Efficacy and safety of statin therapy in children with familial hypercholesterolemia: a randomized controlled trial

Context  Children with familial hypercholesterolemia have endothelial dysfunction and increased carotid intima-media thickness (IMT), which herald the premature atherosclerotic disease they develop later in life. Although intervention therapy in the causal pathway of this disorder has been available for more than a decade, the long-term efficacy and safety of cholesterol-lowering medication have not been evaluated in children. Objective  To determine the 2-year efficacy and safety of pravastatin therapy in children with familial hypercholesterolemia. Design  Randomized, double-blind, placebo-controlled trial that recruited children between December 7, 1997, and October 4, 1999, and followed them up for 2 years. Setting and Participants  Two hundred fourteen children with familial hypercholesterolemia, aged 8 to 18 years and recruited from an academic medical referral center in the Netherlands. Intervention  After initiation of a fat-restricted diet and encouragement of regular physical activity, children were randomly assigned to receive treatment with pravastatin, 20 to 40 mg/d (n = 106), or a placebo tablet (n = 108). Main Outcome Measures  The primary efficacy outcome was the change from baseline in mean carotid IMT compared between the 2 groups over 2 years; the principal safety outcomes were growth, maturation, and hormone level measurements over 2 years as well as changes in muscle and liver enzyme levels. Results  Compared with baseline, carotid IMT showed a trend toward regression with pravastatin (mean [SD], –0.010 [0.048] mm; P = .049), whereas a trend toward progression was observed in the placebo group (mean [SD], +0.005 [0.044] mm; P = .28). The mean (SD) change in IMT compared between the 2 groups (0.014 [0.046] mm) was significant (P = .02). Also, pravastatin significantly reduced mean low-density lipoprotein cholesterol levels compared with placebo (–24.1% vs +0.3%, respectively; P<.001). No differences were observed for growth, muscle or liver enzymes, endocrine function parameters, Tanner staging scores, onset of menses, or testicular volume between the 2 groups. Conclusion  Two years of pravastatin therapy induced a significant regression of carotid atherosclerosis in children with familial hypercholesterolemia, with no adverse effects on growth, sexual maturation, hormone levels, or liver or muscle tissue.      

Improving the use of hospice services in nursing homes: a randomized controlled trial

Context  Hospice care may improve the quality of end-of-life care for nursing home residents, but hospice is underutilized by this population, at least in part because physicians are not aware of their patients’ preferences. Objective  To determine whether it is possible to increase hospice utilization and improve the quality of end-of-life care by identifying residents whose goals and preferences are consistent with hospice care. Design, Setting, and Participants  Randomized controlled trial (December 2003-December 2004) of nursing home residents and their surrogate decision makers (N=205) in 3 US nursing homes. Intervention  A structured interview identified residents whose goals for care, treatment preferences, and palliative care needs made them appropriate for hospice care. These residents’ physicians were notified and asked to authorize a hospice informational visit. Main Outcome Measures  The primary outcome measures were (1) hospice enrollment within 30 days of the intervention and (2) families’ ratings of the quality of care for residents who died during the 6-month follow-up period. Results  Of the 205 residents in the study sample, 107 were randomly assigned to receive the intervention, and 98 received usual care. Intervention residents were more likely than usual care residents to enroll in hospice within 30 days (21/107 [20%] vs 1/98 [1%]; P<.001 [Fisher exact test]) and to enroll in hospice during the follow-up period (27/207 [25%] vs 6/98 [6%]; P<.001). Intervention residents had fewer acute care admissions (mean: 0.28 vs 0.49; P = .04 [Wilcoxon rank sum test]) and spent fewer days in an acute care setting (mean: 1.2 vs 3.0; P = .03 [Wilcoxon rank sum test]). Families of intervention residents rated the resident’s care more highly than did families of usual care residents (mean on a scale of 1-5: 4.1 vs 2.5; P = .04 [Wilcoxon rank sum test]). Conclusion  A simple communication intervention can increase rates of hospice referrals and families’ ratings of end-of-life care and may also decrease utilization of acute care resources.      

Effect of mechanical ventilator weaning protocols on respiratory outcomes in infants and children: a randomized controlled trial

Context  Ventilator management protocols shorten the time required to wean adult patients from mechanical ventilation. The efficacy of such weaning protocols among children has not been studied. Objective  To evaluate whether weaning protocols are superior to standard care (no defined protocol) for infants and children with acute illnesses requiring mechanical ventilator support and whether a volume support weaning protocol using continuous automated adjustment of pressure support by the ventilator (ie, VSV) is superior to manual adjustment of pressure support by clinicians (ie, PSV). Design and Setting  Randomized controlled trial conducted in the pediatric intensive care units of 10 children's hospitals across North America from November 1999 through April 2001. Patients  One hundred eighty-two spontaneously breathing children (<18 years old) who had been receiving ventilator support for more than 24 hours and who failed a test for extubation readiness on minimal pressure support. Interventions  Patients were randomized to a PSV protocol (n = 62), VSV protocol (n = 60), or no protocol (n = 60). Main Outcome Measures  Duration of weaning time (from randomization to successful extubation); extubation failure (any invasive or noninvasive ventilator support within 48 hours of extubation). Results  Extubation failure rates were not significantly different for PSV (15%), VSV (24%), and no protocol (17%) (P = .44). Among weaning successes, median duration of weaning was not significantly different for PSV (1.6 days), VSV (1.8 days), and no protocol (2.0 days) (P = .75). Male children more frequently failed extubation (odds ratio, 7.86; 95% confidence interval, 2.36-26.2; P<.001). Increased sedative use in the first 24 hours of weaning predicted extubation failure (P = .04) and, among extubation successes, duration of weaning (P<.001). Conclusions  In contrast with adult patients, the majority of children are weaned from mechanical ventilator support in 2 days or less. Weaning protocols did not significantly shorten this brief duration of weaning.      

Risk of celiac disease autoimmunity and timing of gluten introduction in the diet of infants at increased risk of disease

Context  While gluten ingestion is responsible for the signs and symptoms of celiac disease, it is not known what factors are associated with initial appearance of the disease. Objective  To examine whether the timing of gluten exposure in the infant diet was associated with the development of celiac disease autoimmunity (CDA). Design, Setting, and Patients  Prospective observational study conducted in Denver, Colo, from 1994-2004 of 1560 children at increased risk for celiac disease or type 1 diabetes, as defined by possession of either HLA-DR3 or DR4 alleles, or having a first-degree relative with type 1 diabetes. The mean follow-up was 4.8 years. Main Outcome Measure  Risk of CDA defined as being positive for tissue transglutaminase (tTG) autoantibody on 2 or more consecutive visits or being positive for tTG once and having a positive small bowel biopsy for celiac disease, by timing of introduction of gluten-containing foods into the diet. Results  Fifty-one children developed CDA. Findings adjusted for HLA-DR3 status indicated that children exposed to foods containing wheat, barley, or rye (gluten-containing foods) in the first 3 months of life (3 [6%] CDA positive vs 40 [3%] CDA negative) had a 5-fold increased risk of CDA compared with children exposed to gluten-containing foods at 4 to 6 months (12 [23%] CDA positive vs 574 [38%] CDA negative) (hazard ratio [HR], 5.17; 95% confidence interval [CI], 1.44-18.57). Children not exposed to gluten until the seventh month or later (36 [71%] CDA positive vs 895 [59%] CDA negative) had a marginally increased risk of CDA compared with those exposed at 4 to 6 months (HR, 1.87; 95% CI, 0.97-3.60). After restricting our case group to only the 25 CDA-positive children who had biopsy-diagnosed celiac disease, initial exposure to wheat, barley, or rye in the first 3 months (3 [12%] CDA positive vs 40 [3%] CDA negative) or in the seventh month or later (19 [76%] CDA positive vs 912 [59%] CDA negative) significantly increased risk of CDA compared with exposure at 4 to 6 months (3 [12%] CDA positive vs 583 [38%] CDA negative) (HR, 22.97; 95% CI, 4.55-115.93; P = .001; and HR, 3.98; 95% CI, 1.18-13.46; P = .04, respectively). Conclusion  Timing of introduction of gluten into the infant diet is associated with the appearance of CDA in children at increased risk for the disease.      

Do quality improvement organizations improve the quality of hospital care for Medicare beneficiaries?

Context  Quality improvement organizations (QIOs) are charged with improving the quality of medical care for Medicare beneficiaries. Objective  To explore whether the quality of hospital care for Medicare beneficiaries improves more in hospitals that voluntarily participate with Medicare’s QIOs compared with nonparticipating hospitals. Design, Setting, and Data  Data from 4 QIOs charged with improving the quality of care in 5 states (Maryland, Nevada, New York, Utah, and Washington) and the District of Columbia were used. Hospitals participate with the QIOs on quality improvement on a voluntary basis. A retrospective study was conducted comparing improvement in the quality of care of patients in hospitals that actively participated with the QIOs vs hospitals that did not. The medical records of approximately 750 Medicare beneficiaries per state in each of 5 clinical areas (atrial fibrillation, acute myocardial infarction, heart failure, pneumonia, and stroke) were abstracted at baseline (1998) and follow-up (2000-2001). Main Outcome Measure  Fifteen quality indicators associated with improved outcomes in the prevention or treatment of the 5 clinical areas were used as quality of care measures. These 15 indicators were specifically targeted by the QIOs for quality improvement during the study period. Results  Hospitals that voluntarily participate with the QIOs are more likely to be larger than nonparticipating hospitals (P<.05). At baseline, there were statistically significant (P<.05) differences between participating and nonparticipating hospitals on 5 of 15 quality indicators, with participating hospitals performing better on 3 of 5. There was no statistically significant difference in change from baseline to follow-up between participating and nonparticipating hospitals on 14 of 15 quality indicators. The one exception was that participating hospitals improved more on the pneumonia immunization indicator than nonparticipating hospitals (P = .005). Conclusion  Hospitals that participate with the QIO program are not more likely to show improvement on quality indicators than hospitals that do not participate.      

Communication of randomization in childhood leukemia trials

Context  Most children diagnosed as having leukemia become research subjects in randomized clinical trials (RCTs), but little is known about how randomization is explained to or understood by parents. Objective  To investigate physicians' explanation and parental understanding of randomization in childhood leukemia RCTs. Design and Setting  A multisite study of the informed consent communication process for RCTs of childhood leukemia. Consecutive cases were recruited from pediatric oncology inpatient wards at 6 US children's hospitals associated with major academic medical centers from July 1, 1999, until December 31, 2001. The informed consent conferences were observed and audiotaped, and the information obtained was coded and analyzed. Parents were interviewed shortly after the conference to ascertain their understanding. Participants  Parents and members of the health care team who participated in 137 informed consent conferences for children with newly diagnosed acute leukemia. Main Outcome Measures  Observed explanations of randomization and parental understanding of randomization after the consent conference. Results  Randomization was explained by physicians in 83% of cases and a consent document was presented during the conference in 95% of cases. Interviews after the conference demonstrated that 68 (50%) of 137 parents did not understand randomization. Parents of racial minority and lower socioeconomic status were less likely to understand randomization (P<.001 for each). Discussion of specific clinical trial details and the presence of a nurse during the conference were associated with understanding. Eighty-four percent of children were enrolled in a leukemia trial. Conclusions  Despite oral and written explanation, half of the parents in this study did not understand randomization for childhood leukemia trials. To make informed consent more effective, future research must seek to improve communication during this critical interchange.      

Opening of specialty cardiac hospitals and use of coronary revascularization in medicare beneficiaries

Context  Although proponents argue that specialty cardiac hospitals provide high-quality cost-efficient care, strong financial incentives for physicians at these facilities could result in greater procedure utilization. Objective  To determine whether the opening of cardiac hospitals was associated with increasing population-based rates of coronary revascularization. Design, Setting, and Patients  In a study of Medicare beneficiaries from 1995 through 2003, we calculated annual population-based rates for total revascularization (coronary artery bypass graft [CABG] plus percutaneous coronary intervention [PCI]), CABG, and PCI. Hospital referral regions (HRRs) were used to categorize health care markets into those where (1) cardiac hospitals opened (n = 13), (2) new cardiac programs opened at general hospitals (n = 142), and (3) no new programs opened (n = 151). Main Outcome Measures  Rates of change in total revascularization, CABG, and PCI using multivariable linear regression models with generalized estimating equations. Results  Overall, rates of change for total revascularization were higher in HRRs after cardiac hospitals opened when compared with HRRs where new cardiac programs opened at general hospitals and HRRs with no new programs (P<.001 for both comparisons). Four years after their opening, the relative increase in adjusted rates was more than 2-fold higher in HRRs where cardiac hospitals opened (19.2% [95% confidence interval {CI}, 6.1%-32.2%], P<.001) when compared with HRRs where new cardiac programs opened at general hospitals (6.5% [95% CI, 3.2%-9.9%], P<.001) and HRRs with no new programs (7.4% [95% CI, 3.2%-11.5%], P<.001). These findings were consistent when rates for CABG and PCI were considered separately. For PCI, this growth appeared largely driven by increased utilization among patients without acute myocardial infarction (42.1% [95% CI, 21.4%-62.9%], P<.001). Conclusion  The opening of a cardiac hospital within an HRR is associated with increasing population-based rates of coronary revascularization in Medicare beneficiaries.      

Blood mercury levels in US children and women of childbearing age, 1999-2000

Context  Humans are exposed to methylmercury, a well-established neurotoxin, through fish consumption. The fetus is most sensitive to the adverse effects of exposure. The extent of exposure to methylmercury in US women of reproductive age is not known. Objective  To describe the distribution of blood mercury levels in US children and women of childbearing age and the association with sociodemographic characteristics and fish consumption. Design and Setting  The 1999-2000 data from the National Health and Nutrition Examination Survey, a cross-sectional survey of the noninstitutionalized US population. Participants  In 1999-2000, 1250 children aged 1 to 5 years and 2314 women aged 16 to 49 years were selected to participate in the survey. Household interviews, physical examinations, and blood mercury levels assessments were performed on 705 children (56% response rate) and 1709 women (74% response rate). Main Outcome Measure  Blood concentration of total mercury. Results  Blood mercury levels were approximately 3-fold higher in women compared with children. The geometric mean concentration of total blood mercury was 0.34 µg/L (95% confidence interval [CI], 0.30-0.39 µg/L) in children and 1.02 µg/L (95% CI, 0.85-1.20 µg/L) in women. Geometric mean mercury levels were almost 4-fold higher among women who ate 3 or more servings of fish in the past 30 days compared with women who ate no fish in that period (1.94 µg/L vs 0.51 µg/L; P<.001). Conclusions  Measures of mercury exposure in women of childbearing age and young children generally fall below levels of concern. However, approximately 8% of women had concentrations higher than the US Environmental Protection Agency's recommended reference dose (5.8 µg/L), below which exposures are considered to be without adverse effects. Women who are pregnant or who intend to become pregnant should follow federal and state advisories on consumption of fish.      

Effect of expanded newborn screening for biochemical genetic disorders on child outcomes and parental stress

Context  Tandem mass spectrometry now allows newborn screening for more than 20 biochemical genetic disorders. Questions about the effectiveness and risks of expanded newborn screening for biochemical genetic disorders need to be answered prior to its widespread acceptance as a state-mandated program. Objectives  To compare newborn identification by expanded screening with clinical identification of biochemical genetic disorders and to assess the impact on families of a false-positive screening result compared with a normal result in the expanded newborn screening program. Design  Prospective study involving an inception cohort of newly diagnosed children. Setting  Massachusetts, Maine, and a private laboratory in Pennsylvania with expanded newborn screening; other New England states with limited screening. Participants  Families of 50 affected children identified through expanded newborn screening (82% of eligible cases); 33 affected children identified clinically (97% of eligible cases); 94 screened children with false-positive results (75% of eligible cases); and 81 screened children with normal results (63% of eligible cases). Main Outcome Measures  Child's health and development and the Parental Stress Index. Results  Within the first 6 months of life, 28% of children identified by newborn screening compared with 55% of clinically identified children required hospitalization (P = .02). One child identified by newborn screening compared with 8 (42%) identified clinically performed in the range of mental retardation (P<.001). Mothers in the screened group reported lower overall stress on the Parental Stress Index than mothers in the clinically identified group (z = 3.38, P<.001). Children with false-positive results compared with children with normal results were twice as likely to experience hospitalization (21% [n = 20] vs 10% [n = 8], respectively; P = .06). Mothers of children in the false-positive group compared with mothers of children with normal screening results attained higher scores on the Parental Stress Index (z = 4.25, P<.001) and the Parent-Child Dysfunction subscale (z = 5.30, P<.001). Conclusions  Expanded newborn screening may lead to improved health outcomes for affected children and lower stress for their parents. However, false-positive screening results may place families at risk for increased stress and parent-child dysfunction.      

Change in cognitive function over time in very low-birth-weight infants

Context  Preterm very low-birth-weight (VLBW) infants have a high prevalence of neurodevelopmental disability when evaluated during the first several years of life. However, recent experimental data suggest that the developing brain may recover from or compensate for injury. Objective  To determine if there is cognitive improvement throughout early and middle childhood following VLBW birth. Design, Setting, and Participants  Follow-up data of 296 infants born weighing 600 to 1250 g who participated in a prospective, randomized, placebo-controlled intraventricular hemorrhage (IVH) prevention study performed at 3 northeastern US hospitals between September 1989 and August 1992 and who were serially evaluated at 36, 54, 72, and 96 months of corrected age (CA). Main Outcome Measures  The age-normed Peabody Picture Vocabulary Test–Revised (PPVT-R) score and measures of intelligence. Results  Overall, the median PPVT-R score increased from 88 at 36 months of CA to 99 at 96 months of CA; when data from 36 and 96 months of CA were compared, 45% of children gained 10 points or more and 12.5% showed a 5- to 9-point increase in test scores. Similar findings were noted for full-scale and verbal IQ scores. Multivariate analyses demonstrated that increasing age, residence in a 2-parent household, and higher levels of maternal education were all significantly associated with higher PPVT-R scores (for each, P<.001). In addition, early intervention led to greater increases over time in PPVT-R scores among children whose mothers had less than a high school education compared with those with a high school education level or greater (P = .03 by test for interaction). Although most children showed improvement in PPVT-R scores with increasing CA, children with early-onset IVH and subsequent significant central nervous system injury had the lowest PPVT-R scores initially and the scores declined over time (P = .009 by test for interaction). Conclusions  The majority of VLBW children had improvement in verbal and IQ test scores over time. Only children with early-onset IVH followed by significant central nervous system injury had low PPVT-R scores that declined over time.      

Chronic conditions, functional limitations, and special health care needs of school-aged children born with extremely low-birth-weight in the 1990s

Context  Information on the school-age functioning and special health care needs of extremely low-birth-weight (ELBW, <1000 g) children is necessary to plan for medical and educational services. Objective  To examine neurosensory, developmental, and medical conditions together with the associated functional limitations and special health care needs of ELBW children compared with normal-birth-weight (NBW) term-born children (controls). Design, Setting, and Participants  A follow-up study at age 8 years of a cohort of 219 ELBW children born 1992 to 1995 (92% of survivors) and 176 NBW controls of similar sociodemographic status conducted in Cleveland, Ohio. Main Outcome Measures  Parent Questionnaire for Identifying Children with Chronic Conditions of 12 months or more and categorization of specific medical diagnoses and developmental disabilities based on examination of the children. Results  In logistic regression analyses adjusting for sociodemographic status and sex, ELBW children had significantly more chronic conditions than NBW controls, including functional limitations (64% vs 20%, respectively; odds ratio [OR], 8.1; 95% confidence interval [CI], 5.0-13.1; P<.001), compensatory dependency needs (48% vs 23%, respectively; OR, 3.0; 95% CI, 1.9-4.7; P<.001), and services above those routinely required by children (65% vs 27%, respectively; OR, 5.4; 95% CI, 3.4-8.5; P<.001). These differences remained significant when the 36 ELBW children with neurosensory impairments were excluded. Specific diagnoses and disabilities for ELBW vs NBW children included cerebral palsy (14% vs 0%, respectively; P<.001), asthma (21% vs 9%; OR, 3.0; 95% CI, 1.6-5.6; P = .001), vision of less than 20/200 (10% vs 3%; OR, 3.1; 95% CI, 1.2-7.8; P = .02), low IQ of less than 85 (38% vs 14%; OR, 4.5; 95% CI, 2.7-7.7; P<.001), limited academic skills (37% vs 15%; OR, 4.2; 95% CI, 2.5-7.3; P<.001), poor motor skills (47% vs 10%; OR, 7.8; 95% CI, 4.5-13.6; P<.001), and poor adaptive functioning (69% vs 34%; OR, 6.5; 95% CI, 4.0-10.6; P<.001). Conclusion  The ELBW survivors in school at age 8 years who were born in the 1990s have considerable long-term health and educational needs.      

Effect of an oral Shiga toxin-binding agent on diarrhea-associated hemolytic uremic syndrome in children: a randomized controlled trial

Context  Diarrhea-associated hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in children. Most cases are caused by an intestinal infection with Shiga toxin–producing strains of Escherichia coli. Objective  To determine if administration of an oral agent that binds Shiga toxin could diminish the severity of diarrhea-associated HUS in pediatric patients. Design, Setting, and Patients  Multicenter, randomized, double-blind, placebo-controlled clinical trial of 145 children (96 experimental and 49 placebo) aged 6 months to 18 years with diarrhea-associated HUS conducted between July 27, 1997, and April 14, 2001, at 26 tertiary care pediatric nephrology centers in the United States and Canada. Trial included 2 phases, the hospital course for treatment of the acute illness and a 60-day outpatient follow-up period after discharge from the hospital. Intervention  Patients were assigned to receive the binding agent, 500 mg/kg daily, or cornmeal placebo orally for 7 days in a 2:1 randomization scheme. Main Outcome Measures  Combined frequency of death or serious extrarenal events and need for dialysis in the experimental vs placebo group. Results  A total of 62 patients (43%) were male and 123 (85%) were white. The median age of the patients was 4.2 years. Most patients (59%) were transferred from other hospitals to participating sites. The severity of disease at the time of randomization was comparable in the 2 groups. The prevalence of death or serious extrarenal events was 18% and 20% in the experimental and placebo groups, respectively (P = .82). Dialysis was required in 42% of experimental and 39% of placebo groups (P = .86). Conclusions  Oral therapy with a Shiga toxin–binding agent failed to diminish the severity of disease in pediatric patients with diarrhea-associated HUS.      

Assessment of severe malnutrition among hospitalized children in rural Kenya: comparison of weight for height and mid upper arm circumference

Context  Severe malnutrition has a high mortality rate among hospitalized children in sub-Saharan Africa. However, reports suggest that malnutrition is often poorly assessed. The World Health Organization recommends using weight for height, but this method is problematic and often not undertaken in practice. Mid upper arm circumference (MUAC) and the clinical sign "visible severe wasting" are simple and inexpensive methods but have not been evaluated in this setting. Objectives  To evaluate MUAC and visible severe wasting as predictors of inpatient mortality at a district hospital in sub-Saharan Africa and to compare these with weight-for-height z score (WHZ). Design, Setting, and Participants  Cohort study with data collected at admission and at discharge or death. Predictive values for inpatient death were determined using the area under receiver operating characteristic curves. Participants were children aged 12 to 59 months admitted to a district hospital in rural Kenya between April 1, 1999, and July 31, 2002. Main Outcome Measure  MUAC, WHZ, and visible severe wasting as predictors of inpatient death. Results  Overall, 4.4% (359) of children included in the study died while in the hospital. Sixteen percent (1282/8190) of admitted children had severe wasting (WHZ –3) (n = 756), kwashiorkor (n = 778), or both. The areas under the receiver operating characteristic curves for predicting inpatient death did not significantly differ (MUAC: 0.75 [95% confidence interval, 0.72-0.78]; WHZ: 0.74 [95% confidence interval, 0.71-0.77]) (P = .39). Although sensitivity and specificity for subsequent inpatient death were 46% and 91%, respectively, for MUAC less than or equal to 11.5 cm, 42% and 92% for WHZ less than or equal to –3, and 47% and 93% for visible severe wasting, the 3 indices identified different sets of children and were independently associated with mortality. Clinical features of malnutrition were significantly more common among children with MUAC less than or equal to 11.5 cm than among those with WHZ less than or equal to –3. Conclusions  MUAC is a practical screening tool that performs at least as well as WHZ in predicting subsequent inpatient mortality among severely malnourished children hospitalized in rural Kenya. Visible severe wasting is also a potentially useful sign at this level, providing appropriate training has been given.      

Effectiveness of Haemophilus influenzae type b Conjugate vaccine introduction into routine childhood immunization in Kenya

Context  Haemophilus influenzae type b (Hib) conjugate vaccine is not perceived as a public health priority in Africa because data on Hib disease burden and vaccine effectiveness are scarce. Hib immunization was introduced in Kenyan infants in 2001. Objective  To define invasive Hib disease incidence and Hib vaccine program effectiveness in Kenya. Design, Setting, and Patients  Culture-based surveillance for invasive Hib disease at Kilifi District Hospital from 2000 through 2005 was linked to demographic surveillance of 38 000 children younger than 5 years in Kilifi District, Kenya. Human immunodeficiency virus (HIV) infection and Hib vaccination status were determined for children with Hib disease admitted 2002-2005. Interventions  Introduction of conjugate Hib vaccine within the routine childhood immunization program at ages 6, 10, and 14 weeks beginning November 2001. Main Outcome Measures  Incidence of culture-proven Hib invasive disease before and after vaccine introduction and vaccine program effectiveness. Results  Prior to vaccine introduction, the median age of children with Hib was 8 months; case fatality was 23%. Among children younger than 5 years, the annual incidence of invasive Hib disease 1 year before and 1 and 3 years after vaccine introduction was 66, 47, and 7.6 per 100 000, respectively. For children younger than 2 years, incidence was 119, 82, and 16 per 100 000, respectively. In 2004-2005, vaccine effectiveness was 88% (95% confidence interval, 73%-96%) among children younger than 5 years and 87% (95% confidence interval, 66%-96%) among children younger than 2 years. Of 53 children with Hib admitted during 2002-2005, 29 (55%) were age-ineligible to have received vaccine, 12 (23%) had not been vaccinated despite being eligible, and 12 (23%) had received 2 or more doses of vaccine (2 were HIV positive). Conclusions  In Kenya, introduction of Hib vaccine into the routine childhood immunization program reduced Hib disease incidence among children younger than 5 years to 12% of its baseline level. This impact was not observed until the third year after vaccine introduction.      

Is there a doctor in the house? . . . Or the Senate? Physicians in US Congress, 1960-2004

Context  The legislative and fiscal influences of Congress, as well as the continuing overall growth in health care spending as a portion of the gross domestic product, make congressional representation by physicians important because physicians have unique expertise in the impact of legislation on patient care and medical practice. Objectives  To describe physician representation in the US Congress between 1960 and 2004 and relate the results to past representation of physicians in Congress. Design and Setting  A retrospective observational study of members of the US Congress from all 50 states and all represented territories, who served from January 1960 to April 2004 (including 108th Congress), using data available in public access databases and congressional biographical records. Main Outcome Measures  Physician representation in Congress, including occupation before taking office, state/territory of representation, sex, party affiliation, and time served. Results  During the past 44 years, 25 (1.1%) of 2196 members of Congress were physicians. Physicians in Congress were more likely to be members of the Republican Party (60% vs 45.1% of all members, P = .007) and were similar to other members of Congress in mean years of service (9.2 years for physicians vs 12.3 years for all members, P = .09) and in sex distribution (4.0% female physicians vs 6.8% all female members, P = .57). Physicians in Congress represented 17 states, the Virgin Islands, and Puerto Rico. Conclusions  Physician representation in Congress is low and is in stark contrast with physician roles during the first century of the United States. However, the 8 physicians currently serving in Congress may be indicative of a shift toward more direct influence of physicians in national politics.      

Neuropsychological and renal effects of dental amalgam in children: a randomized clinical trial

Context  No randomized trials have been published that address the concern that inhalation of mercury vapor released by amalgam dental restorations causes adverse health effects. Objective  To compare the neuropsychological and renal function of children whose dental caries were restored using amalgam or mercury-free materials. Design and Setting  The New England Children's Amalgam Trial was a 2-group randomized safety trial involving 5 community health dental clinics in Boston, Mass, and 1 in Farmington, Me, between September 1997 and March 2005. Participants and Intervention  A total of 534 children aged 6 to 10 years at baseline with no prior amalgam restorations and 2 or more posterior teeth with caries were randomly assigned to receive dental restoration of baseline and incident caries during a 5-year follow-up period using either amalgam (n=267) or resin composite (n =267) materials. Main Outcome Measures  The primary neuropsychological outcome was 5-year change in full-scale IQ scores. Secondary outcomes included tests of memory and visuomotor ability. Renal glomerular function was measured by creatinine-adjusted albumin in urine. Results  Children had a mean of 15 tooth surfaces (median, 14) restored during the 5-year period (range, 0-55). Assignment to the amalgam group was associated with a significantly higher mean urinary mercury level (0.9 vs 0.6 µg/g of creatinine at year 5, P<.001). After adjusting for randomization stratum and other covariates, no statistically significant differences were found between children in the amalgam and composite groups in 5-year change in full-scale IQ score (3.1 vs 2.1, P = .21). The difference in treatment group change scores was 1.0 (95% confidence interval, –0.6 to 2.5) full-scale IQ score point. No statistically significant differences were found for 4-year change in the general memory index (8.1 vs 7.2, P = .34), 4-year change in visuomotor composite (3.8 vs 3.7, P = .93), or year 5 urinary albumin (median, 7.5 vs 7.4 mg/g of creatinine, P = .61). Conclusions  In this study, there were no statistically significant differences in adverse neuropsychological or renal effects observed over the 5-year period in children whose caries were restored using dental amalgam or composite materials. Although it is possible that very small IQ effects cannot be ruled out, these findings suggest that the health effects of amalgam restorations in children need not be the basis of treatment decisions when choosing restorative dental materials. Trial Registration  clinicaltrials.gov Identifier: NCT00065988      

Racial differences in the evaluation of pediatric fractures for physical abuse

Context  Child maltreatment is a significant problem within US society, and minority children have higher rates of substantiated maltreatment than do white children. However, it is unclear whether minority children are abused more frequently than whites or whether their cases are more likely to be reported. Objectives  To determine whether there are racial differences in the evaluation and Child Protective Services (CPS) reporting of young children hospitalized for fractures. Design, Setting, and Patients  Retrospective chart review conducted at an urban US academic children's hospital among 388 children younger than 3 years hospitalized for treatment of an acute primary skull or long-bone fracture between 1994 and 2000. Children with perpetrator-admitted child abuse, metabolic bone disease, birth trauma, or injury caused by vehicular crash were excluded. Main Outcome Measures  Ordering of skeletal surveys and filing reports of suspected abuse. Results  Reports of suspected abuse were filed for 22.5% of white and 52.9% of minority children (P<.001). Abusive injuries, as determined by expert review, were more common among minority children than among white children (27.6% vs 12.5%; P<.001). Minority children aged at least 12 months to 3 years (toddlers) were significantly more likely to have a skeletal survey performed compared with their white counterparts, even after controlling for insurance status, independent expert determination of likelihood of abuse, and appropriateness of performing a skeletal survey (adjusted odds ratio [OR], 8.75; 95% confidence interval [CI], 3.48-22.03; P<.001). This group of children was also more likely to be reported to CPS compared with white toddlers, even after controlling for insurance status and likelihood of abuse (adjusted OR, 4.32; 95% CI, 1.63-11.43; P = .003). By likelihood of abuse, differential ordering of skeletal surveys and reporting of suspected abuse were most pronounced for children at least 12 months old with accidental injuries; however, differences were also noted among toddlers with indeterminate injuries but not among infants or toddlers with abusive injuries. Minority children at least 12 months old with accidental injuries were more than 3 times more likely than their white counterparts to be reported for suspected abuse (for children with Medicaid or no insurance, relative risk [RR], 3.08; 95% CI, 1.37-4.80; for children with private insurance, RR, 3.74; 95% CI, 1.46-6.01). Conclusion  While minority children had higher rates of abusive fractures in our sample, they were also more likely to be evaluated and reported for suspected abuse, even after controlling for the likelihood of abusive injury. This suggests that racial differences do exist in the evaluation and reporting of pediatric fractures for child abuse, particularly in toddlers with accidental injuries.      

Effects of a low-glycemic load diet on resting energy expenditure and heart disease risk factors during weight loss

Context  Weight loss elicits physiological adaptations relating to energy intake and expenditure that antagonize ongoing weight loss. Objective  To test whether dietary composition affects the physiological adaptations to weight loss, as assessed by resting energy expenditure. Design, Study, and Participants  A randomized parallel-design study of 39 overweight or obese young adults aged 18 to 40 years who received an energy-restricted diet, either low–glycemic load or low-fat. Participants were studied in the General Clinical Research Centers of the Brigham and Women’s Hospital and the Children’s Hospital, Boston, Mass, before and after 10% weight loss. The study was conducted from January 4, 2001, to May 6, 2003. Main Outcome Measures  Resting energy expenditure measured in the fasting state by indirect calorimetry, body composition by dual-energy x-ray absorptiometry, cardiovascular disease risk factors, and self-reported hunger. Results  Resting energy expenditure decreased less with the low–glycemic load diet than with the low-fat diet, expressed in absolute terms (mean [SE], 96 [24] vs 176 [27] kcal/d; P = .04) or as a proportion (5.9% [1.5%] vs 10.6% [1.7%]; P = .05). Participants receiving the low–glycemic load diet reported less hunger than those receiving the low-fat diet (P = .04). Insulin resistance (P = .01), serum triglycerides (P = .01), C-reactive protein (P = .03), and blood pressure (P = .07 for both systolic and diastolic) improved more with the low–glycemic load diet. Changes in body composition (fat and lean mass) in both groups were very similar (P = .85 and P = .45, respectively). Conclusions  Changes in dietary composition within prevailing norms can affect physiological adaptations that defend body weight. Reduction in glycemic load may aid in the prevention or treatment of obesity, cardiovascular disease, and diabetes mellitus.      

Efficacy of maintenance treatment approaches for childhood overweight: a randomized controlled trial

Context  No trials for childhood overweight have examined maintenance interventions to augment the effects of initial weight loss programs. Objectives  To determine the short-term and long-term efficacy of 2 distinct weight maintenance approaches vs no continued treatment control following standard family-based behavioral weight loss treatment for childhood overweight, and to examine children's social functioning as a moderator of outcome. Design, Setting, and Participants  A parallel-group, randomized controlled trial conducted between October 1999 and July 2004 in a university-based weight control clinic. Participants were 204 healthy 7- to 12-year-olds, 20% to 100% above median body mass index (BMI) for age and sex, with at least 1 overweight parent. Children enrolled in 5 months of weight loss treatment and 150 were randomized to 1 of 3 maintenance conditions. Follow-up assessments occurred immediately following maintenance treatments and 1 and 2 years following randomization. Interventions  Maintenance conditions included the control group or 4 months of behavioral skills maintenance (BSM) or social facilitation maintenance (SFM) treatment. Main Outcome Measures  BMI z score and percentage overweight. Results  Children receiving either BSM or SFM maintained relative weight significantly better than children assigned to the control group from randomization to postweight maintenance (P.01 for all; effect sizes d = 0.72-0.96; mean changes in BMI z scores = –0.04, –0.04, –0.05, and 0.05 for BSM alone, SFM alone, BSM and SFM together, and the control group, respectively). Active maintenance treatment efficacy relative to the control group declined during follow-up, but the effects of SFM alone (P = .03; d = 0.45; mean change in BMI z score = –0.24) and when analyzed together with BSM (P = .04; d = 0.38; mean change in BMI z score = –0.22) were significantly better than the control group (mean change in BMI z score = –0.06) when examining BMI z score outcomes from baseline to 2-year follow-up. Baseline child social problem scores moderated child relative weight change from baseline to 2-year follow-up, with low social problem children in SFM vs the control group having the best outcomes. Conclusions  The addition of maintenance-targeted treatment improves short-term efficacy of weight loss treatment for children relative to no maintenance treatment. However, the waning of effects over follow-up, although moderated by child initial social problems, suggests the need for the bolstering of future maintenance treatments to sustain effects. Trial Registration  clinicaltrials.gov Identifier: NCT00301197      

Cognitive and motor outcomes of cocaine-exposed infants

Context  Maternal use of cocaine during pregnancy remains a significant public health problem, particularly in urban areas of the United States and among women of low socioeconomic status. Few longitudinal studies have examined cocaine-exposed infants, however, and findings are contradictory because of methodologic limitations. Objective  To assess the effects of prenatal cocaine exposure on child developmental outcomes. Design  Longitudinal, prospective, masked, comparison birth cohort study with recruitment in 1994-1996. Setting  Obstetric unit of a large US urban teaching hospital. Participants  Four hundred fifteen consecutively enrolled infants (218 cocaine-exposed and 197 unexposed) identified from a high-risk, low–socioeconomic status, primarily black (80%) population screened through clinical interview and urine and meconium samples for drug use. The retention rate was 94% at 2 years of age. Main Outcome Measures  The Bayley Mental and Motor Scales of Infant Development, assessed at 6.5, 12, and 24 months of corrected age. Results  Controlled for confounding variables, cocaine exposure had significant effects on cognitive development, accounting for a 6-point deficit in Bayley Mental and Motor Scales of Infant Development scores at 2 years, with cocaine-exposed children twice as likely to have significant delay (mental development index <80) (odds ratio, 1.98; 95% confidence interval, 1.21-3.24; P = .006). For motor outcomes, there were no significant cocaine effects. Conclusions  Cocaine-exposed children had significant cognitive deficits and a doubling of the rate of developmental delay during the first 2 years of life. Because 2-year outcomes are predictive of later cognitive outcomes, it is possible that these children will continue to have learning difficulties at school age.