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1.
Acad Pediatr ; 23(2): 351-358, 2023 03.
Article in English | MEDLINE | ID: mdl-35863738

ABSTRACT

BACKGROUND: Current breastfeeding guidelines promote initiating breastfeeding ≤1 h after birth to establish long-term breastfeeding. Previous studies dichotomized initiation to ≤1 h versus subsequent hours combined. There are limited data evaluating the effect of initiation in each subsequent hour on breastfeeding duration. Our objective was to evaluate the association between breastfeeding initiated at ≤1 h versus the subsequent 23 hours after birth and outpatient breastfeeding duration. METHODS: In this retrospective cohort study, we analyzed real-time, discretely documented electronic health record (EHR) breastfeeding data for 3315 infants born at a university center and followed to age ≥12 mo at 27 university primary care clinics. The primary outcome was breastfeeding duration. The exposure variable was hour of breastfeeding initiation within 24 h postnatally. Data were analyzed by univariable and multivariable linear regression separately for infants born by vaginal versus cesarean delivery. RESULTS: In adjusted models, initiating breastfeeding during each hour from age >1 to ≤6 h and during ages >6 to ≤24 h was not associated with decreased breastfeeding duration versus initiating breastfeeding at ≤1 h after birth for infants born via vaginal or cesarean delivery. CONCLUSIONS: Delaying breastfeeding initiation to >1 to ≤24 h after birth is not associated with decreased breastfeeding duration compared with initiating breastfeeding at ≤1 h after birth. Integration of breastfeeding measures into inpatient and outpatient EHR discrete data fields may clarify best practices that support long-term breastfeeding as a public health imperative.


Subject(s)
Breast Feeding , Outpatients , Infant , Female , Pregnancy , Humans , Retrospective Studies , Linear Models
2.
Hosp Pediatr ; 11(6): 547-553, 2021 06.
Article in English | MEDLINE | ID: mdl-33972349

ABSTRACT

BACKGROUND AND OBJECTIVES: To investigate caregivers' perceptions of physician communication and hospital ratings for hospitalized children with and without autism and assess associations between perceived quality of physician communication and overall ratings of the hospital. METHODS: We studied survey data from caregivers of 543 patients with autism compared with a 2:1 matched control sample of 1086 patients with similar characteristics but without autism from a single children's hospital. We analyzed survey items related to physician communication and hospital ratings from the Consumer Assessment of Healthcare Physicians and Systems Child Hospital Survey. We constructed multivariable regression models to examine the relationship between caregiver-perceived physician communication and caregivers' overall ratings of the hospital. RESULTS: A similar proportion of caregivers of children with and without autism reported that doctors "always" listened carefully to them (71.4% vs 74.3%; adjusted prevalence ratio 0.96; 95% confidence interval 0.90-1.03) and "always" treated them with respect (80.0% vs 84.1%; adjusted prevalence ratio 0.95; 95% confidence interval 0.90-1.00). Caregivers of children with autism were less likely to "definitely" recommend the hospital (87.0% vs 92.3%; adjusted prevalence ratio 0.94; 95% confidence interval 0.91-0.98). All items related to caregiver-perceived physician communication were associated with the highest hospital rating and the highest recommendation of the hospital in both groups. CONCLUSIONS: When matched on the basis of medical and social factors, caregivers of children with and without autism reported similar frequencies of highest-quality physician communication. Improvement of physician communication with caregivers of medically and socially complex children with and without autism may improve caregivers' overall ratings of the hospital.


Subject(s)
Autistic Disorder , Physicians , Caregivers , Child , Child, Hospitalized , Communication , Humans
4.
Pediatrics ; 146(2)2020 08.
Article in English | MEDLINE | ID: mdl-32632024

ABSTRACT

OBJECTIVES: To describe the proportion of children screened by the Modified Checklist for Autism in Toddlers (M-CHAT), identify characteristics associated with screen completion, and examine associations between autism spectrum disorder (ASD) screening and later ASD diagnosis. METHODS: We examined data from children attending 18- and 24-month visits between 2013 and 2016 from 20 clinics within a health care system for evidence of screening with the M-CHAT and subsequent coding of ASD diagnosis at age >4.75 years. We interviewed providers for information about usual methods of M-CHAT scoring and ASD referral. RESULTS: Of 36 233 toddlers, 73% were screened and 1.4% were later diagnosed with ASD. Hispanic children were less likely to be screened (adjusted prevalence ratio [APR]: 0.95, 95% confidence interval [CI]: 0.92-0.98), and family physicians were less likely to screen (APR: 0.12, 95% CI: 0.09-0.15). Compared with unscreened children, screen-positive children were more likely to be diagnosed with ASD (APR: 10.3, 95% CI: 7.6-14.1) and were diagnosed younger (38.5 vs 48.5 months, P < .001). The M-CHAT's sensitivity for ASD diagnosis was 33.1%, and the positive predictive value was 17.8%. Providers routinely omitted the M-CHAT follow-up interview and had uneven referral patterns. CONCLUSIONS: A majority of children were screened for ASD, but disparities exist among those screened. Benefits for screen-positive children are improved detection and younger age of diagnosis. Performance of the M-CHAT can be improved in real-world health care settings by administering screens with fidelity and facilitating timely ASD evaluations for screen-positive children. Providers should continue to monitor for signs of ASD in screen-negative children.


Subject(s)
Autism Spectrum Disorder/diagnosis , Neuropsychological Tests , Primary Health Care/methods , Autism Spectrum Disorder/epidemiology , Checklist , Child, Preschool , Delayed Diagnosis , Early Diagnosis , Female , Follow-Up Studies , Healthcare Disparities , Hispanic or Latino , Humans , Infant , Male , Mass Screening/methods , Predictive Value of Tests , Sensitivity and Specificity , Utah/epidemiology
5.
Clin Pediatr (Phila) ; 58(14): 1528-1533, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31640403

ABSTRACT

We performed a quality improvement intervention to increase universal lipid screening in well-child visits (age 9 to 11 years): 12-month preintervention; phase 1 (8 months) with provider education, group monthly chart review with feedback, and electronic health record cues to order lipids; and phase 2 (16 months) with electronic health record cues and examination room phlebotomy. Outcomes were compared with clinics having no intervention. In phase 1, immediate treatment effect on the regression line for provider behavior (proportion of visits with lipids ordered) showed 34% increase in intervention and 7% decrease in comparison clinics; patient behavior (phlebotomy completed) showed 19% increase in intervention and 5% decrease in comparison clinics. At the beginning of phase 2, the intervention clinic had average 44% orders entered and 33% phlebotomy completed per well-child visit, and these proportions were maintained. Provider education and chart review with feedback were associated with the greatest gains in outcomes.


Subject(s)
Child Health/standards , Lipids/blood , Mass Screening/standards , Quality Improvement , Biomarkers/blood , Child , Female , Humans , Male , Pediatrics/standards , Physical Examination/standards , Quality Indicators, Health Care
6.
J Autism Dev Disord ; 49(2): 794-808, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30173310

ABSTRACT

Despite current guidelines, few children with autism spectrum disorder (ASD) receive genetic evaluations. We surveyed Utah pediatricians to characterize the knowledge, beliefs, current practices and perceived barriers of pediatricians regarding genetic evaluation of children with ASD. We found over half lacked knowledge of current guidelines and many held beliefs about genetic evaluation that did not align with guidelines. Barriers were lack of insurance coverage for genetic evaluation/testing and long wait times to see geneticists. Pediatricians with beliefs aligned with guidelines and those aware of the role of genetic counselors were more likely to adhere to guidelines. Efforts to educate pediatricians are needed along with system level solutions regarding availability of geneticists and reimbursement for genetic testing.


Subject(s)
Autism Spectrum Disorder/genetics , Genetic Testing/standards , Health Knowledge, Attitudes, Practice , Pediatricians/psychology , Autism Spectrum Disorder/diagnosis , Child , Female , Genetic Testing/statistics & numerical data , Guideline Adherence , Humans , Male , Surveys and Questionnaires , Utah
7.
JAMA Pediatr ; 172(5): 482-486, 2018 05 01.
Article in English | MEDLINE | ID: mdl-29582079

ABSTRACT

Importance: Medical overuse has historically focused on adult health care, but interest in how children are affected by medical overuse is increasing. This review examines important research articles published in 2016 that address pediatric overuse. Observations: A structured search of PubMed and a manual review of the tables of contents of 10 journals identified 169 articles related to pediatric overuse published in 2016, from which 8 were selected based on the quality of methods and potential harm to patients in terms of prevalence and magnitude. Articles were categorized by overtreatment, overmedicalization, and overdiagnosis. Findings included evidence of overtreatment with commercial rehydration solution, antidepressants, and parenteral nutrition; overmedicalization with planned early deliveries, immobilization of ankle injuries, and use of hydrolyzed infant formula; and evidence of overdiagnosis of hypoxemia among children recovering from bronchiolitis. Conclusions and Relevance: The articles were of high quality, with most based on randomized clinical trials. The potential harms associated with pediatric overuse were significant, including increased risk of infection, developmental disability, and suicidality.


Subject(s)
Child Health Services/standards , Medical Overuse/statistics & numerical data , Adolescent , Ankle Injuries/diagnostic imaging , Antidepressive Agents/therapeutic use , Bronchiolitis/diagnosis , Child , Child Health Services/statistics & numerical data , Depression/drug therapy , Evidence-Based Medicine/methods , Fluid Therapy/methods , Gastroenteritis/therapy , Humans , Parenteral Nutrition , Radiography , Randomized Controlled Trials as Topic
8.
Pediatr Cardiol ; 39(2): 261-267, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29058030

ABSTRACT

Children with acquired and congenital heart disease (CHD) are increasingly surviving to adulthood. Our aim was to determine the prevalence of coronary artery disease (CAD) risk factors in children at known risk for early CAD or with severe CHD. We recruited children (8-19 years) at risk for early CAD-Kawasaki disease (KD, N = 36) and coarctation (69) or severe CHD: > 1 cardiopulmonary bypass surgery (60), single ventricle (15), prosthetic valves (13). Anthropometric measurements, blood pressure, and fasting lipid data were compared with summaries from National Health and Nutrition Examination Survey (NHANES) publications (1999-2012). Relative risk (RR) ratios were calculated based on age classification and pooled to obtain overall RR. Of 174 subjects, 106 were male (61%) and 138 (79%) had CHD. Compared to NHANES data, hypertension and low HDL were higher in the study cohort [RR 11.7 (CI 6.34-21.6), p < 0.001; and 1.79 (CI 1.36-2.35). p < 0.001] and obesity and elevated total cholesterol were lower [RR 0.59 (CI 0.37-0.96), p = 0.03; and 0.42 (CI 0.19-0.95), p = 0.04]. Elevated non-HDL was similar between groups. Age category had similar RR for all CAD risk factors. Eight subjects had metabolic syndrome. Risk factors were similar between KD versus CHD subgroups. Both coarctation and non-coarctation subjects had increased RR for hypertension. Hypertension is the most common risk factor for children at risk of early CAD and severe CHD. Metabolic syndrome is rare. These patients should be screened and treated for hypertension and current recommendations for universal lipid screening are adequate for follow-up.


Subject(s)
Coronary Artery Disease/epidemiology , Heart Defects, Congenital/complications , Metabolic Syndrome/epidemiology , Mucocutaneous Lymph Node Syndrome/complications , Adolescent , Adult , Anthropometry , Child , Coronary Artery Disease/etiology , Cross-Sectional Studies , Dyslipidemias/complications , Dyslipidemias/epidemiology , Female , Humans , Hypertension/complications , Hypertension/epidemiology , Lipids/blood , Male , Metabolic Syndrome/complications , Prevalence , Prospective Studies , Risk Assessment , Risk Factors , Young Adult
9.
Acad Pediatr ; 18(2): 196-199, 2018 03.
Article in English | MEDLINE | ID: mdl-29180296

ABSTRACT

OBJECTIVE: To determine whether the 2011 guidelines for universal routine screening for dyslipidemia in children aged 9 to 11 years, published by the Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents and National Heart, Lung, and Blood Institute, are being followed by pediatric primary-care providers. METHODS: Retrospective data were obtained for 63,951 well-child visits (WCV) in children aged 9 to 11 years from 2 health care systems and 1 insurance program from 2009 to 2015. The proportion of WCV that had a lipid panel or total cholesterol test performed within 1 year of the visit was compared for 2009-2011 versus 2013-2015. Associations between demographic variables and lipid screening were evaluated with logistic regression. The frequency of tested children who had abnormal lipid results was evaluated. RESULTS: Only 3.5% of 9- to 11-year WCV had lipid tests performed in association with the visit before and after the guidelines. Of those tested, 43% had an abnormal lipid result. CONCLUSIONS: Utah clinicians rarely follow guidelines for universal lipid screening of children aged 9 to 11. This represents a missed opportunity to identify children at risk for early-onset cardiovascular disease.


Subject(s)
Dyslipidemias/diagnosis , Guideline Adherence/statistics & numerical data , Pediatricians , Physicians, Primary Care , Child , Dyslipidemias/epidemiology , Female , Hispanic or Latino , Humans , Logistic Models , Male , Mass Screening , Medicaid , Multivariate Analysis , Pediatric Obesity/epidemiology , Practice Guidelines as Topic , Retrospective Studies , United States , Utah/epidemiology
11.
South Med J ; 110(5): 347-352, 2017 05.
Article in English | MEDLINE | ID: mdl-28464176

ABSTRACT

OBJECTIVES: Increased adiposity increases leptin and decreases adiponectin concentrations, resulting in an increased leptin:adiponectin ratio (LAR). In adults, components of the metabolic syndrome and other cardiometabolic risk factors, what we classify here as "metabolic dysfunction," are associated with both a high LAR and a history of being breast-fed. The relation among breast-feeding, LAR, and degree of metabolic dysfunction in obese youth is unknown. The purpose of our pilot study was to explore this relation and estimate the effect size of the relations to determine the sample size needed to power future prospective studies. METHODS: We obtained fasting levels of leptin, adiponectin, lipids, insulin, and glucose from obese youth (aged 8-17 years). Weight, height, waist circumference, blood pressure, and breast-feeding history also were assessed. RESULTS: Of 96 participants, 78 were breast-fed as infants, 54% of whom were breast-fed for >6 months. Wide variation was observed in LARs among children who were and were not breast-fed (>100% coefficient of variation). Overall, prevalence of metabolic dysfunction in the cohort was 94% and was not proven to be associated with higher LAR. CONCLUSIONS: In this cohort of obese youth, we found a high prevalence of breast-feeding, metabolic dysfunction, and wide variation in the LARs. Based on the effect size estimated, future studies would need to enroll >1500 patients or identify, stratify, and selectively enroll obese patients without metabolic dysfunction to accurately determine whether breast-feeding in infancy influences LARs or metabolic dysfunction among obese youth.


Subject(s)
Adiponectin/blood , Breast Feeding , Leptin/blood , Pediatric Obesity/metabolism , Adolescent , Biomarkers/blood , Child , Cohort Studies , Female , Humans , Male , Pediatric Obesity/blood , Pilot Projects
12.
Pediatrics ; 139(2)2017 Feb.
Article in English | MEDLINE | ID: mdl-28049113

ABSTRACT

As concerns over health care-related harms and costs continue to mount, efforts to identify and combat medical overuse are needed. Although much of the recent attention has focused on health care for adults, children are also harmed by overuse. Using a structured PubMed search and manual tables of contents review, we identified important articles on pediatric overuse published in 2015. These articles were evaluated according to the quality of the methods, the magnitude of clinical effect, and the number of patients potentially affected and were categorized into overdiagnosis, overtreatment, and overutilization. Overdiagnosis: Findings included evidence for overdiagnosis of hypoxemia in children with bronchiolitis and skull fractures in children suffering minor head injuries. Overtreatment: Findings included evidence that up to 85% of hospitalized children with radiographic pneumonia may not have a bacterial etiology; many children are receiving prolonged intravenous antibiotic therapy for osteomyelitis although oral therapy is equally effective; antidepressant medication for adolescents and nebulized hypertonic saline for bronchiolitis appear to be ineffective; and thresholds for treatment of hyperbilirubinemia may be too low. Overutilization: Findings suggested that the frequency of head circumference screening could be relaxed; large reductions in abdominal computed tomography testing for appendicitis appear to have been safe and effective; and overreliance on C-reactive protein levels in neonatal early onset sepsis appears to extend hospital length-of-stay.


Subject(s)
Medical Overuse/statistics & numerical data , Pediatrics/statistics & numerical data , Adolescent , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Medical Overuse/prevention & control , Patient Harm/prevention & control , Patient Harm/statistics & numerical data , Risk Factors
13.
Clin Pediatr (Phila) ; 56(14): 1286-1290, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28006979

ABSTRACT

In 2011, an expert National Institutes of Health panel published the "Integrated Guidelines for CV Health and Risk Reduction in Children and Adolescents," which recommended screening all children aged 9 to 11 years for dyslipidemia. It is unknown if this guideline is being followed. We surveyed members of the Utah chapter of the American Academy of Pediatrics to determine whether they performed universal lipid screening at well-child visits (WCV) on their patients at 9,10, or 11 years and how comfortable they were with evaluating and/or managing children with dyslipidemia. Of the 118 respondents who practiced primary care, only 18 (15%) screened all children at WCV; 86 (73%) tested "some," most commonly children who were obese or had a positive family history. 18% were unfamiliar with the guidelines; 28% were familiar with the guidelines but felt they were "inappropriate;" 98 (84%) of the respondents said they were "very or somewhat comfortable" evaluating children with dyslipidemia.


Subject(s)
Dyslipidemias/diagnosis , Guideline Adherence/statistics & numerical data , Mass Screening/statistics & numerical data , Office Visits/statistics & numerical data , Pediatricians/statistics & numerical data , Child , Female , Humans , Male , Surveys and Questionnaires , Utah
14.
Pediatrics ; 137(6)2016 06.
Article in English | MEDLINE | ID: mdl-27244841

ABSTRACT

BACKGROUND AND OBJECTIVE: Poor adherence to recommended screening for autism spectrum disorder (ASD) and pediatricians' lack of confidence in providing care for children with ASD reflect quality gaps in primary care. This study aimed to increase the proportion of toddlers screened for ASD and improve physicians' self-efficacy in providing care to children with ASD. METHODS: Twenty-six Utah primary care practices participated in a 3 to 6 month learning collaborative (LC) to improve identification and ongoing care of children with ASD. Monthly chart audits assessed whether an ASD screening tool was administered at 18- and 24-month visits. Physicians completed pre-LC and post-LC surveys to assess changes in self-efficacy in providing care and changes in perceived barriers to implementation of screening and caring for children with ASD. RESULTS: Before the LC, 15% of 18- and 24-month visits had documented ASD screening, compared with 91% during the last month of the LC (P < .001). This rate of ASD screening was sustained 4 years after the LC by most practices. Compared with survey responses before the LC, physicians reported significant improvement in their ability to care for children with ASD and decreases in their perceived barriers to screening and caring for children with ASD. CONCLUSIONS: The LC was effective in increasing and sustaining recommended ASD screening of toddlers and improving physicians' perceived self-efficacy in caring for children with ASD. Improving primary care screening, skills, and knowledge may improve the timing of diagnosis, initiation of treatment, quality of care, and outcomes for children with ASD.


Subject(s)
Autism Spectrum Disorder/diagnosis , Education, Medical, Continuing , Mass Screening/statistics & numerical data , Physicians, Primary Care/education , Child, Preschool , Clinical Competence , Education, Medical, Continuing/methods , Female , Humans , Male , Medical Audit , Primary Health Care , Utah
15.
Pediatr Cardiol ; 37(7): 1222-7, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27278630

ABSTRACT

Current guidelines recommend that all neonates with Down syndrome (DS) be screened for congenital heart disease (CHD) with an echocardiogram. We sought to determine the effectiveness of a more accessible and less expensive screening strategy consisting of physical examination, electrocardiogram (ECG), and chest X-ray. The Intermountain Healthcare Enterprise Data Warehouse was used to identify infants with a positive karyotype for DS who were born between January 1, 2000, and June 30, 2012. Infants with the results of an echocardiogram, physical examination, ECG, and chest X-ray documented at age ≤6 months were included. Infants with an abnormality on physical examination, ECG, or chest X-ray were considered to have a positive screen. Echocardiography was the gold standard for calculating sensitivity, specificity, positive and negative predictive values for major CHD, defined as any heart defect that would typically require intervention during early childhood. Of 408 eligible infants, 240 (59 %) had major CHD, of whom 228 (95 %) had a positive screen. Screening missed eight infants with moderate/large patent ductus arteriosus and four infants with a moderate/large atrial septal defect. In 11 of these infants, the defect resolved spontaneously by age ≤4 months. One infant had a moderate atrial septal defect persisting at 2-year follow-up. Sensitivity and specificity of the screening for detecting CHD were 95 % (CI 92-98 %) and 41 % (CI 32-47 %); positive and negative predictive values were 69 % (CI 63-73 %) and 85 % (CI 75-92 %). Screening with physical examination, ECG, and chest X-ray is an effective method of identifying which infants with DS should have an echocardiogram. This method would have resulted in 69 (17 %) fewer echocardiograms without missing infants with major CHD.


Subject(s)
Heart Defects, Congenital , Down Syndrome , Ductus Arteriosus, Patent , Echocardiography , Heart Septal Defects, Atrial , Humans , Infant
16.
Clin Obstet Gynecol ; 59(1): 216-27, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26694497

ABSTRACT

With the increasing prevalence of obesity, including among women of childbearing age, there is increasing concern regarding the short-term and long-term effects on the offspring of women who are overweight and obese. In this paper we report the results of our review of the recent literature suggesting important adverse short-term and long-term consequences of maternal obesity on their children.


Subject(s)
Congenital Abnormalities/epidemiology , Diabetes Mellitus/epidemiology , Fetal Macrosomia/epidemiology , Metabolic Syndrome/epidemiology , Obesity/epidemiology , Pediatric Obesity/epidemiology , Pregnancy Complications/epidemiology , Prenatal Exposure Delayed Effects/epidemiology , Puberty, Precocious/epidemiology , Adolescent , Adult , Cardiovascular Diseases/epidemiology , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Mortality , Pregnancy , Young Adult
17.
Acad Pediatr ; 15(6): 626-35, 2015.
Article in English | MEDLINE | ID: mdl-26547543

ABSTRACT

OBJECTIVE: To compare the prevalence of hospitalizations for ambulatory care sensitive conditions (ACSC) in children with and without autism spectrum disorder (ASD) and to compare inpatient health care utilization (total charges and length of stay) for the same conditions in children with and without ASD. METHODS: The 2009 Kids' Inpatient Database was used to examine hospitalizations for ACSC in children within 3 cohorts: those with ASD, those with chronic conditions (CC) without ASD, and those with no CC. RESULTS: The proportion of hospitalizations for ACSC in the ASD cohort was 55.9%, compared with 28.2% in the CC cohort and 22.9% in the no-CC cohort (P < .001). Hospitalized children with ASD were more likely to be admitted for a mental health condition, epilepsy, constipation, pneumonia, dehydration, vaccine-preventable diseases, underweight, and nutritional deficiencies compared with the no-CC cohort. Compared with the CC cohort, the ASD cohort was more likely to be admitted for mental health conditions, epilepsy, constipation, dehydration, and underweight. Hospitalized children with ASD admitted for mental health conditions had significantly higher total charges and longer LOS compared with the other 2 cohorts. CONCLUSIONS: The proportion of potentially preventable hospitalizations is higher in hospitalized children with ASD compared with children without ASD. These data underscore the need to improve outpatient care of children with ASD, especially in the areas of mental health care and seizure management. Future research should focus on understanding the reasons for increased inpatient health care utilization in children with ASD admitted for mental health conditions.


Subject(s)
Autism Spectrum Disorder , Hospitalization/statistics & numerical data , Adolescent , Ambulatory Care , Case-Control Studies , Child , Child, Preschool , Chronic Disease , Constipation , Cross-Sectional Studies , Databases, Factual , Dehydration , Epilepsy , Female , Humans , Male , Malnutrition , Mental Disorders , Pneumonia , Thinness , Young Adult
18.
Chemistry ; 21(39): 13748-57, 2015 Sep 21.
Article in English | MEDLINE | ID: mdl-26248980

ABSTRACT

Gold(I)-catalysed direct allylic etherifications have been successfully carried out with chirality transfer to yield enantioenriched, γ-substituted secondary allylic ethers. Our investigations include a full substrate-scope screen to ascertain substituent effects on the regioselectivity, stereoselectivity and efficiency of chirality transfer, as well as control experiments to elucidate the mechanistic subtleties of the chirality-transfer process. Crucially, addition of molecular sieves was found to be necessary to ensure efficient and general chirality transfer. Computational studies suggest that the efficiency of chirality transfer is linked to the aggregation of the alcohol nucleophile around the reactive π-bound Au-allylic ether complex. With a single alcohol nucleophile, a high degree of chirality transfer is predicted. However, if three alcohols are present, alternative proton transfer chain mechanisms that erode the efficiency of chirality transfer become competitive.

19.
J Org Chem ; 80(20): 9807-16, 2015 Oct 16.
Article in English | MEDLINE | ID: mdl-26118859

ABSTRACT

A mild gold-catalyzed protodeboronation reaction, which does not require acid or base additives and can be carried out in "green" solvents, is described. As a result, the reaction is very functional-group-tolerant, even to acid- and base-sensitive functional groups, and should allow for the boronic acid group to be used as an effective traceless directing or blocking group. The reaction has also been extended to deuterodeboronations for regiospecific ipso-deuterations of aryls and heteroaryls from the corresponding organoboronic acid. Based on density functional theory calculations, a mechanism is proposed that involves nucleophilic attack of water at boron followed by rate-limiting B-C bond cleavage and facile protonolysis of a Au-σ-phenyl intermediate.

20.
Acad Pediatr ; 15(3): 340-4, 2015.
Article in English | MEDLINE | ID: mdl-25906702

ABSTRACT

OBJECTIVE: Current recommendations are that newborns of mothers with chorioamnionitis have a complete blood count, blood culture, and antibiotic therapy. We hypothesized that utilizing the early-onset sepsis (EOS) risk calculator and a clinical symptom assessment could safely reduce the number of newborns subjected to laboratory testing and antibiotics. METHODS: We reviewed 698 well-appearing newborns of estimated gestational age of ≥34 weeks born to mothers with chorioamnionitis. RESULTS: Sixty-five percent of newborns were managed according to the guidelines; 1 (0.14%) had culture-positive EOS. A strategy based on the use of the EOS calculator and clinical appearance of the newborn would have reduced the proportion having laboratory tests and antibiotics to 12% and would not have missed any cases of EOS. CONCLUSIONS: The EOS risk in well-appearing newborns of mothers with chorioamnionitis is low. Applying a strategy based on readily obtainable measures rather than the obstetrical diagnosis of chorioamnionitis would result in a substantial reduction of newborns undergoing laboratory tests and being exposed to antibiotics. Further prospective trials evaluating the safety of this approach are warranted.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Chorioamnionitis/epidemiology , Practice Guidelines as Topic , Sepsis/prevention & control , Blood Cell Count , Female , Guideline Adherence , Humans , Infant, Newborn , Microbiological Techniques , Pregnancy , Risk Assessment , Sepsis/diagnosis , Sepsis/epidemiology
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