Single-test syphilis serology: A case of not seeing the forest for the trees.

INTRODUCTION: There have been few empirical studies for diagnostic test accuracy of syphilis using a sequence of rapid tests in populations with low prevalence of syphilis such as pregnant women. This analysis describes syphilis test positivity frequency among pregnant women at an antenatal clinic in Zambia using a reverse-sequence testing algorithm for antenatal syphilis screening. METHODS: Between August 2019 and May 2023, we recruited 1510 pregnant women from a peri-urban hospital in Lusaka, Zambia. HIV positive and HIV negative women were enrolled in a 1:1 ratio. Blood collected at recruitment from the pregnant mothers was tested on-site for syphilis using a rapid treponemal test. Samples that tested positive were further tested at a different laboratory, with rapid plasma reagin using archived plasma. RESULTS: Of the total 1,421 sera samples which were screened with a rapid treponemal test, 127 (8.9%) were positive and 1,294 (91.1%) were negative. Sufficient additional samples were available to perform RPR testing on 114 of the 127 (89.8%) RDT positive specimens. Thirty-one (27.2%) of these 114 were reactive by RPR and 83 (72.8%) were negative, resulting in a syphilis overtreatment rate of 3 fold (i.e, 84/114). Insufficient sample or test kit availability prevented any testing for the remaining 89 (5.9%) participants. CONCLUSION: Use of only treponemal tests in low prevalence populations, like pregnant women, subjects individuals with non-active syphilis to the costs and possible risks of overtreatment. The use of the dual treponemal and non-treponemal tests would minimize this risk at some additional cost.

Maternal Education and Child Self-Regulation: Do Maternal Self-Regulation and Responsiveness Mediate the Association?

OBJECTIVE: To examine the mediating role of observed maternal responsiveness and maternal self-regulation on the association between maternal education and children's self-regulation. METHODS: English-speaking mother-child dyads (n = 189) were recruited from a previous study and were eligible if the child was kindergarten eligible at the start of the 2020 to 2021 or 2021 to 2022 school year. Key measures included: Difficulties in Emotion Regulation Scale-Short Form for maternal emotional self-regulation, Culturally Affirming and Responsive Experiences for maternal responsiveness, and the Head-Toes-Knees-Shoulders for child self-regulation. The association between years of maternal education and child self-regulation was examined with linear regression, and the mediation analyses utilized 4 subsequent steps examining their relations. These steps were checked through a series of linear regressions, and beta weights were used to describe associations. Each potential mediator was examined separately. RESULTS: Children of mothers with higher education had significantly higher self-regulation, slope of 1.3 (95% confidence interval 0.3, 2.4, P = 0.015, beta = 0.18). Further, mothers with higher education had significantly higher observed responsiveness. The beta-weight of 0.34 (P < 0.001) supported maternal responsiveness as a mediator. Finally, in the test for direct and indirect effects, observed maternal responsiveness explained 29% (95% confidence interval 3.3%, 115%) of the association between maternal education and child self-regulation. CONCLUSIONS: This study highlights a key mechanism related to children's self-regulation skills and the significant role of observed maternal responsiveness in explaining the association between maternal education and child self-regulation.

Maternal Social Risk, Gestational Age at Delivery, and Cognitive Outcomes among Adolescents Born Extremely Preterm.

Background: Children born extremely preterm (EP) are at increased risk of cognitive deficits that persist into adulthood. Few large cohort studies have examined differential impairment of cognitive function in EP-born adolescents in relation to early life risk factors, including maternal social disadvantage, gestational age at delivery, and neonatal morbidities prevalent among EP neonates. Objectives: To assess cognitive abilities in relation to early life risk factors in an EP-born cohort at 15 years of age. Methods: 681 of 1198 surviving participants (57%) enrolled from 2002 to 2004 in the Extremely Low Gestational Age Newborn Study returned at age 15 years for an assessment of cognitive abilities with the Wechsler Abbreviated Scale of Intelligence-II and the NIH Toolbox Cognition Battery (NTCB) verbal cognition and fluid processing composites, the latter of which measured executive functions and processing speed. Three cognitive outcomes, WASI-II IQ, NTCB verbal cognition, and NTCB fluid processing, were analyzed for associations with maternal social disadvantage and gestational age. Mediation of maternal social disadvantage by gestational age and mediation of gestational age by neonatal morbidities were also examined. Results: Test scores were lower for NTCB fluid processing relative to IQ and NTCB verbal abilities. Social disadvantage and gestational age were associated with all three cognitive outcomes. Mediation analyses indicated partial mediation of gestational age associations with all three outcomes by neonatal morbidities but did not support mediation by gestational age of social risk associations with cognitive outcomes. Conclusions: Greater maternal social disadvantage and lower gestational age are associated with less favorable cognitive outcomes among EP-born adolescents at 15 years of age. Neonatal morbidities partially mediate associations between lower gestational age and cognitive outcomes. These findings highlight the need for improved medical and remedial interventions to mitigate risk of poor cognitive outcomes among EP-born adolescents.

Persistent Immune Activation in Human Immunodeficiency Virus-Infected Pregnant Women Starting Combination Antiretroviral Therapy After Conception.

This study evaluated the impact of human immunodeficiency virus (HIV) and combination antiretroviral therapy (cART) on immune activation during pregnancy in a Zambian cohort of HIV-exposed but uninfected children followed up from birth. Activated CD8+ T cells (CD38+ and HLA-DR+) were compared among HIV-uninfected (n = 95), cART experienced HIV-infected (n = 111), and cART-naive HIV-infected (n = 21) pregnant women. Immune activation was highest among HIV-infected/cART-naive women but decreased during pregnancy. Immune activation HIV-infected women who started cART during pregnancy was reduced but not to levels similar to those in HIV-uninfected women. The effects of elevated maternal immune activation in pregnancy on subsequent infant health and immunity remain to be determined.

Accuracy of the Bayley-II mental development index at 2 years as a predictor of cognitive impairment at school age among children born extremely preterm.

OBJECTIVE: To describe the accuracy of the Bayley Scales of Infant Development-Second Edition (BSID-II) Mental Development Index (MDI) at 2 years of age for prediction of cognitive function at school age of children born extremely preterm. DESIGN: Study participants were enrolled in the Extremely Low Gestational Age Newborn Study between 2002 and 2004. Two-thirds of surviving children (n = 795) were assessed at 2 years with the BSID-II and at 10 years with an intelligence quotient (IQ) test. We computed test characteristics for a low MDI (<70), including predictive value positive. RESULTS: Almost two-thirds of children with a low MDI had a normal IQ (≥ 70) at 10 years. Concordance between MDI and IQ was highest among children with major motor and/or sensory impairment, and when MDI was adjusted for gestational age. CONCLUSION: Most children born extremely preterm with low BSID-II MDI at 2 years have normal intelligence at school age.

Placental CpG methylation of infants born extremely preterm predicts cognitive impairment later in life.

BACKGROUND: The placenta is the central regulator of maternal and fetal interactions. Perturbations of placental structure and function have been associated with adverse neurodevelopmental outcomes later in life. Placental CpG methylation represents an epigenetic modification with the potential to impact placental function, fetal development and child health later in life. STUDY DESIGN: Genome-wide placental CpG methylation levels were compared between spontaneous versus indicated deliveries from extremely preterm births (EPTBs) (n = 84). The association between the identified differentially methylated CpG sites and neurocognitive outcome at ten years of age was then evaluated. RESULTS: Spontaneous EPTB was associated with differential CpG methylation levels in 250 CpG sites (217 unique genes) with the majority displaying hypermethylation. The identified genes are known to play a role in neurodevelopment and are enriched for basic helix-loop-helix transcription factor binding sites. The placental CpG methylation levels for 17 of these sites predicted cognitive function at ten years of age. CONCLUSION: A hypermethylation signature is present in DNA from placentas in infants with spontaneous EPTB. CpG methylation levels of critical neurodevelopment genes in the placenta predicted later life cognitive function, supporting the developmental origins of health and disease hypothesis (DOHaD).

Co-occurrence and Severity of Neurodevelopmental Burden (Cognitive Impairment, Cerebral Palsy, Autism Spectrum Disorder, and Epilepsy) at Age Ten Years in Children Born Extremely Preterm.

BACKGROUND: This study aims to determine the prevalence of neurodevelopmental impairments at age ten years among children born extremely preterm (less than 28 weeks gestational age) and to offer a framework for categorizing neurological limitations. METHODS: A multicenter, prospective cohort follow-up study recruited 889 ten-year-old children born from 2002 to 2004. We assessed prevalence of cognitive impairment, measured by intelligent quotient and tests of executive function, cerebral palsy (CP), autism spectrum disorder (ASD), and epilepsy singly and in combination. The three levels of impairment severity were: category I-no major neurodevelopmental impairment; category II-normal cognitive ability with CP, ASD, and/or epilepsy; and category III-children with cognitive impairment. RESULTS: A total 214 of 873 children (25%) had cognitive impairment, 93 of 849 children (11%) had CP, 61 of 857 children (7%) had ASD, and 66 of 888 children (7%) had epilepsy. Further, 19% of all children had one diagnosis, 10% had two diagnoses, and 3% had three diagnoses. Decreasing gestational age was associated with increasing number of impairments (P < 0.001). Half the children with cognitive impairment and one third of children with CP, ASD, or epilepsy had a single impairment. Six hundred one (68% [95% CI, 64.5%-70.7%]) children were in category I, 74 (8% [95% CI, 6.6%-10.3%]) were in category II, and 214 (24% [95% CI 21.7%-27.4%]) were in category III. CONCLUSIONS: Three quarters of children had normal intellect at age ten years; nearly 70% were free of neurodevelopmental impairment. Forty percent of children with impairments had multiple diagnoses.

Maternal educational status at birth, maternal educational advancement, and neurocognitive outcomes at age 10 years among children born extremely preterm.

BackgroundTo determine if a key marker of socioeconomic status, maternal education, is associated with later neurocognitive and academic outcomes among children born extremely preterm (EP).MethodEight hundred and seventy-three children born at 23 to 27 weeks of gestation were assessed for cognitive and academic ability at age 10 years. With adjustments for gestational age (GA) and potential confounders, outcomes of children whose mothers had fewer years of education at the time of delivery and children whose mother advanced in education between birth and 10 years were examined.ResultsChildren of mothers in the lowest education stratum at birth were significantly more likely to score ≥2 SDs below normative expectation on 17 of 18 tests administered. Children of mothers who advanced in education (n=199) were at reduced risk for scoring ≥2 SDs on 15 of 18 measures, but this reduction was statistically significant on only 2 of 18 measures.ConclusionAmong EP children, socioeconomic disadvantage at birth, indexed by maternal education, is associated with significantly poorer neurocognitive and academic outcomes at 10 years of age, independently of GA. Maternal educational advancement during the child's first 10 years of life is associated with modestly improved neurocognitive outcomes.

Seasonal and Sexual Variation in Metabolism, Thermoregulation, and Hormones in the Big Brown Bat (Eptesicus fuscus).

In response to seasonal variation in energy availability and thermal environment, physiological and endocrine mechanisms have evolved in temperate zone animals. Seasonal changes in hormone activity affect metabolism, body temperature, and reproductive activity. We examined the seasonal regulatory role of hormones on basal metabolic rate (BMR) and regulatory nonshivering thermogenesis (RNST) in 98 female and 17 male adult Eptesicus fuscus (big brown bat). We measured BMR, RNST, and plasma levels of thyroid hormone (T3), leptin, and cortisol in bats captured in maternity colonies in eastern Massachusetts from May to August (from arousal from the hibernation phase to the prehibernation phase). We hypothesized that all three hormones are seasonally primarily metabolic hormones and secondarily thermogenic hormones. In males, only BMR significantly changed seasonally. In females, all five variables significantly changed seasonally. The seasonal pattern of plasma leptin and cortisol levels correlated with the seasonal pattern of BMR, with an initial increase followed by a decrease, suggesting that leptin and cortisol are primarily metabolic hormones. The seasonal pattern of plasma T3 levels generally paralleled the basic seasonal pattern of RNST, with both increasing at the second half of the season, suggesting that T3 is primarily a thermogenic hormone. The observed decrease in plasma leptin levels may be necessary to allow for the observed seasonal decrease in BMR, with the similar cortisol pattern important for leptin regulation. While T3 is needed to maintain BMR, it may play a more critical role in the seasonal regulation of RNST than of BMR.

Neurodevelopment at Age 10 Years of Children Born <28 Weeks With Fetal Growth Restriction.

OBJECTIVES: We sought to evaluate the relationships between fetal growth restriction (FGR) (both severe and less severe) and assessments of cognitive, academic, and adaptive behavior brain function at age 10 years. METHODS: At age 10 years, the Extremely Low Gestational Age Newborns Cohort Study assessed the cognitive function, academic achievement, social-communicative function, psychiatric symptoms, and overall quality of life of 889 children born before 28 weeks' gestation. A pediatric epileptologist also interviewed parents as part of a seizure evaluation. The 52 children whose birth weight z scores were <-2 were classified as having severe FGR, and the 113 whose birth weight z scores were between -2 and -1 were considered to have less severe FGR. RESULTS: The more severe the growth restriction in utero, the lower the level of function on multiple cognitive and academic achievement assessments performed at age 10 years. Growth-restricted children were also more likely than their extremely preterm peers to have social awareness impairments, autistic mannerisms, autism spectrum diagnoses, difficulty with semantics and speech coherence, and diminished social and psychosocial functioning. They also more frequently had phobias, obsessions, and compulsions (according to teacher, but not parent, report). CONCLUSIONS: Among children born extremely preterm, those with severe FGR appear to be at increased risk of multiple cognitive and behavioral dysfunctions at age 10 years, raising the possibility that whatever adversely affected their intrauterine growth also adversely affected multiple domains of cognitive and neurobehavioral development.

The Relationship of Maternal Prepregnancy Body Mass Index and Pregnancy Weight Gain to Neurocognitive Function at Age 10 Years among Children Born Extremely Preterm.

OBJECTIVE: To assess the association between maternal prepregnancy body mass index and adequacy of pregnancy weight gain in relation to neurocognitive function in school-aged children born extremely preterm. STUDY DESIGN: Study participants were 535 ten-year-old children enrolled previously in the prospective multicenter Extremely Low Gestational Age Newborns cohort study who were products of singleton pregnancies. Soon after delivery, mothers provided information about prepregnancy weight. Prepregnancy body mass index and adequacy of weight gain were characterized based on this information. Children underwent a neurocognitive evaluation at 10 years of age. RESULTS: Maternal prepregnancy obesity was associated with increased odds of a lower score for Differential Ability Scales-II Verbal IQ, for Developmental Neuropsychological Assessment-II measures of processing speed and visual fine motor control, and for Wechsler Individual Achievement Test-III Spelling. Children born to mothers who gained an excessive amount of weight were at increased odds of a low score on the Oral and Written Language Scales Oral Expression assessment. Conversely, children whose mother did not gain an adequate amount of weight were at increased odds of a lower score on the Oral and Written Language Scales Oral Expression and Wechsler Individual Achievement Test-III Word Reading assessments. CONCLUSION: In this cohort of infants born extremely preterm, maternal obesity was associated with poorer performance on some assessments of neurocognitive function. Our findings are consistent with the observational and experimental literature and suggest that opportunities may exist to mitigate risk through education and behavioral intervention before pregnancy.

Prevalence and associated features of autism spectrum disorder in extremely low gestational age newborns at age 10 years.

We sought to estimate the prevalence of autism spectrum disorder (ASD) in children born extremely preterm relative to the U.S. population risk of 1.5% [CDC, 2014] using the best-available diagnostic procedures and minimizing confounding with other neurodevelopmental impairments. Eight hundred and eighty nine of 966 (92%) 10-year-old children from the Extremely Low Gestational Age Newborn birth cohort, delivered at 23-27 weeks gestation in 2002-2004, participated. Children meeting ASD screening criteria on the Social Communication Questionnaire were evaluated with the Autism Diagnostic Interview-Revised (ADI-R). Those meeting ADI-R criteria were assessed with the Autism Diagnostic Observation Schedule-2 (ADOS-2). A positive ADOS-2 score was the criterion for ASD. Twenty-six participants were not assessed for ASD because of severe sensory or motor impairment. In the remaining sample, 61 children met criteria for ASD, resulting in a prevalence of 7.1% (95% CI = 5.5-9.0). ASD risk decreased with increasing gestational age, from 15.0% (95% CI = 10.0-21.2) for 23-24 weeks, 6.5% (95% CI = 4.2-9.4) for 25-26 weeks, to 3.4% (95% CI = 1.6-6.1) for 27 weeks gestational age, and this association was independent of IQ. Among children with ASD, 40% had intellectual disability. The male-to-female ratio of children with ASD was 2.1:1 (95% CI = 1.2:1-3.5:1), lower than in the general population (4:1). ASD prevalence in the ELGAN cohort was four times higher than in the general population, and was strongly associated with gestational age, underscoring the need for enhanced ASD screening of children born preterm, and suggesting that some risk factors associated with preterm birth may also play a role in the etiology of autism. Autism Res 2017, 10: 224-232. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Extremely low gestational age and very low birthweight for gestational age are risk factors for autism spectrum disorder in a large cohort study of 10-year-old children born at 23-27 weeks' gestation.

BACKGROUND: No prospective cohort study of high-risk children has used rigorous exposure assessment and optimal diagnostic procedures to examine the perinatal antecedents of autism spectrum disorder separately among those with and without cognitive impairment. OBJECTIVE: We sought to identify perinatal factors associated with increased risk for autism spectrum disorder with and without intellectual disability (intelligence quotient <70) in children born extremely preterm. STUDY DESIGN: This prospective multicenter (14 institutions in 5 states) birth cohort study included children born at 23-27 weeks' gestation in 2002 through 2004 who were evaluated for autism spectrum disorder and intellectual disability at age 10 years. Pregnancy information was obtained from medical records and by structured maternal interview. Cervical-vaginal "infection" refers to maternal report of bacterial infection (n = 4), bacterial vaginosis (n = 30), yeast infection (n = 62), mixed infection (n = 4), or other/unspecified infection (n = 43; eg, chlamydia, trichomonas, or herpes). We do not know the extent to which infection per se was confirmed by microbial colonization. We use the terms "fetal growth restriction" and "small for gestational age" interchangeably in light of the ongoing challenge to discern pathologically from constitutionally small newborns. Severe fetal growth restriction was defined as a birthweight Z-score for gestational age at delivery <-2 (ie, ≥2 SD below the median birthweight in a referent sample that excluded pregnancies delivered for preeclampsia or fetal indications). Participants were classified into 4 groups based on whether or not they met rigorous diagnostic criteria for autism spectrum disorder and intellectual disability (autism spectrum disorder+/intellectual disability-, autism spectrum disorder+/intellectual disability+, autism spectrum disorder-/intellectual disability+, and autism spectrum disorder-/intellectual disability-). Temporally ordered multinomial logistic regression models were used to examine the information conveyed by perinatal factors about increased risk for autism spectrum disorder and/or intellectual disability (autism spectrum disorder+/intellectual disability-, autism spectrum disorder+/intellectual disability+, and autism spectrum disorder-/intellectual disability+). RESULTS: In all, 889 of 966 (92%) children recruited were assessed at age 10 years, of whom 857 (96%) were assessed for autism spectrum disorder; of these, 840 (98%) children were assessed for intellectual disability. Autism spectrum disorder+/intellectual disability- was diagnosed in 3.2% (27/840), autism spectrum disorder+/intellectual disability+ in 3.8% (32/840), and autism spectrum disorder-/intellectual disability+ in 8.5% (71/840). Maternal report of presumed cervical-vaginal infection during pregnancy was associated with increased risk of autism spectrum disorder+/intellectual disability+ (odds ratio, 2.7; 95% confidence interval, 1.2-6.4). The lowest gestational age category (23-24 weeks) was associated with increased risk of autism spectrum disorder+/intellectual disability+ (odds ratio, 2.9; 95% confidence interval, 1.3-6.6) and autism spectrum disorder+/intellectual disability- (odds ratio, 4.4; 95% confidence interval, 1.7-11). Severe fetal growth restriction was strongly associated with increased risk for autism spectrum disorder+/intellectual disability- (odds ratio, 9.9; 95% confidence interval, 3.3-30), whereas peripartum maternal fever was uniquely associated with increased risk of autism spectrum disorder-/intellectual disability+ (odds ratio, 2.9; 95% confidence interval, 1.2-6.7). CONCLUSION: Our study confirms that low gestational age is associated with increased risk for autism spectrum disorder irrespective of intellectual ability, whereas severe fetal growth restriction is strongly associated with autism spectrum disorder without intellectual disability. Maternal report of cervical-vaginal infection is associated with increased risk of autism spectrum disorder with intellectual disability, and peripartum maternal fever is associated with increased risk for intellectual disability without autism spectrum disorder.

Neurocognitive and Academic Outcomes at Age 10 Years of Extremely Preterm Newborns.

BACKGROUND AND OBJECTIVE: Despite reductions in mortality and morbidity among children born extremely preterm, they remain at high risk of neurocognitive deficits, with up to 40% having significant cognitive deficits at school age. We assessed the rate of neurocognitive impairment in a contemporary US cohort of 873 children aged 10 years who were born <28 weeks' gestation. METHODS: The families of 889 of 966 (92%) children enrolled from 2002 to 2004 at 14 sites in 5 states returned at age 10 years for a comprehensive assessment of IQ, language, attention, executive function, processing speed, visual perception, visual-motor function, and academic achievement. RESULTS: A total of 873 children were assessed with well-validated tests of cognitive and academic function. Distributions of test scores were consistently and markedly shifted below normative expectation, with one-third to two-thirds of children performing >1 SD below age expectation. The most extreme downward shifts were on measures of executive control and processing speed. Multivariate analyses, adjusted for socioeconomic status, growth restriction, and other potential confounders, revealed that the risk of poor outcome was highest at the lowest gestational age across all 18 measures. CONCLUSIONS: More than half of our extremely preterm cohort exhibited moderate or severe neurocognitive deficits at age 10 years, with the most extensive impairments found among those born at the lowest gestational age. Children born extremely preterm continue to be at significant risk of persistent impairments in neurocognitive function and academic achievement, underscoring the need for monitoring and remediating such outcomes beginning in early childhood.

Assessing the agreement between 3-meter and 6-meter walk tests in 136 community-dwelling older adults.

OBJECTIVE: Walking speed is an important marker of functionality that is measured over courses of varying lengths, but it is unclear if course length affects measured pace. METHOD: A total of 136 older adults completed two consecutive trials each of 3-m and 6-m walking courses, the order of which was randomly assigned. We calculated concordance correlation coefficients (CCC) and created Bland-Altman plots to evaluate the relationship between the two course distances. RESULTS: Average walking speed was faster for the 6-m course and the second trial of each course. There was high concordance between the first and second trials for both the 3-m and 6-m courses. DISCUSSION: The 3- and 6-m courses had excellent test-retest reliability and faster walking speed in later than earlier trials. Higher concordance between courses for later trials suggests the utility of practice trials and adjusting for course length when combining walking speed measurements between different course lengths.

The breadth and type of systemic inflammation and the risk of adverse neurological outcomes in extremely low gestation newborns.

BACKGROUND: We hypothesized that the risk of brain damage in extremely preterm neonates increases with the breadth and type of systemic inflammation, indexed by the number of elevated inflammation-related proteins and the number of functional categories of inflammation-related proteins exhibiting an elevated concentration. METHODS: In blood from 881 infants born before 28 weeks gestation, we measured the concentrations of 25 inflammation-related proteins, representing six functional categories (cytokines, chemokines, growth factors, adhesion molecules, metalloproteinases, and liver-produced acute phase reactant proteins) on postnatal days 1, 7, and 14. We evaluated associations between the number and type of proteins whose concentrations were elevated on two separate occasions a week apart and the diagnoses of ventriculomegaly as a neonate, and at 2 years, microcephaly, impaired early cognitive functioning, cerebral palsy, and autism risk as assessed with the Modified Checklist for Autism in Toddlers screen, and in a subset of these children from 12 of 14 sites (n = 826), an attention problem identified with the Child Behavior Checklist. RESULTS: The risk of abnormal brain structure and function overall was increased among children who had recurrent and/or persistent elevations of the 25 proteins. The risk for most outcomes did not rise until at least four proteins in at least two functional categories were elevated. When we focused our analysis on 10 proteins previously found to be associated consistently with neurological outcomes, we found the risk of low Mental Development Index on the Bayley Scales of Infant Development-II, microcephaly, and a Child Behavior Checklist-defined attention problem increased with higher numbers of these recurrently and/or persistently elevated proteins. INTERPRETATION: Increasing breadth of early neonatal inflammation, indexed by the number of protein elevations or the number of protein functional classes elevated, is associated with increasing risk of disorders of brain structure and function among infants born extremely preterm.

Impact of depression on the intensity of patient navigation for women with abnormal cancer screenings.

Patient navigation is increasingly being used to support vulnerable patients to receive timely and quality medical care. We sought to understand whether patients with depression utilize additional patient navigation services after abnormal cancer screening. We compared depressed and non-depressed women using three different measures of intensity of patient navigation: number of patient-navigator encounters, encounter time, and number of unique barriers to care. The study population consisted of 1,455 women who received navigation after abnormal screening for breast or cervical cancer at one of six community health centers in Boston. Navigators spent a median of 60-75 minutes over one or two encounters per participant, with 49% of participants having one or more documented barrier to care. Depressed women did not differ in total numbers of encounters, encounter time, or unique barriers compared with non-depressed women. Our findings suggest that pre-existing depression does not predict which women will utilize additional navigation services.

Effects of caffeine on intermittent hypoxia in infants born prematurely: a randomized clinical trial.

IMPORTANCE: Preterm infants have immature respiratory control and resulting intermittent hypoxia (IH). The extent of IH after stopping routine caffeine treatment and the potential for reducing IH with extended caffeine treatment are unknown. OBJECTIVES: To determine (1) the frequency of IH in premature infants after discontinuation of routine caffeine treatment and (2) whether extending caffeine treatment to 40 weeks' postmenstrual age (PMA) reduces IH. DESIGN, SETTING, AND PARTICIPANTS: A prospective randomized clinical study was conducted at 16 neonatal intensive care units in the United States, with an 18-month enrollment period. Preterm infants (<32 weeks' gestation) previously treated with caffeine were randomized to extended caffeine treatment or usual care (controls) at a PMA of at least 34 weeks but less than 37 weeks. Continuous pulse oximeter recordings were obtained through 40 weeks' PMA. Oximeter data were analyzed by persons masked to patient group. INTERVENTION: Continued treatment with caffeine. MAIN OUTCOMES AND MEASURES: Number of IH events and seconds with less than 90% hemoglobin oxygen saturation (Sao2) per hour of recording. RESULTS: Our analysis included 95 preterm infants. In control infants, the mean (SD) time at less than 90% Sao2 at 35 and 36 weeks' PMA was 106.3 (89.0) and 100.1 (114.6) s/h, respectively. The number of IH events decreased significantly from 35 to 39 weeks' PMA (P = .01). Extended caffeine treatment reduced the mean time at less than 90% Sao2 by 47% (95% CI, -65% to -20%) to 50.9 (48.1) s/h at 35 weeks and by 45% (95% CI, -74% to -17%) to 49.5 (52.1) s/h at 36 weeks. CONCLUSIONS AND RELEVANCE: Substantial IH persists after discontinuation of routine caffeine treatment and progressively decreases with increasing PMA. Extended caffeine treatment decreases IH in premature infants. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01875159.

Depression and anxiety diagnoses are not associated with delayed resolution of abnormal mammograms and pap tests among vulnerable women.

BACKGROUND: Delays in care after abnormal cancer screening contribute to disparities in cancer outcomes. Women with psychiatric disorders are less likely to receive cancer screening and may also have delays in diagnostic resolution after an abnormal screening test. OBJECTIVE: To determine if depression and anxiety are associated with delays in resolution after abnormal mammograms and Pap tests in a vulnerable population of urban women. DESIGN: We conducted retrospective chart reviews of electronic medical records to identify women who had a diagnosis of depression or anxiety in the year prior to the abnormal mammogram or Pap test. We used time-to-event analysis to analyze the outcome of time to resolution after abnormal cancer screening, and Cox proportional hazards regression modeling to control for confounding. PARTICIPANTS: Women receiving care in six Boston-area community health centers 2004-2005: 523 with abnormal mammograms, 474 with abnormal Pap tests. RESULTS: Of the women with abnormal mammogram and pap tests, 19% and 16%, respectively, had co-morbid depression. There was no difference in time to diagnostic resolution between depressed and not-depressed women for those with abnormal mammograms (aHR = 0.9, 95 CI 0.7,1.1) or Pap tests (aHR = 0.9, 95 CI 0.7,1.3). CONCLUSIONS: An active diagnosis of depression and/or anxiety in the year prior to an abnormal mammogram or Pap test was not associated with a prolonged time to diagnostic resolution. Our findings imply that documented mood disorders do not identify an additional barrier to resolution after abnormal cancer screening in a vulnerable population of women.

Risk factors for uterine rupture among women who attempt a vaginal birth after a previous cesarean: a case-control study.

OBJECTIVE: To identify risk factors associated with uterine rupture among term pregnancies attempting a vaginal birth after a previous cesarean. STUDY DESIGN: A case-control study was done of 348 uterine ruptures in Massachusetts between 1991 and 1998, initially screened by ICD-9 code and confirmed by medical record review, with 424 control women with a trial of labor randomly selected proportional to cases on year of delivery. Multivariable regression was used to estimate odds ratios and 95% confidence intervals. RESULTS: Successful previous vaginal birth decreased risk for uterine rupture, and gestation > 40 weeks and macrosomia increased risk. Oxytocin for induction increased risk, with a slightly lower effect when used for augmentation. Prostaglandin use in conjunction with oxytocin did not have an additive uterine rupture risk. Women using epidural analgesia have an increased uterine rupture risk. CONCLUSION: Certain labor management practices increase the risk for uterine rupture 2-3 times, although the absolute increase is small from a baseline uterine rupture rate of 0.5% to 1.0-1.5%. The association between epidural analgesia and uterine rupture deserves further study.