Transferring care to enhance access to early-phase cancer clinical trials: Protocol to evaluate a novel program.

Involving diverse populations in early-phase (phase I and II) cancer clinical trials is critical to informed therapeutic development. However, given the growing costs and complexities of early-phase trials, trial activation and enrollment barriers may be greatest for these studies at healthcare facilities that provide care to the most diverse patient groups, including those in historically underserved communities (e.g., safety-net healthcare systems). To promote diverse and equitable access to early-phase cancer clinical trials, we are implementing a novel program for the transfer of care to enhance access to early-phase cancer clinical trials. We will then perform a mixed-methods study to determine perceptions and impact of the program. Specifically, we will screen, recruit, and enroll diverse patients from an urban, integrated safety-net healthcare system to open and active early-phase clinical trials being conducted in a university-based cancer center. To evaluate this novel program, we will: (1) determine program impact and efficiency; and (2) determine stakeholder experience with and perceptions of the program. To achieve these goals, we will conduct preliminary cost analyses of the program. We will also conduct surveys and interviews with patients and caregivers to elucidate program impact, challenges, and areas for improvement. We hypothesize that broadening access to early-phase cancer trials conducted at experienced centers may improve equity and diversity. In turn, such efforts may enhance the efficiency and generalizability of cancer clinical research.

The blurring boundaries between placental and maternal preeclampsia: a critical appraisal of 1800 consecutive preeclamptic cases.

OBJECTIVES: To present a comprehensive overview of different risk factors for early onset preeclampsia (<34 weeks gestation, EOP) vs. late onset (LOP). STUDY DESIGN: South-Reunion University's maternity (Reunion Island, Indian Ocean). 18.5 year-observational population-based cohort study (2001-2019). Epidemiological perinatal database with information on obstetrical and neonatal risk factors. All consecutive singleton pregnancies (>21 weeks) compared with all preeclamptic pregnancies delivered in the south of Reunion island. MAIN OUTCOME MEASURES: Comparing risk factors between EOP and LOP. RESULTS: Among 1814 singleton preeclamptic pregnancies (600 EOP and 1214 LOP), EOP women were older than LOP 29.5 vs. 28.6 years, p = .009, primigravidas (OR 0.78 [0.63-0.96], p = .02) were prone to LOP. History of preeclampsia (PE) (aOR 12.8 vs. 7.1), chronic hypertension (aOR 6.5 vs. 4.5) had much higher adjusted odds ratios for EOP than for LOP, p < .001. Specific to EOP: coagulopathies (aOR 2.95, p = .04), stimulated pregnancies (aOR 3.9, p = .02). Specific to LOP: renal diseases (aOR 2.0, p = .05) and protective effect for smoking (aOR 0.75, p = .008). EOP women were prone to have a lower BMI. CONCLUSION: "Placental preeclampsia" (defective placentation) being linked to early onset PE (<34 weeks gestation) while "maternal preeclampsia" (maternal cardiovascular predisposition) being typically manifesting as the late form of the disease LOP is not systematically verified. Future researches are needed to propose a more adapted paradigm.Highlights  Risk factors for different preeclampsia phenotypes (early/late); challenging proposed models.

Ethnic differences in postmaturity syndrome in newborns. Reflections on different durations of gestation.

OBJECTIVE: To describe the prevalence, by weeks of gestation, of post-maturity signs in newborns by ethnic origins. STUDY DESIGN: Observational cohort study (2001-2018), of all consecutive singleton births delivered at Center Hospitalier Universitaire Hospitalier Sud Reunion's maternity (Reunion Island, French overseas department, Indian Ocean). The presence of clinical post-maturity signs was recorded by a week of gestation using Clifford's clinical post-maturity signs in newborns (desquamation, dry skin, wrinkling fingers and cracked skin). RESULTS: Of the 67,463 singleton births during the period, 58,503 newborns were from Reunion island, 5756 were of European origin (mainland France), and 4061 newborns from the archipelago of Comoros (North of Madagascar). Mean duration of gestation was 276 days in Caucasian women, 272 days in Comorian mothers and 273 days in Reunionese (p < .001). Post-maturity is defined by WHO as gestation greater than 293 days (41 weeks + 6 days). At 41 weeks (287 days) 12.1% of Caucasian babies presented post-maturity signs and 22.4% meconium-stained liquid versus respectively, 22.8 and 27.1% in Reunionese and 44 and 39.8% in Comorians (p < .001). CONCLUSION: Among African (Black) pregnancies, duration of gestation was approximately 7 days shorter than in Caucasian (White) pregnancies. In the Reunionese intermixed population and Comorians, the gestation was shorter by 3-4 days. Black newborns presented severe clinical post-maturity signs beginning around 40 weeks and 4-6 days, while it was 1 week later in white infants. Consequences of these differences, with respect to clinical outcomes, are discussed.

Variations in Hepatitis B Vaccine Series Completion by Setting Among Adults at Risk in West Virginia.

INTRODUCTION: West Virginia leads the nation with the highest rate of acute hepatitis B. From 2013 to 2015, the West Virginia hepatitis B Vaccination Pilot Project distributed more than 10,000 doses of hepatitis B vaccine to at-risk adults through local health department clinics and through outreach to correctional facilities and substance use treatment centers. This study aims to determine which setting type is associated with the greatest likelihood of at-risk adults receiving all 3 or at least 2 doses of hepatitis B vaccine. METHODS: Data for this retrospective cohort study were accessed, extracted, and analyzed in 2019 from Pilot Project participant forms initially completed from 2013 to 2015. Odds of receiving all 3 or at least 2 doses were calculated using bivariate, multivariable, and mixed-effects regression models. RESULTS: Data were available for 1,201 participants. In multivariable logistic regression, participants vaccinated at substance use treatment centers (AOR=1.37, 95% CI=1.01, 1.86) and local health department family planning clinics (AOR=3.74, 95% CI=1.98, 7.06) were more likely to receive the 3-dose series versus those vaccinated at local health department sexually transmitted disease clinics. Participants vaccinated through substance use treatment centers (AOR=1.79, 95% CI=1.31, 2.44), correctional facilities (AOR=3.34, 95% CI=2.09, 5.34), and local health department family planning clinics (AOR=3.97, 95% CI=1.72, 9.16) were more likely to receive at least 2 doses. CONCLUSIONS: Hepatitis B vaccination delivered at local health department family planning clinics, substance use treatment centers, or correctional facilities may increase vaccine dose completion in West Virginia.

Safety Aspects of a Randomized Clinical Trial of Maternal and Infant Vitamin D Supplementation by Feeding Type Through 7 Months Postpartum.

Background: The safety of higher dose vitamin D (vitD) supplementation in women who change from exclusive or full breastfeeding to combination feeding or who continue supplementation after cessation of breastfeeding is unknown. Objective: Compare vitD supplementation safety of 6,400 to 400 IU/day and 2,400 IU/day using specific laboratory parameters in postpartum women and their infants through 7 months postpartum by feeding type. Design: In this randomized controlled trial, mothers (exclusively breastfeeding or formula-feeding) were randomized at 4-6 weeks' postpartum to 400, 2,400, or 6,400 IU vitD3 (cholecalciferol)/day for 6 months. Breastfeeding infants in 400 IU group received oral 400 IU vitD3/day; infants in 2,400 and 6,400 IU groups received placebo. Maternal safety parameters (serum vitD, 25-hydroxy-vitamin D [25(OH)D; calcidiol], calcium, phosphorus, intact PTH; urinary calcium/creatinine ratios; and feeding type/changes) were measured monthly; infant parameters were measured at months 1, 4, and 7. Sufficiency was defined as 25(OH)D >50 nmol/L. Feeding type was defined as exclusive/full, combination, or formula-feeding. Data were analyzed using SAS 9.4. Results: Four hundred nineteen mother-infant pairs were randomized into the three treatment groups and followed: 346 breastfeeding and 73 formula-feeding pairs. A dose of 6400 IU/day safely and significantly increased maternal vitD and 25(OH)D from baseline in all mothers regardless of feeding type (p < 0.0001) and was superior to the 400 and 2,400 IU groups in achieving vitD sufficiency with no other differences in safety parameters by treatment or feeding type. Infants in the 2,400 IU group were more likely vitD-deficient than the other groups; otherwise, there were no infant safety parameter differences. Conclusions: While 6,400 IU/day was more effective than 400 or 2,400 IU/day in achieving maternal vitD sufficiency in all feeding groups, the groups did not differ on other safety parameters. Similarly, infant safety parameters did not differ by treatment group or feeding status. Clinical Trial Registration: FDA IND Number: 66,346; ClinicalTrials.gov Number: NCT00412074.

Gestational weight gain and rate of late-onset preeclampsia: a retrospective analysis on 57 000 singleton pregnancies in Reunion Island.

OBJECTIVES: To investigate in singleton term pregnancies (≥37 weeks gestation) if applying optimal gestational weight gains (optGWG) on our population could have an effect on the incidence of late-onset preeclampsia (LOP). DESIGN: 18.5-year-observational cohort study (2001-2019). SETTINGS: Centre Hospitalier Universitaire Hospitalier Sud Reunion's maternity (French overseas department, Indian Ocean), the only maternity providing services to take care of all preeclamptic cases in an area with approximately 360 000 inhabitants. MAIN OUTCOMES AND MEASURES: Simulation rates of LOP between women achieving optimal versus inappropriate GWG (insufficient and excessive) in the non-overweight, overweight and class I-III obesity categories. RESULTS: Among 66 373 singleton term pregnancies with a live birth, and 716 LOP (≥37 weeks, LOP37), the GWG could be determined in 87% of cases. In a logistic regression model validating the independent association of optGWG, maternal ages and body mass index (BMI), primiparity, smoking habit, chronic hypertension with term preeclampsia, optGWG reduced the risk of LOP37, aOR 0.74, p=0.004. Primiparity, higher maternal BMI, chronic hypertension and higher maternal age increased the risk of LOP37. The 'protective' effect of optGWG appeared stronger in patients with overweight and obesity in a linear manner: 0.57% versus 1.07% (OR 0.53, p=0.003), overweight; class I obese (30-34.9 kg/m²), 0.70% vs 1.56% (OR 0.44, p=0.01); severe obesity (≥35 kg/m²) 0.86% vs 2.55% (OR 0.33, p=0.06). All patients with overweight/obesity together, OR 0.42, p<0.0001. CONCLUSIONS: Overweight and obesity may not result in a higher risk of developing LOP at term when a optGWG is achieved. The results of this large retrospective population cohort study suggest that targeted and strictly monitored interventions on achieving an optGWG might represent an effective method to reduce the rate of LOP and would have the potential to halve its rate in women with overweight/obesity. These findings suggest a potentially achievable pathway to actively counterbalance the morbid effects of high BMIs, so we solicit adequately powered prospective trials.

Validation of the 34-week gestation as definition of late onset preeclampsia: Testing different cutoffs from 30 to 37 weeks on a population-based cohort of 1700 preeclamptics.

INTRODUCTION: Early onset preeclampsia (EOP) and late onset preeclampsia (LOP) have been differentiated with a cut-point of ≤34 weeks. This classical definition has never been examined with respect to maternal characteristics by different gestational age cut-points. We examined maternal characteristics in a population-based cohort of 1736 preeclamptic deliveries at different gestational age cut-points from 30 to 37 weeks (CO30 to CO37). MATERIAL AND METHODS: Eighteen-year observational population-based historical cohort study (2001-2018). All consecutive births delivered at the Centre Hospitalier Universitaire Hospitalier Sud Reunion's maternity. Standardized epidemiological perinatal database. RESULTS: The incidence of EOP was lower in adolescents (1.8% vs 3.5%, odds ratio [OR] 0.50, P = .17). Conversely, the odds of LOP was increased for women over 35, beginning at C030 (OR 1.13, P = .02) and this effect (OR = 1.2) was still detectable at C037 (P = .06). Among primigravid women, the incidence of EOP was lower than LOP (OR ranging from 0.71 to 0.82 for different CO). Conversely, the incidence of LOP was higher (adjusted OR about 2.7 [CO30-CO34] with a rise to 3.3 at CO37 (P < .001). Women with EOP had a lower body mass index (BMI) as compared with LOP at CO34 and CO37. The adjusted OR (per 5 kg/m2 increment) declined from 1.06 to 1.03 from CO30 to C037 in EOP women. Conversely, for LOP, the adjusted odds ratio (aOR) increased from 1.04 to 1.06 from CO30 to CO37 (P < .001). Gestational diabetes mellitus was not associated with LOP at any cut-off (aOR 1.07, NS) but was protective against EOP from CO30 to CO34 (aOR 0.42, 0.61 and 0.73, respectively, P < .001). This protective effect disappeared at CO37. Chronic hypertension and history of preeclampsia were both EOP and LOP risks but with a much stronger effect for EOP (chronic hypertension: aOR 6.0-6.5, history of preeclampsia: aOR 12-17). CONCLUSIONS: The 34th week of gestation appears to provide a reasonable cut-point to differentiate between EOP and LOP. Additional research is needed to better describe the possible differences in the pathophysiology of these different phenotypes.

Increased BMI has a linear association with late-onset preeclampsia: A population-based study.

BACKGROUND: To investigate the ongoing controversy on the effect of BMI (body mass index) on EOP (early onset preeclampsia) vs LOP (late onset), especially focusing on diabetes and maternal booking/pre-pregnancy BMI as possible independent variables. METHODS: 18 year-observational cohort study (2001-2018). The study population consisted of all consecutive births delivered at the Centre Hospitalier Universitaire Hospitalier Sud Reunion's maternity (ap. 4,300 birth per year, only level 3 maternity in the south of Reunion Island, sole allowed to follow and deliver all preeclampsia cases of the area). History of pregnancies, deliveries and neonatal outcomes have been collected in standardized fashion into an epidemiological perinatal data base. RESULTS: Chronic hypertension and, history of preeclampsia in multigravidas, were the strongest risk factors for EOP. Primiparity, age over 35 years and BMI ≥ 35 kg/m² were rather associated with LOP. In a multivariate analysis with EOP or LOP as outcome variables compared with controls (normotensive), maternal age and pre-pregnancy BMI were independent risk factors for both EOP and LOP (p < 0.001). However, analyzing by increment of 5 (years of age, kg/m² for BMI) rising maternal ages and incidence of preeclampsia were strictly parallel for EOP and LOP, while increment of BMI was only associated with LOP. Controlling for maternal ages and booking/pre-pregnancy BMI, diabetes was not an independent risk factor neither for EOP or LOP. CONCLUSIONS: Metabolic factors, other than diabetes, associated with pre-pregnancy maternal corpulence are specifically associated with LOP. This may be a direction for future researches on the maternal preeclamptic syndrome. This may explain the discrepancy we are facing nowadays where high-income countries report 90% of their preeclampsia being LOP, while it is only 60-70% in medium-low income countries.

Updating a Perinatal Risk Scoring System to Predict Infant Mortality.

OBJECTIVE: The Birth Score Project (Project WATCH) began in the rural state of West Virginia (WV) in the United States in 1984. The project is intended to identify newborns with a greater risk of infant mortality. The primary objective of this study was to update the current Birth Score based on current literature and rigorous statistical methodology. STUDY DESIGN: The study merged data from the Birth Score, Birth Certificate (birth years 2008-2013), and Infant Mortality Data (N = 121,640). The merged data were randomly divided into developmental (N = 85,148) and validation (N = 36,492) datasets. Risk scoring system was developed using the weighted multivariate risk score functions and consisted of infant and maternal factors. RESULTS: The updated score ranged from 0 to 86. Infants with a score of ≥17 were categorized into the high score group (n = 15,387; 18.1%). The odds of infant mortality were 5.6 times higher (95% confidence interval: 4.4, 7.1) among those who had a high score versus low score. CONCLUSION: The updated score is a better predictor of infant mortality than the current Birth Score. This score has practical relevance for physicians in WV to identify newborns at the greatest risk of infant mortality and refer the infants to primary pediatric services and case management for close follow-up.

Preeclampsia and the 20th century: "Le siècle des Lumières".

The authors delineate seven quantum leap forward and, or revolutions having occurred during the 20th century in the understanding of the physiopathology of preeclampsia. First the discovery of the inflatable arm band permitting to measure blood pressure in 1896. Second, the discovery that eclamptic (convulsions), and later "pre"eclamptic (proteinuria) women presented hypertension in 1897 and confirmed in 1903, discovery of the hypertensive disorders of pregnancy. Third, the eight major textbooks published all along the 20th century by delineating risk factors of preeclampsia with the concept of "preeclampsia, disease of primigravidae". Fourth, the discovery in the 1970's that human trophoblast implantation was far deeper than in other mammalian species. Fifth, and a major step forward, description at the end of the 1980's that the maternal syndrome in preeclampsia (glomeruloendotheliosis, HELLP syndrome, eclampsia) could be unified in a global endothelial cell inflammation. Sixth, the epidemiological descriptions in the 1970-1990's that indeed preeclampsia was a disease of first pregnancies at the level of a couple ("primipaternity concept"), leading to an explosion in immunological research in the last decade, beginning in 1998. Seventh and finally, in the search for the "factor X" explaining the vascular inflammation in preeclamptic women (inositol phospho glycans P-type were described in 2000, while soluble Flt-1 and S-endoglins have been clearly predicted since 1997). The majority of the seeds or findings have been grounded or realized in the 20th century. Indeed, for preeclampsia, the 20th century has been le "Siècle des Lumières" (the Enlightments).

Relationship between pre-pregnancy maternal BMI and optimal weight gain in singleton pregnancies.

BACKGROUND: There is a peculiar phenomenon: two separate individuals (mother and foetus) have a mutually interactive dependency concerning their respective weight. Very thin mothers have a higher risk of small for gestational age (SGA) infants, and rarely give birth to a large for gestational age (LGA) infant. While morbidly obese women often give birth to LGA infants, and rarely to SGA. Normal birthweight (AGA) infants (>10th and <90th centile of a neonatal population) typically have the lowest perinatal and long-term morbidity. The aim of the current study is (1) to determine the maternal body mass index (BMI) range associated with a balanced risk (10% SGA, 10% LGA), and (2) to investigate the interaction between maternal booking BMI, gestational weight gain (GWG) and neonatal birthweight centiles. METHODS: 16.5 year-observational cohort study (2001-2017). The study population consisted of all consecutive singleton term (37 weeks onward) live births delivered at University's maternity in Reunion island, French Overseas Department. FINDINGS: Of the 59,717 singleton term live births, we could define the booking BMI and the GWG in 52,092 parturients (87.2%). We had 2 major findings (1) Only women with a normal BMI achieve an equilibrium in the SGA/LGA risk (both 10%). We propose to call this crossing point the Maternal Fetal Corpulence Symbiosis (MFCS). (2) This MFCS shifts with increasing GWG. We tested the MFCS by 5 kg/m2 incremental BMI categories. The result is a linear law:opGWG (kg) = -1.2 ppBMI (Kg/m²) + 42 ± 2 kg. INTERPRETATION: IOM-2009 recommendations are adequate for normal and over-weighted women but not for thin and obese women: a thin woman (17 kg/m2) should gain 21.6 ± 2 kg (instead of 12.5-18). An obese 32 kg/m2 should gain 3.6 kg (instead of 5-9). Very obese 40 kg/m2 should lose 6 kg.

A Retrospective Database Analysis of Neonatal Morbidities to Evaluate a Composite Endpoint for Use in Preterm Labor Clinical Trials.

Objective To propose and assess a composite endpoint (CE) of neonatal benefit based on neonatal mortality and morbidities by gestational age (GA) for use in preterm labor clinical trials. Study Design A descriptive, retrospective analysis of the Medical University of South Carolina Perinatal Information System database was conducted. Neonatal morbidities were assessed for inclusion in the CE based on clinical significance/risk of childhood neurodevelopmental impairment, frequency, and association with GA in a mother-neonate linked cohort, comprising women with uncomplicated singleton pregnancies delivered at ≥24 weeks' GA. Results Among 17,912 mother-neonate pairs, neonates were at a risk of numerous severe but infrequent morbidities. Clinically important, predominantly rare events were combined into a CE comprising neonatal mortality and morbidities, which decreased in frequency with increasing GA. The highest CE frequency occurred at <31 weeks. High frequency of respiratory distress syndrome, bronchopulmonary dysplasia, and sepsis drove the CE. Median length of hospital stay was longer at all GAs in those with the CE compared with those without. Conclusions Descriptive epidemiological assessment and clinical input were used to develop a CE to measure neonatal benefit, comprising clinically meaningful outcomes. These empirical data and CE allowed trials investigating tocolytics to be sized appropriately.

Linear association between maternal age and spontaneous breech presentation in singleton pregnancies after 32 weeks gestation.

PURPOSE: To investigate the association between maternal age and spontaneous breech presentation. MATERIAL AND METHODS: Fifteen-year observational study over (2001-2015). All consecutive singleton births delivered at the Centre Hospitalier Universitaire Sud Reunion's maternity. The only single exclusion criterion was uterine malformations (N = 123) women. RESULTS: Of the 60,963 singleton births, there was a linear association (χ2 for linear trend, p< 0.0001) between maternal age and spontaneous breech presentation. Overall rate of breech presentation was 2.7% in deliveries over 32 weeks gestation, while it was 1.9% in women aged 15 to 19 years and 4.0% in women aged 45+, with a linear progression for each 5-year age category. This linearity remained significant controlling for early prematurity (<33 weeks) and severe fetal malformations (χ2 for linear trend = 64, p < 0.0001). Controlling in a multiple logistic regression model for other major risk factors gestational age, female sex, primiparity, maternal age remained significantly an independent risk factor, p < 0.0001. CONCLUSION: Maternal age (x) is an independent factor for breech presentation in singleton pregnancies after 32 weeks gestation with a linear association that may be approximated at y = 0.1x. (y: incidence, percent).

Linear association between maternal age and need of medical interventions at delivery in primiparae: a cohort of 21,235 singleton births.

OBJECTIVES: We sought to investigate the potential association between maternal age and the need for active obstetrical intervention intrapartum in primiparas. STUDY DESIGN: Observational study over 14 years (2001-2014) of all consecutive primiparous singleton births having delivered at the Centre Hospitalier Universitaire Hospitalier Sud Reunion's maternity (French overseas department, Indian Ocean). RESULTS: Of the 21,235 singleton primiparous births, there were three significant linear associations between maternal age from 12 years of age to 42 + (all χ2 for linear trend, p < .0001) (a) vaginal deliveries without any medical intervention, (b) rate of cesarean sections, and (c) rate of operative vaginal procedures. These three linear associations persisted when controlling for maternal obesity (±30 kg/m2), "heavy babies" (>3.5 kg), and ethnicity. Using maternal age remained significantly an independent risk factor (p < .0001), after controlling for the major confounders: maternal BMI, maternal height, birthweight ≥3500 g, p < .0001. CONCLUSIONS: Increasing maternal age has a linear association with vaginal deliveries without any medical intervention, rate of cesarean sections, and rate of operative vaginal procedures. These associations are independent of maternal BMI and maternal height. We currently do not have a specific explanation why younger women appear to be protected from requiring intrapartum obstetric intervention. Nevertheless, these strong facts deserve acknowledgement and further research.

Historical evolution of ideas on eclampsia/preeclampsia: A proposed optimistic view of preeclampsia.

Eclampsia (together with epilepsy) being the first disease ever written down since the beginning of writings in mankind 5000 years ago, we will make a brief presentation of the different major steps in comprehension of Pre-eclampsia. 1) 1840. Rayer, description of proteinuria in eclampsia, 2) 1897 Vaquez, discovery of gestational hypertension in eclamptic women, 3) In the 1970's, description of the "double" trophoblastic invasion existing only in humans (Brosens & Pijnenborg,), 4) between the 1970's and the 1990's, description of preeclampsia being a couple disease. The "paternity problem" (and therefore irruption of immunology), 5) at the end of the 1980's, a major step forward: Preeclampsia being a global endothelial cell disease (glomeruloendotheliosis, hepatic or cerebral endotheliosis, HELLP, eclampsia), inflammation (J.Roberts.C Redman, R Taylor), 6) End of the 1990's: Consensus for a distinction between early onset preeclampsia EOP and late onset LOP (34 weeks gestation), EOP being rather a problem of implantation of the trophoblast (and the placenta), LOP being rather a pre-existing maternal problem (obesity, diabetes, coagulopathies etc…). LOP is predominant everywhere on this planet, but enormously predominant in developed countries: 90% of cases. This feature is very different in countries where women have their first child very young (88% of world births), where the fatal EOP (early onset) occurs in more than 30% of cases. 7) What could be the common factor which could explain the maternal global endotheliosis in EOP and LOP? Discussion about the inositol phospho glycans P type.

Prenatal vitamin D and enamel hypoplasia in human primary maxillary central incisors: a pilot study.

BACKGROUND: Enamel hypoplasia (EH) increases risk for dental caries and also is associated with vitamin D deficiencies. This pilot study evaluates the feasibility to determine the association of human maternal circulating vitamin D concentrations during pregnancy and EH in infant's teeth that develop in utero. METHODS: A pilot population of 37 children whose mothers participated in a RCT of vitamin D supplementation during pregnancy was evaluated. Major outcome was EH and major exposure was maternal monthly serum circulating 25(OH)D concentrations during pregnancy. EH was assessed using the Enamel Defect Index and digital images made by a ProScope High Resolution™ handheld digital USB microscope at 50x magnification. RESULTS: During initial 8 weeks of study, 29/37 children had evaluable data with mean age of 3.6 ± 0.9 years; 48% male; and 45% White, 31% Hispanic, and 24% Black. EH was identified in 13 (45%) of the children. Maternal mean 25(OH)D concentrations were generally lower for those children with EH. CONCLUSIONS: Preliminary results suggest follow-up of children of mothers in a vitamin D supplementation RCT during pregnancy provides an important approach to study the etiology of EH in the primary teeth. Further study is needed to discern thresholds and timing of maternal serum 25(OH)D concentrations during pregnancy associated with absence of EH in teeth that develop in utero. Potential dental public health implications for prevention of early childhood caries via sound tooth structure as related to maternal vitamin D sufficiency during pregnancy need to be determined.

The Role of Limited Head Computed Tomography in the Evaluation of Pediatric Ventriculoperitoneal Shunt Malfunction.

BACKGROUND: The evaluation of children with suspected ventriculoperitoneal shunt (VPS) malfunction has evolved into a diagnostic dilemma. This patient population is vulnerable not only to the medical risks of hydrocephalus and surgical complications but also to silent but harmful effects of ionizing radiation secondary to imaging used to evaluate shunt efficacy and patency. The combination of increased medical awareness regarding ionizing radiation and public concern has generated desire to reduce the reliance on head computed tomography (CT) for the evaluation of VPS malfunction. Many centers have started to investigate the utility of low-dose CT scans and alternatives, such as fast magnetic resonance imaging for the investigation of VP shunt malfunction in order to keep radiation exposure as low as reasonably achievable. This pilot study hopes to add to the armamentarium available to the clinician charged with evaluating this challenging patient population by testing the feasibility of a limited CT protocol as an alternative to a full head CT examination. OBJECTIVE: To evaluate the efficacy of a limited head CT protocol compared with a complete head CT for the evaluation of children presenting to the pediatric emergency department with suspected shunt malfunction. METHODS: We retrospectively reviewed all pediatric patients who received a head CT for suspected VPS malfunction evaluation at a tertiary care children's hospital from January 2001 through January 2013. Children were included in the pilot study if they had at least 2 CT scans in this study period interpreted by a specific senior attending neuroradiologist. For each patient enrolled, a limited series was generated from the most recent CT scan by selecting four representative axial slices based on the sagittal scout image. These 4 slices where selected at the level of the fourth ventricle, third ventricle, basal ganglia level, and lateral ventricles, respectively. A blinded, senior attending neuroradiologist first reviewed the limited 4-slice CT data set and was asked to determine if the ventricular system had increased, decreased, or remained stable. Subsequently, the neuroradiologist compared their interpretation of the limited examination with the official report from the full CT data set as the standard of reference as well as the interpretation of the most recent prior scan. RESULTS: Forty-six patients (age range, 2 months to 18 years; average age, 6.4 years (SD, 4.2), 54% male) were included in the study. Forty-four of 46 (95.7%) limited CT scans matched the official report of the full CT scan. No cases of increased ventricular size were missed (100% positive predictive value for increased ventricular size). The use of a limited head CT (4 axial images) instead of a complete head CT (average of 31 axial images in our studied patients) confers a radiation dose reduction of approximately 87%. CONCLUSIONS: Our pilot study demonstrates that utilization of limited head CT scan in the evaluation of children with suspected VP shunt malfunction is a feasible strategy for the evaluation of the ventricular size. Further prospective and multidisciplinary studies are needed to evaluate the reliability of limited head CT for the clinical evaluation of VP shunt malfunction.

Evaluating the Potential Severity of Look-Alike, Sound-Alike Drug Substitution Errors in Children.

OBJECTIVE: Look-alike, sound-alike (LASA) drug name substitution errors in children may pose potentially severe consequences. Our objective was to determine the degree of potential harm pediatricians ascribe to specific ambulatory LASA drug substitution errors. METHODS: We developed a unified list of LASA pairs from published sources, removing selected drugs on the basis of preparation type (eg, injectable drugs). Using a modified Delphi method over 3 rounds, 38 practicing pediatricians estimated degree of potential harm that might occur should a patient receive the delivered drug in error and the degree of potential harm that might occur from not receiving the intended drug. RESULTS: We identified 3550 published LASA drug pairs. A total of 1834 pairs were retained for the Delphi surveys, and 608 drug pairs were retained for round 3. Final scoring demonstrated that participants were able to identify pairs where the substitutions represented high risk of harm for receiving the delivered drug in error (eg, did not receive methylphenidate/received methadone), high risk of harm for not receiving the intended drug (eg, did not receive furosemide/received fosinopril), and pairs where the potential harm was high from not receiving the intended drug and from erroneously receiving the delivered drug (eg, did not receive albuterol/received labetalol). CONCLUSIONS: Pediatricians have identified LASA drug substitutions that pose a high potential risk of harm to children. These results will allow future efforts to prioritize pediatric LASA errors that can be screened prospectively in outpatient pharmacies.

Potential Acetaminophen and Opioid Overdoses in Young Children Prescribed Combination Acetaminophen/Opioid Preparations.

INTRODUCTION: Combination preparations of acetaminophen/opioid are the most common opioid form prescribed to children. We tested the hypothesis that dispensed prescriptions of acetaminophen/opioid preparations more appropriately match acetaminophen dosing parameters than opioid dosing parameters. We also hypothesized that the frequency of potential overdose was inversely related to subject age. METHODS: Using 2011 to 2012 South Carolina outpatient Medicaid data, the authors identified acetaminophen/opioid preparations dispensed to children 0 to 36 months. Utilizing Centers for Disease Control and Prevention (CDC) data to impute subject weights as the 97th percentile for age and gender, the authors used imputed weights to calculate the maximum recommended daily dose (expected dose) of each component. We calculated the dose delivered per day (observed dose) based on drug concentration, volume dispensed, and days' supply and then calculated the frequency of overdose (observed dose/expected dose, >1.10) by each component, comparing overdose frequency of acetaminophen to the overdose frequency of opioid using a risk ratio. Logistic regression evaluated differences in potential overdose by age, controlling for race/ethnicity and gender. RESULTS: Among 2,653 dispensed prescriptions of study drugs to 2,308 children 0 to 36 months old, the frequency of potential overdose was 0.7% for acetaminophen and 1.6% for opioid (risk ratio, 2.28). Age less than 3 months was associated with a greater frequency of potential overdose of either acetaminophen or opioid, even after controlling for gender and race/ethnicity. CONCLUSIONS: Prescriptions of acetaminophen-opioid drugs dispensed to children 0 to 36 months old contained potential overdoses of opioid at greater than twice the frequency of acetaminophen and were more likely to occur in infants less than 3 months old.