Comparative safety of different antibiotic regimens for the treatment of outpatient community-acquired pneumonia among otherwise healthy adults.

BACKGROUND: Evidence is limited about the comparative safety of antibiotic regimens for treatment of community-acquired pneumonia (CAP). We compared the risk of adverse drug events (ADEs) associated with antibiotic regimens for CAP treatment among otherwise healthy, non-elderly adults. METHODS: We conducted an active comparator new-user cohort study (2007-2019) of commercially-insured adults 18-64 years diagnosed with outpatient CAP, evaluated via chest x-ray, and dispensed a same-day CAP-related oral antibiotic regimen. ADE follow-up duration ranged from 2-90 days (e.g., renal failure [14 days]). We estimated risk differences [RD] per 100 treatment episodes and risk ratios using propensity score weighted Kaplan-Meier functions. Ankle/knee sprain and influenza vaccination were considered as negative control outcomes. RESULTS: Of 145,137 otherwise healthy CAP patients without comorbidities, 52% received narrow-spectrum regimens (44% macrolide, 8% doxycycline) and 48% received broad-spectrum regimens (39% fluoroquinolone, 7% ß-lactam, 3% ß-lactam + macrolide). Compared to macrolide monotherapy, each broad-spectrum antibiotic regimen was associated with increased risk of several ADEs (e.g., ß-lactam: nausea/vomiting/abdominal pain [RD per 100, 0.32; 95% CI, 0.10-0.57]; non-Clostridioides difficile diarrhea [RD per 100, 0.46; 95% CI, 0.25-0.68]; vulvovaginal candidiasis/vaginitis [RD per 100, 0.36; 95% CI, 0.09-0.69]). Narrow-spectrum antibiotic regimens largely conferred similar risk of ADEs. We generally observed similar risks of each negative control outcome, indicating minimal confounding. CONCLUSIONS: Broad-spectrum antibiotics were associated with increased risk of ADEs among otherwise healthy adults treated for CAP in the outpatient setting. Antimicrobial stewardship is needed to promote judicious use of broad-spectrum antibiotics and ultimately decrease antibiotic-related ADEs.

Supporting the Resilience and Mental Health of Missouri Healthcare Workers Through COVID-19 and Beyond: the Gateway2Wellness Program.

The COVID-19 pandemic is over, but US healthcare workers (HCWs) continue to report high levels of work-related exhaustion and burnout but are unlikely to seek help. Digital tools offer a scalable solution. Between February and June 2022, we surveyed Missouri hospital administrators to assess HCW mental health and identify related evidence-based or evidence-informed resources. Simultaneously, we conducted a digital survey and focus groups with HCWs and leaders at Washington University School of Medicine (WUSOM) in St. Louis to evaluate HCW mental health needs, and preferences for digital support. Here, we describe the results and subsequent development of the Gateway to Wellness (G2W) program, a digital precision engagement platform that links HCWs to the most effective tailored resources for their mental health needs.

Predictors of intracranial hypertension in children undergoing ICP monitoring after severe traumatic brain injury.

PURPOSE: Intracranial hypertension (ICH) is a common and treatable complication after severe traumatic brain injury (sTBI) in children. Describing the incidence and risk factors for developing ICH after sTBI could impact clinical practice. METHODS: Retrospective cohort study from 2006 to 2015 at two university-affiliated level I pediatric trauma centers of children admitted with accidental or abusive TBI, a post-resuscitation Glasgow Coma Score (GCS) of 8 or less, and an invasive intracranial pressure (ICP) monitor. Bivariate and multivariable logistic regression analysis were performed to identify demographic, injury, and imaging characteristics in patients who received ICP directed therapies for ICH (ICP > 20 mmHg). RESULTS: Eight to 5% (271/321) of monitored patients received ICP directed therapy for ICH during their PICU stay. Ninety-seven percent of patients had an abnormality on CT scan by either the Marshall or the Rotterdam score. Of the analyzed clinical and radiologic variables, only presence of hypoxia prior to PICU arrival, female sex, and a higher Injury Severity Score (ISS) were associated with increased risk of ICH (p < 0.05). CONCLUSIONS: In this retrospective study of clinical practice of ICP monitoring in children after sTBI, the vast majority of children had an abnormal CT scan and experienced ICH requiring clinical intervention. Commonly measured clinical variables and radiologic classification scores did not significantly add to the prediction for developing of ICH and further efforts are needed to define low-risk populations that would not develop ICH.

Outcomes Related to the Use of Frozen Plasma or Pooled Solvent/Detergent-Treated Plasma in Critically Ill Children.

OBJECTIVE: To determine if the use of fresh frozen plasma/frozen plasma 24 hours compared to solvent detergent plasma is associated with international normalized ratio reduction or ICU mortality in critically ill children. DESIGN: This is an a priori secondary analysis of a prospective, observational study. Study groups were defined as those transfused with either fresh frozen plasma/frozen plasma 24 hours or solvent detergent plasma. Outcomes were international normalized ratio reduction and ICU mortality. Multivariable logistic regression was used to determine independent associations. SETTING: One hundred one PICUs in 21 countries. PATIENTS: All critically ill children admitted to a participating unit were included if they received at least one plasma unit during six predefined 1-week (Monday to Friday) periods. All children were exclusively transfused with either fresh frozen plasma/frozen plasma 24 hours or solvent detergent plasma. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 443 patients enrolled in the study. Twenty-four patients (5%) were excluded because no plasma type was recorded; the remaining 419 patients were analyzed. Fresh frozen plasma/frozen plasma 24 hours group included 357 patients, and the solvent detergent plasma group included 62 patients. The median (interquartile range) age and weight were 1 year (0.2-6.4) and 9.4 kg (4.0-21.1), respectively. There was no difference in reason for admission, severity of illness score, pretransfusion international normalized ratio, or lactate values; however, there was a difference in primary indication for plasma transfusion (p < 0.001). There was no difference in median (interquartile range) international normalized ratio reduction, between fresh frozen plasma/frozen plasma 24 hours and solvent detergent plasma study groups, -0.2 (-0.4 to 0) and -0.2 (-0.3 to 0), respectively (p = 0.80). ICU mortality was lower in the solvent detergent plasma versus fresh frozen plasma/frozen plasma 24 hours groups, 14.5% versus 29.1%%, respectively (p = 0.02). Upon adjusted analysis, solvent detergent plasma transfusion was independently associated with reduced ICU mortality (odds ratio, 0.40; 95% CI, 0.16-0.99; p = 0.05). CONCLUSIONS: Solvent detergent plasma use in critically ill children may be associated with improved survival. This hypothesis-generating data support a randomized controlled trial comparing solvent detergent plasma to fresh frozen plasma/frozen plasma 24 hours.

Association of Fetal Heart Rate Baseline Change and Neonatal Outcomes.

Objective The objective of this study was to describe the incidence of baseline change within normal range during labor and its prediction of neonatal outcomes. Materials and Methods This was a prospective cohort of singleton, nonanomalous, term neonates with continuous electronic fetal monitoring and normal baseline fetal heart rate throughout the last 2 hours of labor. We determined baseline in 10-minute segments using Eunice Kennedy Shriver National Institute of Child Health and Human Development criteria. We evaluated baseline changes of ≥ 20 and ≥ 30 bpm for association with acidemia (umbilical cord arterial pH ≤ 7.10) and neonatal intensive care unit (NICU) admission. Finally, we performed a sensitivity analysis of normal neonates, excluding those with acidemia, NICU admission, or 5-minute Apgar < 4. Results Among all neonates (n = 3,021), 1,267 (41.9%) had change ≥ 20 bpm; 272 (9.0%) had ≥ 30 bpm. Among normal neonates (n = 2,939), 1,221 (41.5%) had change ≥20 bpm. Acidemia was not associated with baseline change of any direction or magnitude. NICU admission was associated with decrease ≥ 20 bpm (adjusted odds ratio [aOR]: 2.93; 95% confidence interval [CI]: 1.19 - 7.21) or any direction ≥ 20 bpm (aOR: 4.06; 95% CI: 1.46-11.29). For decrease ≥ 20 bpm, sensitivity and specificity were 40.0 and 81.7%; for any direction ≥ 20 bpm, 75.0 and 58.3%. Conclusion Changes of normal baseline are common in term labor and poorly predict morbidity, regardless of direction or magnitude.

Nonreassuring Fetal Status in the Second Stage of Labor: Fetal Monitoring Features and Association with Neonatal Outcomes.

Objective To examine features of electronic fetal monitoring that prompt a diagnosis of nonreassuring fetal status (NRFS) and their association with acidemia. Study Design We identified all operative (cesarean or operative vaginal) deliveries from a retrospective cohort study of term singletons delivered in the second stage. The primary exposure was indication for delivery, NRFS versus other. We compared fetal monitoring features in the 30 minutes prior to delivery. In those delivered for NRFS, we assessed features associated with acidemia (pH < 7.2). Logistic regression adjusted for confounders. Results Of 5,388 patients, 770 (14%) were delivered operatively. NRFS (77%) was associated with acidemia (adjusted odds ratio 3.7, 95% confidence interval 2.1-6.5). Total deceleration area, repetitive late decelerations, and marked variability were associated with NRFS. However, only number of prolonged decelerations and total deceleration area were associated with acidemia in the NRFS group. Conclusion The majority of deliveries for NRFS and the features that prompt that diagnosis are not associated with acidemia.

Treatment Utility of Postpartum Antibiotics in Chorioamnionitis Study.

Objective To determine if postpartum antibiotics are necessary for patients with chorioamnionitis after a cesarean delivery (CD). Study Design Multicenter randomized controlled trial. Laboring patients with singleton gestations and chorioamnionitis who underwent CD were eligible. Patients were treated with ampicillin and gentamicin per standard protocol, then given clindamycin prior to skin incision. Patients were randomized to either postpartum antibiotic prophylaxis or no treatment following delivery. The primary outcome was the rate of endometritis. Assuming a 30% risk of endometritis in patients with chorioamnionitis who undergo CD, 119 patients per arm would be required to detect a 50% decrease in endometritis. Results The trial was stopped for futility following a planned interim analysis after 80 patients were randomized. There was no difference in the rate of the primary outcome between the two groups (9.8 vs. 7.7%, relative risk [RR]: 1.27; 95% confidence interval [CI]: 0.30, 5.31). A meta-analysis comparing post-CD antibiotics versus no treatment did not find a statistically significant difference between the groups (16.7 vs. 12.0%, pooled RR: 1.43; 95% CI: 0.72, 2.84). Conclusion Additional postpartum antibiotics do not decrease the rate of endometritis in patients with chorioamnionitis who undergo CD. The current preoperative antibiotic regimen including clindamycin should remain the standard of care in these patients.

Markers of Glycemic Control and Neonatal Morbidity in High-Risk Insulin-Resistant Pregnancies.

OBJECTIVE: This study aims to determine whether fructosamine, glycated hemoglobin A1C (HbA1c), or mean fasting glucose levels associate with birth outcomes in diabetic women. STUDY DESIGN: A prospective cohort study of women with singleton, nonanomalous pregnancies and diagnosis of diabetes (gestational or pregestational). Daily average self-measured fasting serum glucose levels were collected, as well as HbA1c and fructosamine levels at delivery. The primary outcome was neonatal composite morbidity, defined as having one or more of the following: respiratory distress syndrome, hyperbilirubinemia, perinatal death, shoulder dystocia, and hypoglycemia requiring treatment. Secondary outcomes included macrosomia (≥ 4,000 g). RESULTS: Among neonates delivered by 301 study-eligible women (97 with gestational and 204 with pregestational diabetes), incidences of composite morbidity (n = 147, 48.8%) and macrosomia (n = 49, 16.3%) were high. Macrosomia occurred more frequently in infants of pregestational than gestational diabetic mothers (22.7 vs. 13.2%, p = 0.04), composite morbidities were not significantly different (52.2 vs. 42.3%, p = 0.14). HbA1c > 8.0 significantly increased risk of morbidity and macrosomia (relative risk, 4.29; 95% confidence interval, 1.62-11.3). CONCLUSIONS: Late third-trimester HbA1c, but not fructosamine or mean blood glucose levels, was associated with increased morbidity in infants of diabetic mothers. Third-trimester HbA1c could be clinically useful for counseling regarding neonatal risks in women with diabetes.

Neonatal morbidity associated with shoulder dystocia maneuvers.

OBJECTIVE: We sought to examine neonatal morbidity associated with different maneuvers used among term patients who experience a shoulder dystocia. STUDY DESIGN: We conducted a retrospective cohort study of all women who experienced a clinically diagnosed shoulder dystocia at term requiring obstetric maneuvers at a single tertiary care hospital from 2005 through 2008. We excluded women with major fetal anomaly, intrauterine death, multiple gestation, and preterm. Women exposed to Rubin maneuver, Wood's screw maneuver, or delivery of the posterior arm were compared to women delivered by McRoberts/suprapubic pressure only, which served as the reference group. The primary outcome was a composite morbidity of neonatal injury (defined as clavicular or humeral fracture or brachial plexus injury) and neonatal depression (defined as Apgar <7 at 5 minutes, arterial cord pH <7.1, continuous positive airway pressure use, intubation, or respiratory distress). Logistic regression was used to adjust for nulliparity and duration of shoulder dystocia, defined as time from delivery of fetal head to delivery of shoulders. RESULTS: Among the 231 women who met inclusion criteria, 135 were delivered by McRoberts/suprapubic pressure alone (57.9%), 83 women were exposed to Rubin maneuver, 53 women were exposed to Wood's screw, and 36 women were exposed to delivery of posterior arm. Individual maneuvers were not associated with composite morbidity, neonatal injury, or neonatal depression after adjusting for nulliparity and duration of shoulder dystocia. CONCLUSION: We found no association between shoulder dystocia maneuvers and neonatal morbidity after adjusting for duration, a surrogate for severity. Our results demonstrate that clinicians should utilize the maneuver most likely to result in successful delivery.

Accuracy of Estimated Blood Loss in Predicting Need for Transfusion after Delivery.

OBJECTIVE: The definition of postpartum hemorrhage (PPH) was developed more than 50 years ago. Since then, the obstetric population has changed dramatically. We sought to determine how well we estimated blood loss (EBL) and find thresholds predicting need for transfusion. STUDY DESIGN: We performed a prospective cohort study from 2010 to 2012, comparing those who needed transfusion postpartum and those who did not. EBL, calculated EBL (cEBL), and change in hematocrit were calculated for patients who did not receive transfusion, and EBL was calculated for those who did receive transfusion, stratified by delivery type. Receiver operator curves were created and optimal thresholds of EBL to predict transfusion were estimated. RESULTS: Among 4,804 patients, transfusion was required for 0.65% of vaginal and 8.7% of cesarean deliveries. Median EBL was higher in women requiring transfusion. A weak correlation was noted between EBL and cEBL for all deliveries. Thresholds of 500 mL blood loss for vaginal delivery and 1,000 mL for cesarean had the best predictive ability for transfusion. CONCLUSION: In this modern obstetric, cohort EBL is weakly correlated with cEBL, suggesting that accuracy of clinical estimates of blood loss is modest. However, EBL predicts need for transfusion, with optimal thresholds of 500 mL for a vaginal delivery and 1,000 mL in a cesarean. This validates the traditional definitions of PPH in our modern population.

Changes in fetal heart tracing characteristics after magnesium exposure.

OBJECTIVE: The aim of this study is to describe the changes in term fetal heart tracings after magnesium exposure. MATERIALS AND METHODS: This was a retrospective cohort study of consecutive women delivering at a gestational age of ≥ 37 weeks with severe preeclampsia, receiving magnesium for seizure prophylaxis. Overall 90 minutes of electronic fetal monitoring (30 before magnesium, 30 during magnesium bolus, and 30 during steady state infusion) was prospectively interpreted by formally trained and blinded research nurses using American Congress of Obstetricians and Gynecologists guidelines. Multivariable analyses were performed using generalized estimating equations, comparing preexposure patterns to bolus, and steady state. RESULTS: Out of the 238 women evaluated, an average decrease of 2.4 beats per minute (p = 0.02) was found after magnesium bolus. This persisted into the steady state (p < 0.01). Minimal/absent variability increased during bolus infusion (odds ratio [OR] 2.40, 95% confidence interval [CI] 1.10-5.62) but corrected by steady state (OR 1.44, 95% CI 0.76-2.80). There were no significant changes in the fetal heart rate (FHR) baseline < 120, tachycardia, or presence of accelerations or decelerations. CONCLUSION: Exposure to magnesium is associated with a transient decrease in variability and a clinically insignificant decrease in FHR baseline without an increased incidence in bradycardia or category change.

Impact of obesity on maternal and neonatal outcomes in insulin-resistant pregnancy.

OBJECTIVE: To determine the impact of obesity on pregnancies complicated by insulin resistance. STUDY DESIGN: Secondary analysis of prospective cohort of women with gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (DM). The exclusion criteria were type 1 DM, multiple gestation, fetal anomalies, unknown prepregnancy, and body mass index (BMI). Primary maternal outcome was a composite of any of the following: severe preeclampsia, eclampsia, third- to fourth-degree laceration, readmission, wound infection, or antepartum hospitalization. Primary neonatal outcome was a composite of any of the following: hypoglycemia, preterm delivery, admission to level 3 nursery, oxygen requirement > 6 hours after birth, shoulder dystocia, 5-minute Apgar ≤3, cord pH < 7.0, and cord base excess < -12 mmol/L. Obese women (BMI ≥30.0 kg/m(2)) were compared with nonobese women (BMI < 30.0 kg/m(2)). RESULTS: Of 356 subjects with DM, 233 (66%) were obese. Obese women were not at further increased risk of the composite maternal outcome (adjusted odds ratio [AOR] = 0.68, 95% confidence interval [CI] = 0.43-1.09), the composite neonatal outcome (AOR = 0.76, 95% CI = 0.48-1.21), or cesarean (58.8 vs. 52.9%, p = 0.28, AOR = 1.47, 95% CI = 0.91-2.39). CONCLUSION: We did not find evidence that obesity worsened pregnancy outcomes in women with GDM and type 2 DM, suggesting that obese women may not require more stringent antepartum treatment strategies.

Correlation of vitamin E, uric acid, and diet composition with histologic features of pediatric NAFLD.

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children in the United States. Although changes in diet are often recommended to improve NAFLD, little is known regarding the influence of diet on histologic features of the disease. SUBJECTS AND METHODS: This was a prospective, cross-sectional registry-based study. Children (n = 149) enrolled in the multicenter nonalcoholic steatohepatitis (NASH) Clinical Research Network had demographic, anthropometric, clinical, laboratory, and histology data obtained, including the Block Brief Food Questionnaire. Subjects were grouped by presence or absence of steatohepatitis and grades of histologic features according to NASH Clinical Research Network criteria. RESULTS: No significant differences were found between children with steatosis compared with steatohepatitis for fraction of energy from fat, carbohydrates, and protein. Sugar-sweetened beverage consumption was low and did not correlate with histologic features, although uric acid, a surrogate marker for fructose intake, was significantly increased in those with definite NASH (P = 0.008). For all groups, vitamin E consumption was insufficient compared with the recommended daily allowance. Median consumption of vitamin E was lower in children with higher grade of steatosis (8.4 vs 6.1 vs 6.9 for grades I, II, and III, respectively, P = 0.05). Those consuming less vitamin C had increased ballooning degeneration (P = 0.05). CONCLUSIONS: Children with NAFLD have a diet that is insufficient in vitamin E and this may contribute to the pathophysiology of NAFLD. In children with NAFLD, reported sugar-sweetened beverage consumption is low; however, uric acid, which may reflect total fructose consumption, was significantly associated with NASH and should be further evaluated.

Impacts of a Workplace-Based Weight-Control Intervention on Objective and Perceived Physical Activity among a Subgroup of Workers.

Physical activity (PA) has many benefits; however, groups facing barriers to health-promoting behaviors are less likely to be physically active. This may be addressed through workplace interventions. The current study employs objective (accelerometry) and perceived (International Physical Activity Questionnaire [IPAQ]) measures of PA among a subset of participants from the "Working for You" study, which tests a multi-level (work group and individual) workplace intervention targeted at workers with low-incomes. Linear mixed and hierarchical logistic regression models are used to determine the intervention's impact on moderate- to vigorous-PA (MVPA) and achieving the PA Guideline for Americans (≥150 minutes MVPA/week), respectively from baseline to 6- and 24-months, relative to a control group. Correlations (Spearman Rho) between perceived and objective PA are assessed. Of the 140 workers (69 control, 71 intervention) in the sub-study, 131 (94%) have valid data at baseline, 88 (63%) at 6-months, and 77 (55%) at 24-months. Changes in MVPA are not significantly different among intervention relative to control participants assessed by accelerometer or IPAQ at 6- or 24-months follow-up. The percent achieving the PA Guideline for Americans does not vary by treatment group by any measure at any time point (e.g., baseline accelerometry: [control: n=37 (57%); intervention: n=35 (53%)]). This study identifies limited agreement (correlation range: 0.04 to 0.42, all p>.05) between perceived and objective measures. Results suggest the intervention did not improve PA among the sub-study participants. Though agreement between objective and perceived MVPA is low, similar conclusions regarding intervention effectiveness are drawn.

Smoking and severity of hepatic fibrosis in nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Although many predictors of disease severity of nonalcoholic fatty liver disease (NAFLD) have been proposed, studies of the potential effects of specific environmental exposures on human NAFLD are lacking. Smoking increases insulin resistance. Given the pathophysiological role of insulin resistance in NAFLD, characterization of the influence of smoking in NAFLD is warranted. The aim of this paper was to study the potential association between cigarette smoking and advanced fibrosis in NAFLD. METHODS: All adults enrolled in the NASH CRN studies, between October 2004 and February 2008, who had liver biopsies, were included (n=1091). Advanced fibrosis was defined as stages 3-4. Analyses were performed. RESULTS: Significant bivariate associations were demonstrated between advanced fibrosis and age, gender, ethnicity, diabetes, and smoking history. History of smoking ≥ 10 pack-years was more common (p <0.0001) among patients with advanced fibrosis. Multivariate analysis demonstrated an association between smoking history of ≥ 10 pack-years and advanced fibrosis (OR=1.63). Among non-diabetics, history of ≥ 10 pack-years was associated with an OR of 2.48 for advanced fibrosis. High frequencies of advanced fibrosis were observed among diabetics (with or without ≥ 10 pack-years history) and non-diabetics with ≥ 10 pack-years history as compared to non-diabetics without significant smoking history. CONCLUSIONS: Smoking history was associated with advanced liver fibrosis in this large multicenter cohort of NAFLD patients. The results indicate that smoking may enhance the progression of NAFLD partly through its effect on insulin resistance. Our results are consistent with recent animal studies suggesting that cigarette smoke may aggravate fatty liver. To our knowledge, this is the first study to show that cigarette smoking is associated with increased fibrosis severity in human NALFD, suggesting it may accelerate disease progression. These results may support a formal recommendation of smoking cessation in patients with NAFLD.

Characteristics of patients with chronic unexplained nausea and vomiting and normal gastric emptying.

BACKGROUND & AIMS: Chronic nausea and vomiting with normal gastric emptying is a poorly understood syndrome; we analyzed its characteristics. METHODS: We collected and analyzed data from 425 patients with chronic nausea and vomiting, enrolled at 6 centers by the Gastroparesis Clinical Research Consortium in the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Registry. RESULTS: Among the patients, 319 (75%) had delayed emptying, defined by the results of a standardized, low-fat meal, and 106 had normal gastric emptying. Patients with or without delayed emptying did not differ in age, sex, or race, although those with normal gastric emptying were less likely to be diabetic. Symptom severity indexes were similar between groups for nausea, retching, vomiting, stomach fullness, inability to complete a meal, feeling excessively full after meals, loss of appetite, bloating, and visibly larger stomach. There were no differences in health care utilization, quality of life indexes, depression, or trait anxiety scores. However, state anxiety scores were slightly higher among patients with delayed gastric emptying. Total gastroparesis cardinal symptom index scores were not correlated with gastric retention after 2 or 4 hours in either group. Patients with the syndrome were not adequately captured by the stand-alone criteria for the Rome III diagnoses of chronic idiopathic nausea and functional vomiting. With rare exceptions, the diagnosis remained stable after a 48-week follow-up period. CONCLUSIONS: Patients with nausea and vomiting with normal gastric emptying represent a significant medical problem and are, for the most part, indistinguishable from those with gastroparesis. This syndrome is not categorized in the medical literature--it might be a separate clinical entity.

Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease.

UNLABELLED: The rising incidence of obesity and diabetes coincides with a marked increase in fructose consumption. Fructose consumption is higher in individuals with nonalcoholic fatty liver disease (NAFLD) than in age-matched and body mass index (BMI)-matched controls. Because fructose elicits metabolic perturbations that may be hepatotoxic, we investigated the relationship between fructose consumption and disease severity in NAFLD. We studied 427 adults enrolled in the NASH Clinical Research Network for whom Block food questionnaire data were collected within 3 months of a liver biopsy. Fructose consumption was estimated based on reporting (frequency x amount) of Kool-aid, fruit juices, and nondietary soda intake, expressed as servings per week, and classified into none, minimum to moderate (<7 servings/week), and daily (> or =7 servings/week). The association of fructose intake with metabolic and histological features of NAFLD was analyzed using multiple linear and ordinal logistic regression analyses with and without controlling for other confounding factors. Increased fructose consumption was univariately associated with decreased age (P < 0.0001), male sex (P < 0.0001), hypertriglyceridemia (P < 0.04), low high-density lipoprotein (HDL) cholesterol (<0.0001), decreased serum glucose (P < 0.001), increased calorie intake (P < 0.0001), and hyperuricemia (P < 0.0001). After controlling for age, sex, BMI, and total calorie intake, daily fructose consumption was associated with lower steatosis grade and higher fibrosis stage (P < 0.05 for each). In older adults (age > or = 48 years), daily fructose consumption was associated with increased hepatic inflammation (P < 0.05) and hepatocyte ballooning (P = 0.05). CONCLUSION: In patients with NAFLD, daily fructose ingestion is associated with reduced hepatic steatosis but increased fibrosis. These results identify a readily modifiable environmental risk factor that may ameliorate disease progression in patients with NAFLD.

Flow-down of safety from general contractors to subcontractors working on commercial construction projects.

Small and medium construction firms have high injury rates but lack resources to establish and maintain effective safety programs. General contractors with exemplary safety programs may serve as intermediaries to support development of smaller firm's safety programs. The purpose of this study was to examine the flow-down influence of general contractors' safety programs on the safety climate and safety behaviors among workers employed by small and medium sized subcontractors. This study collected workers' perception of safety climate and safety behaviors while working on projects with general contractors with exemplary safety programs and other general contractors. We also documented the safety program policies and practices of subcontractors, and recorded the changes in safety policies required from general contractors with exemplary programs. We examined differences in safety program changes between small and medium sized subcontractors. Results showed workers perceived general contractors with exemplary safety programs had stronger safety climates than other general contractors. Smaller subcontractors had less robust safety programs with fewer safety elements than larger subcontractors, and therefore, many of the smaller subcontractors had to adopt more safety policies and practices to work for general contractors than large subcontractors. These findings suggest that general contractors with robust safety programs can serve as intermediaries and influence the development of the safety programs of small sized firms. Future work will need to determine if smaller firms eventually adopt safety policies and practices as part of their permanent safety program.

Context-Responsive Anticoagulation Reduces Complications in Pediatric Extracorporeal Membrane Oxygenation.

Purpose: We sought to determine the impact of a comprehensive, context-responsive anticoagulation and transfusion guideline on bleeding and thrombotic complication rates and blood product utilization during extracorporeal membrane oxygenation (ECMO). Design: Single-center, observational pre- and post-implementation cohort study. Setting: Academic pediatric hospital. Patients: Patients in the PICU, CICU, and NICU receiving ECMO support. Interventions: Program-wide implementation of a context-responsive anticoagulation and transfusion guideline. Measurements: Pre-implementation subjects consisted of all patients receiving ECMO between January 1 and December 31, 2012, and underwent retrospective chart review. Post-implementation subjects consisted of all ECMO patients between September 1, 2013, and December 31, 2014, and underwent prospective data collection. Data collection included standard demographic and admission data, ECMO technical specifications, non-ECMO therapies, coagulation parameters, and blood product administration. A novel grading scale was used to define hemorrhagic complications (major, intermediate, and minor) and major thromboembolic complications. Main Results: Seventy-six ECMO patients were identified: 31 during the pre-implementation period and 45 in the post-implementation period. The overall observed mortality was 33% with no difference between groups. Compared to pre-implementation, the post-implementation group experienced fewer major hemorrhagic and major thrombotic complications and less severe hemorrhagic complications and received less RBC transfusion volume per kg. Conclusions: Use of a context-responsive anticoagulation and transfusion guideline was associated with a reduction in hemorrhagic and thrombotic complications and reduced RBC transfusion requirements. Further evaluation of guideline content, compliance, performance, and sustainability is needed.

The association between subcontractor safety management programs and worker perceived safety climate in commercial construction projects.

PROBLEM: Safety management programs (SMPs) are designed to mitigate risk of workplace injuries and create a safe working climate. The purpose of this project was to evaluate the relationship between contractors' SMPs and workers' perceived safety climate and safety behaviors among small and medium-sized construction subcontractors. METHODS: Subcontractor SMP scores on 18 organizational and project-level safety items were coded from subcontractors' written safety programs and interviews. Workers completed surveys to report perceptions of their contractor's safety climate and the safety behaviors of coworkers, crews, and themselves. The associations between SMP scores and safety climate and behavior scales were examined using Spearman correlation and hierarchical linear regression models (HLM). RESULTS: Among 78 subcontractors working on large commercial construction projects, we found striking differences in SMP scores between small, medium, and large subcontractors (p < 0.001), related to a number of specific safety management practices. We observed only weak relationships between SMP scales and safety climate scores reported by 746 workers of these subcontractors (ß = 0.09, p = 0.04 by HLM). We saw no differences in worker reported safety climate and safety behaviors by contractor size. DISCUSSION: SMP only weakly predicted safety climate scales of subcontractors, yet there were large differences in the quality and content of SMPs by size of employers. SUMMARY: Future work should determine the best way to measure safety performance of construction companies and determine the factors that can lead to improved safety performance of construction firms. Practical applications: Our simple assessment of common elements of safety management programs used document review and interviews with knowledgeable representatives. These methods identified specific safety management practices that differed between large and small employers. In order to improve construction safety, it is important to understand how best to measure safety performance in construction companies to gain knowledge for creating safer work environments.