunodeficiency virus disease in a community setting.

OBJECTIVE: To characterize the pattern of utilization, effectiveness, and safety profile of rifabutin for Mycobacterium avium complex (MAC) prophylaxis among individuals with advanced human immunodeficiency virus disease in a community setting. METHODS: Individuals who, while registered in the provincial drug distribution program, had at least one CD4 count below 100 cells/mm3 for the period 1 May 1993 to 31 March 1994 were included. MAC diagnoses were identified through a record linkage with the mycobacterial reference laboratory of the Provincial Centre for Disease Control. In order to determine the occurrence of adverse events, a survey was sent in March 1994 to the 98 primary care physicians prescribing rifabutin prophylaxis in the province. We achieved 100% response rate to the survey. RESULTS: During the study period 515 patients in our drug treatment program were eligible to receive MAC prophylaxis. Of these, 340 (66%) were being prescribed rifabutin as recommended by current guidelines. Rifabutin prophylaxis use was significantly associated with use of antiretroviral therapy. The product limit estimate of the cumulative incidence of MAC at 10 months was 13.0% among those receiving rifabutin prophylaxis. Diagnosis of MAC was significantly associated with a lower baseline CD4 count (cumulative incidence 7.1% and 18.1% for CD4 > or = 50 and < 50 cells/mm3, respectively, P = 0.01). A total of four cases of uveitis, eight cases of pseudo-jaundice, and five cases of arthralgia in 16 patients were identified by our survey. CONCLUSION: Our data demonstrates that rifabutin prophylaxis of MAC is being used by approximately 66% of eligible individuals. Rifabutin use was associated with antiretroviral use, which may reflect individuals' attitudes towards medications. Our intention-to-treat analysis, with a 10 month cumulative MAC incidence of 13.0% among those receiving rifabutin prophylaxis, is in keeping with break-through rates previously reported in the context of clinical trials. Our results also support previous observations that the risk of MAC infection greatly increases at CD4 counts < 50 cells/mm3. Rifabutin prophylaxis was generally well-tolerated in our program.

AIDS-Related Opportunistic Infections↗
PubMed1996

Variation in plasma RNA levels, CD4 cell counts, and p24 antigen levels in clinically stable men with human immunodeficiency virus infection.

Short-term variability in CD4 cell counts, plasma RNA levels, and p24 antigenemia was measured in clinically stable men with human immunodeficiency virus infection. Blood samples were obtained three times in each of 2 weeks 4 weeks apart. Differences between duplicate assays were considered to be due to technical factors; variation among visits was attributed to physiologic factors. Median enrollment values of CD4 cell counts, plasma RNA levels, and immune complex-dissociated (ICD) p24 antigenemia were 400 cells/mm3, 3.4 log10 copies/mL, and 38 pg/mL, respectively. Median absolute differences between duplicate CD4 cell counts, plasma RNA levels, and ICD p24 antigen were 16 cells/mm3, 0.21 log10 copies/mL, and 9.3 pg/mL. Median intraindividual ranges were 119 cells/mm3, 0.83 log10 copies/mL, and 18 pg/mL. Above 500 copies/mL, plasma RNA levels have a variability of 0.5 log10; the test is unreliable below this level.

CD4 Lymphocyte Count↗
PubMed1996

Epidemiology.

Explore the source record for details and available documents.

HIV Infections↗
PubMed1996

Lack of consistency between five definitions of nonprogression in cohorts of HIV-infected seroconverters.

OBJECTIVE: To identify appropriate criteria for characterizing HIV-infected nonprogressors. DESIGN: Five definitions were compared as follows: (1) last CD4 count > 500 x 10(6)/l; (2) two most recent CD4 counts > 500 x 10(6)/l; (3) calculated CD4 count based on linear regression > 500 x 10(6)/l; (4) CD4 slope > or = 0 with no antiretroviral use; (5) all CD4 counts > 500 x 10(6)/l, decline in CD4 slope < 5 cells per year, no antiretroviral use. PARTICIPANTS: Five prospective cohorts of homosexual men with documented dates of HIV-1 seroconversion. MAIN OUTCOME MEASURES: Proportions of nonprogressors were calculated 7, 8, 9 and 10 years following seroconversion (n = 285). Definitions were evaluated with respect to consistency over time and across sites. Subjects lacking CD4 counts within 3 years preceding end of follow-up were excluded. RESULTS: Across sites, proportions of nonprogressors ranged from 1% (definition 5) to 17.5% (definition 1) 10 years after seroconversion. Definitions based on absolute CD4 counts (definitions 1-3) had higher proportions and were less consistent than those based on stable slopes (definitions 4 and 5). For each definition, proportions decreased as follow-up increased, but were most stable for definition 4 (3%). Site differences decreased as follow-up increased, but remained nearly threefold for definitions 1-3. None of the definitions classified the same subjects as nonprogressors at any timepoint. CONCLUSIONS: Observations regarding nonprogression are highly dependent on the definition and the duration of follow-up. Our findings highlight methodological challenges which will need to be overcome in natural history studies of nonprogression.

CD4-Positive T-Lymphocytes↗
PubMed1996

Unexpected lung lesions in high resolution computed tomography (HRTC) among patients with advanced HIV disease.

The present pilot study was undertaken to characterize the frequency of lung lesions in asymptomatic human deficiency virus (HIV) infected individuals with advanced HIV disease. Thirty two consecutive HIV+ homosexual males assessed for initiation of Pneumocystis carinii pneumonia (PCP) prophylaxis, were prospectively studied. All patients underwent a complete medical history, physical examination, pulmonary function tests and high resolution computed tomography (HRCT). HRCT scans were read by a single radiologist, who was blind as to the clinical status of the patient. Unexpected HRCT scan lesions were found in 60% of patients. There were no statistically significant differences between patients with normal and abnormal HRCT with respect to age, height, weight, CD4+ count, smoking history, serum albumin, alpha 1-antitrypsin level or body mass index. Forced vital capacity (FVC) (% of predicted) and peak expiratory flow rate (PEFR) (% pred) were not significantly different between groups. For patients with normal and abnormal HRCT forced expiratory volume in one second (FEV1) (% pred) was 99 +/- 12 vs 92 +/- 16, FEV1/FVC was 82 +/- 5 vs 76 +/- 9, and forced mid-expiratory flow (FEF25-75) (% pred) was 100 +/- 24 vs 77 +/- 27, respectively. There were no statistically significant differences between patients presenting with destructive versus nondestructive lung HRCT lesions. Our results demonstrate that as many as 60% of HIV-infected patients have unexpected abnormalities on HRCT at the time of starting PCP prophylaxis. We speculate that these lesions may contribute to the high frequency of spontaneous pneumothoraces previously reported in this patient population.

Adult↗
PubMed1996

Adherence to guidelines for the prevention of HIV-related respiratory diseases.

In this study we characterized the pattern of use of preventive therapies for specific respiratory diseases within a cohort of homosexual men and assessed the impact of targeted feedback on the level of compliance with guidelines for these diseases. All human immunodeficiency virus seronegative (HIV-) (n=169) and acquired immune deficiency syndrome (AIDS)-free human immunodeficiency virus seropositive (HIV+) (n=154) participants in our cohort, who completed four annual visits between October 1989 and December 1993, were identified. Information about the use of purified protein derivative (PPD) (tuberculin) testing, history of pneumococcal vaccinations, influenza vaccinations, use of Pneumocystis carinii pneumonia (PCP) prophylaxis, symptoms and CD4 counts was obtained yearly for each subject. In 1992, participating physicians were provided with feedback regarding the overall levels of compliance with contemporary guidelines for the prevention of respiratory disease. As part of this exercise, the guidelines were distributed and discussed. The percentage of HIV+ patients who underwent PPD testing increased from 43 to 65% during the study (p=0.001). Significantly more HIV+ than HIV- patients underwent PPD testing (p<0.001). A total of 144 (94%) HIV+ men received at least one influenza vaccination compared to 60 (35%) HIV- men (p<0.001). Utilization of influenza vaccination in the HIV+ group significantly increased from 78% in 1992 to 92% in 1993 (p<0.001). A total of 104 (68%) HIV+ men received pneumococcal vaccination compared to 2 (1%) HIV- men (p<0.001). Among HIV+ individuals whose absolute CD4+ count was less than 200 cells x mm(-3), the percentage of men who received primary PCP prophylaxis was 0, 86, 72 and 88 for the years 1990-1993, respectively. Among HIV+ patients whose only eligibility criterion for PCP prophylaxis was a CD4+ percentage <20%, compliance was 55, 30, 37 and 50% for the years 1990-1993, respectively. Among HIV+ subjects, increases in the compliance level were noted for all preventive therapies after targeted feedback was provided during the last quarter of 1992. However, only utilization of influenza vaccine exceeded a 90% compliance in 1993. These data demonstrate that a suboptimal level of compliance with current guidelines for the prevention of respiratory disease among human immunodeficiency virus-infected individuals can be significantly improved using targeted feedback. Although it is likely that similar effects could be achieved in other populations or the community at large, this remains to be demonstrated.

AIDS-Related Opportunistic Infections↗
PubMed1996

Heterogeneity of physician agreement with recommended therapeutic guidelines for the management of HIV-associated disease.

The aims of this study were to assess the degree of heterogeneity in the knowledge of therapeutic management of HIV infection among HIV-experienced physicians in British Columbia, Canada, and to identify associations between physician characteristics and their agreement with contemporary therapeutic guidelines. A self-administered anonymous questionnaire was mailed to 6500 physician members of the British Columbia Medical Association. The questionnaire provided information about demographic and personal characteristics, including sex, age, medical specialization and practice location; level of experience in treating HIV-infected patients; use of HIV testing procedures; use of preventative vaccinations and tests; and preferred approaches to antiretroviral therapy and the prophylaxis and acute treatment of opportunistic infections. We compared physicians' patterns of knowledge with contemporary recommendations. Logistic regression identified associations between physician characteristics and their agreement with contemporary guidelines. A total of 463 HIV-experienced physicians (a high proportion of the HIV-experienced physicians in British Columbia, Canada) responded to the questionnaire. The agreement with contemporary guidelines about HIV testing and preventative vaccinations and tests among responders ranged from 27% to 71%. For antiretroviral therapy, agreement with the guidelines ranged from 12% to 35%. For the prophylaxis and treatment of opportunistic infections, agreement with the guidelines ranged from 11% to 89% (prophylaxis) and from 46% to 91% (treatment). Regression analysis revealed that physicians actively involved in the care of HIV-infected patients were more likely to agree with the guidelines in all areas of patient care. General practitioners were more likely to agree with the guidelines regarding preventative therapies, and male general practitioners under 45 years old were more likely to agree with the guidelines on antiretroviral therapy. Our data confirm that there is substantial heterogeneity in the management of HIV-associated disease, including some deviations from contemporary guidelines. Concordance with contemporary guidelines increased with the physician's level of HIV-related experience. Our results support the idea that adherence to state-of-the-art practices may be responsible, at least in part, for the recently described association between physician experience and improved survival of HIV-infected individuals.

AIDS-Related Opportunistic Infections↗