Craig J. Newschaffer

THE EFFICACY OF EARLY ADJUVANT RADIATION THERAPY FOR pT3N0 PROSTATE CANCER: A MATCHED-PAIR ANALYSIS

PURPOSE: This study examines the effect of adjuvant radiation therapy (RT) on outcome in patients with pT3N0 prostate cancer and makes comparisons to a matched control group. METHODS AND MATERIALS: At our center, 149 patients undergoing radical prostatectomy were found to have pT3N0 prostate cancer, had an undetectable postoperative prostate-specific antigen (PSA) level, and had no immediate hormonal therapy. Fifty-two patients received adjuvant RT within 3 to 6 months of surgery. Ninety-seven underwent radical prostatectomy alone and were observed until PSA failure. From these two cohorts, we matched patients 1:1 according to preoperative PSA ( 10 ng/ml), Gleason score ( or =7), seminal vesicle invasion, and surgical margin status. Seventy-two patients (36 pairs) were included in the analysis. Median follow-up time was 41 months. We calculated a matched-pairs risk ratio for cumulative risk of PSA relapse (a rise above 0.2 ng/ml). RESULTS: After controlling for the prognostic factors by matching, there was an 88% reduction (95% confidence interval [CI]: 78-93%) in the risk of PSA relapse associated with adjuvant RT. The 5-year freedom from PSA relapse rate was 89% (95% CI: 76-100%) for patients receiving adjuvant RT as compared to 55% (95% CI: 34-79%) for those undergoing radical prostatectomy alone. CONCLUSIONS: These data suggest that adjuvant RT for pT3N0 prostate cancer may significantly reduce the risk of PSA failure as compared to radical prostatectomy alone. Its effect on clinical outcome awaits further follow-up.

Adherence to antiretroviral therapy by pregnant women infected with human immunodeficiency virus: a pharmacy claims-based analysis.

Objective To assess adherence to antiretroviral therapy with the use of Medicaid pharmacy claims data for human immunodeficiency virus (HIV)-infected pregnant women and to identify associated maternal and health care factors. Methods We retrospectively studied a cohort of 2714 HIV-infected women in New York State who delivered live infants from 1993–96. Among 682 women prescribed antiretroviral therapy in the last two trimesters, we studied 549 who started therapy more than 2 months before delivery. Adherence was defined as adequate if the supplied drug covered at least 80% of the days from the first prescription in the last two trimesters until delivery. Multivariable analyses were used to examine associations between maternal and health care factors and adherence. Results Only 34.2% of 549 subjects had at least 80% adherence based on pharmacy data, a rate that remained stable over time. The adjusted odds ratios (ORs) of adherence for black (OR 0.47, 95% confidence interval [CI] 0.30, 0.75) and Hispanic (OR 0.49, 95% CI 0.29, 0.82) women were nearly 50% lower than for white women. The OR of adherence was 0.32 (95% CI 0.12, 0.90) for teenagers compared with women aged 25–29 years and 0.56 (95% CI 0.34, 0.92) for women in New York City versus those residing elsewhere. Women on antiretroviral therapy before pregnancy were more likely to adhere (OR 1.55, 95% CI 1.02, 2.35). Conclusion Teenagers, women of minority groups, and women living in New York City had greater risks of poor antiretroviral adherence, whereas women already prescribed antiretrovirals before pregnancy had better adherence. Our conservative pharmacy data–based measure showed that most HIV-infected women adhered poorly and adherence did not improve over the 4-year study.

Translating clinical trial results into practice: the effect of an AIDS clinical trial on prescribed antiretroviral therapy for HIV-infected pregnant women.

Community practitioners have usually been slow to adopt advances from clinical trials, and serious deficiencies in the use of these advances can continue for years (1-3). Because of the urgent need to make major advances in combating HIV and the serious consequences of a slow response to such advances, policymakers, medical leaders, and community activists have strenuously promoted their adoption in community practice. Few clinical trials have received as much widespread publicity and attention as Pediatric AIDS Clinical Trials Group (PACTG) Protocol 076 (4). This trial resulted in the first major breakthrough in HIV prevention: Vertical transmission of HIV decreased by two thirds when women received zidovudine therapy in the second and third trimester of pregnancy, as well as intrapartum, and their children received a short course of zidovudine after delivery. Because of these dramatic findings, the trial was terminated in February 1994 after its first interim analysis, and the results were announced. Diverse approaches were used to educate patients and providers about PACTG Protocol 076, including news media (5), state and Public Health Service expert panel endorsement and treatment guidelines (6), direct mailings to practitioners, and community-based educational efforts that targeted women with or at risk for HIV infection (7). Publication of the trials findings in November 1994 was met with further efforts to ensure that this preventive intervention would be used in community practice. We sought to evaluate the pace at which prescribed antiretroviral treatment for HIV-infected pregnant women enrolled in the New York State Medicaid program changed after PACTG Protocol 076 and to identify factors of health care delivery associated with early adoption of this new standard of care. We expected that women whose providers were under state contract to deliver HIV-focused ambulatory services and coordination of care (8, 9) would be more likely to receive antiretroviral therapy because of the beneficial effect of HIV-experienced care on survival (10, 11) and on appropriate use of HIV-related treatments (12). We also predicted that women who were treated at an institution conducting trials to prevent vertical transmission would be more likely to benefit from the PACTG Protocol 076 advance. More frequent use of prenatal care and receipt of enhanced prenatal services (13) were predicted to be associated with being prescribed antiretroviral therapy because these two factors indicate increased access to comprehensive prenatal care and more opportunities for providers to initiate treatment. Among women who used illicit drugs, we hypothesized that those receiving methadone treatment would be more likely to receive antiretroviral therapy during pregnancy because of improved access to care (14). We also discuss potentially important approaches that can ensure expeditious integration of important clinical breakthroughs into community practice. Methods Study Sample On the basis of physician review, we updated a tested method of identifying HIV-infected women [15] to account for changes in coding of HIV infection, treatments, and services. The review encompassed more than 1000 randomly selected clinical and treatment histories of women who were enrolled in the New York State Medicaid program; had delivered children from 1993 through 1994; and had at least one International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis, treatment, or service code that suggested HIV disease. The revised HIV case finding required 1) one inpatient or two outpatient diagnoses of HIV seropositivity or infection, 2) one outpatient diagnosis of HIV seropositivity or infection with one HIV care rate code, 3) an AIDS-defining diagnosis, or 4) receipt of antiretroviral therapy. We created a file on claims and eligibility longitudinal data for women who were enrolled in the New York State Medicaid program, were identified as HIV-infected, and had one or more deliveries (total deliveries, n=3037) from January 1993 through September 1996. The files included data from 3 years before and 1 year after each womans last delivery and were stripped of patient identifiers for analysis. For women who had multiple deliveries in the study years, we selected the last delivery for analysis; thus, 261 deliveries were eliminated. We then linked vital statistics birth certificates for 2655 of 2776 deliveries (95%) by using Social Security number, date of admission for delivery, site of delivery, childs date of birth, and fathers name. Vital statistics records offered demographic data, education, parity, gestational age at delivery, birth weight, and self-reported substance use during pregnancy. Claims provided information on diagnoses (up to five per inpatient claim and two per outpatient claim), procedures, payment rates, and filled prescriptions. Because key data were missing or sample size was small, we excluded the few persons who lacked data on ethnicity (n=32) or were Asian or Native American (n=16). Outcome Measures We identified pharmacy claims during the study period for all antiretroviral drugs approved by the Food and Drug Administration. Gestational age at delivery was usually determined from physician estimate or, when this estimate was unavailable (3.3% of persons), from the mothers estimate of the date of her last menstrual cycle. From these data, we determined prescribed antiretroviral therapy during the second or third trimester. Maternal and Health Care Measures We did not have access to the results of laboratory tests, such as data on viral load or CD4 cell count. To evaluate maternal HIV disease stage, we identified diagnoses that strongly predicted mother-to-child HIV transmission (16). The three clinical groups of HIV status were the following: severe (one or more AIDS-defining conditions, such as Pneumocystis carinii pneumonia, before or<1 year after delivery), moderate (bacterial or unspecified pneumonia or anemia during pregnancy), and mild (no moderate or severe conditions). Chronic medical conditions, including hypertension, asthma, and diabetes, were identified from claims made during, before, and after pregnancy. We determined use of illicit drugs by applying a tested approach to the claims [17]. This approach searched for methadone maintenance service codes, medically supervised nondrug treatment service codes, or diagnoses for illicit drug use. Self-reported illicit drug use was also identified from vital statistics. Pregnant women were divided into four categories of drug use: 1) use of regulated methadone, 2) current use of illicit drugs, 3) history of use of illicit drugs, and 4) no evidence of use of illicit drugs. Smoking and drinking during pregnancy were determined from self-reported vital statistics. We assessed the adequacy of the timing and number of prenatal care visits by using Kotelchucks Adequacy of Prenatal Care Utilization (APNCU) measures (18) and by following a previously reported approach (19). We applied the APNCU measures to visits to primary care physicians, obstetricians or gynecologists, or HIV-specific physicians or clinics (that is, physicians or clinics specializing in infectious disease, allergy or immunology, oncology, or HIV-focused care). The APNCU categories of intermediate care (50% to 79% of expected visits) and adequate care (80% to 109% of expected visits) were grouped together, as recommended (20). The APNCU category of adequate-plus care ( 110% of expected visits) was also included with the adequate care group because prescribed antiretroviral therapy was similarly expected to be greater. To determine receipt of services from providers who were likely to have greater expertise in HIV care, we examined receipt of HIV-focused services and provider specialty. We identified any visit to any provider who was under contract to New York State to offer many HIV-specific services and to coordinate care in exchange for increased Medicaid payment (8, 9). We also created a variable for at least one visit to a provider in an HIV-related specialty (infectious disease, hematology, oncology, or allergy and immunology). We then created dummy variables for the four combinations of these variables. Because only nine women received HIV-focused services but no specialty care, we grouped these women with those who received both, leaving three dummy variables. We also flagged women who had one or more visits to centers that participated in any federally sponsored trials of antiretroviral therapy for prevention of mother-to-child transmission. Finally, we identified any visit to a provider in the Prenatal Care Assistance Program who was under contract to the state to deliver many prenatal services, such as case management, health education, assessment or prevention of adverse outcomes, and nutritional services, to Medicaid enrollees (13). Statistical Analysis We determined the proportion of women delivering in each study month who were prescribed antiretroviral therapy. Nonparametric (lowess) smoothed averages over calendar time were plotted. We divided our analysis into three time periods: period 1January 1993 through February 1994 (the month when the trial results were announced), period 2March 1994 through November 1994 (the month when the trial results were published), and period 3December 1994 through September 1996. We used the chi-square test to examine bivariate associations of maternal demographic, clinical, and health care characteristics with receipt of antiretroviral therapy during pregnancy. Age was grouped into five categories. For each time period, a series of multivariable logistic regression models were estimated to determine the independent effects of maternal and health care variables on outcome. We first fit a baseline multivariate model including only maternal variables in any of the time periods that were bivariately associated with outcome (P<0.2). To examine the effect

Predictors of Medicare costs in elderly beneficiaries with breast, colorectal, lung, or prostate cancer

Background: Determining the apportionment of costs of cancer care and identifying factors that predict costs are important for planning ethical resource allocation for cancer care, especially in markets where managed care has grown.Design: This study linked tumor registry data with Medicare administrative claims to determine the costs of care for breast, colorectal, lung and prostate cancers during the initial year subsequent to diagnosis, and to develop models to identify factors predicting costs.Subjects: Patients with a diagnosis of breast (n=1,952), colorectal (n=2,563), lung (n=3,331) or prostate cancer (n=3,179) diagnosed from 1985 through 1988.Results: The average costs during the initial treatment period were

Improved birth outcomes associated with enhanced Medicaid prenatal care in drug-using women infected with the human immunodeficiency virus.

12,141 (s.d.=

Clinic characteristics associated with reduced hospitalization of druc users with aids

10,434) for breast cancer,

Improved birth outcomes among HIV-infected women with enhanced Medicaid prenatal care.

24,910 (s.d.=

Breast cancer mortality in black and in white women: A historical perspective by menopausal status

14,870) for colorectal cancer,

Sources of prenatal care data and their association with birth outcomes of HIV-infected women.

21,351 (s.d.=

Re: The Impact of Co-Morbidity on Life Expectancy Among Men with Localized Prostate Cancer

14,813) for lung cancer, and