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Biomedical subjects

N S Weiss

Publications and source records attributed to N S Weiss.

At least 19 recordsLinked to original sources

Volunteer bias in nonrandomized evaluations of the efficacy of needle-exchange programs.

OBJECTIVE: Nonrandomized comparisons of the incidence of HIV and hepatitis B and C between injection drug users (IDUs) who do and do not attend voluntary needle-exchange programs may be subject to bias. To explore possible sources of bias, we examined characteristics associated with voluntarily beginning or ceasing to participate in the Seattle needle exchange. METHODS: In a cohort of 2,879 IDUs, a standardized questionnaire measured characteristics present at enrollment. We examined the relation of these characteristics to the proportion of IDUs who began to use the program during the ensuing 12-month follow-up period and to the proportion of current exchangers who dropped out during that period of time. RESULTS: Of the 494 never-exchangers at baseline, 32% attended the exchange program during follow-up; those who reported sharing syringes or who were homeless at enrollment were more likely to become new exchange users (adjusted risk ratio [ARR] for becoming an exchange user = 1.8 for those who shared syringes, and ARR = 2.2 for those who were homeless). Of 1,274 current exchangers, 16% stopped using the exchange during followup, with daily injectors (ARR = 0.6) and those who reported backloading (ARR = 0.6) being relatively less likely to drop out of the exchange. CONCLUSIONS: The analysis suggests that IDUs participating in needle-exchange programs at a given point in time may include a particularly high proportion of those injectors whose pattern of drug use puts them at elevated risk of blood-borne viral infections.

Adult↗

Adherence to postmenopausal hormone therapy during the year after the initial prescription: A population-based study.

OBJECTIVE: In randomized trials a higher proportion of women prescribed continuous combined hormone replacement therapy complete the full course of treatment compared with those prescribed sequential therapy. We sought to determine adherence to hormone therapy in a less-selected population. STUDY DESIGN: Women enrolled in a prepaid health plan participated in a telephone interview 12 to 15 months after newly initiating use of hormone replacement therapy. The interview elicited information on whether the women were still taking the hormones as first prescribed and reasons for switching or discontinuation. A computerized pharmacy database was used to determine initial doses, prescription renewal, and dates of switching or discontinuation. RESULTS: The proportion continuing the originally prescribed hormone regimen at 1 year was higher among continuous combined therapy users (68.9%, 62/90) than among sequential therapy users (54.4%, 62/114). Women who initiated continuous combined therapy were less likely to have switched regimens (10.0%) than were sequential users (20.2%; relative risk, 0.5; 95% confidence interval, 0.2-1.0) but only somewhat less likely to have discontinued use (21.2% vs 25.4%; relative risk, 0.7; 95% confidence interval, 0.4-1.3). Examined as a whole, women prescribed continuous combined therapy were less likely than those prescribed sequential therapy to quit or switch during the first year (relative risk, 0.6; 95% confidence interval, 0.4-1.0). CONCLUSION: Although adherence was higher among women prescribed continuous combined hormone replacement therapy than sequential therapy, the high level of nonadherence in both groups suggests room for improvement of menopausal therapies so that women find them acceptable for sustained use.

Aged↗

Fetal antigen hypothesis and ovarian cancer: is there an immunogenic explanation for the reduction in risk associated with parity?

The hypothesis that a woman's immunologic response to fetal antigens arising from paternal genes may explain some of the reduction in risk of ovarian cancer associated with parity has not, to our knowledge, been examined. We analyzed data from a case-control study to evaluate the risk of epithelial ovarian cancer among women of similar parity associated with proposed indices of paternally derived fetal antigen exposure. Cases included white women 20-79 years of age diagnosed with epithelial ovarian cancer in three counties in Washington State between January 1, 1986, and December 31, 1988 (N = 322). Controls (N = 426) were selected by random-digit dialing and were broadly similar to cases in age and county of residence. After excluding women who had fewer than two pregnancies (or, in some analyses, fewer than two livebirths) and adjusting for age and number of livebirths, we observed no reduction in risk associated with number of marriages or number of partners with whom a study participant conceived a pregnancy and/or had a child. Nevertheless, these relatively crude indices of exposure to paternally derived fetal antigens do not preclude the possibility that a woman's response to other fetal or pregnancy-related antigens may antagonize the development of ovarian cancer.

Adult↗

Outcome of children who require mechanical ventilatory support after bone marrow transplantation.

OBJECTIVE: To identify clinically measurable factors that could predict outcome for pediatric patients undergoing mechanical ventilatory support after bone marrow transplant. DESIGN: Cohort study. SETTING: A referral center for bone marrow transplant patients in Seattle, Washington. PATIENTS: Children <17 yrs old who received a bone marrow transplant and subsequently required mechanical ventilatory support for > or =24 hrs between 1983 and 1996. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were abstracted from the charts of 121 pediatric patients who received a bone marrow transplant and subsequently required mechanical ventilatory support. A total of 19 patients (16%) survived to be extubated and survived for > or =30 days postextubation. Major risk factors for death included respiratory failure as the reason for endotracheal intubation (4% survival), the presence of pulmonary infection (6% survival), and impairment of more than one organ system (2% survival if more than one organ system was dysfunctional on day 7 postintubation). CONCLUSIONS: Although the prognosis generally is poor among pediatric bone marrow transplant recipients who subsequently require mechanical ventilatory support, there appear to be some groups within this population in whom the likelihood of survival is close to 0. Because the chance of survival was so small for children with dysfunction of more than one organ system on day 7 after intubation, a recommendation to limit medical support for these children could be considered pending the results of other studies.

Adolescent↗

Glutathione S-transferase theta 1 gene deletion and risk of acute myeloid leukemia.

Individuals with a homozygous deletion of the glutathione S-transferase theta 1 (GSTT1) gene lack GSTT1 enzymatic detoxification of environmental carcinogens by conjugation with glutathione. The GSTT1 gene deletion has been associated with carcinogen-induced chromosomal changes in lymphocytes, and some but not all epidemiological evidence has suggested that the GSTT1 gene deletion may increase susceptibility to myelodysplasia. We conducted a case-control study to test whether individuals with an inherited homozygous deletion of the GSTT1 gene are at increased risk of acute myeloid leukemia (AML). The GSTT1 and GST mu 1 (GSTM1) genotypes were determined by PCR using lymphocyte or bone marrow DNA from 297 AML patients and 152 controls. AML patients were selected from Southwest Oncology Group clinical studies, and controls were identified by random digit dialing in Washington state. No association was observed between the GSTT1 gene deletion and AML [race-adjusted odds ratio (OR), 0.94; 95% confidence interval (CI), 0.55-1.60] or between the GSTM1 gene deletion and AML (race-adjusted OR, 1.26; 95% CI, 0.85-1.88). Patients with secondary AML had a slightly higher prevalence of the GSTT1 and GSTM1 gene deletions compared with de novo AML patients or controls, but this was consistent with chance. Exploratory analyses of AML cytogenetics suggested a few associations, i.e., between the GSTT1 gene deletion and trisomy 8, and between the GSTM1 gene deletion and non-8 trisomies or inv(16). These results do not support the hypothesis that the GSTT1 gene deletion is related to the incidence of AML.

Acute Disease↗

Glutathione S-transferase M1 genotypes and the risk of squamous carcinoma of the cervix: a population-based case-control study.

The authors determined the GSTM1 genotype of 190 Caucasian women with invasive squamous cell cervical cancer in western Washington State between January 1986 and June 1994 and of 206 controls. It was found that 53% of cases and 57% of controls had the GSTM1 null genotype. The age-adjusted odds ratio associated with GSTM1 null genotype was 0.8 (95% confidence interval 0.6, 1.3). The lack of association between cervical cancer risk and GSTM1 genotype was true both for smokers and nonsmokers of cigarettes and for heavy and light smokers. These data suggest that women with the GSTM1 null genotype are not at increased risk of cervical cancer.

Adult↗

Glutathione S-transferase M1 genotypes and the risk of vulvar cancer: a population-based case-control study.

Glutathione S-transferases (GSTs) facilitate the excretion of a variety of potential carcinogens. Some 50-60% of Caucasians are homozygous for the null allele of GSTM1, a gene responsible for the presence of one of these enzymes. The authors examined whether women with the GSTM1 null genotype are at altered risk of vulvar cancer. They obtained peripheral blood specimens from 18- to 79-year-old residents of King, Pierce, and Snohomish counties of western Washington who were diagnosed with vulvar cancer between April 1991 and June 1994. Blood specimens were also obtained from controls identified via random digit telephone dialing of western Washington households. The authors determined the GSTM1 genotype of 137 cases (120 in situ and 17 invasive cases) and 248 controls. The frequency of the GSTM1 null genotype was 46.7% among cases and 57.3% among controls. The age-adjusted odds ratio associated with the GSTM1 null genotype was 0.7 (95% confidence interval: 0.4, 1.0). Among current smokers of cigarettes, the age-adjusted odds ratio associated with the GSTM1 null genotype was 0.5 (95% confidence interval: 0.2, 0.9), differing little between heavy and light smokers. Our data suggest that women with the GSTM1 null genotype are not at increased risk of vulvar cancer.

Adult↗

Incidence of testicular cancer in the United States: has the epidemic begun to abate?

In response to a report that testicular cancer incidence in non-Hispanic White males in Los Angeles county had fallen in the 1990s, particularly in young men, the authors analyzed data collected by the Surveillance, Epidemiology, and End Results (SEER) program from 1973 to 1995. While the incidence rate of testicular cancer in US White males ages 15-64 years did stabilize in the first half of the 1990s, after a number of years of a steady increase, there was no indication of an actual decline.

Adolescent↗

Pregnancy after breast carcinoma: outcomes and influence on mortality.

BACKGROUND: To the authors' knowledge, no previous studies have identified an adverse effect of pregnancy on patient survival after breast carcinoma. However, results are difficult to interpret because of failure to control for stage of disease at the time the pregnancy occurred. METHODS: Study participants were women diagnosed with invasive breast carcinoma between 1983-1992 who previously had participated in a population-based case-control study or, if deceased, proxy respondents. Information regarding subsequent pregnancies was obtained by self-administered questionnaire or telephone interview. Information regarding breast carcinoma recurrences was obtained by questionnaire and from cancer registry abstracts. Women who became pregnant after a diagnosis of breast carcinoma (n = 53) were matched with women without subsequent pregnancies based on stage of disease at diagnosis and a recurrence free survival time in the comparison women greater than or equal to the interval between breast carcinoma diagnosis and onset of pregnancy in the women with a subsequent pregnancy. RESULTS: Sixty-eight percent of women who became pregnant after being diagnosed with breast carcinoma delivered one or more live-born infants. Miscarriages occurred in 24% of the patients who became pregnant compared with 18% of the controls (women without breast carcinoma) of similar ages from the case-control study. Five of the 53 women who had been pregnant after breast carcinoma died of the disease. The age-adjusted relative risk (RR) of death associated with any subsequent pregnancy was 0.8 (95% confidence interval [95% CI], 0.3-2.3). All five deaths occurred among the 36 women who had a live birth (age-adjusted RR = 1.1; 95% CI, 0.4-3.7). CONCLUSIONS: The findings of the current study are based on a small number of deaths but do not suggest that pregnancy after a diagnosis of breast carcinoma has an adverse effect on survival.

Adult↗

Logistic regression analysis for more than one characteristic of exposure.

When more than one characteristic of an exposure is under study, it is easy to misinterpret the results of a logistic regression analysis that incorporates terms for each characteristic. For example, in a study of the risk of endometrial cancer in relation to the duration and the recency of use of estrogen replacement therapy (ERT), simultaneously including terms for duration and recency of exposure to ERT in a logistic model may leave the mistaken impression that it is possible to adjust for recency when a given duration of ERT use is compared with no use. In this article, the authors show why such an adjusted comparison is impossible, and they discuss several pitfalls in the interpretation of logistic regression coefficients when two or more characteristics of exposure are under study. They also suggest a method for avoiding these pitfalls.

Confounding Factors, Epidemiologic↗

Hypertension, antihypertensive medication use, and risk of renal cell carcinoma.

To investigate whether diuretic medication use increases risk of renal cell carcinoma (RCC), the authors conducted a case-control study of health maintenance organization members in western Washington State. Cases (n = 238) diagnosed between January 1980 and June 1995 were compared with controls (n = 616) selected from health maintenance organization membership files. The computerized health maintenance organization pharmacy database provided information on medications prescribed after March 1977. Additional exposure information was collected from medical records. For women, use of diuretics was associated with increased risk of RCC (odds ratio (OR) = 1.8, 95% confidence interval (CI) 1.0-3.1), but the association was not independent of a diagnosis of hypertension (adjusted for hypertension, OR = 1.1, 95% CI 0.5-2.1). Similarly, nondiuretic antihypertensive use was associated with increased risk, but only when unadjusted for hypertension. For men, neither diuretic nor nondiuretic antihypertensive use was associated with risk of RCC. A diagnosis of hypertension was clearly associated with RCC risk for women (OR = 2.5, 95% CI 1.2-5.1), but not men (OR = 1.3, 95% CI 0.7-2.5). High systolic and diastolic blood pressures were associated with increased risk in both sexes. These results do not support the hypothesis that use of diuretic medication increases RCC risk; they are more consistent with an association between RCC and high blood pressure.

Adolescent↗

Syringe exchange and risk of infection with hepatitis B and C viruses.

The authors utilized a cohort study among Seattle injection drug users (IDUs) to assess whether participation in a syringe exchange program was associated with incidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Susceptible IDU subjects (187 seronegative for antibody to HCV, and 460 seronegative for core antibody to HBV) were identified in drug treatment, corrections, and social service agencies from June 1994 to January 1996, and followed for seroconversion one year later. The subjects included in the analysis were Seattle-King County (Washington State) area IDUs enrolled in a larger multipurpose cohort study, the Risk Activity Variables, Epidemiology, and Network Study (RAVEN Study). There were 39 HCV infections (20.9/100/year) and 46 HBV infections (10.0/100/year). There was no apparent protective effect of syringe exchange against HBV (former exchange users, relative risk (RR) = 0.68, 95% confidence interval (CI) 0.2-2.5; sporadic exchange users, RR = 2.4, 95% CI 0.9-6.5; regular users, RR = 1.81, 95% CI 0.7-4.8; vs. RR = 1.0 for nonusers of the exchange; adjusted for daily drug injection). Neither did the exchange protect against HCV infection (sporadic users, RR = 2.6, 95% CI 0.8-8.5; regular users, RR = 1.3, 95% CI 0.8-2.2; vs. RR = 1.0 for nonusers; adjusted for recent onset of injection and syringe sharing prior to enrollment). While it is possible that uncontrolled confounding or other bias obscured a true beneficial impact of exchange use, these data suggest that no such benefit occurred during the period of the study.

Adult↗

Natural history of interstitial cystitis in 274 patients receiving sulfated polysaccharide therapy.

OBJECTIVES: To assess the natural history of interstitial cystitis in the presence of sulfated polysaccharide treatment. METHODS: This was a longitudinal study of 274 patients. Questionnaires were administered at first visit to obtain information on demographic characteristics, medical history, other risk factors, and type and severity of symptoms. Follow-up questionnaires were administered at subsequent visits to measure symptom progress. Patient status over time was measured for three symptoms: pain, urgency, and nocturia. Changes in symptom and severity were assessed at 6, 12, and 24 months on treatment. Comparisons of symptom change from baseline to 6 and 12 months were assessed for different characteristics among patients with the most severe symptoms. RESULTS: After 1 year of treatment, a decrease of two or more points in symptom score was observed for 33.5% of all patients for pain and 35.4% for urgency. Among patients with the most severe symptoms, a decrease of two or more points was observed in more than 54% for pain and urgency; 55.7% experienced remission to the moderate and mild level (49.2% and 6.5%, respectively). There was no appreciable decrease in nocturia at any severity level. With the exception of feeling heavy and experiencing dull pain at baseline, patients who did not report a specific type of pain improved more than those who did. CONCLUSIONS: The results of this study suggest that treatment with sulfated polysaccharides can help alleviate the symptoms of patients suffering from the most severe stages of interstitial cystitis.

Adult↗