Infants presenting with recurrent infections and low immunoglobulins: characteristics and analysis of normalization.

To better characterize infants presenting with diminished immunoglobulin levels and intact antibody formation, we present 49 such infants, correlating presenting characteristics with history and time to immunoglobulin normalization. Term infants with the following characteristics were included: 1) one or more immunoglobulin classes > 2SD below mean, 2) protective antibody titer to tetanus and diphtheria, 3) intact cellular immunity, 4) no features of other syndromes. The children were 69.4% male and had recurrent otitis media (77.6%), wheezing (61.2%), and atopy (26.5%). Diminished IgA (95.9%) was most common, but 65.3% had multiple isotypes diminished. During follow-up, 25/49 (51%) normalized immunoglobulins, of whom 80% were male; only 48% normalized in infancy. Female immunoglobulin normalization was significantly delayed (p < .001). No deaths or serious infections occurred. This phenotype is predominantly seen in male infants with otitis media and wheezing. Female infants have significantly delayed immunoglobulin normalization. Transient hypogammaglobulinemia of infancy can be diagnosed only retrospectively.

Complete diagnostic evaluation in colorectal cancer screening: research design and baseline findings.

BACKGROUND: While indicated by guidelines, complete diagnostic evaluation, or CDE (i.e., colonoscopy or combined flexible sigmoidoscopy plus barium enema X ray), is often not recommended and performed for persons with an abnormal screening fecal occult blood test (FOBT) result. We initiated a randomized trial to assess the impact of a physician-oriented intervention on CDE rates in primary care practices. METHODS: In 1998, we identified 1,184 primary care physicians (PCPs) in 584 practices whose patients received FOBTs that are mailed annually by a managed care organization screening program. A total of 470 PCPs in 318 practices completed a baseline survey. Practices were randomly assigned either to a Control Group (N = 198) or to an Intervention Group (N = 120). Control Group practices received the screening program. Intervention Group practices received the screening program and the intervention (i.e., CDE reminder-feedback plus educational outreach). Practice CDE recommendation and performance rates are the primary outcomes to be measured in the study. RESULTS: Baseline CDE recommendation and performance rates were low and were comparable in Control and Intervention Group practices (54 to 57% and 39 to 40%, respectively). PCPs in the practices tended to view FOBT screening and CDE favorably, but had concerns about screening efficacy, time involved in CDE, and patient discomfort and adherence. Control Group physicians were more likely than Intervention Group physicians to believe that a mail-out FOBT screening program helps in the practice of medicine. CONCLUSIONS: We were able to enroll a high proportion of targeted primary care practices, measure practice characteristics and CDE rates at baseline, and develop and implement the intervention. Study outcome analyses will take into account baseline differences in practice characteristics.

Limits of 80%-125% for AUC and 70%-143% for Cmax. What is the impact on bioequivalence studies?

OBJECTIVE: The US Food and Drug Administration (FDA) currently uses bioequivalence (BE) limits for fasting BE studies that are based on the 90% confidence interval for the ratio of difference of the test and reference products Cmax and AUC falling within 80% to 125%. The FDA has also proposed that BE limits be used similarly for AUC and Cmax measurements from fed BE studies. In some cases, regulatory agencies have considered a wider BE limit for Cmax, because of the typically higher variability of Cmax compared to AUC. We investigated the consequences of changing from an 80%/ 125% limit for both pharmacokinetic measures to one that uses a limit of 80%/125% for AUC and 70%/143% for Cmax. METHODS: We computed the sample sizes required for BE studies using 80%/125% for AUC and 70%/143% for Cmax as BE limits. We also determined the range of the ratios of Cmax and AUC values in a study that could meet the 70%/143% and 80%/125% BE limits. RESULTS: The sample size for the study, in order to have adequate power with 80%/125% for AUC and 70%/143% for Cmax, will be determined primarily by the intrasubject variability of AUC, though with a substantial proportion of studies (about one third) still determined by the variability of Cmax. The ratio of mean Cmax values that can pass a wider 70%/143% BE limit could easily be as high as 128%. CONCLUSION: Without further scientific or clinical rationale, we find it difficult to justify widening the bioequivalence limit for Cmax to 70%/143% for either fasting or fed BE studies.

Association of provider and patient characteristics with HIV-infected women's antiretroviral therapy regimen.

OBJECTIVE: We explored the effect of patient and provider factors on the type of antiretroviral regimen among women receiving therapy. PATIENTS: Five hundred ninety-five New York State nonpregnant HIV+ women with full Medicaid eligibility and at least 1 month of a prescribed antiretroviral regimen in federal fiscal years (FFY) 1997-1998 and intervals in FFY 1997-1998, who had delivered a liveborn baby within 5 years. MEASUREMENTS: From pharmacy claims in 4 6-month intervals in FFY 1997-1998, data were extracted on (1) an acceptable > or = 2 antiretroviral combination regimen per expert guidelines; and (2) a highly active regimen, including a protease inhibitor or nonnucleoside analog (highly active antiretroviral therapy [HAART]). RESULTS: Of 1514 woman-6-month intervals with filled antiretroviral prescriptions, 82% had an acceptable regimen, and of 1246 woman-6-month intervals on acceptable antiretroviral therapy, half demonstrated the use of HAART. Adjusted odds ratios (AORs) of acceptable antiretroviral therapy were higher (p < .05) for HIV specialty care (AOR = 1.71 for one or two visits; AOR = 2.10 for 3+ visits) or HIV clinical trials site care (AOR = 1.43; 95% confidence interval [CI]: 1.01, 2.04). Among women on acceptable antiretroviral regimens, those aged older than 25 years (AOR = 1.69; CI: 1.13, 2.53) or who were high school graduates (AOR = 1.50; CI: 1.09, 2.06) had higher odds of HAART. Methadone-treated women had twofold and nearly threefold higher AORs of acceptable antiretroviral regimens and HAART, respectively, than current drug users. CONCLUSION: Provider HIV expertise is associated with receipt of an acceptable antiretroviral regimen in women, although receipt of HAART is affected more by age, education, and current drug abuse. Methadone treatment seems to improve access to acceptable antiretroviral regimens as well as to HAART.

Regular outpatient medical and drug abuse care and subsequent hospitalization of persons who use illicit drugs.

CONTEXT: Patients and the public could benefit from identification of factors that prevent drug users' heavy reliance on inpatient care; however, optimal health care delivery models for illicit drug users remain ill-defined. OBJECTIVE: To evaluate associations of outpatient medical and drug abuse care with drug users' subsequent hospitalization rates. DESIGN AND SETTING: Retrospective cohort study of data from longitudinally linked claims for all ambulatory physician/clinic services and drug abuse services covered by the New York State Medicaid program. SUBJECTS: A total of 11 556 human immunodeficiency virus (HIV)-positive and 46 687 HIV-negative drug users. MAIN OUTCOME MEASURES: Hospitalization in federal fiscal year (FFY) 1997 compared by 4 patterns of care in FFY 1996: regular drug abuse care (>/=6 months in 1 program), regular medical care (>35% of care from 1 clinic, group practice, or individual physician), both, or neither. RESULTS: Hospitalization occurred in 55.6% of HIV-positive and 37.5% of HIV-negative drug users, with a mean of 27.5 and 24.5 inpatient days, respectively. In HIV-positive drug users, the adjusted odds ratio (AOR) for hospitalization was lowest among those with both regular medical and drug abuse care (AOR, 0.76; 95% confidence interval [CI], 0.67-0.85) followed by those with regular medical care alone (AOR, 0.82; 95% CI, 0.74-0.91) and regular drug abuse care alone (AOR, 0.85; 95% CI, 0.76-0.96) vs those with neither. In HIV-negative drug users, the AOR of hospitalization was lower for those with regular medical and drug abuse care (AOR, 0.73; 95% CI, 0.68-0.79), regular drug abuse care alone (AOR, 0.71; 95% CI, 0.66-0.76), and regular medical care (AOR, 0.91; 95% CI, 0.86-0.95) vs those with neither. Both types of care showed favorable effects for all but drug abuse-related hospitalizations. CONCLUSION: Our data indicate that regular drug abuse care with regular medical care for drug users is associated with less subsequent hospitalization.

Measuring complete diagnostic evaluation in colorectal cancer screening.

Complete diagnostic evaluation, or CDE (i.e., a colonoscopy or combined barium enema X-ray and flexible sigmoidoscopy) is recommended for individuals who have an abnormal screening fecal occult blood test result. Accurate measures of CDE use are needed in colorectal cancer (CRC) screening programs. This study compares the sensitivity and specificity of different methods for measuring CDE recommendation and performance. We identified 17 primary-care practices with 120 patients who had a positive fecal occult blood test result in a CRC screening program operated by a managed-care organization. Approaches used to measure CDE recommendation and performance included external chart audit (ECA) only; internal chart audit (ICA) only; administrative data review (ADR) of electronic claims data; ICA plus ADR; and ECA plus ADR (the "gold standard"). Sensitivity and specificity of each method were assessed relative to CDE recommendation and performance as measured by ECA plus ADR. For CDE recommendation, sensitivity measures were ECA only, 0.926; ICA only, 0.790; ADR only, 0.617; and ICA plus ADR, 0.901. The specificity of each method for CDE recommendation was no less than 0.95. In terms of CDE performance, sensitivity measures were ECA only, 0.877; ICA only, 0.790; ADR only, 0.877; and ICA plus ADR, 0.965. The specificity of each method for CDE performance was 1.0. The ICA-plus-ADR method was a highly sensitive and specific measure of CDE use. This method should be considered in situations that involve primary-care physician follow-up of patients with abnormal CRC screening test results.

A randomized, controlled trial of a home environmental intervention: effect on efficacy and upset in caregivers and on daily function of persons with dementia.

PURPOSE OF STUDY: The authors determined short-term effects of a home environmental intervention on self-efficacy and upset in caregivers and daily function of dementia patients. They also determined if treatment effect varied by caregiver gender, race, and relationship to patient. DESIGN AND METHODS: Families (N = 171) of dementia patients were randomized to intervention or usual care control group. The intervention involved 5 90-min home visits by occupational therapists who provided education and physical and social environmental modifications. RESULTS: Compared with controls, intervention caregivers reported fewer declines in patients' instrumental activities of daily living (p = .030) and less decline in self-care and fewer behavior problems in patients at 3 months post-test. Also, intervention spouses reported reduced upset (p = .049), women reported enhanced self-efficacy in managing behaviors (p = .038), and women (p = .049) and minorities (p = .037) reported enhanced self-efficacy in managing functional dependency. IMPLICATIONS: The environmental program appears to have a modest effect on dementia patients' IADL dependence. Also, among certain subgroups of caregivers the program improves self-efficacy and reduces upset in specific areas of caregiving.

Sample sizes for batch acceptance from single- and multistage designs using two-sided normal tolerance intervals with specified content.

One quality control test in the pharmaceutical industry is a test for uniformity of content of a batch prior to release of the batch to market. For batch acceptance by this or other quantitative tests of batch quality, one approach uses two-sided tolerance intervals of specified content. If the tolerance interval falls entirely within an acceptance interval, the batch is accepted. This has the form of a statistical hypothesis test. Once we recognize this approach as a statistical test, we can ask what sample size is required to be able to accept the batch with a desired power. The power for a single-stage design is a bivariate noncentral t probability and can be determined using previously published algorithms. Using standard methods for interim analyses, the approach is extended to multistage designs. Power and sample size for multistage designs are validated with simulations. We demonstrate it is possible to design one- and two-stage designs for batch acceptance with desired power and specified type I level.

An individual bioequivalence criterion: regulatory considerations.

Over the years, concerns have been raised regarding the appropriateness of using the average bioequivalence approach for evaluation of comparability between formulations. In lieu of average bioequivalence, scientists from academia, industry and regulatory agencies have spent considerable effort and time in exploring the concepts of population and individual bioequivalence, and developing the statistical methods to assess the bioavailability metrics using these approaches. Recently, the Food and Drug Administration (FDA) has published a preliminary draft guidance entitled 'In vivo bioequivalence studies based on population and individual bioequivalence approaches'. The concept of prescribability and switchability underscores the difference between the population and individual bioequivalence approaches. The most important consideration for individual bioequivalence, the focus of this paper, rests on the assurance that products deemed bioequivalent can be used interchangeably in the target population (switchability). In addition to the comparison of averages, the individual bioequivalence approach compares within-subject variabilities and assesses subject-by-formulation interaction. The proposed criterion represents substantial departure from the current practice and thus has resulted in extensive public discussion. In contrast to the current average bioequivalence procedure, the proposed individual bioequivalence approach offers flexible equivalence criteria based on the individual therapeutic window and variability of the reference drug product. The proposed criterion rewards manufacture of less variable drug products, allows scaling criteria for highly variable/narrow therapeutic range drugs, and promotes the use of subjects from the general population in bioequivalence studies. The FDA is currently considering various approaches for resolution of issues raised from the public debate on the subject-by-formulation interaction term, statistical methods and resource implications.

Antiretroviral use and pharmacy-based measurement of adherence in postpartum HIV-infected women.

BACKGROUND: Antiretroviral treatment for HIV-infected women is standard during pregnancy to prevent vertical transmission, but data on postpartum therapy for the mother are lacking. OBJECTIVE: The objective of this study was to examine the impact of provider and patient characteristics on receipt of antiretroviral therapy and pharmacy-based measurement of adherence by postpartum HIV-infected women. RESEARCH DESIGN: This was a retrospective cohort study. SUBJECTS: The study included 2,648 New York State Medicaid-enrolled HIV-infected women who delivered from January 1993 through October 1996 and were followed up through September 1997. MEASURES: From Medicaid claims in the first postpartum year, the study examined any prescribed antiretroviral therapy and, among women treated >2 months, adherence, defined as > or =80% days covered by prescribed therapy from first to last antiretroviral prescription. RESULTS: Antiretroviral therapy was prescribed for 681 (26%) study women. Of 292 women treated >2 months, 28% were adherent on the basis of the pharmacy-based measure. The proportion of treated women was highest in 1996 (40%), and adherence was best in 1995 (44%) when most women took monotherapy. The adjusted odds ratios (AORs) of treatment were 1.67 (95% CI, 1.24 to 2.25) for women receiving HIV-focused services and 2.71 (95% CI, 1.99 to 3.69) for women with a provider in an HIV-related specialty. The AORs of adherence were greater for women with HIV-focused services (2.13; 95% CI, 1.05 to 4.30) and for former illicit drug users versus nonusers (2.40; 95% CI, 1.05 to 5.50). CONCLUSIONS: This population-based pharmacy analysis reveals improving antiretroviral use but continuing poor pharmacy-based adherence by postpartum HIV-infected women. Receipt of HIV-focused services appears to be particularly beneficial in increasing the likelihood of treatment and adherence.

Prenatal zidovudine use and congenital anomalies in a medicaid population.

OBJECTIVES: To examine the association of prescribed zidovudine (ZDV) during pregnancy with congenital anomalies in a population-based cohort. METHODS: Medicaid claims were used to assess prescribed ZDV and children's major congenital anomalies in 1932 liveborn deliveries from 1993 to 1996 to HIV-infected women in the state of New York (NYS), U.S.A. Prevalence of anomalies in the cohort was compared with that of a general NYS population. Within the cohort, adjusted odds of any anomaly were compared by receipt of ZDV and by trimester of first prescription. RESULTS: The adjusted prevalence of any anomaly in the study cohort was 2.76 times greater than in the general population (95% confidence interval [CI], 2.36-3. 17). Children of study women who were prescribed ZDV had increased adjusted odds of any anomaly (adjusted odds ratio [OR], 1.55; 95% CI, 1.01-2.29). Adjusted ORs (with CIs) by trimester of first prescription were 1.20 (0.58-2.51), 1.47 (0.85-2.55), and 1.84 (1. 04-3.25) for the first, second, and third trimesters, respectively. CONCLUSION: Children of HIV-infected women in this cohort had a greater prevalence of major anomalies than did the general NYS population. An increased risk of major anomalies was not evident for first trimester exposure when the association would have been most biologically plausible.

Low serum insulin-like growth factor 1 (IGF-1): a significant association with prostate cancer.

PURPOSE: Insulin-like growth factor 1 (IGF-1) is an important mitogenic and antiapoptotic peptide that affects the proliferation of normal and malignant cells. Contradictory reports on the association between serum IGF-1 level and prostate cancer have been highlighted in the recent literature. The purpose of this study was to investigate the relation between serum levels of IGF-1 and prostate cancer. MATERIALS AND METHODS: We analyzed a population of 57 patients who underwent radical prostatectomy (RP) for adenocarcinoma. Serum samples were collected before RP (T0), 6 months after RP (T6), and from 39 age-matched controls. IGF-1 levels were determined by the active IGF-1 Elisa kit (Diagnostic Systems Laboratories, Inc.). Parallel samples were evaluated for prostate-specific antigen (PSA) levels. Data between groups were analyzed using Welch's t-test and levels before RP and after 6 months were compared by paired t-test. RESULTS: The normal mean serum IGF-1 for case patients at T0 (124.6+/-58.2 ng/mL) was significantly lower than the control subjects (157.5+/-70.8 ng/mL; p = .0192). The normal mean serum IGF-1 for case patients at T0 (124.91+/-58.6 ng/mL) also was significantly lower when it was compared with the T6 group (148.49+/-57.2 ng/mL; p = .0056). No association was found between IGF-1 and PSA blood levels, or IGF-1 and patient weight (p = 0.2434). An inverse relation between IGF-1 levels and age in the normal controls (p = .0041) was observed. CONCLUSION: Findings of this study indicate a significant association between low serum levels of IGF-1 and prostate cancer.

Subject-by-formulation interaction in bioequivalence: conceptual and statistical issues. FDA Population/Individual Bioequivalence Working Group. Food and Drug Administration.

PURPOSE: The FDA has proposed replacing the current average bioequivalence criterion with population and individual bioequivalence criteria that consider variances in addition to the difference of averages. One of these variances in the individual bioequivalence criterion measures subject-by-formulation interaction, the extent to which the test-reference difference varies from person to person. This paper discusses conceptual and statistical issues raised in various publications and presentations with respect to the presence and estimation of such an interaction. METHODS: We focus on the importance of subject-by-formulation interaction, an understanding of what is a large interaction, and the assessment of the magnitude of this interaction in bioequivalence studies. Simulation studies, examples from the literature, and data from FDA files are used to demonstrate the magnitude of the interaction and its distribution under various conditions. RESULTS: The concept of a large interaction is tied to the concept of a large mean difference. We suggest that an interaction greater than 0.15 is a conservative criterion for a large interaction. Magnitudes of estimated interaction are affected by variability, sample size, and the selection of data sets that pass average bioequivalence. CONCLUSIONS: Examples of substantial interactions are beginning to appear. More data is needed before reaching definitive conclusions regarding the frequency and importance of observed interactions.

Recovery of upper-extremity strength in complete and incomplete tetraplegia: a multicenter study.

OBJECTIVE: To examine upper-extremity motor recovery of subjects with tetraplegia with both complete and incomplete injuries, to predict which patients and at what time they would recover a motor level. DESIGN: Prospective, multicenter clinical study of upper-extremity motor recovery in subjects with acute traumatic spinal cord injury. SETTING: Three regional spinal cord injury centers. SUBJECTS: One hundred sixty-seven individuals with acute traumatic tetraplegia (144 males [86%], and 23 females [14%]) between the ages of 15 and 75 years (mean age, 35.5 yrs). METHODS: Subjects were examined and classified using sequential manual muscle tests performed on admission, 72 hours, 1, 2, and 3 weeks, and 1, 2, 3, 6, 12, 18, and 24 months postinjury. C5 biceps, C6 extensor carpi radialis, C7 triceps, and C8 flexor digitorum profundus were evaluated using a 0-5 scale. Analyses of the right motor levels used a series of logistic regression models, and for multiple measurements on each subject, models were estimated using generalized estimating equations. RESULTS: The analysis for recovery of the biceps for the C4 group showed 70% of complete compared with 90% of incomplete injuries recovered (p < .001); of the extensor carpi radialis in the C5 group, 75% complete and 90% incomplete recovered (p < .002); and of the triceps in the C6 group, 85% of complete and 90% of incomplete injuries recovered (p < .16). CONCLUSION: Predicting future potential for upper-extremity motor recovery and for independence in self-care in groups of patients at a specific motor level is possible within the first week of injury.

The effects of propranolol on cognitive function and quality of life: a randomized trial among patients with diastolic hypertension.

PURPOSE: We sought to determine whether propranolol has adverse effects on cognitive function, depressive symptoms, and sexual function in patients treated for diastolic hypertension. SUBJECTS AND METHODS: We performed a placebo-controlled trial among 312 men and women, 22 to 59 years of age, who had untreated diastolic hypertension (90 to 104 mm Hg). Patients were randomly assigned to treatment with propranolol (80 to 400 mg/day) or matching placebo tablets. Thirteen tests of cognitive function were assessed at baseline, 3 months, and 12 months. Five tests measured reaction time to, or accuracy in, interpreting visual stimuli; one test measured the ability to acquire, reproduce, and change a set of arbitrary stimulus-response sets; and seven tests measured memory or learning verbal information. Depressive symptoms and sexual function were assessed by questionnaires at baseline and 12 months. RESULTS: There were no significant differences by treatment assignment for 11 of the 13 tests of cognitive function at either 3 or 12 months of follow-up. Compared with placebo, participants treated with propranolol had slightly fewer correct responses at 3 months (33 +/- 3 [mean +/- SD] versus 34 +/- 2, P = 0.02) and slightly more errors of commission at 3 months (4 +/-5 versus 3 +/- 3, P = 0.04) and at 12 months (4 +/- 4 versus 3 +/- 3, P = 0.05). At 12 months, depressive symptoms and sexual function and desire did not differ by treatment assignment. CONCLUSIONS: Treatment of hypertension with propranolol had limited adverse effects on tests of cognitive function that were of questionable clinical relevance, and there were no documented adverse effects on depressive symptoms or sexual function. Selection of beta-blockers for treatment of hypertension should be based on other factors.

Generalized treatment effects for clinical trials.

Practice in the analysis of clinical trials with continuously measured endpoints is to focus on the difference or percentage change in mean or median response. However, treatments may have effects on the distribution of responses other than on the average response. We sought an approach to such generalized treatment effects that: (i) targets a parameter that is easily understood by our clinical colleagues; and (ii) employs confidence intervals as the basis for inference. We consider one such approach based on work in reliability theory, namely setting Pr[Y>X] as the target parameter, and compare this approach to an earlier one due to O'Brien. The two approaches have similar properties when they both seek to reject the null hypothesis of no effect due to different variances but differ when the larger variance corresponds to the larger mean. In that case, our approach views that the larger variance attenuates the effect of the larger mean. Out suggested approach applies easily to positive control (clinical) equivalence trials.

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.

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

OBJECTIVES: This study evaluated the impact of enhanced prenatal care on the birth outcomes of HIV-infected women. METHODS: Medicaid claims files linked to vital statistics were analyzed for 1723 HIV-infected women delivering a live-born singleton from January 1993 to October 1995. Prenatal care program visits were indicated by rate codes. Logistic models controlling for demographic, substance use, and health care variables were used to assess the program's effect on preterm birth (less than 37 weeks) and low birthweight (less than 2500 g). RESULTS: Of the women included in the study, 75.3% participated in the prenatal care program. Adjusted program care odds were 0.58 (95% confidence interval [CI] = 0.42, 0.81) for preterm birth and 0.37 (95% CI = 0.24, 0.58) for low-birthweight deliveries in women without a usual source of prenatal care. Women with a usual source had lower odds of low-birthweight deliveries if they had more than 9 program visits. The effect of program participation persisted in sensitivity analyses that adjusted for an unmeasured confounder. CONCLUSIONS: A statewide prenatal care Medicaid program demonstrates significant reductions in the risk of adverse birth outcomes for HIV-infected women.

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

OBJECTIVES: Different sources of prenatal care data were used to examine the association between birth outcomes of HIV-infected women and the Adequacy of Prenatal Care Utilization (APNCU) index. METHODS: Adjusted odds ratios of birth outcomes for 1858 HIV-positive mothers were calculated for APNCU indexes on the basis of birth certificate data or 3 types of physician visits on Medicaid claims. RESULTS: Claims- and birth certificate-based APNCU indexes agreed poorly (kappa < 0.3). Only the broadest claims-based APNCU index had lower adjusted odds ratios for low birthweight (0.64; 95% confidence interval [CI] = 0.49, 0.84) and preterm birth (0.70; 95% CI = 0.54, 0.91). The birth certificate-based index had a reduced adjusted odds ratio (0.73; 95% CI = 0.56, 0.95) only for preterm birth. CONCLUSIONS: The association of birth outcomes and adequacy of prenatal care in this HIV-infected cohort differed significantly depending on the source of prenatal care data.

Fhit expression in gastric adenocarcinoma: correlation with disease stage and survival.

BACKGROUND: The FHIT gene is inactivated by deletion in a large fraction of human tumors, including gastric carcinomas, and the Fhit protein has been proposed to act as a tumor suppressor in multiple tumor types. A large fraction of gastric adenocarcinomas have lost expression of the candidate tumor suppressor protein, Fhit, whereas normal gastric epithelial cells are strongly positive and Fhit loss has been found to correlate with alterations of the FHIT locus. Because the majority of gastric tumors in the current study were found to be entirely negative for Fhit protein, it is possible that alteration of the carcinogen-susceptible fragile region within the FHIT gene is an early event in gastric carcinoma, as it is in lung carcinoma. METHODS: To determine whether the absence of Fhit protein correlates with expression of tumor markers or with clinical parameters, such as grade, stage, and survival time, the authors assessed Fhit expression using immunohistochemistry in a well characterized set of 55 gastric adenocarcinomas resected over several years, with longitudinal follow-up of patients for outcome. RESULTS: In this set of 55 gastric cancers, the absence of Fhit protein correlated with higher tumor stage (P = 0.003) and higher histologic grade (P = 0.007). In addition, patients whose tumors had lost expression of Fhit died of disease significantly earlier than those with Fhit positive tumors (P = 0.017). The absence of Fhit expression did not correlate with the expression of any tumor markers. CONCLUSIONS: Larger studies will be required to elucidate further the relation between tumor stage, grade, and Fhit loss and to determine whether inclusion of Fhit antiserum in immunophenotyping of gastric adenocarcinomas will be a useful indicator of post-diagnosis prognosis.