Veronika Northrup

Translating the Diabetes Prevention Program to Primary Care: A Pilot Study

Background: Research on the translation of efficacious lifestyle change programs to prevent type 2 diabetes into community or clinical settings is needed. Objective: The objective of this study was to examine the reach, implementation, and efficacy of a 6-month lifestyle program implemented in primary care by nurse practitioners (NPs) for adults at risk of type 2 diabetes. Methods: The NP sites (n = 4) were randomized to an enhanced standard care program (one NP and one nutrition session) or a lifestyle program (enhanced standard care and six NP sessions). These NPs recruited adults at risk of diabetes from their practice (n = 58), with an acceptance rate of 70%. Results: The program reached a diverse, obese, and moderately low income sample. The NPs were able to successfully implement the protocols. The average length of the program was 9.3 months. Attendance was high (98%), and attrition was low (12%). The NPs were able to adopt the educational, behavioral, and psychosocial strategies of the intervention easily. Motivational interviewing was more difficult for NPs. Mixed-model repeated-measures analysis indicated significant trends or improvement in both groups for nutrition and exercise behavior. Participants of the lifestyle program demonstrated trends for better high-density lipoprotein (HDL) and exercise behavior compared with the enhanced standard care participants. Twenty-five percent of lifestyle participants met treatment goals of 5% weight loss compared with 11% of standard care participants. Discussion: A lifestyle program can be implemented in primary care by NPs, reach the targeted population, and be modestly successful. Further research is indicated.

Antibiotic Exposure in the Newborn Intensive Care Unit and the Risk of Necrotizing Enterocolitis

OBJECTIVE To determine whether duration of antibiotic exposure is an independent risk factor for necrotizing enterocolitis (NEC). STUDY DESIGN A retrospective, 2:1 control-case analysis was conducted comparing neonates with NEC to those without from 2000 through 2008. Control subjects were matched on gestational age, birth weight, and birth year. In each matched triad, demographic and risk factor data were collected from birth until the diagnosis of NEC in the case subject. Bivariate and multivariate analyses were used to assess associations between risk factors and NEC. RESULTS One hundred twenty-four cases of NEC were matched with 248 control subjects. Cases were less likely to have respiratory distress syndrome (P = .018) and more likely to reach full enteral feeding (P = .028) than control subjects. Cases were more likely to have culture-proven sepsis (P < .0001). Given the association between sepsis and antibiotic use, we tested for and found a significant interaction between the two variables (P = .001). When neonates with sepsis were removed from the cohort, the risk of NEC increased significantly with duration of antibiotic exposure. Exposure for >10 days resulted in a nearly threefold increase in the risk of developing NEC. CONCLUSIONS Duration of antibiotic exposure is associated with an increased risk of NEC among neonates without prior sepsis.

Central Role of Fatty Liver in the Pathogenesis of Insulin Resistance in Obese Adolescents

OBJECTIVE We evaluated the role of fatty liver in the alteration of insulin sensitivity and β-cell function in two groups of obese adolescents, differing in hepatic fat content (hepatic fat fraction [HFF]) but with similar intrabdominal intramyocellular lipid content (IMCL) and overall degree of obesity. RESEARCH DESIGN AND METHODS We studied 23 obese adolescents with high HFF (HFF >5.5%) and 20 obese adolescents with low HFF (HFF <5.5%), matched for age, Tanner stage, BMI z score, and percentages of body fat, visceral fat, and IMCL. All subjects underwent an oral glucose tolerance test and a two-step hyperinsulinemic-euglycemic clamp, magnetic resonance imaging and 1H nuclear magnetic resonance to assess abdominal fat distribution, HFF, and IMCL, respectively. RESULTS The high HFF group showed significantly lower whole-body insulin sensitivity index (P = 0.001) and estimates of insulin secretion (P = 0.03). The baseline hepatic glucose production (EGP) rate was not different between the two groups. Suppression of EGP was significantly lower (P = 0.04) in the high HFF group during low-dose insulin; no differences were observed during the second step. Baseline fatty acids, glycerol concentrations, and clamp suppression of glycerol turnover did not differ between the groups. During the second step, the glucose disposal rate was significantly lower (P = 0.01) in the high HFF group. CONCLUSIONS Fatty liver, independent of visceral fat and IMCL, plays a central role in the insulin-resistant state in obese adolescents.

A quality improvement initiative to reduce central line-associated bloodstream infections in a neonatal intensive care unit.

OBJECTIVE To reduce the rate of late-onset sepsis in a neonatal intensive care unit (NICU) by decreasing the rate of central line-associated bloodstream infection (CLABSI). METHODS We conducted a quasi-experimental study of an educational intervention designed to improve the quality of clinical practice in an NICU. Participants included all NICU patients with a central venous catheter (CVC). Data were collected during the period from July 1, 2005, to June 30, 2007, to document existing CLABSI rates and CVC-related practices. A multidisciplinary quality improvement committee was established to review these and published data and to create guidelines for CVC placement and management. Educational efforts were conducted to implement these practices. Postintervention CLABSI rates were collected during the period from January 1, 2008, through March 31, 2009, and compared with preintervention data and with benchmark data from the National Healthcare Safety Network (NHSN). RESULTS The rate of CLABSI in the NICU decreased from 8.40 to 1.28 cases per 1,000 central line-days (adjusted rate ratio, 0.19 [95% confidence interval, 0.08-0.45]). This rate was lower than the NHSN benchmark rate for level III NICUs. The overall rate of late-onset sepsis was reduced from 5.84 to 1.42 cases per 1,000 patient-days (rate difference, -4.42 cases per 1,000 patient-days [95% confidence interval, -5.55 to -3.30 cases per 1,000 patient-days]). CONCLUSIONS It is possible to reduce the rate of CLABSI, and therefore the rate of late-onset sepsis, by establishing and adhering to evidence-based guidelines. Sustainability depends on continued data surveillance, knowledge of medical and nursing literature, and timely feedback to the staff. The techniques established are applicable to other populations and areas of inpatient care.

Effects of Coping Skills Training in School-age Children with Type 1 Diabetes

Children with type 1 diabetes are at risk for negative psychosocial and physiological outcomes, particularly as they enter adolescence. The purpose of this randomized trial (n = 82) was to determine the effects, mediators, and moderators of a coping skills training intervention (n = 53) for school-aged children compared to general diabetes education (n = 29). Both groups improved over time, reporting lower impact of diabetes, better coping with diabetes, better diabetes self-efficacy, fewer depressive symptoms, and less parental control. Treatment modality (pump vs. injections) moderated intervention efficacy on select outcomes. Findings suggest that group-based interventions may be beneficial for this age group.

Comparison of Neurocognitive Functioning in Children Previously Randomly Assigned to Intrathecal Methotrexate Compared With Triple Intrathecal Therapy for the Treatment of Childhood Acute Lymphoblastic Leukemia

PURPOSE For the majority of children with acute lymphoblastic leukemia (ALL), CNS prophylaxis consists of either intrathecal (IT) methotrexate or triple IT therapy (ie, methotrexate with both cytarabine and hydrocortisone). The long-term neurotoxicities of these two IT strategies have not yet been directly compared. PATIENTS AND METHODS In this multisite study, 171 children with standard-risk ALL, age 1 to 9.99 years at diagnosis, previously randomly assigned to IT methotrexate (n = 82) or to triple IT therapy (n = 89) on CCG 1952, underwent neurocognitive evaluation by a licensed psychologist at a mean of 5.9 years after random assignment. RESULTS Patients who received IT methotrexate had a mean Processing Speed Index that was 3.6 points lower, about one fourth of a standard deviation, than those who received triple IT therapy (P = .04) after analysis was adjusted for age, sex, and time since diagnosis. Likewise, 19.5% of children in the IT methotrexate group had a Processing Speed Index score in the below-average range compared with 6.9% in the triple IT therapy group (P = .02). Otherwise, the groups performed similarly on tests of full-scale intelligence quotient, academic achievement, attention/concentration, memory, and visual motor integration. The association of treatment with measures of cognitive functioning was not modified by sex or age at diagnosis. In the post-therapy period, there were no group differences in special education services, neurologic events, or use of psychotropic medications. CONCLUSION This study did not show any clinically meaningful differences in neurocognitive functioning between patients previously randomly assigned to IT methotrexate or triple IT therapy except for a small difference in processing speed in the IT methotrexate group.

Human POLB Gene Is Mutated in High Percentage of Colorectal Tumors

Background: Previous small scale studies indicate that DNA polymerase β variants are present in 30% of human tumors. Results: 40% of samples in a large human colorectal tumor collection harbor coding region variants, many of which exhibit altered function. Conclusion: Aberrant activity or fidelity phenotypes exhibited by variants may contribute to tumorigenesis. Significance: Expression of variants in human tumors plays a role in driving carcinogenesis. Previous small scale sequencing studies have indicated that DNA polymerase β (pol β) variants are present on average in 30% of human tumors of varying tissue origin. Many of these variants have been shown to have aberrant enzyme function in vitro and to induce cellular transformation and/or genomic instability in vivo, suggesting that their presence is associated with tumorigenesis or its progression. In this study, the human POLB gene was sequenced in a collection of 134 human colorectal tumors and was found to contain coding region mutations in 40% of the samples. The variants map to many different sites of the pol β protein and are not clustered. Many variants are nonsynonymous amino acid substitutions predicted to affect enzyme function. A subset of these variants was found to have reduced enzyme activity in vitro and failed to fully rescue pol β-deficient cells from methylmethane sulfonate-induced cytotoxicity. Tumors harboring variants with reduced enzyme activity may have compromised base excision repair function, as evidenced by our methylmethane sulfonate sensitivity studies. Such compromised base excision repair may drive tumorigenesis by leading to an increase in mutagenesis or genomic instability.

Ethnic differences in lipoprotein subclasses in obese adolescents: importance of liver and intraabdominal fat accretion

BACKGROUND Recently, the deleterious metabolic effects of visceral fat [visceral adipose tissue (VAT)] deposition were challenged, and liver fat emerged as having a key independent role in the modulation of cardiometabolic risk factors. OBJECTIVE We explored the relation between liver fat content and VAT in 3 ethnic groups and evaluated whether the ethnic differences in the distributions of lipoprotein concentrations and sizes were associated with the hepatic fat fraction (HFF), VAT, or both. DESIGN In a multiethnic group of 33 white, 33 African American, and 33 Hispanic obese adolescents with normal glucose tolerance, we measured VAT and HFF by using magnetic resonance imaging. Fasting lipoprotein particle number and size were measured by using nuclear magnetic resonance spectroscopy. To assess the association between VAT and HFF, we categorized VAT into tertiles. RESULTS In each ethnic group, HFF values increased between successive tertiles of VAT. After multivariate adjustment and in comparison with the 2 other groups, African Americans showed lower triglyceride (P = 0.001) and higher HDL (P = 0.03) concentrations, lower concentrations of total (P = 0.007), large (P = 0.005), and medium (P lt 0.0001) VLDL, but higher concentrations of large HDL particles (P = 0.01) and larger HDL (P = 0.005). In multivariate linear models, independent of ethnicity, VAT was a significant predictor for large HDL (P = 0.003) and total small LDL (P = 0.001) concentrations, whereas HFF significantly predicted large VLDL (P = 0.03) concentrations. CONCLUSION Liver fat accretion, independent of VAT, may play a role in the ethnic differences seen in large VLDL particles. This trial was registered at clinicaltrials.gov as NCT00536250.

Neutrophil CD64 as a diagnostic marker in neonatal sepsis.

We assessed neutrophil CD64 as a diagnostic marker for neonatal sepsis. For early-onset sepsis, the CD64 index with a cut-point value of 2.38 had sensitivity, specificity and negative predictive values of 100%, 68% and 100%, respectively. For late-onset sepsis, the respective values were 3.62, 75%, 77% and 96%. Neutrophil CD64 index can be incorporated as a valuable marker for excluding neonatal sepsis.

Incidence and Acute Complications of Asymptomatic Central Venous Catheter–Related Deep Venous Thrombosis in Critically Ill Children

OBJECTIVE To determined the current incidence and acute complications of asymptomatic central venous catheter (CVC)-related deep venous thrombosis (DVT) in critically ill children. STUDY DESIGN We performed a prospective cohort study in 3 pediatric intensive care units. A total of 101 children with newly inserted untunneled CVC were included. CVC-related DVT was diagnosed using compression ultrasonography with color Doppler. RESULTS Asymptomatic CVC-related DVT was diagnosed in 16 (15.8%) children, which equated to 24.7 cases per 1000 CVC-days. Age was independently associated with DVT. Compared with children aged <1 year, children aged >13 years had significantly higher odds of DVT (aOR, 14.1, 95% CI, 1.9-105.8; P = .01). Other patient demographics, interventions (including anticoagulant use), and CVC characteristics did not differ between children with and without DVT. Mortality-adjusted duration of mechanical ventilation, a surrogate for pulmonary embolism, was statistically similar in the 2 groups (22 ± 9 days in children with DVT vs 23 ± 7 days in children without DVT; P = .34). Mortality-adjusted intensive care unit and hospital lengths of stay also were similar in the 2 groups. CONCLUSION Asymptomatic CVC-related DVT is common in critically ill children. However, the acute complications do not seem to differ between children with and without DVT. Larger studies are needed to confirm these results. Future studies should also investigate the chronic complications of asymptomatic CVC-related DVT.