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To use national mortality and state death certificate records to estimate disease specific mortality rates among pediatric and adult populations for 23 leukodystrophies (LDs) with pediatric forms. Additionally, to calculate yearly prevalence and caseload of the most severe LD cases that will eventually result in pediatric death (i.e., pediatric fatality cases). Death certificate records describing cause of death were collected from states based on 10 ICD-10 codes associated with the 23 LDs. Deaths in the U.S. with these codes were distributed into categories based on proportions identified in state death certificate data. Mortality rates, prevalence, and caseload were calculated from resulting expected numbers, population sizes, and average lifetimes. An estimated 1.513 per 1,000,000 0-17 year old's died of these LDs at average age 5.2 years and 0.194 for those ≥18 at an average age of 42.3 years. Prevalence of pediatric fatality cases of these LDs declined from 1999 through 2007 and then remained constant at 6.2 per million children per year through 2012. Epidemiological information, currently lacking for rare diseases, is useful to newborn screening programs, research funding agencies, and care centers for LD patients. Methods used here are generally useful for studying rare diseases.

Purpose Newborn screening for Krabbe disease (KD) originated in New York State in 2006 but has proven to have a high false positive rate and low positive predictive value. To improve accuracy of presymptomatic prediction, we propose a screening tool based on two biomarkers, psychosine and galactocerebrosidase enzyme activity (GalC). Methods We developed the tool using measures from dried blood spots of 166 normal newborns and tested it on dried blood spot measures from 15 newborns who later developed KD, 8 newborns identified as "high risk" by the New York screening protocol but were disease-free at follow-up, and 3 symptomatic children with onset before 4 years of age. The tool was developed from the (1–10−6)100% prediction region of the natural logarithms of psychosine and GalC measures, assuming bivariate normality, and their univariate normal limits. Results Krabbe disease was predicted correctly for every patient who developed symptoms in infancy or early childhood. None of the high-risk patients were incorrectly identified as having early KD. Conclusion Bivariate analysis of psychosine and GalC in newborn blood spots can accurately predict early Krabbe symptoms, control false positive rates, and permit presymptomatic treatment.

Krabbe's disease (KD) is a fatal neurodegenerative disorder, with the early-infantile form (EIKD) defined by onset of symptoms before age 6 months. Early and highly accurate identification of EIKD is required to maximize benefits of hematopoietic stem cell transplantation treatment. This study investigates the potential for accurate prediction of EIKD based on a novel newborn screening (NBS) tool developed from two biomarkers, galactocerebrosidase (GALC) enzyme activity and galactosylsphingosine concentration (psychosine [PSY]). Normative information about PSY and GALC, derived from distinct samples of normal newborns, was used to develop the novel diagnostic tool. Bivariate normal limits (BVNL) were constructed, assuming a multivariate normal distribution of natural logarithms of GALC and PSY of normal newborns. The (lnGALC, lnPSY) points for newborns in various "abnormal groups," including one group of infants who subsequently suffered EIKD, were plotted on a graph of BVNL. The points for all EIKD patients fell outside of BVNL (100% sensitivity). In a simulation study to compare the false-positive rate of existing univariate methods of diagnosis with our new BVNL-based method, we generated 100 million normal newborn data points. All fell within BVNL (i.e., zero false positives), whereas 5,682 false positives were observed when applying a two-tiered univariate method of the type suggested in the literature. These results suggest that (lnGALC, lnPSY) BVNLs will allow highly accurate prediction of EIKD, whereas two-tiered univariate approaches will not. Redevelopment of the BVNL based on GALCs and PSYs measured on a common large sample of normal newborns is required for NBS use. © 2016 Wiley Periodicals, Inc.

Krabbe's disease (KD) is a severe neurodegenerative disorder affecting white matter in the brain and peripheral nerves. Transplantation of hematopoietic stem cells (HSCT), although not curative, has been shown to extend survival and alleviate neurodevelopmental symptoms when treatment precedes the onset of symptoms. Existing evidence, although not tested statistically, seems clearly to show that postsymptomatic transplantation does not improve neurodevelopmental outcomes. The impact of postsymptomatic HSCT treatment on survival, however, is an open question. This study uses a KD registry to examine the effect of HSCT on survival of symptomatic KD patients. Sixteen transplanted patients were matched by age of onset to 68 nontransplanted patients. The potential confounding effect of age of onset was, therefore, avoided. To quantify the effect of HSCT over time, we used Cox regression analysis, and we observed a sustained and nearly 2.2-fold risk of death from KD in patients who were not transplanted relative to those who were transplanted (one-tailed P = 0.0365; 95% lower bound = 1.07). The improvement of survival resulting from HSCT did not appear to depend on the age of symptom onset. Thus, these results establish a long-term, quantitative benefit of HSCT even in patients who are already experiencing symptoms. They also provide a benchmark for improved survival that can be used for potential new treatments for KD. © 2016 Wiley Periodicals, Inc.

In the absence of gold standard diagnoses, we estimate age-specific false-positive and false-negative prediction rates of HPV-, cytology-, and histology-based tests for significant cervical lesions (SCL) in US women with AGC-NOS Pap smear diagnoses. Modified Latent Class Model (LCM) analyses, with prevalence of SCL modeled as a function of age, were applied to GOG-0171 study data (n = 122). The accuracies of several HPV-based tests, including Hybrid Capture II high-risk HPV (HC2 H-HPV); carbonic anhydrase IX (CA-IX); and invasive histological diagnosis, were compared. 1-PPV and 1-NPV were written as functions of sensitivity, specificity, and prevalence to obtain age-specific false-positive and false-negative rates. The histology-based test was nearly perfect (sensitivity = 1.00, CI = 0.98–1.00; specificity = 0.99, CI = 0.96–1.00). Otherwise, HC2 H-HPV performed best (sensitivity = 1.00, CI = 1.00–1.00; specificity = 0.87, CI = 0.79–0.94). The false-positive detection rates (1-PPV) for HC2 H-HPV were high (>17 %) at each age, while those of the histological diagnoses were low (

The majority of newborns screening positive for Krabbe disease have not exhibited the expected early infantile phenotype, with most clinically normal despite low galactocerebrosidase activity and two mutations. Most are expected to develop the later onset phenotypes. The World-Wide Krabbe Registry was developed in part to expand our understanding of the natural history of these rare variants. As of June 2011, 122 patients were enrolled in the registry: 62% manifested early infantile onset (previously reported), 10% manifested onset at 7-12 months (late infantile), 22% manifested onset at 13 months to 10 years (later onset), and 5% manifested adolescent/adult onset. Data on disease course, galactocerebrosidase activity, DNA mutations, and results of neurodiagnostic studies were obtained from questionnaires and medical records. Initial signs (late infantile) included loss of milestones and poor feeding, whereas later onset and adolescent/adult phenotypes presented with changes in gait. Elevated cerebrospinal fluid protein and abnormal magnetic resonance imaging results were present in most, but not all, patients at diagnosis. Phenotypic variability occurred in four sibships. Five-year and 10-year survivals for all later onset phenotypes were at least 50%. The later onset Krabbe phenotypes differ from those with early infantile disease, but no specific predictor of phenotype was identified.

article i nfo Objective. To describe trends in mortality rates, in New York State, due to cervical, endometrial and ovarian cancer and to assess how these rates varied with proximity to a comprehensive cancer treatment center or population density (rural/urban). Methods. Data were obtained from the Centers for Disease Control and Prevention (CDC)'s Compressed Mortality Files, Census Bureau records, and online maps. Poisson regression models were fitted to estimate death rates (mean number of deaths per 100,000 women per year) due to gynecologic cancer type. Trends in death rates were compared with respect to driving time to the nearest comprehensive cancer treatment center and population density, controlling for race, county income level, and age at death. Results. Cervical and endometrial but not ovarian death rates declined over time. For both cervical and endometrial cancers, death rates varied significantly with driving time and between rural and urban counties. In the case of cervical cancer, the decline over time was steeper in rural than in urban counties. For endometrial cancer, the decline steepened with increasing distance from a treatment center. Conclusion. Improvements in cervical and endometrial cancer mortality from 1979 to 2001 followed increases in gynecologic cancer treatment research efforts, number of specialists trained to treat such cases, and in the emphasis on gynecologic cancer in the training of physicians in general. Our results are consistent with an interpretation that the progressive actions by leaders in the gynecologic oncology profession during the late 1960's and early 1970's contributed to improvements in mortality rates in subsequent decades.

PurposeThe aim of this study was to identify patient and physician factors related to enrollment onto Gynecologic Oncology Group (GOG) trials.MethodsProspective study of women with primary or recurrent cancer of the uterus or cervix treated at a GOG institution from July 2010 to January 2012. Logistic regression examined probability of availability, eligibility and enrollment in a GOG trial. Odds ratios (OR) and 95% confidence intervals (CI) for significant (p4 comorbidities (OR 4.5; CI 1.7–11.8) had higher odds of trial ineligibility. Non-White patients (OR 7.9; CI 1.3–46.2) and patients of Black physicians had greater odds of enrolling (OR 56.5; CI 1.1–999.9) in a therapeutic trial. Significant patient therapeutic trial enrollment factors: belief trial may help (OR 76.9; CI 4.9–>1000), concern about care if not on trial (OR12.1; CI 2.1–71.4), pressure to enroll (OR .27; CI 0.12–.64), caregiving without pay (OR 0.13; CI .02–.84). Significant physician beliefs were: patients would not do well on standard therapy (OR 3.6; CI 1.6–8.4), and trial would not be time consuming (OR 3.3; CI 1.3–8.1).ConclusionsTrial availability, patient and physician beliefs were factors identified that if modified could improve enrollment in cancer cooperative group clinical trials.

Descriptions of significant associations found from a logistic regression analysis typically are based on adjusted odds ratios. Unfortunately, odds ratios provide no information about the prevalence of response. In this paper, we justify and recommend using standardized risks, i.e., standardized probabilities, which do provide information about prevalence, in addition to adjusted odds ratios, for pairwise comparisons of the levels of a significant factor. We illustrate the advantages of generally reporting standardized risk estimates, in the context of assessing the effect of blood lead levels during the preschool years on occurrence of academic problems in kindergarten. Results are more meaningfully interpreted when accompanied by standardized risk estimates.

Chromosomal instability, manifesting as copy number alterations (CNAs), is characteristic of pancreatic adenocarcinoma. We used bacterial artificial chromosome (BAC) array-based comparative genomic hybridization (aCGH) to examine the pancreatic adenocarcinoma genome for submicroscopic amplifications and deletions. Profiles of 33 samples (17 first-passage xenografts and 16 cell lines) identified numerous chromosomal regions with CNAs, including losses at 1p36.33 approximately p34.3, 1p13.3 approximately p13.2, 3p26, 3p25.2 approximately p22.3, 3p22.1 approximately p14.1, 4q28.3, 4q31, 4q35.1, 5q14.3, 6p, 6q, 8p23.3 approximately p12, 9p, 9q22.32 approximately q31.1, 13q33.2, 15q11.2, 16p13.3, 17p, 18q11.21 approximately q23 , 19p13.3 approximately p13.12, 19q13.2, 21p, 21q, and 22p, 22q and gains at 7p21.1 approximately p11.2, 7q31.32, 7q33, 8q11.1 approximately q24, 11p13, 14q22.2, 20p12.2, and 20q11.23 approximately q13.33. Novel regions containing CNAs were identified and refined by combining the increased resolution of our BAC CGH array with a statistical algorithm developed for assigning significance values to altered BACs across samples. A subset of array-based CNAs was validated using polymerase chain reaction-based techniques, immunohistochemistry and fluorescence in situ hybridization. BAC aCGH proved to be a powerful genome-wide strategy to identify molecular alterations in pancreatic cancer and to distinguish differences between cell line and xenograft aberration profiles. These findings should greatly facilitate further research in understanding the pathogenesis of this lethal disease, and could lead to the identification of novel therapeutic targets and biomarkers for early detection.

Objective Patency rates for autogenous accesses are presumed to be better than for polytetrafluoroethylene (PTFE) accesses, although the strength of the supporting evidence is limited. We undertook this study to test the hypothesis that patency rates for upper extremity autogenous hemodialysis arteriovenous accesses in adults are superior to those for PTFE counterparts. Methods A systematic review of relevant literature and meta-analysis of the patency data were performed. Studies were considered acceptable if patency data were reported by either life table or Kaplan-Meier method, including number of patients at risk. Results The thirty-four studies that satisfied the inclusion criteria were composed predominantly of case series or nonrandomized controlled studies; no randomized, controlled studies comparing autogenous and PTFE accesses were included. The primary patency rate for autogenous accesses was 72% (95% confidence interval [CI], 70%-74%) at 6 months and 51% (95% CI, 48%-53%) at 18 months, and the corresponding primary patency rate for PTFE accesses was 58% (95% CI, 56%-61%) and 33% (95% CI, 31%-36%), respectively. The secondary patency rate for autogenous accesses was 86% (95% CI, 84%-88%) at 6 months and 77% (95% CI, 74%-79%) at 18 months, and the corresponding secondary patency rate for PTFE accesses was 76% (95% CI, 73%-79%) and 55% (95% CI, 51%-59%), respectively. Conclusions The patency rate for autogenous upper extremity arteriovenous hemodialysis accesses in adults is superior to that for PTFE counterparts, although the overall quality of the studies in the meta-analysis was less than ideal. Randomized, controlled studies to further examine the differences in outcome between these two access types are necessary.

To assess the frequency of cytogenetic abnormalities in children with autism spectrum disorders (ASDs), routine G-banded cytogenetic analyses and FISH studies to rule out 15q11.2 and 17p11.2 duplications were performed on 49 children with ASDs. Blood samples were further studied using a complete set of subtelomeric FISH probes. Routine chromosome study showed that one child had a small duplication of chromosome 5: 46,XY,dup(5)(p?14.2p?15.1). Another child had an interstitial duplication of the Prader-Willi and Angelman syndrome critical region of chromosome 15, detected by FISH analysis. The detection of these two cases underscores the importance of obtaining routine chromosome and 15q11-q13 FISH analyses in children with ASDs. No instance of 17p11.2 duplication was observed. Subtelomeric analysis did not reveal abnormalities in any of the subjects.

We consider the problem of record linkage in the situation where we have only non-unique identifiers, like names, sex, race etc., as common identifiers in databases to be linked. For such situations much work on probabilistic methods of record linkage can be found in the statistical literature. However, although many groups undoubtedly still use deterministic procedures, not much literature is available on deterministic strategies. Furthermore, there appears to exist almost no documentation on the comparison of results for the two strategies. In this work we compare a stepwise deterministic linkage strategy with a probabilistic strategy, as implemented in AUTOMATCH, for a situation in which the truth is known. The comparison was carried out on a linkage between medical records from the Regional Perinatal Intensive Care Centers database and educational records from the Florida Department of Education. Social security numbers, available in both databases, were used to decide the true status of each record pair after matching. Match rates and error rates for the two strategies are compared and a discussion of their similarities and differences, strengths and weaknesses is presented.

For confidentiality reasons, US federal death certificate data are incomplete with regards to the dates of birth and death for the decedents, making calculation of total lifetime of a decedent impossible and thus estimation of mortality incidence difficult. This paper proposes the use of natality data and an imputation-based method to estimate age-specific mortality incidence rates in the face of this missing information. By utilizing previously determined probabilities of birth, a birth date and death date are imputed for every decedent in the dataset. Thus, the birth cohort of each individual is imputed, and the total on-study time can be calculated. This idea is implemented in two approaches for estimation of mortality incidence rates. The first is an extension of a person-time approach, while the second is an extension of a life table approach. Monte Carlo simulations showed that both approaches perform well in comparison to the ideal complete data methods, but that the person-time method is preferred. An application to Tay-Sachs disease is demonstrated. It is concluded that the imputation methods proposed provide valid estimates of the incidence of death from death certificate data without the need for additional assumptions under which usual mortality rates provide valid estimates.

© 2014 John Wiley & Sons, Ltd. Multiple indicators, multiple causes (MIMIC) models are often employed by researchers studying the effects of an unobservable latent variable on a set of outcomes, when causes of the latent variable are observed. There are times, however, when the causes of the latent variable are not observed because measurements of the causal variable are contaminated by measurement error. The objectives of this paper are as follows: (i) to develop a novel model by extending the classical linear MIMIC model to allow both Berkson and classical measurement errors, defining the MIMIC measurement error (MIMIC ME) model; (ii) to develop likelihood-based estimation methods for the MIMIC ME model; and (iii) to apply the newly defined MIMIC ME model to atomic bomb survivor data to study the impact of dyslipidemia and radiation dose on the physical manifestations of dyslipidemia. As a by-product of our work, we also obtain a data-driven estimate of the variance of the classical measurement error associated with an estimate of the amount of radiation dose received by atomic bomb survivors at the time of their exposure.

This study sought to determine whether galactocerebrosidase activity is predictive of Krabbe onset age, or of survival from onset when controlling for age at onset of signs. We analyzed data on 55 symptomatic patients from the Hunter James Kelly Research Institute's World-Wide Registry. They were tested for galactocerebrosidase activity at Jefferson Medical College (Philadelphia, PA), using survival models in a path model context. Higher galactocerebrosidase activity was predictive of later symptom onset times ( P = 0.0011), but did not predict survival after symptom onset ( P = 0.9064) when controlling for the logarithm of age at onset. No child with early infantile (aged 0-6 months) phenotype demonstrated galactocerebrosidase activity >0.1 nmol/hour/mg protein. Survival times within a given phenotype did not vary with galactocerebrosidase activity. Although low galactocerebrosidase activity does not predict phenotype, higher activity in the abnormal range (>0.1 nmol/hour/mg protein in this sample) was not identified in the early infantile variant. Galactocerebrosidase activity may be important to consider when predicting phenotype in the newborn screening population. Our findings provide empiric evidence that the upper end (0.15 nmol/hour/mg protein) of the high-risk galactocerebrosidase group in the New York State newborn screening program is conservatively appropriate.

Based on the Atomic Bomb Casualty Commission/Radiation Effects Research Foundation series of over 5,000 autopsies, we examined death certificate accuracy for 12 disease categories and assessed the effect of potential modifying factors on agreement and accuracy. The overall percentage agreement between death certificate and autopsy diagnoses was only 52.5%. Although neoplasms had the highest detection rate, almost 25% of cancers diagnosed at autopsy were nevertheless missed on death certificates. Confirmation and detection rates were above 70% for neoplasms and external causes of death only. Confirmation rates were between 50 and 70% for infectious diseases and heart and other vascular diseases. Detection rates reached a similar level for infectious, cerebrovascular, and digestive diseases. Specificity rates were above 90% for all except the cerebrovascular disease category. Overall agreement decreased with increasing age at death and was worse for deaths occurring outside of hospital. There was some suggestion that agreement improved over time, but no indication that radiation dose, sex, city of residence, or inclusion in a biennial clinical examination program influenced agreement. Since the inaccuracy of death certificate diagnoses can have major implications for health research and planning, it is important to be aware that their accuracy is low and that it can vary widely depending on cause, age and place of death.

Leukodystrophies (LD) and lysosomal storage disorders (LSD) have generated increased interest recently as targets for newborn screening programs. Accurate epidemiological benchmarks are needed in the U.S. Age-specific mortality rates were estimated for Krabbe disease (KD) and nine related disorders. U.S. mortality records with E75.2 cause of death code during 1999-2004 were collected from 11 open record states. All E75.2 deaths in the United States were distributed into specific disease type based on proportions observed in these states. Yearly population sizes were obtained from the CDC and averaged. Mortality rates (per million individuals per year) by age group for the specific diseases were (for

New York State began screening for Krabbe disease in 2006 to identify infants with Krabbe disease before symptom onset. Because neither galactocerebrosidase activity nor most genotypes reliably predict phenotype, the World Wide Registry was developed to determine whether other clinical/neurodiagnostic data could predict early infantile Krabbe disease in the newborn screening population. Data on disease course, galactocerebrosidase activity, DNA mutations, and initial neurodiagnostic studies in 67 symptomatic children with early infantile Krabbe disease were obtained from parent questionnaires and medical records. Initial signs included crying/irritability, cortical fisting, and poor head control. Galactocerebrosidase activity was uniformly low. Eight of 17 manifested novel mutations. Ninety-two percent (n = 25) exhibited elevated cerebrospinal fluid protein; 76% (n = 42) demonstrated abnormal magnetic resonance images; 67% (n = 15) exhibited abnormal computed tomography findings; 43% (n = 28) produced abnormal electroencephalogram findings; 100% (n = 5) demonstrated abnormal nerve conduction velocities; 83% (n = 6) produced abnormal brainstem evoked responses; and 50% (n = 6) exhibited abnormal visual evoked responses. One, 2, and 3 year survivals were 60%, 26%, and 14%, respectively. Although most symptomatic patients with the early infantile phenotype manifested abnormal cerebrospinal fluid protein, magnetic resonance imaging, brainstem evoked responses, and nerve conduction velocities, studies of affected children may be normal. Other biomarkers are needed to predict phenotype in the newborn screening population.

In many medical studies, longitudinal data are collected on each of a sample of patients. The objectives of such studies often are: to estimate and test bivariate or multivariate relationships within each of several groups of patients from these repeated measures data; to compare these relationships among groups; and to test for the effects of baseline covariates on the relationships. This paper illustrates the use of statistical methods for growth curve analysis recently proposed by Vonesh and Carter for achieving these goals by relating a measure of preschool cognitive development to age in four race by sex groups of low-birth-weight infants. Significant declines in Bayley's Mental Development Index (MDI) with increasing age were found in all groups. Birth-weight did not significantly influence the rate of decline but did influence the overall level of performance. Even so, in the group most comparable to Bayley's normative population, predicted MDI was near the norm even for extremely low-birth-weight infants (that is, 1000 grams). Although there is some risk of mental deficit associated with prematurity, eventual developmental delays in low-birth-weight infants frequently are acquired with age. The rate of decline in MDI was significantly associated with race and mother's education. Assumptions required for the valid application of these methods are discussed and tested in the setting of this applied problem. The assumptions appeared valid in this application. We conclude with a brief discussion of available alternatives when the assumptions are violated and point to areas for future research.

Improving medical treatment of extremely low-birth-weight infants over the last 20 to 30 years resulted in increased survival rates. The developmental sequela of salvaged infants is of great interest to perinatologists. The primary purposes of the current study were to assess the effect of birth weight (BW) on developmental delay or disability (DDD) in the first three years of life and determine whether there is a BW threshold below which all infants should be evaluated to determine if intervention services for children with DDD should be received. Three statewide databases were merged: 1998 Birth Vital Statistics; 1997-1998 Medicaid eligibility files; and 1998-2001 Children's Medical Services' Early Intervention Program (CMS-EIP) data. Infants who died within the first year of life and plural births were excluded. The final dataset consisted of 170,874 records. A child was determined to have a DDD if a developmental delay, or an established condition, such as sensory impairment, genetic, metabolic, neurological, or severe attachment disorders, was diagnosed through a multidisciplinary evaluation. Logistic regression models were used to relate BW to DDD, controlling for sociodemographic, behavioral, and perinatal variables. Adjusted odds ratios (OR) were calculated to describe the effects of BW on DDD. There was a significant effect of BW on DDD (Adjusted OR &equals 97.50, 40.01, 15.84, 3.29, 1.39, 1.00, 1.52 for BW categories 450-749, 750-999, 1000-1499, 1500- 2499, 2500-2999, 3000-4749, 4750-6050 g, respectively). In these categories, 70%, 56%, 36%, 11%, 4%, 3%, and 6% of surviving singleton infants, respectively, suffered a DDD in their first 3 years of life. Four medical, five sociodemographic, and two behavioral factors were significant in addition to BW. An equation for predicting the probability of DDD given these factors was obtained, and its use exemplified. BW is strongly associated with DDD. Over 60% of infants weighing < 1000 g and nearly half (46%) of those weighing < 1500 g at birth are diagnosed with a DDD before 3 years of age. The probability of DDD for a specific infant also varies by sociodemographic, other perinatal, and behavioral factors. The results of this paper suggest that all surviving infants of BW < 1000 g, and perhaps < 1500 g, should be automatically referred for evaluation.

Context: Of the approximately 900,000 children who were determined to be victims of abuse or neglect by US child protective services in 2002, the birth-to-3 age group had the highest rate of victimization (1.6%) and children younger than 1 accounted for the largest percentage of victims (9.6%). Objective: To identify perinatal and sociodemographic risk factors associated with maltreatment of infants up to 1 year of age. Design and Setting: Observational cohort study. Participants: 189,055 children born in 1996 in Florida. Main Outcome Measure: Infant maltreatment, defined as a verified report of abuse, neglect, or threatened harm that occurred between day 3 of life and 1 year. Results: 1,602 children (.85%) of the 1996 birth cohort had verified instances of maltreatment by age 1. Of 15 perinatal and sociodemographic variables studied, 11 were found to be significantly related to infant maltreatment. Five factors had adjusted relative risks (RR) of two or greater: Mother smoked during pregnancy (RR 2.8); more than two siblings (RR 2.7); Medicaid beneficiary (RR 2.1); unmarried marital status (RR 2.0); low birth weight infant (RR 2.0). Infants who had four of these five risk factors had a maltreatment rate seven times higher than the population average. Conclusions: Data on nearly all risk factors found to be significantly associated with infant maltreatment are available on the birth certificate. Such information can be incorporated into a population-based risk-assessment tool that could identify subpopulations at highest risk for infant maltreatment. Because resources are limited, these groups should be given priority for enrollment in child abuse prevention programs.

To develop a risk-assessment screening tool for very low birth weight (VLBW) and to compare our empirically derived tool to the nonempirically derived screening tool used by the State of Florida.Birth records from the State of Florida Vital Statistics between 04/01/92 and 12/07/94 were matched with State Healthy Start prenatal records, reported from 04/01/92 through 03/31/94. Known and additional potentially important risk factors were identified from both sources. Generalized Linear Modeling techniques were used to estimate associations between risk factors and VLBW. A risk assessment system was then developed using the estimated model. The resulting screening test was compared with the one used by the Florida State Department of Health in terms of sensitivity and specificity on an independent validation sample.The proposed screening tool had comparable specificity to the Healthy Start screening tool but significantly better sensitivity. Both instruments are simple and easy to implement.Identification of women at high risk for VLBW would be improved using the model-based screening tool developed in this paper. Public health policy makers should use statistical methods in addition to expert opinion to improve existing risk assessment methods. The actual value of an improved screening instrument is dependent on the availability of effective intervention programs.

Teenage pregnancies have become a public health issue because of their observed negative effects on perinatal outcomes and long-term morbidity. The association of young maternal age and long-term morbidity is usually confounded, however, by the high prevalence of poverty, low level of education, and single marital status among teenage mothers. The authors assess the independent effect of teenage pregnancy on educational disabilities and educational problems in a total population of children who entered kindergarten in Florida in 1992--1994 and investigate how controlling for potentially confounding factors affects the relation between teenage pregnancies and poor outcome. When no other factors are taken into account, children of teenage mothers have significantly higher odds of placement in certain special education classes and significantly higher occurrence of milder education problems, but when maternal education, marital status, poverty level, and race are controlled, the detrimental effects disappear and even some protective effects are observed. Hence, the increased risk for educational problems and disabilities among children of teenage mothers is attributed not to the effect of young age but to the confounding influences of associated sociodemographic factors. In contrast to teen age, older maternal age has an adverse effect on a child's educational outcome regardless of whether other factors are controlled for or not.

Objectives: The purpose of this study was to determine outcome and identify predictors of death after thoracoabdominal aortic aneurysm (TAA) repair, renal artery bypass (RAB), and revascularization for chronic mesenteric ischemia (CMI). Patients and Methods: In this retrospective analysis, data were obtained from the Nationwide Inpatient Sample, a 20% all-payer stratified sample of hospitals in the United States during 1993 to 1997. Patients were identified by the presence of a diagnostic or procedure code from the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). The main outcomes we examined were death, ICD-9-CM –based complications, length of stay, hospital charges, and disposition. A multivariate model was constructed to predict death. Results: A total of 2934 patients were identified (TAA, 540; RAB, 2058; CMI, 336) in the database. The mean age was comparable (TAA, 69 ± 9 years; RAB, 66 ± 12 years; CMI, 66 ± 11 years), but the breakdown between the sexes varied by procedure (male: TAA, 53%; RAB, 55%; CMI, 24%). The mortality rate (TAA, 20.3%; RAB, 7.1%; CMI, 14.7%), complication rate (TAA, 62.2%; RAB, 37.4%; CMI, 44.6%), and the percentage of patients discharged to another institution (TAA, 21.2%; RAB, 9.3%; CMI, 12.0%) were clinically significant for all procedures. The mortality rate for RAB was greater when performed concomitant with an aortic reconstruction (4.4% vs 8.3%). All three procedures were resource intensive as reflected by the median length of stay (TAA, 14 days; RAB, 9 days; CMI, 14 days) and median hospital charges (TAA, $64,493; RAB, $36,830; CMI, $47,390). The multivariate model identified several variables for each procedure that had an impact on the predicted mortality rate (TAA, 14%-76%; RAB, < 1%-46%; CMI, < 2%-87%). Conclusions: The operative mortality rates across the United States for patients undergoing TAA repair and RAB are greater than commonly reported in the literature and mandate reexamining the treatment strategies for these complex vascular problems. (J Vasc Surg 2001;34:54-61.)

Objective. To assess the relative effects and the impact of perinatal and sociodemographic risk factors on long-term morbidity within a total birth population in Florida. Methods. School records for 339 171 children entering kindergarten in Florida public schools in the 1992–1993, 1993–1994, or 1994–1995 academic years were matched with Florida birth records from 1985 to 1990. Effects on long-term morbidity were assessed through a multivariate analysis of an educational outcome variable, defined as placement into 9 mutually exclusive categories in kindergarten. Of those categories, 7 were special education (SE) classifications determined by statewide standardized eligibility criteria, 1 was academic problems, and the reference category was regular classroom. Generalized logistic regression was used to simultaneously estimate the odds of placement in SE and academic problems. The impact of all risk factors was assessed via estimated attributable excess/deficit numbers, based on the multivariate analysis. Results. Educational outcome was significantly influenced by both perinatal and sociodemographic factors. Perinatal factors had greater adverse effects on the most severe SE types, with birth weight 10 times greater than that of very low birth weight, presence of a congenital anomaly, or prenatal care. Conclusions. Results are consistent with the hypothesis that adverse perinatal conditions result in severe educational disabilities, whereas less severe outcomes are influenced by sociodemographic factors. Overall, sociodemographic factors have a greater total impact on adverse educational outcomes than perinatal factors.

Objective. To determine the relationship between perinatal and sociodemographic factors in low birth weight and sick infants hospitalized at regional neonatal intensive care units (NICUs) and subsequent educational disabilities.Method. NICU graduates born between 1980 and 1987 at nine statewide regionalized level III centers were located in Florida elementary schools (kindergarten through third grade) during academic year 1992–1993 (n = 9943). Educational disability was operationalized as placement into eight mutually exclusive types of special education (SE) classifications determined by statewide standardized eligibility criteria: physically impaired, sensory impaired (SI), profoundly mentally handicapped, trainable mentally handicapped, educable mentally handicapped, specific learning disabilities, emotionally handicapped, and speech and language impaired (SLI). Logistic regression was used to estimate the odds of placement in SE for selected perinatal and sociodemographic variables.Results. Placement into SE ranged from .8% for SI to 9.9% for SLI. Placement was related to four perinatal factors (birth weight, transport, medical conditions [congenital anomalies, seizures or intraventricular hemorrhage] and ventilation), and five sociodemographic factors (child's sex, mother's marital status, mother's race, mother's educational level, and family income). Perinatal factors primarily were associated with placement in physically impaired, SI, profoundly mentally handicapped, and trainable mentally handicapped. Perinatal and sociodemographic factors both were associated with placement in educable mentally handicapped and specific learning disabilities whereas sociodemographic factors primarily were associated with placement in emotionally handicapped and SLI.Conclusions. Educational disabilities of NICU graduates are influenced differently by perinatal and sociodemographic variables. Researchers must take into account both sets of these variables to ascertain the long-term risk of educational disability for NICU graduates. Birth weight alone should not be used to assess NICU morbidity outcomes.

Background Chronic kidney disease is associated with disruption of the endocrine system that distorts the balance between calcitriol, calcium, phosphate and parathyroid hormone in the calcium regulation system. This can lead to calcification of the arterial tree and increased risk of cardiovascular disease and death. In this study we develop a health metric, based on biomarkers involved in the calcium regulation system, for use in identifying patients at high risk for future high-cost complications. Methods This study is a retrospective observational study involving a secondary analysis of data from the kidney disease registry of a regional managed care organization. Chronic kidney disease patients in the registry from November 2007 through November 2011 with a complete set of observations of estimated glomerular filtration rate, calcitriol, albumin, free calcium, phosphate, and parathyroid hormone were included in the study (n = 284). Weibull regression model was used to identify the most significant lab tests in predicting “waiting time to hospitalization”. A multivariate linear path model was then constructed to investigate direct and indirect effects of the biomarkers on this outcome. Results The results showed negative significant direct effects of phosphate and parathyroid hormone on “waiting time to hospitalization”. Base on this result, the risk of hospitalization increases 16.8% for each 0.55 mg/dl increase in phosphate level and 13.5% for each 0.467 increase in the natural logarithm of parathyroid hormone. Positive indirect effects of calcitriol surrogate (calcidiol), free calcium, albumin and estimated glomerular filtration rate were observed but were relatively small in magnitude. Conclusion Variables involved in the calcium regulation system should be included in future efforts to develop a quality of care index for Chronic Kidney disease patients.

Objective: To determine changes in survival patterns among very low-birth-weight ( Methods: The records of 12960 infants treated in nine perinatal intensive care centers in Florida were analyzed on the basis of survival (discharged alive from hospital) according to four independent variables: birth weight, race, sex, and transport status. Survival curves were generated using log linear regression techniques for each race by sex by transport status group. Results: Race, sex, and transport status correlated significantly with survival: survival percentages were higher among black infants, female infants, and infants transported to the perinatal intensive care centers than among white infants, male infants, and those admitted initially to the tertiary care centers. After 1985, 95% of neonates with birth weights between 1200 and 1500 g survived. In addition, survival of 500- to 550-g transported black male infants increased from zero to near 80% during the 13-year period; that of 500- to 550-g inborn white female infants rose from 35% to 70%. Conclusions: These results illustrate the value of taking into account race, sex, and transport status in efforts to understand the contribution that neonatal intensive care of extremely low-birth-weight infants makes to the lowering of infant mortality, and of using multivariable statistical procedures to generate predicted survival probabilities for different subpopulations. These probabilities can be applied to (1) predicting survival for specific subgroups of extremely low-birth-weight infants, and (2) helping physicians develop clinical guidelines for extending care to infants at the threshold of viability. (Arch Pediatr Adolesc Med. 1995;149:1311-1317)

Since its development in the 1950s, the Apgar index has come into widespread use as a tool to evaluate neonatal condition, with predictive implications for mortality and morbidity. However, Apgar scores were validated in predominantly term infants and have questionable prognostic value for low birthweight infants. The purpose of this study was to develop a survival index applicable to premature infants. Thirty-six perinatal variables were evaluated initially, based on data from 441 neonates weighing 500 to 1800 g. A multifactorial index of nine variables was derived, each independently related to mortality. Sensitivity of the index was 95%, specificity was 68%, positive predictive value was 90%, and negative predictive value was 81%. This index provides the most accurate tool yet reported in the literature for predicting concurrent survival of premature infants. The tool is recommended for use as an index of neonatal condition for low birthweight infants. Its additional use, as a predictor of the likelihood of survival would require time and place specific validation.

Background Controversy exists in predicting costly hospitalization in patients with chronic kidney disease and co-morbid conditions. We therefore tested associations between serum chemistry values and the occurrence of in-patient hospital costs over a thirteen month study period. Secondarily, we derived a linear combination of variables to estimate probability of such occurrences in any patient. Method We calculated parsimonious values for select variables associated with in-patient hospitalization and compared sensitivity and specificity of these models to ordinal staging of renal disease. Data from 1104 de-identified patients which included 18 blood chemistry observations along with complete claims data for all medical expenses. We employed multivariable logistic regression for serum chemistry values significantly associated with in-patient hospital costs exceeding $3,000 in any single month and contrasted those results to other models by ROC area curves. Results The linear combination of weighted Z scores for parathyroid hormone, phosphorus, and albumin correlated with in-patient hospital care at p < 0.005. ROC curves derived from weighted variables of age, eGFR, hemoglobin, albumin, creatinine, and alanine aminotransferase demonstrated significance over models based on non-weighted Z scores for those same variables or CKD stage alone. In contrast, the linear combination of weighted PTH, PO4 and albumin demonstrated better prediction, but not significance over non-weighted Z scores for PTH alone. Conclusion Further study is justified to explore indices that predict costly hospitalization. Such metrics could assist Accountable Care Organizations in evaluating risk adjusted compensation for providers.

Background Evaluation of mortality data is an important tool in assessing both disease time trends and differences in populations. However, the reasons for changes in cancer mortality rates have been controversial. Questions have been raised concerning whether these increases are real or simply the result of changing diagnoses and death certificate reporting. Purpose Our purpose was to determine on the basis of autopsy data if death certificate reporting varies over age, time, and cancer type and to explore the effect of death certificate error on recent cancer mortality trends. Methods Data were analyzed from 5886 autopsies collected by the Radiation Effects Research Foundation in Hiroshima, Japan, between 1961 and 1987. Death certificates were linked to autopsy data for analyses. An adjustment factor was calculated as a ratio of the accuracy of these death certificates in identifying cancer (detection rate) and listing cancer (confirmation rate) as the cause of death. This adjustment factor measures bias in mortality rates due to death certification errors and quantifies underestimation and overestimation of cancer mortality rates. Results Our analyses focused on lymphoma, breast cancer, neoplasms of the brain, multiple myeloma, and melanoma because of reported mortality increases. For these cancers, the adjustment factor decreased significantly (P = .02) over time, implying that death certificate accuracy has improved. This change appears to account for 60% of the observed increase in these cancers during the time period of study. For total cancer, persons 75 years or older have a high adjustment factor but it decreased over time. This decrease suggests an artifactual increase in total cancer mortality rates of about 1% per year for this older group. Conclusions The quality of death certificate reporting has generally remained constant for most groups during the period 1961-1987. In the study population, there was a consistent underestimation of total cancer mortality of about 18%. For the five types of cancer studied, there has been less underestimation of cancer mortality since 1976. For some specific cancers and for persons 75 years or older, improvements in death certificate accuracy have occurred over time. These data imply that the total death certificate error rate varies considerably by cancer type, time period, and age at death. Implications The changes in death certificate reporting for some sites and the elderly appear to have artifactually created increases in cancer mortality rates. These artifacts need to be considered when using mortality data for prevention research and health care planning.

Growth was assessed in children following 128 separate kidney transplants using a generalized growth curve multivariate analysis. The height standard deviation score was the dependent variable. Time since transplant, prednisone dosage, and creatinine clearance were the independent variables. For the purposes of comparison patients were grouped according to sex, race, age at transplantation, initial allograft function, acute rejection episodes and the use of cyclosporin A. Patient's height standard deviation scores tended to increase negatively after transplantation. However, children who received transplants before their 7th birthday, with initial allograft function greater than 60 ml/min per 1.73 m2, exhibited “catch-up” growth. Height standard deviation scores positively improved in males but not in females, as prednisone dosage was decreased. Height standard deviation scores became more negative as renal function decreased after transplantation. Changes in renal function produced the greatest effect upon height in black children, children less than 7 years, and males.

Neonatal intensive care unit survivors (N = 494) from 10 tertiary care centers were evaluated over the first 4 to 5 years of life to determine the relative contributions of birth weight and sociodemographic factors to mental development. Six sociodemographic factors were studied: sex, race, family income, and mother's marital status, age, and educational level; the last five factors also are known to be associated with premature birth. Mental development was measured with the Bayley Scales of Infant Development (12 to 24 months) and the Stanford Binet Intelligence Test (4 to 5 years). Each factor's influence was assessed by multivariate analysis. Birth weight had limited long-term implications; at 4 to 5 years, only infants with birth weights less than 1000 gm had significantly lower scores than those in other birth weight categories. Sociodemographic variables had a greater impact on mental development, with age-dependent differences found between nonwhite and white children and between children with mothers of low, medium, and high educational levels.

The purpose of this study was to determine if exposure to atomic bomb radiation affects immune responsiveness, such as the occurrence of autoantibodies and levels of immunoglobulins. Rheumatoid factor, antinuclear antibody, antithyroglobulin antibody, anti-thyroid-microsomal antibody and immunoglobulin levels (IgG, IgM, IgA and IgE) were measured among 2,061 individuals exposed to atomic bomb radiation in Hiroshima and Nagasaki whose estimated doses ranged from 0 to 5.6 Gy. The prevalence and titers of rheumatoid factor were found to be increased in the individuals exposed to higher radiation doses. The IgA level in females and the IgM level in both sexes increased as radiation dose increased, although the effects of radiation exposure were not large. No effect of radiation was found on the prevalence of antinuclear antibody, antithyroglobulin antibody and anti-thyroid-microsomal antibody or on the levels of IgG and IgE.

This study assessed change in the frequency of primary nocturnal enuresis as produced by either behavioral conditioning with a urine alarm, pharmacotherapy with imipramine hydrochloride, or assignment to a clinical waiting list. The study also investigated the effect of treatment method and outcome on subjects' level of emotional and behavioral adjustment. An attempt was made to identify pretreatment predictors of treatment outcome and premature withdrawal from the treatment program. The results indicated a significantly more effective outcome for the conditioning approach. Comparison of pre- and post-treatment measures of adjustment provided insufficient evidence to support the hypotheses that either change in the frequency of nighttime wetting or the method of treatment received would influence the subject's level of emotional and behavioral adjustment. The enuresis tolerance scale was found to be a highly significant predictor of early termination from conditioning treatment.

Rheumatoid vasculitis is an uncommon but potentially catastrophic complication of RA. There are few extensive experiences recorded in the current literature and there is no consensus regarding the clinical features, laboratory findings, histologic pattern, prognosis, or appropriate management of this syndrome. We therefore surveyed 1,947 North American ARA members for their perceptions of rheumatoid vasculitis. Four hundred twenty-eight surveys were returned, of which 290 were suitable for analysis. The majority of respondents were within 10 years of fellowships and were evenly distributed among private practice, and part-time and full-time academic positions. The respondents saw 15-50 rheumatoid arthritis (RA) patients weekly and less than five RA vasculitis patients annually. The majority correctly diagnosed two actual and complex case histories from patients with and without autopsy-proven vasculitis. Respondents associated the following features most strongly with rheumatoid vasculitis - mononeuritis multiplex, digital gangrene, digital ischemic lesions, nailfold ischemic lesions, non-healing leg ulcers, palpable purpura, fingertip nodules, sensory neuropathy, scleromalacia perforans, high titer rheumatoid factor, positive visceral angiography, cryoglobulinemia, hypocomplementemia, circulating immune complexes, and histologic necrotizing vasculitis or vascular transmural neutrophilia. Digital lesions or sensory neuropathy alone were not viewed as portending an ominous prognosis by most respondents and would have been treated with nonsteroidal anti-inflammatory drugs, antimalarials, gold salts, or D-penicillamine. Other clinical manifestations considered as reflecting rheumatoid vasculitis (gangrene, mononeuritis multiplex, ulcers) were thought to worsen prognosis and would have been managed more often with corticosteroids, D-penicillamine, cytotoxic agents or plasmapheresis. Rheumatoid vasculitis is viewed as a heterogeneous group of syndromes with varying clinical and histopathologic features,which have different prognostic implications, and therefore should be managed differently. While these dta do not substitute for an extensive recorded series of patients, they provide useful information about community perceptions of an uncommon but difficult clinical problem. They identify the need for additional data to examine the validity of these attitudes.

The purpose of the present study was to determine whether patients with recurrent low back pain display a different pattern of mood fluctuations across days than matched healthy controls and whether these mood states are related to pain occurrence and/or magnitude using a prospective design. The questions addressed are whether mood states prior to a pain episode are associated with the episode or whether mood relates to pain as a secondary reaction. Similarly, the relationship between mood state recorded prior to, during or following pain and magnitude of pain experienced was investigated. Thirty-three ambulatory chronic low pack pain patients and an equivalent group of asymptomatic controls matched for age, sex, socioeconomic status, and reported activity level monitored mood state (anxiety, tension, depression, anger, vigor, fatigue, confusion) and pain before breakfast, at 4 p.m. and at bedtime for 14 consecutive days. Groups were successfully matched. Analyses revealed significantly higher levels of tension, anxiety and fatigue and lower levels of vigor in the pain cases. No mood state was predictive of pain onset but fatigue was associated with pain 24 h following pain, indicating fatigue as secondary to pain. While mood state recorded prior to or following pain was unable to predict magnitude of pain, fatigue was associated with the level of pain experienced during the pain episode itself. The findings reveal a pattern of anxiety, tension and fatigue where fatigue is associated with increased pain during the pain episode and is increased 24 h following pain. This fatigue-pain relationship is superimposed upon a continuous elevation of anxiety and tension. These findings suggest the importance of pain management efforts directed at decreasing patients' fatigue levels, and increasing functional endurance while simultaneously reducing anxiety. The results also question the role of negative mood states in the initiation or exacerbation of pain and highlights the influence of physical mood states such as fatigue on pain in low back pain.

The effect of an intravenous bolus of 25 mg of conjugated estrogen (Premarin) on vaginal blood flow in seven surgically menopausal women was measured by a thermal conductance probe. Electrical power (0.8 W) was supplied to a resistance wire incorporated in the surface of the probe, and its surface temperature was monitored continuously for 30 minutes six times daily for 3 days. The mean temperature difference (delta T) between the heated probe surface and the vagina remained unchanged during a preinjection control day. While there were individual differences in response, analysis of mean delta T during the first day following the injection of the estrogen revealed a significant linear downward trend at delta T, indicating a rise in vaginal blood flow. Delta T plateaued on day 2 and showed a slight rise in the morning of day 3. It may be concluded that estrogen administered in this dose and form markedly increases vaginal blood flow.

This correlational study investigated possible behavioral, parental, and environmental differences in enuretic children who were either receiving or not receiving treatment for bed-wetting. The subjects wer 5- to 12-year-old children who were nocturnally incontinent at least once a week and physically normal in all other respects. Seventeen of these youngsters were receiving pharmacologic treatment for enuresis (clinical enuretic group) and 20 were not (nonclinical enuretic group). Clinical enuretic children were older and wet more frequently than youngsters whose parents had not sought treatment for this problem. Their fathers more often held blue-collar jobs and their mothers were more intolerant of enuresis than were parents of the nonclinical enuretic sample. These two groups did not differ in number and type of child behavior problems, number of life-stress events, age toilet training commenced, or parental child-rearing practices employed. However, enuretic youngsters displayed more conduct problems and immature behavior than their nonenuretic counterparts. Mothers of enuretic youngsters applied more rule-oriented child-rearing practices than mothers of nonenuretic controls. There were no differences between the enuretic and nonenuretic groups in number of early-life stressful events or the age at which toilet training commenced.

One hundred sixty-eight patients with childhood diabetes (6 to 19 years of age) and their parents participated in 24-hr recall interviews concerning daily diabetes management behavior. Each patient and parent was interviewed independently on three separate occasions. The information obtained was used to construct measures of 13 different adherence behaviors. Parent-patient agreement was good to excellent for most of the 13 behaviors. Agreement was influenced by the patient's age, with the most consistently high parent-child agreement found in the 10- to 15-year-old age group. Factor analysis of the 13 adherence behaviors resulted in a five-factor solution accounting for 70.6% of the variance. Adherence in childhood diabetes appears to be a complex construct, consisting of at least five different components unrelated to each other. Teenagers in this sample were less adherent than their younger counterparts on most of the adherence measures studied.

A long-standing controversy concerns whether lateralized cerebral specialization for speech and language is present at the time of language origins (developmental invariance) or whether it gradually develops from initial bilaterality (developmental progression). Thus controversy is complicated by conflicting reports of the incidence of childhood aphasia. The discrepancies are largely due to one early study. When methods for estimating speech organization distributions are applied to later studies, the developmental invariance position is supported.

This paper presents a method to infer the cerebral mode of speech in the left- and right-handed. The method is applied to the known reports on the incidence of aphasia following a unilateral brain injury in adults (1935–1973) [1]. Two different models were found. In the left-handed, a complex model of unilateral (left=0.24, right=0.00) and bilateral speech (0.76) was inferred. In the right-handed, a less complex model of unilateral speech specialization (left=0.95, right=0.05) was inferred.

A prospective investigation was initiated to assess the effect of a low-dose oral contraceptive containing 35 μg of ethinyl estradiol and 0.4 mg of norethindrone on blood coagulation and fibrinolysis. Twenty-four women were studied before, during, and after one year of treatment. Positive results included an accelerated activated partial thromboplastin time and an increase in fibrinolytic and anticoagulation factors as measured by α 1 -antitrypsin antigen and plasminogen antigen and activity. Antithrombin III antigen was decreased but its activity was unaffected. There was no evidence of ongoing intravascular coagulation. No patient had a detectable thromboembolic event. In short, one year's usage of this low-dose oral contraceptive was not associated with a procoagulant hematologic profile.

Although diet therapy for arthritis has received considerable publicity, there is little objective information about its efficacy. We undertook a 10-week, controlled, double-blind, randomized trial of patients with active rheumatoid arthritis (RA). Twenty-six patients completed the study; 11 were on an experimental diet (a specific popular diet free of additives, preservatives, fruit, red meat, herbs, and dairy products) and 15 were on a "placebo" diet. Of 183 variables analyzed, there were no clinically important differences among rheumatologic, laboratory, immunologic, radiologic, or nutritional findings between patients on experimental and placebo diets. Six RA patients on the placebo and 5 on the experimental diet improved by objective criteria. Improvement averaged 29% for patients on placebo and 32% for patients on experimental diets. Two patients on the experimental diet improved notably, elected to remain on the experimental diet following the study period, have continued to improve, and noted exacerbations of disease upon consuming nonexperimental diet foods. Our study failed to provide evidence of objective overall clinical benefit of this diet as followed by a group of patients with longstanding, progressive, active RA. However, our data are not inconsistent with the possibility that individualized dietary manipulations might be beneficial for selected patients with rheumatic disease.

SUMMARY Statistical methods of estimating speech-organization distributions from aphasia data are presented. Under certain assumptions, estimators for the proportions of individuals with unilateral righthemisphere speech, unilateral left-hemisphere speech and bilateral speech organization are derived, and the large-sample properties of these estimators are presented. It is shown that useful results can be obtained when the most questionable assumption is relaxed. The general methodology is presented in terms of a specific example-the estimation of speech organization distributions of right- and lefthanded adults across the three speech types. Under the relaxed assumptions a test of the hypothesis that all left-handers are unilaterally organized is derived. Conservative bounds on the proportions of unilaterally organized (left- and right-hemisphere) and bilaterally organized left-handers are also derived. As an illustration, the results are applied to aphasia-incidence data from the literature. Several uncertainties and inadequacies of the available data are discussed. Although minor modifications of the present methods might be required for other examples, the main ideas would be the same.

The Family Adaptability and Cohesion Evaluation Scales (FACES), a measure of family functioning, contains three scales: cohesion, adaptability, and social desirability. These were slightly modified (FACES- R) on the basis of pilot data and were administered to 42 clinic families (families seeking or receiving psychological services) and 206 nonclinic families. Support for the scales was found in high coefficient alpha reliabilities and similarity of the sample means and standard deviations to those of the standardization sample. However, there was little agreement among family members' scale scores. Therapists' ratings of cohesion and adaptability did not correlate with scale scores among clinic families. There was no difference between clinic and nonclinic samples on the cohesion or adaptability scales, although the social desirability scale did discriminate between groups. Factor analysis suggested that cohesion, adaptability, and social desirability cannot be clearly differentiated using this measure.

Survival for low-birth-weight infants has traditionally been analyzed by birth weight categories spanning considerable ranges of weight. We developed a finer description of survival rates to allow estimation of survival percentages for infants of any specific birth weight between 500 and 2500 gm. Our sample consisted of 16,183 infants treated in tertiary neonatal intensive care between 1980 and 1987. Their survival data were analyzed by 50 gm increments between 500 and 2500 gm, and a continuous survival curve was constructed by log linear regression methods. Mortality differences between males and females and blacks and whites were analyzed. Survival for females was higher than males between 500 and 1500 gm and higher for blacks than whites between 650 and 1500 gm. Between 1500 and 2500 gm, no significant effects of birth weight, race, or sex were observed, with survival remaining stable at approximately 95% across all combinations of variables.