A prospective cohort study of obesity and risk of oesophageal and gastric adenocarcinoma in the NIH-AARP Diet and Health Study

Objective: The incidence of oesophageal adenocarcinoma (EAC) has increased rapidly over the past 40 years and accumulating evidence suggests that obesity, as measured by body mass index (BMI), is a major risk factor. It remains unclear whether abdominal obesity is associated with EAC and gastric adenocarcinoma.

Design: Cox proportional hazards regression was used to examine associations between overall and abdominal obesity with EAC and gastric adenocarcinoma among 218 854 participants in the prospective NIHeAARP cohort.

Results: 253 incident EAC, 191 gastric cardia adenocarcinomas and 125 gastric non-cardia adenocarcinomas accrued to the cohort. Overall obesity (BMI) was positively associated with EAC and gastric
cardia adenocarcinoma risk (highest ($35 kg/m2) vs referent (18.5e<25 kg/m2); HR 2.11, 95% CI 1.09 to 4.09 and HR 3.67, 95% CI 2.00 to 6.71, respectively). Waist circumference was also positively associated with EAC and gastric cardia adenocarcinoma risk (highest vs referent; HR 2.01, 95% CI 1.35 to 3.00 and HR 2.22, 95% CI 1.43 to 3.47, respectively), whereas waist-to-hip ratio (WHR) was positively associated with EAC risk only (highest vs referent; HR 1.81, 95% CI 1.24 to 2.64) and persisted in patients with normal BMI (18.5e<25 kg/m2). Mutual adjustment of WHR and BMI attenuated
both, but did not eliminate the positive associations for either with risk of EAC. In contrast, the majority of the anthropometric variables were not associated with adenocarcinomas of the gastric non-cardia.

Conclusion Overall obesity was associated with a higher risk of EAC and gastric cardia adenocarcinoma, whereas abdominal obesity was found to be associated with increased EAC risk; even in people with normal BMI

No major schizophrenia locus detected on chromosome 1q in a large multicenter sample

Reports of substantial evidence for genetic linkage of schizophrenia to chromosome 1q were evaluated by genotyping 16 DNA markers across 107 centimorgans of this chromosome in a multicenter sample of 779 informative schizophrenia pedigrees. No significant evidence was observed for such linkage, nor for heterogeneity in allele sharing among the eight individual samples. Separate analyses of European-origin families, recessive models of inheritance, and families with larger numbers of affected cases also failed to produce significant evidence for linkage. If schizophrenia susceptibility genes are present on chromosome 1q, their population-wide genetic effects are likely to be small.

The Role of Growth Trajectories in Classifying Fetal Growth Restriction

OBJECTIVE: To examine the validity of a growth trajectory method to discriminate between pathologically and constitutionally undergrown fetuses using repeated measures of estimated fetal weight.

METHODS: In a prospective, observational, multicenter study in Ireland, 1,116 women with a growth-restricted fetus diagnosed participated with the objective of evaluating ultrasound findings as predictors of pediatric morbidity and mortality. Fetal growth trajectories were based on estimated fetal weight.

RESULTS: Between 22 weeks of gestation and term, two fetal growth trajectories were identified: normal (96.7%) and pathologic (3.3%). Compared with the normal trajectory, the pathologic trajectory was associated with an increased risk for preeclampsia (odds ratio [OR] 8.1, 95% confidence interval [CI] 2.6–23.4), increased umbilical artery resistance at 30 weeks of gestation (OR 12.6, 95% CI 4.6–34.1) or 34 weeks of gestation (OR 28.0, 95% CI 8.9–87.7), reduced middle cerebral artery resistance at 30 weeks of gestation (OR 0.33, 95% CI 0.12–0.96) or 34 weeks of gestation (OR 0.14, 95% CI 0.03–0.74), lower gestational age at delivery (mean 32.02 weeks of gestation compared with 38.02 weeks of gestation; P<.001), and higher perinatal complications (OR 21.5, 95% CI 10.5–44.2). In addition, 89.2% of newborns with pathologic fetal growth were admitted to neonatal intensive care units compared with 25.9% of those with normal growth.

CONCLUSIONS: Fetal growth trajectory analysis reliably differentiated fetuses with a pathologic growth pattern among a group of women with growth-restricted fetuses. With further development, this approach could provide clarity to how we define, identify, and ultimately manage pathologic fetal growth.

LEVEL OF EVIDENCE: II

Dietary Carbohydrate Intake, Glycemic Index, and Glycemic Load and Endometrial Cancer Risk: A Prospective Cohort Study

Endometrial cancer risk has been directly associated with glycemic load. However, few studies have investigated this link, and the etiological role of specific dietary carbohydrate components remains unclear. Our aim was to investigate associations of carbohydrate intake, glycemic index, and glycemic load with endometrial cancer risk in the US Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Recruitment took place in 1993-2001. Over a median of 9.0 years of follow-up through 2009, 386 women developed endometrial cancer among 36,115 considered in the analysis. Dietary intakes were assessed using a 124-item diet history questionnaire. Cox proportional hazards models were applied to calculate hazard ratios and 95% confidence intervals. Significant inverse associations were detected between endometrial cancer risk and total available carbohydrate intake (hazard ratio (HR) = 0.66, 95% confidence interval (CI): 0.49, 0.90), total sugars intake (HR = 0.71, 95% CI: 0.52, 0.96), and glycemic load (HR = 0.63, 95% CI: 0.46, 0.84) when women in the highest quartile of intake were compared with those in the lowest. These inverse associations were strongest among overweight and obese women. No associations with endometrial cancer risk were observed for glycemic index or dietary fiber. Our findings contrast with previous evidence and suggest that high carbohydrate intakes and glycemic loads are protective against endometrial cancer development. Further clarification of these associations is warranted.

Prospective investigation of body mass index, colorectal adenoma, and colorectal cancer in the prostate, lung, colorectal, and ovarian cancer screening trial

Obesity has consistently been linked to an increased risk of colorectal cancer, particularly among men. Whether body mass index (BMI) differentially influences the risk across the stages of colorectal cancer development remains unclear. We evaluated the associations of BMI with colorectal adenoma incidence, adenoma recurrence, and cancer in the context of a large screening trial, in which cases and controls had an equal chance for disease detection.

Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial: study protocol for a randomized controlled trial

Background: Acute lung injury (ALI) is a common devastating clinical syndrome characterized by life-threatening respiratory failure requiring mechanical ventilation and multiple organ failure. There are in vitro, animal studies and pre-clinical data suggesting that statins may be beneficial in ALI. The Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial is a multicenter, prospective, randomized, allocation concealed, double-blind, placebo-controlled clinical trial which aims to test the hypothesis that treatment with simvastatin will improve clinical outcomes in patients with ALI.

Methods/Design: Patients fulfilling the American-European Consensus Conference Definition of ALI will be randomized in a 1: 1 ratio to receive enteral simvastatin 80 mg or placebo once daily for a maximum of 28 days. Allocation to randomized groups will be stratified with respect to hospital of recruitment and vasopressor requirement. Data will be recorded by participating ICUs until hospital discharge, and surviving patients will be followed up by post at 3, 6 and 12 months post randomization. The primary outcome is number of ventilator-free days to day 28. Secondary outcomes are: change in oxygenation index and sequential organ failure assessment score up to day 28, number of non pulmonary organ failure free days to day 28, critical care unit mortality; hospital mortality; 28 day post randomization mortality and 12 month post randomization mortality; health related quality of life at discharge, 3, 6 and 12 months post randomization; length of critical care unit and hospital stay; health service use up to 12 months post-randomization; and safety. A total of 540 patients will be recruited from approximately 35 ICUs in the UK and Ireland. An economic evaluation will be conducted alongside the trial. Plasma and urine samples will be taken up to day 28 to investigate potential mechanisms by which simvastatin might act to improve clinical outcomes.

Obesity and occupational injury:a prospective cohort study of 69,515 public sector employees

Obesity and overweight are suggested to increase the risk of occupational injury but longitudinal evidence to confirm this is rare. We sought to evaluate obesity and overweight as risk factors for occupational injuries.

Genetic Markers Enhance Coronary Risk Prediction in Men: The MORGAM Prospective Cohorts

Background: More accurate coronary heart disease (CHD) prediction, specifically in middle-aged men, is needed to reduce the burden of disease more effectively. We hypothesised that a multilocus genetic risk score could refine CHD prediction beyond classic risk scores and obtain more precise risk estimates using a prospective cohort design.

Methods: Using data from nine prospective European cohorts, including 26,221 men, we selected in a case-cohort setting 4,818 healthy men at baseline, and used Cox proportional hazards models to examine associations between CHD and risk scores based on genetic variants representing 13 genomic regions. Over follow-up (range: 5-18 years), 1,736 incident CHD events occurred. Genetic risk scores were validated in men with at least 10 years of follow-up (632 cases, 1361 non-cases). Genetic risk score 1 (GRS1) combined 11 SNPs and two haplotypes, with effect estimates from previous genome-wide association studies. GRS2 combined 11 SNPs plus 4 SNPs from the haplotypes with coefficients estimated from these prospective cohorts using 10-fold cross-validation. Scores were added to a model adjusted for classic risk factors comprising the Framingham risk score and 10-year risks were derived.

Results: Both scores improved net reclassification (NRI) over the Framingham score (7.5%, p = 0.017 for GRS1, 6.5%, p = 0.044 for GRS2) but GRS2 also improved discrimination (c-index improvement 1.11%, p = 0.048). Subgroup analysis on men aged 50-59 (436 cases, 603 non-cases) improved net reclassification for GRS1 (13.8%) and GRS2 (12.5%). Net reclassification improvement remained significant for both scores when family history of CHD was added to the baseline model for this male subgroup improving prediction of early onset CHD events.

Conclusions: Genetic risk scores add precision to risk estimates for CHD and improve prediction beyond classic risk factors, particularly for middle aged men.

Nilotinib 300mg BID as frontline treatment of CML:Prospective analysis of the Xpert BCR-ABL Monitor system and significance of 3-month molecular response

Sixty patients with early chronic phase CML (ECPCML) received Nilotinib on a phase II study which included a comparison of the Xpert BCR-ABL Monitor™ PCR system with standardized (IS) BCR-ABL1 real-time quantitative PCR (RQ-PCR). 88% patients achieved MMR with 45% achieving MR4.5. At 3 months BCR-ABL1/ABL1 IS >1% and

The prospective effects of workplace violence on physicians' job satisfaction and turnover intentions: the buffering effect of job control

Background: Health care professionals, including physicians, are at high risk of encountering workplace violence. At the same time physician turnover is an increasing problem that threatens the functioning of the health care sector worldwide. The present study examined the prospective associations of work-related physical violence and bullying with physicians’ turnover intentions and job satisfaction. In addition, we tested whether job control would modify these associations.

Methods: The present study was a 4-year longitudinal survey study, with data gathered in 2006 and 2010.The present sample included 1515 (61% women) Finnish physicians aged 25–63 years at baseline. Analyses of covariance (ANCOVA) were conducted while adjusting for gender, age, baseline levels, specialisation status, and employment sector.

Results: The results of covariance analyses showed that physical violence led to increased physician turnover intentions and that both bullying and physical violence led to reduced physician job satisfaction even after adjustments. We also found that opportunities for job control were able to alleviate the increase in turnover intentions resulting from bullying.

Conclusions: Our results suggest that workplace violence is an extensive problem in the health care sector and may lead to increased turnover and job dissatisfaction. Thus, health care organisations should approach this problem through different means, for example, by giving health care employees more opportunities to control their own work.

Physical activity, sedentary behaviour and fetal macrosomia in uncomplicated pregnancies: A prospective cohort study

Objective: to explore maternal energy balance, incorporating free living physical activity and sedentary behaviour, in uncomplicated pregnancies at risk of macrosomia.

Methods: a parallel-group cross-sectional analysis was conducted in healthy pregnant women predicted to deliver infants weighing Z4000 g (study group) or o4000 g (control group). Women were recruited in a 1:1 ratio from antenatal clinics in Northern Ireland. Women wore a SenseWears Body Media Pro3 physical activity armband and completed a food diary for four consecutive days in the third trimester. Physical activity was measured in Metabolic Equivalent of Tasks (METs) where 1 MET¼1 kcal per kilogram of body weight per hour. Analysis of covariance (ANCOVA) was employed using the General Linear Model to adjust for potential confounders.

Findings: of the 112 women recruited, 100 complete datasets were available for analysis. There was no significant difference in energy balance between the two groups. Intensity of free living physical activity (average METs) of women predicted to deliver macrosomic infants (n¼50) was significantly lower than that of women in the control group (n¼50) (1.3 (0.2) METs (mean, standard deviation) versus 1.2 (0.2) METs; difference in means 0.1 METs (95% confidence interval: 0.19, 0.01); p¼0.021). Women predicted to deliver macrosomic infants also spent significantly more time in sedentary behaviour (r1 MET) than the control group (16.1 (2.8) hours versus 13.8 (4.3) hours; 2.0 hours (0.3, 3.7), p¼0.020).

Key conclusions and implications for practice: although there was no association between predicted fetal macrosomia and energy balance, those women predicted to deliver a macrosomic infant exhibited increased sedentary behaviour and reduced physical activity in the third trimester of pregnancy. Professionals caring for women during pregnancy have an important role in promoting and supporting more active lifestyles amongst women who are predicted to deliver a macrosomic infant given the known associated risks.

Is a single item stress measure independently associated with subsequent severe injury: a prospective cohort study of 16,385 forest industry employees

Background: A previous review showed that high stress increases the risk of occupational injury by three- to five-fold. However, most of the prior studies have relied on short follow-ups. In this prospective cohort study we examined the effect of stress on recorded hospitalised injuries in an 8-year follow-up.
Methods: A total of 16,385 employees of a Finnish forest company responded to the questionnaire. Perceived stress was measured with a validated single-item measure, and analysed in relation recorded hospitalised injuries from 1986 to 2008. We used Cox proportional hazard regression models to examine the prospective associations between work stress, injuries and confounding factors.
Results: Highly stressed participants were approximately 40% more likely to be hospitalised due to injury over the follow-up period than participants with low stress. This association remained significant after adjustment for age, gender, marital status, occupational status, educational level, and physical work environment.
Conclusions: High stress is associated with an increased risk of severe injury.

Prospective clinical audit of chloral hydrate administration practices in a neonatal unit

Aim: Chloral hydrate is generally considered a safe and effective single dosing procedural sedative for neonates in the clinical setting. However, its safety profile as a repetitive dosing maintenance sedative is largely unknown. This study aimed to document current administration practices of chloral hydrate in the Neonatal Unit, Royal Children's Hospital, Melbourne, Australia, over a 6-month period.

Methods: Patients who had been prescribed chloral hydrate during the specified audit period were recruited into the study and prospectively followed for a period of 28 days, or until they were discharged from the unit. Demographic data were collected on recruitment, and daily documentation of chloral hydrate administration was recorded.

Results: A total of 238 doses of chloral hydrate were administered to a cohort of 32 patients during the study period. The majority of the audited doses (84%) were ordered as repeating doses. Doses were more likely to be given at night than during the day, and the median dosage for repetitive dosing was found to be above the study site's recommended dosing range. Pre-dose and/or post-dose assessment of distress/agitation accompanied dosage approximately half of the time. The audit did not reveal any recognisable pattern of sedation maintenance or weaning process for patients who received multiple doses.

Conclusions: Health-care professionals caring for hospitalised infants should be made aware of the potential risks of chloral hydrate as a repetitive dosing sedative, and of the importance of systematically evaluating the appropriateness and effectiveness of utilising such pharmacological intervention for managing and treating distress.

Plasma total homocysteine and carotid intima-media thickness in type 1 diabetes: A prospective study

Objective: Plasma total homocysteine (tHcy) has been positively associated with carotid intima-media thickness (IMT) in non-diabetic populations and in a few cross-sectional studies of diabetic patients. We investigated cross-sectional and prospective associations of a single measure of tHcy with common and internal carotid IMT over a 6-year period in type 1 diabetes. Research design and methods: tHcy levels were measured once, in plasma obtained in 1997–1999 from patients (n = 599) in the Epidemiology of Diabetes Interventions and Complications (EDIC) study, the observational follow-up of the Diabetes Control and Complications Trial (DCCT). Common and internal carotid IMT were determined twice, in EDIC “Year 6” (1998–2000) and “Year 12” (2004–2006), using B-mode ultra-sonography. Results: After adjustment, plasma tHcy [median (interquartile range): 6.2 (5.1, 7.5) μmol/L] was significantly correlated with age, diastolic blood pressure, renal dysfunction, and smoking (all p < 0.05). In an unadjusted model only, increasing quartiles of tHcy correlated with common and internal carotid IMT, again at both EDIC time-points (p < 0.01). However, multivariate logistic regression revealed no significant associations between increasing quartiles of tHcy and the 6-year change in common and internal carotid IMT (highest vs. lowest quintile) when adjusted for conventional risk factors. Conclusions: In a type 1 diabetes cohort from the EDIC study, plasma tHcy measured in samples drawn in 1997–1999 was associated with measures of common and internal carotid IMT measured both one and seven years later, but not with IMT progression between the two time-points. The data do not support routine measurement of tHcy in people with Type 1 diabetes.