Opioid Treatment Is Associated with Recurrent Healthcare Visits, Increased Side Effects, and Pain

Introduction: Pain is a major driver of visits to the emergency department (ED). Clinicians must consider not only the efficacy of treatment options but also subsequent healthcare utilization and patient-centered outcomes such as side effects from prescribed medications. Our goal in this study was to determine whether there was an association between acute pain treatment regimen (opioids, intranasal non-steroidal anti-inflammatory drugs [NSAIDs], or both) and unscheduled healthcare visits following ED discharge. Methods: This study was a secondary analysis of the Acute Management of Pain from the Emergency Department (AMPED) prospective, observational cohort study. We used Cox proportional hazards analysis to assess the relationship between treatment regimen and time to first unscheduled healthcare visit. Repeated measures logistic regression analyses were used to determine the relationship between treatment regimen and any unscheduled visits, and to evaluate whether this relationship was mediated by pain severity and/or medication side effects. Results: Of 831 total enrolled participants, 141 (16.9%) experienced an unplanned healthcare visit within five days of ED discharge. A majority of these visits happened one day after the ED visit. Those who were treated with intranasal NSAIDs only were less likely to have an unscheduled healthcare visit compared to those who received opioids only, with an adjusted odds ratio (AOR) of 0.63. The higher odds of unscheduled healthcare visits with opioids were mediated by both the presence of side effects and higher pain levels, with AORs of 2.24 and 1.33, respectively. Conclusion: Opioid treatment for acute pain is associated with increased unscheduled healthcare visits compared to those treated with intranasal ketorolac. This difference can be explained by higher levels of ongoing pain and greater medication side effects

Validation of a sonographic checklist for the detection of histologic placenta accreta spectrum

Background: To standardize research terminology and reduce unanticipated placenta accreta spectrum (PAS), the European Working Group for Abnormally Invasive Placenta (EW-AIP) developed a consensus checklist for reporting PAS suspected on antenatal ultrasound. The diagnostic accuracy of the EW-AIP checklist has not been assessed. Objective: To test the performance of the EW-AIP sonographic checklist in predicting histologic PAS. Study Design: This is a multi-site, blinded, retrospective review of transabdominal ultrasound studies performed between 26-32 weeks gestation for subjects with histologic PAS between 2016-2020. We matched a 1:1 control cohort of subjects without histologic PAS. To reduce reader bias, we matched the control cohort for known risk factors including previa, number of prior cesarean deliveries, prior dilation and curettage (D&C), in vitro fertilization (IVF), and clinical factors affecting image quality including multiple gestation, body mass index (BMI) and gestational age at the ultrasound. Nine sonologists from 5 referral centers, blinded to the histologic outcomes, interpreted the randomized ultrasound studies using the EW-AIP checklist. The primary outcome was the sensitivity and specificity of the checklist to predict PAS. Two separate sensitivity analyses were performed: 1) we excluded subjects with mild disease (i.e. only assessed subjects with histologic increta and percreta); 2) we excluded interpretations from the 2 most junior sonologists. Results: 78 subjects were included (39 PAS, 39 matched control). Clinical risk factors and image quality markers were statistically similar between cohorts. The checklist sensitivity (95% Confidence Interval, CI) was 76.6% (63.4%-90.6%) and specificity (95% CI) was 92.0% (63.4%-99.9%), with a positive and negative likelihood ratio of 9.6 and 0.3, respectively. When we excluded subjects with mild PAS disease, the sensitivity (95% CI) increased to 84.7% (73.6%-96.4%) and specificity was unchanged at 92.0% (83.2%-99.9%). Sensitivity and specificity were unchanged when the interpretations from the 2 most junior sonologists were excluded. Conclusion: The 2016 EW-AIP checklist for interpreting PAS has a reasonable performance in detecting and excluding histologic placenta accreta spectrum

Bayesian Bootstrap Inference for the ROC Surface

Accurate diagnosis of disease is of great importance in clinical practice and medical research. The receiver operating characteristic (ROC) surface is a popular tool for evaluating the discriminatory ability of continuous diagnostic test outcomes when there exist three ordered disease classes (e.g., no disease, mild disease, advanced disease). We propose the Bayesian bootstrap, a fully nonparametric method, for conducting inference about the ROC surface and its functionals, such as the volume under the surface. The proposed method is based on a simple, yet interesting, representation of the ROC surface in terms of placement variables. Results from a simulation study demonstrate the ability of our method to successfully recover the true ROC surface and to produce valid inferences in a variety of complex scenarios. An application to data from the Trail Making Test to assess cognitive impairment in Parkinson's disease patients is provided

Development of a clinical decision model for thyroid nodules

<p>Abstract</p> <p>Background</p> <p>Thyroid nodules represent a common problem brought to medical attention. Four to seven percent of the United States adult population (10–18 million people) has a palpable thyroid nodule, however the majority (>95%) of thyroid nodules are benign. While, fine needle aspiration remains the most cost effective and accurate diagnostic tool for thyroid nodules in current practice, over 20% of patients undergoing FNA of a thyroid nodule have indeterminate cytology (follicular neoplasm) with associated malignancy risk prevalence of 20–30%. These patients require thyroid lobectomy/isthmusectomy purely for the purpose of attaining a definitive diagnosis. Given that the majority (70–80%) of these patients have benign surgical pathology, thyroidectomy in these patients is conducted principally with diagnostic intent. Clinical models predictive of malignancy risk are needed to support treatment decisions in patients with thyroid nodules in order to reduce morbidity associated with unnecessary diagnostic surgery.</p> <p>Methods</p> <p>Data were analyzed from a completed prospective cohort trial conducted over a 4-year period involving 216 patients with thyroid nodules undergoing ultrasound (US), electrical impedance scanning (EIS) and fine needle aspiration cytology (FNA) prior to thyroidectomy. A Bayesian model was designed to predict malignancy in thyroid nodules based on multivariate dependence relationships between independent covariates. Ten-fold cross-validation was performed to estimate classifier error wherein the data set was randomized into ten separate and unique train and test sets consisting of a training set (90% of records) and a test set (10% of records). A receiver-operating-characteristics (ROC) curve of these predictions and area under the curve (AUC) were calculated to determine model robustness for predicting malignancy in thyroid nodules.</p> <p>Results</p> <p>Thyroid nodule size, FNA cytology, US and EIS characteristics were highly predictive of malignancy. Cross validation of the model created with Bayesian Network Analysis effectively predicted malignancy [AUC = 0.88 (95%CI: 0.82–0.94)] in thyroid nodules. The positive and negative predictive values of the model are 83% (95%CI: 76%–91%) and 79% (95%CI: 72%–86%), respectively.</p> <p>Conclusion</p> <p>An integrated predictive decision model using Bayesian inference incorporating readily obtainable thyroid nodule measures is clinically relevant, as it effectively predicts malignancy in thyroid nodules. This model warrants further validation testing in prospective clinical trials.</p

Upper abdominal body shape is the risk factor for postoperative pancreatic fistula after splenectomy for advanced gastric cancer: A retrospective study

<p>Abstract</p> <p>Background</p> <p>Postoperative pancreas fistula (POPF) is a major complication after total gastrectomy with splenectomy. We retrospectively studied the effects of upper abdominal shape on the development of POPF after gastrectomy.</p> <p>Methods</p> <p>Fifty patients who underwent total gastrectomy with splenectomy were studied. The maximum vertical distance measured by computed tomography (CT) between the anterior abdominal skin and the back skin (U-APD) and the maximum horizontal distance of a plane at a right angle to U-APD (U-TD) were measured at the umbilicus. The distance between the anterior abdominal skin and the root of the celiac artery (CAD) and the distance of a horizontal plane at a right angle to CAD (CATD) were measured at the root of the celiac artery. The CA depth ratio (CAD/CATD) was calculated.</p> <p>Results</p> <p>POPF occurred in 7 patients (14.0%) and was associated with a higher BMI, longer CAD, and higher CA depth ratio. However, CATD, U-APD, and U-TD did not differ significantly between patients with and those without POPF. Logistic-regression analysis revealed that a high BMI (≥25) and a high CA depth ratio (≥0.370) independently predicted the occurrence of POPF (odds ratio = 19.007, p = 0.002; odds ratio = 13.656, p = 0.038, respectively).</p> <p>Conclusion</p> <p>Surgical procedures such as total gastrectomy with splenectomy should be very carefully executed in obese patients or patients with a deep abdominal cavity to decrease the risk of postoperative pancreatic fistula. BMI and body shape can predict the risk of POPF simply by CT.</p

Genes, Environments, and Developmental Research: Methods for a Multi-Site Study of Early Substance Abuse

The importance of including developmental and environmental measures in genetic studies of human pathology is widely acknowledged, but few empirical studies have been published. Barriers include the need for longitudinal studies that cover relevant developmental stages and for samples large enough to deal with the challenge of testing gene–environment–development interaction. A solution to some of these problems is to bring together existing data sets that have the necessary characteristics. As part of the National Institute on Drug Abuse-funded Gene-Environment-Development Initiative, our goal is to identify exactly which genes, which environments, and which developmental transitions together predict the development of drug use and misuse. Four data sets were used of which common characteristics include (1) general population samples, including males and females; (2) repeated measures across adolescence and young adulthood; (3) assessment of nicotine, alcohol, and cannabis use and addiction; (4) measures of family and environmental risk; and (5) consent for genotyping DNA from blood or saliva. After quality controls, 2,962 individuals provided over 15,000 total observations. In the first gene–environment analyses, of alcohol misuse and stressful life events, some significant gene–environment and gene–development effects were identified. We conclude that in some circumstances, already collected data sets can be combined for gene–environment and gene–development analyses. This greatly reduces the cost and time needed for this type of research. However, care must be taken to ensure careful matching across studies and variables

Necrosis related HIF-1α expression predicts prognosis in patients with endometrioid endometrial carcinoma

<p>Abstract</p> <p>Background</p> <p>Hypoxia inducible factor 1α (HIF-1α) plays an essential role in the adaptive response of cells to hypoxia and is associated with aggressive tumour behaviour. We have shown p27^kip1, which is generally reduced in endometrial cancer, to be re-expressed in hypoxic regions. This possibly contributes to survival of cancer cells. The aim of this study was to evaluate the prognostic value of HIF-1α and p27^kipexpression in patients with endometrioid endometrial cancer.</p> <p>Methods</p> <p>Expression levels of HIF-1α, CAIX, Glut-1, and p27^kip1were analyzed by immunohistochemistry. Percentage of positive cells, staining pattern (perinecrotic, diffuse, or mixed) and presence of necrosis were noted.</p> <p>Results</p> <p>Necrosis was correlated with shortened disease free survival (DFS) (p <it>= </it>0.008) and overall survival (OS) (p <it>= </it>0.045). For DFS, perinecrotic HIF-1α expression was also prognostic (p <it>= </it>0.044). Moreover, high p27^kip1expression was an additional prognostic factor for these patients with perinecrotic HIF-1α expression. In multivariate Cox regression, perinecrotic HIF-expression emerged as an independent prognostic factor. Perinecrotic HIF-1α expression was significantly associated with CAIX and Glut-1 expression, pointing towards functional HIF-1.</p> <p>Conclusions</p> <p>In patients with endometrioid endometrial cancer, necrosis and necrosis-related expression of HIF-1α are important prognostic factors. More aggressive adjuvant treatment might be necessary to improve the outcome of patients with these characteristics.</p

Genome-Wide Meta-Analysis of Longitudinal Alcohol Consumption Across Youth and Early Adulthood

The public health burden of alcohol is unevenly distributed across the life course, with levels of use, abuse, and dependence increasing across adolescence and peaking in early adulthood. Here, we leverage this temporal patterning to search for common genetic variants predicting developmental trajectories of alcohol consumption. Comparable psychiatric evaluations measuring alcohol consumption were collected in three longitudinal community samples ( N = 2,126, obs = 12,166). Consumption-repeated measurements spanning adolescence and early adulthood were analyzed using linear mixed models, estimating individual consumption trajectories, which were then tested for association with Illumina 660W-Quad genotype data (866,099 SNPs after imputation and QC). Association results were combined across samples using standard meta-analysis methods. Four meta-analysis associations satisfied our pre-determined genome-wide significance criterion (FDR &lt; 0.1) and six others met our ‘suggestive’ criterion (FDR &lt;0.2). Genome-wide significant associations were highly biological plausible, including associations within GABA transporter 1, SLC6A1 (solute carrier family 6, member 1), and exonic hits in LOC100129340 (mitofusin-1-like). Pathway analyses elaborated single marker results, indicating significant enriched associations to intuitive biological mechanisms, including neurotransmission, xenobiotic pharmacodynamics, and nuclear hormone receptors (NHR). These findings underscore the value of combining longitudinal behavioral data and genome-wide genotype information in order to study developmental patterns and improve statistical power in genomic studies