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BackgroundThe positive effects of early developmental intervention (EDI) on early child development have been reported in numerous controlled trials in a variety of countries. An important aspect to determining the efficacy of EDI is the degree to which dosage is linked to outcomes. However, few studies of EDI have conducted such analyses. This observational cohort study examined the association between treatment dose and children's development when EDI was implemented in three low and low-middle income countries as well as demographic and child health factors associated with treatment dose.MethodsInfants (78 males, 67 females) born in rural communities in India, Pakistan, and Zambia received a parent-implemented EDI delivered through biweekly home visits by trainers during the first 36 months of life. Outcome was measured at age 36 months with the Mental (MDI) and Psychomotor (PDI) Development Indices of the Bayley Scales of Infant Development-II. Treatment dose was measured by number of home visits completed and parent-reported implementation of assigned developmental stimulation activities between visits. Sociodemographic, prenatal, perinatal, and child health variables were measures as correlates.ResultsAverage home visits dose exceeded 91% and mothers engaged the children in activities on average 62.5% of days. Higher home visits dose was significantly associated with higher MDI (mean for dose quintiles 1-2 combined = 97.8, quintiles 3-5 combined = 103.4, p = 0.0017). Higher treatment dose was also generally associated with greater mean PDI, but the relationships were non-linear. Location, sociodemographic, and child health variables were associated with treatment dose.ConclusionsReceiving a higher dose of EDI during the first 36 months of life is generally associated with better developmental outcomes. The higher benefit appears when receiving ≥91% of biweekly home visits and program activities on ≥67% of days over 3 years. It is important to ensure that EDI is implemented with a sufficiently high dose to achieve desired effect. To this end groups at risk for receiving lower dose can be identified and may require special attention to ensure adequate effect.

Abstract Background This randomized controlled trial aims to evaluate the effects of an early developmental intervention program on the development of young children in low- and low-middle-income countries who are at risk for neurodevelopmental disability because of birth asphyxia. A group of children without perinatal complications are evaluated in the same protocol to compare the effects of early developmental intervention in healthy infants in the same communities. Birth asphyxia is the leading specific cause of neonatal mortality in low- and low-middle-income countries and is also the main cause of neonatal and long-term morbidity including mental retardation, cerebral palsy, and other neurodevelopmental disorders. Mortality and morbidity from birth asphyxia disproportionately affect more infants in low- and low-middle-income countries, particularly those from the lowest socioeconomic groups. There is evidence that relatively inexpensive programs of early developmental intervention, delivered during home visit by parent trainers, are capable of improving neurodevelopment in infants following brain insult due to birth asphyxia. Methods/Design This trial is a block-randomized controlled trial that has enrolled 174 children with birth asphyxia and 257 without perinatal complications, comparing early developmental intervention plus health and safety counseling to the control intervention receiving health and safety counseling only, in sites in India, Pakistan, and Zambia. The interventions are delivered in home visits every two weeks by parent trainers from 2 weeks after birth until age 36 months. The primary outcome of the trial is cognitive development, and secondary outcomes include social-emotional and motor development. Child, parent, and family characteristics and number of home visits completed are evaluated as moderating factors. Discussion The trial is supervised by a trial steering committee, and an independent data monitoring committee monitors the trial. Findings from this trial have the potential to inform about strategies for reducing neurodevelopmental disabilities in at-risk young children in low and middle income countries. Trial Registration Clinicaltrials.gov NCT00639184

Pulmonary hypertension (PH) is a significant health problem that contributes to high morbidity and mortality in diverse cardiac, pulmonary, and systemic diseases in children. Evidence-based advances in PH care have been challenged by a paucity of quality endpoints for assessing clinical course and the lack of robust clinical trial data to guide pharmacologic therapies in children. While the landmark adult AMBITION trial demonstrated the benefit of up-front combination PH therapy with ambrisentan and tadalafil, it remains unknown whether upfront combination therapy leads to more rapid and sustained clinical benefits in children with various categories of PH. In this article, we describe the inception of the Kids Mod PAH Trial, a multicenter Phase III trial, to address whether upfront combination therapy (sildenafil and bosentan vs. sildenafil alone) improves PH outcomes in children, recognizing that marked differences between the etiology and therapeutic response between adults and children exist. The primary endpoint of this study is WHO functional class (FC) 12 months after initiation of study drug therapy. In addition to the primary outcome, secondary endpoints are being assessed, including a composite measure of time to clinical worsening, WHO FC at 24 months, echocardiographic assessment of PH and quantitative assessment of right ventricular function, 6-min walk distance, and NT-proBNP levels. Exploratory endpoints include selected biomarkers, actigraphy, and assessments of quality of life. This study is designed to pave the way for additional clinical trials by establishing a robust infrastructure through the development of a PPHNet Clinical Trials Network. [ABSTRACT FROM AUTHOR]

Correlated categorical data often arise from studies involving cluster randomized trials, a cluster sampling scheme, or repeated measurements. The intra-cluster correlation coefficient (ICC) is used to estimate the average correlation within clusters. There have been numerous methods proposed to estimate ICC for correlated binary data, the ANOVA method for continuous data, and several methods for time-to-event outcomes. However, no method currently exists to estimate ICC for nominal or ordinal categorical responses with more than two categories. We developed a method based on resampling principles to estimate the ICC and its 95% confidence interval for categorical variables. We conducted a simulation study to show how our method estimates the population ICC under varying event rates, numbers of clusters, and cluster sizes. We also used real study datasets to estimate the ICC for ordinal and nominal categorical variables. We observed that the resampling method estimates the population ICC well for moderate to large numbers of clusters and moderate to large cluster sizes. [ABSTRACT FROM AUTHOR]

Opioid prescribing for postoperative pain management is challenging because of inter‐patient variability in opioid response and concern about opioid addiction. Tramadol, hydrocodone, and codeine depend on the cytochrome P450 2D6 (CYP2D6) enzyme for formation of highly potent metabolites. Individuals with reduced or absent CYP2D6 activity (i.e., intermediate metabolizers [IMs] or poor metabolizers [PMs], respectively) have lower concentrations of potent opioid metabolites and potentially inadequate pain control. The primary objective of this prospective, multicenter, randomized pragmatic trial is to determine the effect of postoperative CYP2D6‐guided opioid prescribing on pain control and opioid usage. Up to 2020 participants, age ≥8 years, scheduled to undergo a surgical procedure will be enrolled and randomized to immediate pharmacogenetic testing with clinical decision support (CDS) for CYP2D6 phenotype‐guided postoperative pain management (intervention arm) or delayed testing without CDS (control arm). CDS is provided through medical record alerts and/or a pharmacist consult note. For IMs and PM in the intervention arm, CDS includes recommendations to avoid hydrocodone, tramadol, and codeine. Patient‐reported pain‐related outcomes are collected 10 days and 1, 3, and 6 months after surgery. The primary outcome, a composite of pain intensity and opioid usage at 10 days postsurgery, will be compared in the subgroup of IMs and PMs in the intervention (n = 152) versus the control (n = 152) arm. Secondary end points include prescription pain medication misuse scores and opioid persistence at 6 months. This trial will provide data on the clinical utility of CYP2D6 phenotype‐guided opioid selection for improving postoperative pain control and reducing opioid‐related risks. [ABSTRACT FROM AUTHOR]

The study attempts to evaluate the efficacy of newborn-care training in reducing the rate of perinatal mortality in developing countries. The results indicate that programs like Essential Newborn Care training of community-based attendants as well as subsequent training did not result in a reduction in neonatal death within 7 days after birth, but did result in a reduction in stillbirths.

Objectives. This study evaluated the iron sufficiency of the Russian diet. Methods. Data were obtained from 24-hour dietary recalls conducted in 4 rounds (1992 through 1994) of a nationally representative longitudinal survey of 10 548 women and children. Iron bioavailability was estimated via algorithms adjusting for enhancers (heme, vitamin C) and inhibitors (tannins in tea, phytates in grains) consumed at the same meal. Results. Dietary iron intakes were deficient in the most vulnerable groups: young children and women of reproductive age. Poverty status was strongly associated with deficiency. After adjustment for enhancers and inhibitors, estimated bio-available iron intakes at 3% to 4% of total iron were inadequate in all women and children. Conclusions. These dietary data suggest that Russian women and children are at high risk of iron deficiency. Grain products rich in phytates, which inhibit absorption, were the major food source of iron in Russia. High intakes of tea and low consumption of vitamin C also inhibited iron bioavailability. Since changes in eating behavior could potentially double iron bioavailability, educational programs should be explored as a strategy for improving iron nutriture. (Am J Public Health. 1998;88:576-580)

Although determining iron intakes is essential in assessing adequacy of iron in the diet, estimating iron availability may be more useful for evaluating whether iron requirements are met. Our objectives were to describe the dietary information, analytical steps, and computer algorithms needed for iron bioavailability adjustments and to demonstrate the effects of various dietary factors on calculated iron absorption. Our study was based on 9890 women and children participating in the Russian Longitudinal Monitoring Survey. Between August 1992 and February 1993, two 24-h recalls were collected from each participant, and total, heme and nonheme iron intakes were calculated. Nonheme iron availability was adjusted for meat, fish and poultry and vitamin C consumed in the same meal and then further adjusted for tea and phytates. We found mean total iron intakes to be comparable to those of women of reproductive age in the United States and lower than those of United States children. When these intakes were adjusted for enhancers and inhibitors of absorption, the iron bioavailability in these vulnerable Russian groups was extremely low. Mean bioavailable iron as well as the 25th-75th percentile ranges of intake were below the bottom of the range of requirements, indicating that iron adequacy in this population may be considerably less than expected based on total iron intakes alone. Furthermore, rural and urban food availability had a significant effect on iron bioavailability. Future research on dietary iron adequacy should be based on estimates of available iron by collecting meal-level dietary data and using detailed information on mixed dishes and phytates. KEY WORDS: absorption; biological availability; humans; iron; rural residency

Abstract Background Oral clefts are one of the most common birth defects with significant medical, psychosocial, and economic ramifications. Oral clefts have a complex etiology with genetic and environmental risk factors. There are suggestive results for decreased risks of cleft occurrence and recurrence with folic acid supplements taken at preconception and during pregnancy with a stronger evidence for higher than lower doses in preventing recurrence. Yet previous studies have suffered from considerable design limitations particularly non-randomization into treatment. There is also well-documented effectiveness for folic acid in preventing neural tube defect occurrence at 0.4 mg and recurrence with 4 mg. Given the substantial burden of clefting on the individual and the family and the supportive data for the effectiveness of folic acid supplementation as well as its low cost, a randomized clinical trial of the effectiveness of high versus low dose folic acid for prevention of cleft recurrence is warranted. Methods/design This study will assess the effect of 4 mg and 0.4 mg doses of folic acid, taken on a daily basis during preconception and up to 3 months of pregnancy by women who are at risk of having a child with nonsyndromic cleft lip with/without palate (NSCL/P), on the recurrence of NSCL/P. The total sample will include about 6,000 women (that either have NSCL/P or that have at least one child with NSCL/P) randomly assigned to the 4 mg and the 0.4 mg folic acid study groups. The study will also compare the recurrence rates of NSCL/P in the total sample of subjects, as well as the two study groups (4mg, 0.4 mg) to that of a historical control group. The study has been approved by IRBs (ethics committees) of all involved sites. Results will be disseminated through publications and presentations at scientific meetings. Discussion The costs related to oral clefts are high, including long term psychological and socio-economic effects. This study provides an opportunity for huge savings in not only money but the overall quality of life. This may help establish more specific clinical guidelines for oral cleft prevention so that the intervention can be better tailored for at-risk women. ClinicalTrials.gov Identifier NCT00397917