Naji Younes

Longitudinal growth of hospitalized very low birth weight infants

Background. The interpretation of growth rates for very low birth weight infants is obscured by limited data, recent changes in perinatal care, and the uncertain effects of multiple therapies. Objectives. To develop contemporary postnatal growth curves for very low birth weight preterm infants and to relate growth velocity to birth weight, nutritional practices, fetal growth status (small- or appropriate-for-gestational-age), and major neonatal morbidities (chronic lung disease, nosocomial infection or late-onset infection, severe intraventricular hemorrhage, and necrotizing enterocolitis). Design. Large, multicenter, prospective cohort study. Methods. Growth was prospectively assessed for 1660 infants with birth weights between 501 to 1500 g admitted by 24 hours of age to 1 of the 12 National Institute of Child Health and Human Development Neonatal Research Network centers between August 31, 1994 and August 9, 1995. Infants were included if they survived >7 days (168 hours) and were free of major congenital anomalies. Anthropometric measures (body weight, length, head circumference, and midarm circumference) were performed from birth until discharge, transfer, death, age 120 days, or a body weight of 2000 g. To obtain representative data, nutritional practices were not altered by the study protocol. Results. Postnatal growth curves suitable for clinical and research use were constructed for body weight, length, head circumference, and midarm circumference. Once birth weight was regained, weight gain (14.4–16.1 g/kg/d) approximated intrauterine rates. However, at hospital discharge, most infants born between 24 and 29 weeks of gestation had not achieved the median birth weight of the reference fetus at the same postmenstrual age. Gestational age, race, and gender had no effect on growth within 100-g birth weight strata. Appropriate-for-gestational age infants who survived to hospital discharge without developing chronic lung disease, severe intraventricular hemorrhage, necrotizing enterocolitis, or late onset-sepsis gained weight faster than comparable infants with those morbidities. More rapid weight gain was also associated with a shorter duration of parenteral nutrition providing at least 75% of the total daily fluid volume, an earlier age at the initiation of enteral feedings, and an earlier age at achievement of full enteral feedings. Conclusions. These growth curves may be used to better understand postnatal growth, to help identify infants developing illnesses affecting growth, and to aid in the design of future research. They should not be taken as optimal. Randomized clinical trials should be performed to evaluate whether different nutritional management practices will permit birth weight to be regained earlier and result in more rapid growth, more appropriate body composition, and improved short- and long-term outcomes.

Antenatal corticosteroid administration and neonatal outcome in very low birth weight infants: The NICHD Neonatal Research Network

Air leak: Extrapleural air diagnosed by CXR or thoracentesis; NICHD included pneumothorax or pneumopericardium; VT-OX included only pneumothorax. BW and ROSS included pneumothorax, pneumomediastinum, and pneumopericardium; BW also included pulmonary interstitial emphysema and pneumoperitoneum. Covariates GA: NICHD defined by best obstetric estimate; VT OX defined by best neonatology estimate. BW trials defined GA by menstrual history; if this GA differed by more than 2 weeks from the neonatologists’ estimate, the neonatologists estimate was used. RUM: NICHD used premature rupture of membranes (ROM) (ROM 2 1 hour before labor). ROSS analyzed ROM 2 24 hours; BW defined as 2 1 hour between ROM and delivery. Steroid treatment NICHD: Any form of corticosteroids given within 1 week of delivery; a complete course defined as 2 two doses for lung maturity with delivery occurring at least 12 hours after the second dose or at least 24 hours after the first dose. VT-OX: Any corticosteroid administered before delivery. A complete course defined as delivery occurring more than 24 hours and less than 1 week after any dose of corticosteroids. A partial dose defined as delivery occurring ~24 hours after the first dose or more than 1 week after the last dose of steroids. ROSS: Any corticosteroid administered before delivery. A complete course defined as ~two doses at least 12 hours apart with delivery occ&ing 24 hours to 7 days after first dose. Incomplete defined as any other steroid exposure. B W/BW TIND: Partial defined as < 24 hours from corticosteroid dose to delivery. Full defined as corticosteroid dose ~-24 hours before delivery.

Evidence from multicenter neworks on the current use and effectiveness of antenatal corticosteroids in low birth weight infants

Corticosteroid treatment of pregnant women at risk for preterm delivery enhances fetal lung maturity and improves neonatal outcomes.’ Despite convincing evidence of these effects, a consensus has not been reached about the indications for antenatal steroids, and the frequency with which they are used remains low in some countries, including the United States. In response to this situation, the National Institutes of Health (NIH) convened a Consensus Development Conference on the Effects of Corticosteroids for Fetal Maturation on Perinatal Outcomes.’ The following reports were prepared at the request of the panel; they describe the effects of antenatal steroid treatment on neonatal outcome from five current observational databases: those of the National Institute of Child Health and Development (NICHD) Neonatal Research Network, the Vermont-Oxford Trials Network, Ross Laboratories, and Burroughs Wellcome (BW) Co. The purpose of this article is to present an overview of the findings of these five large databases.

LINK-BASED MODELS FOR SURVIVAL DATA WITH INTERVAL AND CONTINUOUS TIME CENSORING

We present a flexible family of link-based regression models with time-independent (baseline) covariates. Particular choices of the link function yield a proportional hazard or a proportional odds model, among others. The background hazard function in the model is estimated using B-splines. This yields a full likelihood under both continuous time and random interval censoring. Residuals for influence and goodness-of-fit are described. Two examples are shown, one in continuous time and the other under interval censoring.

Comparison of urinary albumin-creatinine ratio and albumin excretion rate in the diabetes control and complications trial/epidemiology of diabetes interventions and complications study

BACKGROUND AND OBJECTIVES The objective of this study was to compare random urine albumin-creatinine ratio (ACR) with timed urine albumin excretion rate (AER) in patients with type 1 diabetes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A total of 1186 participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study provided spot urine specimens concurrent with 4-hour timed urine collections. ACR and AER were compared using Bland-Altman plots, cross-classification of albuminuria status and its change over time, and within-person variability. RESULTS Despite moderate correlation (r=0.62), ACR levels (mg/g) were lower than AER levels (mg/24 hr). This difference was greatest for men. Gender-specific estimated AER (eAER) values were empirically derived from ACR. Comparing the eAER with measured AER, agreement of prevalent microalbuminuria and macroalbuminuria classification was fair to moderate, and classification of change in albuminuria status over time was different. Intraclass correlations were 0.697 for ACR and 0.803 for AER. Effects of DCCT intensive versus conventional diabetes therapy on urine albumin excretion or classification of albuminuria were similar using the eAER versus measured AER, as were the effects of the previous glycosylated hemoglobin. CONCLUSIONS Systematic differences exist between urine ACR and AER, related to gender and other determinants of muscle mass. Use of ACR (or eAER) versus AER yields differences in classification of prevalent albuminuria states and changes in albuminuria states over time. These findings support the use of consistent ascertainment methods over time and further efforts to standardize and optimally interpret measurement of urine albumin excretion.

Trends in the Incidence of Fatal Prostate Cancer in the United States by Race

BACKGROUND Prostate-specific antigen (PSA) testing has dramatically changed the composition of prostate cancer (PCa), making it difficult to interpret incidence trends. New methods are needed to examine temporal trends in the incidence of clinically significant PCa and whether trends vary by race. OBJECTIVE To conduct an in-depth analysis of incidence trends in clinically significant PCa, defined as cases in which PCa was the underlying cause of death within 10 yr of diagnosis. DESIGN, SETTING, AND PARTICIPANTS We extracted incident PCa cases during the period 1975-2002 and associated causes of death and survival through 2012 from nine cancer registries in the population-based Surveillance Epidemiology and End Results program database. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS We applied joinpoint regression analysis to identify when significant changes in trends occurred and age-period-cohort models to examine longitudinal and cross-sectional trends in the incidence of fatal PCa. RESULTS AND LIMITATIONS Among 51 680 fatal PCa cases, incidence increased 1% per year prior to 1992, declined 15% per year from 1992 to 1995, and further declined by 5% per year through 2002. Age-specific incidence rates of fatal disease decreased >2% per year among men aged ≥60 yr, yet rates remained relatively stable among men aged ≤55 yr. Fatal disease rates were >2-fold higher in black men compared with white men, a racial disparity that increased to 4.2-fold among younger men. CONCLUSIONS The incidence of fatal PCa substantially declined after widespread PSA screening and treatment advances. Nevertheless, rates of fatal disease among younger men have remained relatively stable, suggesting the need for additional attention to early onset PCa, especially among black men. The persistent black-to-white racial disparity observed in fatal PCa underscores the need for greater understanding of the causes of this difference so that strategies can be implemented to eliminate racial disparities. PATIENT SUMMARY We assessed how the incidence of ultimately fatal prostate cancer (PCa) changed over time. We found that the incidence of fatal PCa declined by >50% since the introduction of prostate-specific antigen testing and advances in treatment options; however, incidence rates among younger men remained relatively stable, and younger black men exhibited a 4.2-fold higher risk for fatal disease compared with white men.

Women's Angiographic Vitamin and Estrogen trial: design and methods

The Womens Angiographic Vitamin and Estrogen trial was a randomized, double-blind, placebo-controlled study designed to test the efficacy of estrogen replacement and antioxidant vitamins for preventing angiographic progression of coronary artery disease. Postmenopausal women with one or more angiographically documented coronary stenoses of 15-75% at baseline were assigned in a 2 x 2 factorial randomization to active hormone replacement therapy (conjugated estrogens for women who had had a hysterectomy or conjugated estrogens with medroxyprogesterone for women with intact uteri) or placebo and to active vitamins E and C or their placebos. Seven clinical centers, five in the United States and two in Canada, randomized 423 women between July 1997 and July 1999. Quantitative coronary angiography was performed at baseline and repeated after projected mean follow-up of 3 years.

Incidence and Trends of Blastomycosis-Associated Hospitalizations in the United States

We used the State Inpatient Databases from the United States Agency for Healthcare Research and Quality to provide state-specific age-adjusted blastomycosis-associated hospitalization incidence throughout the entire United States. Among the 46 states studied, states within the Mississippi and Ohio River valleys had the highest age-adjusted hospitalization incidence. Specifically, Wisconsin had the highest age-adjusted hospitalization incidence (2.9 hospitalizations per 100,000 person-years). Trends were studied in the five highest hospitalization incidence states. From 2000 to 2011, blastomycosis-associated hospitalizations increased significantly in Illinois and Kentucky with an average annual increase of 4.4% and 8.4%, respectively. Trends varied significantly by state. Overall, 64% of blastomycosis-associated hospitalizations were among men and the median age at hospitalization was 53 years. This analysis provides a complete epidemiologic description of blastomycosis-associated hospitalizations throughout the endemic area in the United States.

Cancer-specific mortality, cure fraction, and noncancer causes of death among diffuse large B-cell lymphoma patients in the immunochemotherapy era.

Survival after the diagnosis of diffuse large B‐cell lymphoma (DLBCL) has been increasing since 2002 because of improved therapies; however, long‐term outcomes for these patients in the modern treatment era are still unknown.

Second primary breast, endometrial, and ovarian cancers in Black and White breast cancer survivors over a 35-year time span: effect of age

Breast cancer incidence increases with age and exhibits a Black-to-White crossover around age 45. Breast cancer survivors are at a significantly elevated risk of developing a second primary breast or gynecological cancer compared with the general population. The purpose of this study was to determine whether a similar crossover occurs in hormonally related second primary breast, endometrial, or ovarian cancers in Black and White women. The Surveillance, Epidemiology, and End Results’ Registry 9 was used to follow 415,664 White and 39,887 Black female breast cancer survivors, diagnosed at age 19 or older, for a second primary breast, endometrial, or ovarian cancer between 1973 and 2007. Cumulative incidence curves were generated; Pepe and Mori’s test was used to test for significance. Second primary breast cancer followed the incidence pattern of the first primary breast cancer in Black and White women diagnosed before age 45. It was opposite of the pattern of first primary breast cancer in Black and White women diagnosed at age 45 or later. Second primary endometrial and ovarian cancers paralleled the incidence pattern of first primaries of the same anatomic site among Black and White women, independent of the age at diagnosis of the first primary breast cancer. Despite the Black-to-White crossover of first primary breast cancer around age 40, the incidence of hormonally related second primaries does not appear affected by the age at diagnosis of the first primary.