Maternal dietary intake during pregnancy and offspring body composition: The Healthy Start Study

Consistent evidence of an influence of maternal dietary intake during pregnancy on infant body size and composition in human populations is lacking, despite robust evidence in animal models

An Assessment of Oral Health on the Pine Ridge Indian Reservation

An assessment on the oral health of 292 Oglala Lakota residents of the Pine Ridge Indian Reservation in South Dakota looks at dental issues, periodontal disease, oral lesions and need for dental care. The research was conducted by the University of Colorado, Center for Native Oral Health Research and funded by the W.K. Kellogg Foundation

Risk Factors for Recurrent Acute Kidney Injury in Children Who Undergo Multiple Cardiac Surgeries: A Retrospective Analysis

Objectives: Determine the risk factors for repeated episodes of acute kidney injury in children who undergo multiple cardiac surgical procedures. Design: Single-center retrospective chart review. Setting: Cardiac ICU at a quaternary pediatric care center. Patients: Birth to 18 years who underwent at least two cardiac surgical procedures with cardiopulmonary bypass. Interventions: None. Measurements and main results: One-hundred eighty patients underwent two cardiac surgical procedures and 89 underwent three. Acute kidney injury was defined by the Kidney Disease: Improving Global Outcomes serum creatinine criteria. Acute kidney injury frequency was 26% (n = 46) after surgery 1, 20% (n = 36) after surgery 2, and 24% (n = 21) after surgery 3, with most acute kidney injury occurring on postoperative days 1 and 2. The proportion of patients with severe acute kidney injury increased from surgery 1 to surgery 3. Patients with acute kidney injury had a significantly longer duration of ventilation and length of stay after each surgery. The odds of acute kidney injury after surgery 3 was 2.40 times greater if acute kidney injury was present after surgery 1 or 2 (95% CI, 1.26-4.56; p = 0.008) after adjusting for confounders. The time between surgeries was not significantly associated with acute kidney injury (p = 0.85). Conclusions: In a heterogeneous population of pediatric patients with congenital heart disease undergoing multiple cardiopulmonary bypass surgeries, odds of acute kidney injury after a third surgery was increased by the presence of acute kidney injury after prior procedures. Time between surgery did not play a role in increasing odds of acute kidney injury. Further studies in a larger multicenter investigation are necessary to confirm these findings

Risk factors for acute kidney injury in neonates with congenital diaphragmatic hernia

This article is made available for unrestricted research re-use and secondary analysis in any form or be any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Objective: To examine incidence of acute kidney injury (AKI), antenatal and postnatal predictors, and impact of AKI on outcomes in infants with congenital diaphragmatic hernia (CDH). Study design: Single center retrospective study of 90 CDH infants from 2009-2017. Baseline characteristics, CDH severity, possible AKI predictors, and clinical outcomes were compared between infants with and without AKI. Result: In total, 38% of infants developed AKI, 44% stage 1, 29% stage 2, 27% stage 3. Lower antenatal lung volumes and liver herniation were associated with AKI. Extracorporeal life support (ECLS), diuretics, abdominal closure surgery, hypotension, and elevated plasma free hemoglobin were associated with AKI. Overall survival was 79%, 47% with AKI, and 35% with AKI on ECLS. AKI is associated with increased mechanical ventilation duration and length of stay. Conclusion: AKI is common among CDH infants and associated with adverse outcomes. Standardized care bundles addressing AKI risk factors may reduce AKI incidence and severity

Associations of maternal BMI and gestational weight gain with neonatal adiposity in the Healthy Start study

Background: Maternal obesity and weight gain during pregnancy are risk factors for child obesity. Associations may be attributable to causal effects of the intrauterine environment or genetic and postnatal environmental factors

Bias in trials comparing paired continuous tests can cause researchers to choose the wrong screening modality

<p>Abstract</p> <p>Background</p> <p>To compare the diagnostic accuracy of two continuous screening tests, a common approach is to test the difference between the areas under the receiver operating characteristic (ROC) curves. After study participants are screened with both screening tests, the disease status is determined as accurately as possible, either by an invasive, sensitive and specific secondary test, or by a less invasive, but less sensitive approach. For most participants, disease status is approximated through the less sensitive approach. The invasive test must be limited to the fraction of the participants whose results on either or both screening tests exceed a threshold of suspicion, or who develop signs and symptoms of the disease after the initial screening tests.</p> <p>The limitations of this study design lead to a bias in the ROC curves we call <it>paired screening trial bias</it>. This bias reflects the synergistic effects of inappropriate reference standard bias, differential verification bias, and partial verification bias. The absence of a gold reference standard leads to inappropriate reference standard bias. When different reference standards are used to ascertain disease status, it creates differential verification bias. When only suspicious screening test scores trigger a sensitive and specific secondary test, the result is a form of partial verification bias.</p> <p>Methods</p> <p>For paired screening tests with bivariate normally distributed scores, we give formulae and programs to quantify the effect of <it>paired screening trial bias </it>on a paired comparison of area under the curves. We fix the prevalence of disease, and the chance a diseased subject manifests signs and symptoms. We derive the formulas for true sensitivity and specificity, and those for the sensitivity and specificity observed by the study investigator.</p> <p>Results</p> <p>The observed area under the ROC curves is quite different from the true area under the ROC curves. The typical direction of the bias is a strong inflation in sensitivity, paired with a concomitant slight deflation of specificity.</p> <p>Conclusion</p> <p>In paired trials of screening tests, when area under the ROC curve is used as the metric, bias may lead researchers to make the wrong decision as to which screening test is better.</p

Nonsteroidal Anti-inflammatory Drugs and Endometrial Carcinoma Mortality and Recurrence

Background: Recent data suggest that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with reductions in endometrial cancer risk, yet very few have examined whether their use is related to prognosis among endometrial cancer patients

Effects of Icosapent Ethyl on Total Ischemic Events: From REDUCE-IT.

BACKGROUND: In time-to-first-event analyses, icosapent ethyl significantly reduced the risk of ischemic events, including cardiovascular death, among patients with elevated triglycerides receiving statins. These patients are at risk for not only first but also subsequent ischemic events. OBJECTIVES: Pre-specified analyses determined the extent to which icosapent ethyl reduced total ischemic events. METHODS: REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) randomized 8,179 statin-treated patients with triglycerides ≥135 and 40 and ≤100 mg/dl (median baseline of 75 mg/dl), and a history of atherosclerosis (71% patients) or diabetes (29% patients) to icosapent ethyl 4 g/day or placebo. The main outcomes were total (first and subsequent) primary composite endpoint events (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or hospitalization for unstable angina) and total key secondary composite endpoint events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke). As a pre-specified statistical method, we determined differences in total events using negative binomial regression. We also determined differences in total events using other statistical models, including Andersen-Gill, Wei-Lin-Weissfeld (Li and Lagakos modification), both pre-specified, and a post hoc joint frailty analysis. RESULTS: In 8,179 patients, followed for a median of 4.9 years, 1,606 (55.2%) first primary endpoint events and 1,303 (44.8%) subsequent primary endpoint events occurred (which included 762 second events, and 541 third or more events). Overall, icosapent ethyl reduced total primary endpoint events (61 vs. 89 per 1,000 patient-years for icosapent ethyl versus placebo, respectively; rate ratio: 0.70; 95% confidence interval: 0.62 to 0.78; p < 0.0001). Icosapent ethyl also reduced totals for each component of the primary composite endpoint, as well as the total key secondary endpoint events (32 vs. 44 per 1,000 patient-years for icosapent ethyl versus placebo, respectively; rate ratio: 0.72; 95% confidence interval: 0.63 to 0.82; p < 0.0001). CONCLUSIONS: Among statin-treated patients with elevated triglycerides and cardiovascular disease or diabetes, multiple statistical models demonstrate that icosapent ethyl substantially reduces the burden of first, subsequent, and total ischemic events. (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial [REDUCE-IT]; NCT01492361)

Dysregulation of PRMT5 in chronic lymphocytic leukemia promotes progression with high risk of Richter's transformation

: Richter's Transformation (RT) is a poorly understood and fatal progression of chronic lymphocytic leukemia (CLL) manifesting histologically as diffuse large B-cell lymphoma. Protein arginine methyltransferase 5 (PRMT5) is implicated in lymphomagenesis, but its role in CLL or RT progression is unknown. We demonstrate herein that tumors uniformly overexpress PRMT5 in patients with progression to&nbsp;RT. Furthermore, mice with B-specific overexpression of hPRMT5 develop a B-lymphoid expansion with increased risk of death, and Eµ-PRMT5/TCL1 double transgenic mice develop a highly aggressive disease with transformation that histologically resembles RT; where large-scale transcriptional profiling identifies oncogenic pathways mediating PRMT5-driven disease progression. Lastly, we report the development of a SAM-competitive PRMT5 inhibitor, PRT382, with exclusive selectivity and optimal in vitro and in vivo activity compared to available PRMT5 inhibitors. Taken together, the discovery that PRMT5 drives oncogenic pathways promoting RT provides a compelling rationale for clinical investigation of PRMT5 inhibitors such as PRT382 in aggressive CLL/RT cases