METHODS AND FINDINGS: Genetic instruments to proxy 12 risk factors were constructed by identifying single nucleotide polymorphisms (SNPs) that were robustly (P < 5 × 10-8) and independently associated with each respective risk factor in previously reported genome-wide association studies. These risk factors included genetic liability to 3 factors (endometriosis, polycystic ovary syndrome, type 2 diabetes) scaled to reflect a 50% higher odds liability to disease. We obtained summary statistics for the association of these SNPs with risk of overall and histotype-specific invasive epithelial ovarian cancer (22,406 cases; 40,941 controls) and low malignant potential tumours (3,103 cases; 40,941 controls) from the Ovarian Cancer Association Consortium (OCAC). The OCAC dataset comprises 63 genotyping project/case-control sets with participants of European ancestry recruited from 14 countries (US, Australia, Belarus, Germany, Belgium, Denmark, Finland, Norway, Canada, Poland, UK, Spain, Netherlands, and Sweden). SNPs were combined into multi-allelic inverse-variance-weighted fixed or random effects models to generate effect estimates and 95% confidence intervals (CIs). Three complementary sensitivity analyses were performed to examine violations of MR assumptions: MR-Egger regression and weighted median and mode estimators. A Bonferroni-corrected P value threshold was used to establish strong evidence (P < 0.0042) and suggestive evidence (0.0042 < P < 0.05) for associations. In MR analyses, there was strong or suggestive evidence that 2 of the 12 risk factors were associated with invasive epithelial ovarian cancer and 8 of the 12 were associated with 1 or more invasive epithelial ovarian cancer histotypes. There was strong evidence that genetic liability to endometriosis was associated with an increased risk of invasive epithelial ovarian cancer (odds ratio [OR] per 50% higher odds liability: 1.10, 95% CI 1.06-1.15; P = 6.94 × 10-7) and suggestive evidence that lifetime smoking exposure was associated with an increased risk of invasive epithelial ovarian cancer (OR per unit increase in smoking score: 1.36, 95% CI 1.04-1.78; P = 0.02). In analyses examining histotypes and low malignant potential tumours, the strongest associations found were between height and clear cell carcinoma (OR per SD increase: 1.36, 95% CI 1.15-1.61; P = 0.0003); age at natural menopause and endometrioid carcinoma (OR per year later onset: 1.09, 95% CI 1.02-1.16; P = 0.007); and genetic liability to polycystic ovary syndrome and endometrioid carcinoma (OR per 50% higher odds liability: 0.89, 95% CI 0.82-0.96; P = 0.002). There was little evidence for an association of genetic liability to type 2 diabetes, parity, or circulating levels of 25-hydroxyvitamin D and sex hormone binding globulin with ovarian cancer or its subtypes. The primary limitations of this analysis include the modest statistical power for analyses of risk factors in relation to some less common ovarian cancer histotypes (low grade serous, mucinous, and clear cell carcinomas), the inability to directly examine the association of some ovarian cancer risk factors that did not have robust genetic variants available to serve as proxies (e.g., oral contraceptive use, hormone replacement therapy), and the assumption of linear relationships between risk factors and ovarian cancer risk.
CONCLUSIONS: Our comprehensive examination of possible aetiological drivers of ovarian carcinogenesis using germline genetic variants to proxy risk factors supports a role for few of these factors in invasive epithelial ovarian cancer overall and suggests distinct aetiologies across histotypes. The identification of novel risk factors remains an important priority for the prevention of epithelial ovarian cancer.
METHODS: A total of 497 patients with type 2 diabetes mellitus were recruited from public hospitals in the state of Selangor through convenience sampling. Construct validity was evaluated through confirmatory factor analysis. Internal consistency of the instrument was tested by Cronbach α. Criterion validity and discriminant validity were also used.
RESULTS: The PAID instrument consisted of 3 factors: social support problem, food-related problem, and emotional distress problem. The Cronbach α values of the 3 factors showed adequate internal consistency with α values greater than 0.90. The present confirmatory factor analysis model achieved a good fit with a comparative fit index value of 0.923. Satisfactory criterion validity was also demonstrated because there existed positive significant association between glycated hemoglobin A1c and diabetes duration.
CONCLUSIONS: The PAID questionnaire in Malaysia was found to be a reliable and valid instrument exhibiting good psychometric properties.
OBJECTIVES: The aim of this study was to evaluate the adequacy of prophylactic dosing of enoxaparin in patients with severe obesity by performing an antifactor Xa (AFXa) assay.
SETTING: An academic medical center METHODS: In this observational study, all bariatric surgery cases at an academic center between December 2016 and April 2017 who empirically received prophylactic enoxaparin (adjusted by body mass index [BMI] threshold of 50 kg/m2) were studied. The AFXa was measured 3-5 hours after the second dose of enoxaparin.
RESULTS: A total of 105 patients were included; 85% were female with a median age of 47 years. In total, 16 patients (15.2%) had AFXa levels outside the prophylactic range: 4 (3.8%) cases were in the subprophylactic and 12 (11.4%) cases were in the supraprophylactic range. Seventy patients had a BMI <50 kg/m2 and empirically received enoxaparin 40 mg every 12 hours; AFXa was subprophylactic in 4 (5.7%) and supraprophylactic in 6 (8.6%) of these patients. Of the 35 patients with a BMI ≥50 who empirically received enoxaparin 60 mg q12h, no AFXa was subprophylactic and 6 (17.1%) were supraprophylactic. Five patients (4.8%) had major bleeding complications. One patient developed pulmonary embolism on postoperative day 35.
CONCLUSION: BMI-based thromboprophylactic dosing of enoxaparin after bariatric surgery could be suboptimal in 15% of patients with obesity. Overdosing of prophylactic enoxaparin can occur more commonly than underdosing. AFXa testing can be a practical way to measure adequacy of pharmacologic thromboprophylaxis, especially in patients who are at higher risk for venous thromboembolism or bleeding.
METHODS: We did an individual patient data meta-analysis, in which we searched PubMed and Web of Science for studies published from database inception until April 30, 2019. Studies reporting original biopsy-controlled data of CAP for non-invasive grading of steatosis were eligible. Probe recommendation was based on automated selection, manual assessment of skin-to-liver-capsule distance, and a body-mass index (BMI) criterion. Receiver operating characteristic methods and mixed models were used to assess diagnostic properties and covariates. Patients with non-alcoholic fatty liver disease (NAFLD) were analysed separately because they are the predominant patient group when using the XL probe. This study is registered with PROSPERO, CRD42018099284.
FINDINGS: 16 studies reported histology-controlled CAP including the XL probe, and individual data from 13 papers and 2346 patients were included. Patients with a mean age of 46·5 years (SD 14·5) were recruited from 20 centres in nine countries. 2283 patients had data for BMI; 673 (29%) were normal weight (BMI <25 kg/m2), 530 (23%) were overweight (BMI ≥25 to <30 kg/m2), and 1080 (47%) were obese (BMI ≥30 kg/m2). 1277 (54%) patients had NAFLD, 474 (20%) had viral hepatitis, 285 (12%) had alcohol-associated liver disease, and 310 (13%) had other liver disease aetiologies. The XL probe was recommended in 1050 patients, 930 (89%) of whom had NAFLD; among the patients with NAFLD, the areas under the curve were 0·819 (95% CI 0·769-0·869) for S0 versus S1 to S3 and 0·754 (0·720-0·787) for S0 to S1 versus S2 to S3. CAP values were independently affected by aetiology, diabetes, BMI, aspartate aminotransferase, and sex. Optimal cutoffs differed substantially across aetiologies. Risk of bias according to QUADAS-2 was low.
INTERPRETATION: CAP cutoffs varied according to cause, and can effectively recognise significant steatosis in patients with viral hepatitis. CAP cannot grade steatosis in patients with NAFLD adequately, but its value in a NAFLD screening setting needs to be studied, ideally with methods beyond the traditional histological reference standard.
FUNDING: The German Federal Ministry of Education and Research and Echosens.
METHODS: A case-control study comprising 134 breast cancer patients and 265 cancer-free controls were conducted. Dietary intakes were assessed using a validated food frequency questionnaire (FFQ), from which the HEI-2015 score was calculated. Logistic regression was used to derive the odds ratios (ORs) for measuring the association between HEI-2015 scores and breast cancer risk.
RESULTS: Subjects in the top quartile of HEI-2015 had a 46% lower chance of breast cancer compared with subjects in the bottom quartile (OR 0.54; 95% CI 0.30, 0.98). After adjustment for potential confounders such as age, age at menarche, oral contraceptive drug use, menopausal status, marital status, body mass index, smoking and education level, the association between HEI-2015 score and a lower risk of breast cancer was enhanced (OR 0.32; 95% CI 0.16, 0.65).
CONCLUSION: We successfully demonstrated that a higher HEI-2015 score was associated with a reduced breast cancer risk.