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Background: Preventive therapy among patients with established atherosclerotic cardiovascular disease (ASCVD) is generally underused. Whether new guideline recommendations and a focus on implementation have improved the use of high-intensity statins is unknown.Objectives: This study sought to evaluate the patterns and predictors of statin use among patients with ASCVD.Methods: In this retrospective cohort study, pharmacy and medical claims data from a commercial health plan were queried for patients with established ASCVD between January 31, 2018, and January 31, 2019. Statin use on an index date of January 31, 2019, was evaluated, as was 12-month adherence and discontinuation. Multivariable logistic regression was used to determine independent associations with statin use of varying intensities.Results: Of the 601,934 patients with established ASCVD, 41.7% were female, and the mean age was 67.5 ± 13.3 years. Overall, 22.5% of the cohort were on a high-intensity statin, 27.6% were on a low- or moderate-intensity statin, and 49.9% were not on any statin. In multivariable analysis, younger patients, female patients, and those with higher Charlson comorbidity score were less likely to be prescribed any statin. Among statin users, female patients, older patients, and those with peripheral artery disease were less likely to be on a high-intensity formulation, whereas a cardiology encounter in the prior year increased the odds. The majority of high-intensity stain users achieved high levels of adherence.Conclusions: Substantial underuse of statins persists in a large, insured, and contemporary cohort of patients with ASCVD from the United States. In particular, concerning gaps in appropriate statin use remain among younger patients, women, and those with noncoronary ASCVD. [ABSTRACT FROM AUTHOR]

Background: Many studies showing underuse of oral anticoagulants (OACs) in patients with atrial fibrillation (AF) predated the advent of the non-vitamin K antagonist OACs. We retrospectively examined use of OACs in a large commercially insured population.Methods: Administrative claims data from 4 research partners participating in FDA-Catalyst, a program of the Sentinel Initiative, were queried in September 2017. Patients were included if they were ≥30 years old with ≥365 days of medical/pharmacy coverage, and had ≥2 diagnosis codes for AF, a CHA2DS2-VASc score ≥2, absence of contraindications to OAC use, and no evidence of OAC use in the 365 days before the index AF diagnosis. The main outcome measures of the current analysis were rates of OAC use in the prior 12 months of cohort identification and factors associated with non-use.Results: A total of 197,806 AF patients met the eligibility criteria prior to assessment of OAC treatment. Of these, 179,580 (91%) patients were ≥65 years old and 73,286 (37%) patients were ≥80 years old. Half of the patients (98,903) were randomized to the early intervention arm in the IMPACT-AFib trial and constitute the cohort for this analysis. Of these, 32,295 (33%) had no evidence of OAC use in the prior 12 months. Compared with patients with evidence of OAC use in the prior 12 months, patients without OAC use were more likely to be ≥80 years old, women, and have a history of anemia (51% vs 47%) and less likely to have diabetes (41% vs 44%), history of stroke or TIA (15% vs 19%), and history of heart failure (39% vs 48%).Conclusions: Despite a high risk of stroke, one-third of privately insured patients with AF and no obvious contraindications to an OAC were not treated with an OAC. There is an unmet need for evidence-based interventions that could lead to greater use of OACs in patients with AF at risk for stroke. [ABSTRACT FROM AUTHOR]

We sought to estimate the incidence, prevalence, and racial-ethnic distribution of physician-diagnosed inflammatory bowel disease (IBD) in the United States. The study used 4 administrative claims data sets: a 20% random sample of national fee-for-service Medicare data (2007 to 2017); Medicaid data from Florida, New York, Pennsylvania, Ohio, and California (1999 to 2012); and commercial health insurance data from Anthem beneficiaries (2006 to 2018) and Optum's deidentified Clinformatics Data Mart (2000 to 2017). We used validated combinations of medical diagnoses, diagnostic procedures, and prescription medications to identify incident and prevalent diagnoses. We computed pooled age-, sex-, and race/ethnicity-specific insurance-weighted estimates and pooled estimates standardized to 2018 United States Census estimates with 95% confidence intervals (CIs). The age- and sex-standardized incidence of IBD per 100,000 person-years was 10.9 (95% CI, 10.6–11.2). The incidence of IBD peaked in the third decade of life, decreased to a relatively stable level across the fourth to eighth decades, and declined further. The age-, sex- and insurance-standardized prevalence of IBD was 721 per 100,000 population (95% CI, 717–726). Extrapolated to the 2020 United States Census, an estimated 2.39 million Americans are diagnosed with IBD. The prevalence of IBD per 100,000 population was 812 (95% CI, 802–823) in White, 504 (95% CI, 482–526) in Black, 403 (95% CI, 373–433) in Asian, and 458 (95% CI, 440–476) in Hispanic Americans. IBD is diagnosed in >0.7% of Americans. The incidence peaks in early adulthood and then plateaus at a lower rate. The disease is less commonly diagnosed in Black, Asian, and Hispanic Americans. [Display omitted] Approximately 2.4 to 2.7 million Americans are diagnosed with inflammatory bowel diseases. The prevalence of inflammatory bowel diseases was highest among non-Hispanic Whites and residents of the Northeast. [ABSTRACT FROM AUTHOR]

Background: Emergency treatment of bleeding esophageal varices (BEV) in cirrhotic patients is of prime importance because of the high mortality rate surrounding the episode of acute bleeding. Nevertheless, there is a paucity of randomized controlled trials of emergency surgical therapy and no reports of the costs of any of the widely used forms of emergency treatment. The important issue of direct costs of care was examined in a randomized controlled trial that compared endoscopic sclerotherapy (EST) to emergency portacaval shunt (EPCS).Methods: Two hundred eleven unselected consecutive patients with ultimately biopsy-proven cirrhosis and endoscopically proven acute BEV were randomized to EST (n = 106) or EPCS (n = 105). Diagnostic workup was completed, and EST or EPCS was initiated within 8 h. Criteria for failure of EST or EPCS were clearly defined, and crossover rescue treatment was applied, when primary therapy failed. Ninety-six percent of patients underwent more than 10 years follow-up, or until death. Complete charges for all aspects of care were obtained continuously for more than 10 years.Results: Direct charges for all aspects of care were significantly lower in patients treated by EPCS than in patients treated by emergency EST followed by long-term repetitive sclerotherapy. Charges per patient, per year of treatment, and per year in each child's risk class were significantly lower in patients randomized to EPCS. Charges in patients who failed endoscopic sclerotherapy and underwent a rescue portacaval shunt were significantly higher than the charges in both the unshunted sclerotherapy patients and the patients randomized to EPCS. This result was particularly noteworthy given the widespread practice of using surgical portacaval shunt as rescue treatment only when all other forms of therapy have failed.Conclusions: In this randomized controlled trial of emergency treatment of acute BEV, EPCS was significantly superior to EST with regard to direct costs of care as reflected in charges for care as well as in survival rate, control of bleeding, and incidence of portal-systemic encephalopathy. These results provide support for the use of EPCS as a first line of emergency treatment of BEV in cirrhosis. [ABSTRACT FROM AUTHOR]

Background Hypergastrinemia was shown to stimulate colonic epithelial cell proliferation. Aims To evaluate the association between pernicious anemia (PA), a disease with hypergastrinemia, and colorectal cancer (CRC) risk. Methods We conducted a nested case–control study within a large database from the UK. Cases were defined as all individuals in the cohort with at least one medical code for CRC. Controls were selected based on incidence-density sampling. For each case, up to four eligible controls were matched on age at diagnosis, sex, practice-site, and both duration and calendar time of follow-up. Exposure of interest was diagnosis of PA prior to CRC diagnosis date. The primary analysis was a multivariable conditional logistic regression. Results Our study included 22,098 CRC cases and 85,969 matched controls. We identified 154 (0.70%) cases and 563 (0.65%) controls with past history of PA. The adjusted OR for the association between PA and CRC risk was 1.02 (95% CI 0.85–1.22). There was no difference in the results after stratification according to sex. In a sensitivity analysis only among individuals without chronic use of proton pump inhibitors (PPIs) the adjusted OR was 1.14 (95% CI 0.90–1.45). There was no association between duration of PA and CRC risk. Conclusion PA is not associated with higher CRC risk. [ABSTRACT FROM AUTHOR]

Background & Aims Few studies have evaluated the ability of laboratory tests to predict risk of acute liver failure (ALF) among patients with drug-induced liver injury (DILI). We aimed to develop a highly sensitive model to identify DILI patients at increased risk of ALF. We compared its performance with that of Hy’s Law, which predicts severity of DILI based on levels of alanine aminotransferase or aspartate aminotransferase and total bilirubin, and validated the model in a separate sample. Methods We conducted a retrospective cohort study of 15,353 Kaiser Permanente Northern California members diagnosed with DILI from 2004 through 2010, liver aminotransferase levels above the upper limit of normal, and no pre-existing liver disease. Thirty ALF events were confirmed by medical record review. Logistic regression was used to develop prognostic models for ALF based on laboratory results measured at DILI diagnosis. External validation was performed in a sample of 76 patients with DILI at the University of Pennsylvania. Results Hy’s Law identified patients that developed ALF with a high level of specificity (0.92) and negative predictive value (0.99), but low level of sensitivity (0.68) and positive predictive value (0.02). The model we developed, comprising data on platelet count and total bilirubin level, identified patients with ALF with a C statistic of 0.87 (95% confidence interval [CI], 0.76–0.96) and enabled calculation of a risk score (Drug-Induced Liver Toxicity ALF Score). We found a cut-off score that identified patients at high risk patients for ALF with a sensitivity value of 0.91 (95% CI, 0.71–0.99) and a specificity value of 0.76 (95% CI, 0.75–0.77). This cut-off score identified patients at high risk for ALF with a high level of sensitivity (0.89; 95% CI, 0.52–1.00) in the validation analysis. Conclusions Hy’s Law identifies patients with DILI at high risk for ALF with low sensitivity but high specificity. We developed a model (the Drug-Induced Liver Toxicity ALF Score) based on platelet count and total bilirubin level that identifies patients at increased risk for ALF with high sensitivity. [ABSTRACT FROM AUTHOR]

Importance Bleeding esophageal varices has been studied extensively, but bleeding gastric varices (BGV) has received much less investigation. However, BGV has been reported in ≤30% of patients with acute variceal bleeding. In our studies of 1,836 bleeding cirrhotics, 12.7% were bleeding from gastric varices. BGV mortality rate of 45–55% has been reported. The BGV literature has mainly involved retrospective case reports, often with short-term follow-up. Objective We sought to describe the results of a prospective, randomized, controlled trial (RCT) in unselected, consecutive patients with BGV comparing endoscopic therapy (ET) with portacaval shunt (PCS; n = 518), and later comparing emergency transjugular intrahepatic portosystemic shunt (TIPS) with emergency portacaval shunt (EPCS; n = 70). Design, setting, and participants Initially, our RCT involved 518 patients with BGV comparing ET with direct PCS regarding control of bleeding, mortality rate, and disability. When entry of patients ended, the RCT was expanded to compare emergency TIPS with EPCS ( n = 70). This RCT of BGV was separate from our other RCTs of bleeding esophageal varices. Interventions Initially, ET was compared with PCS. In the second part of our RCT, emergency TIPS was compared with emergency PCS (EPCS). Main outcome measures Outcomes were survival, control of bleeding, portal-systemic encephalopathy (PSE), quality of life, and direct costs of care. In the RCT of ET versus PCS, 28 and 30%, respectively, were in Child class C. In the expanded RCT of TIPS versus EPCS, 40 and 41%, respectively, were in Child class C. Permanent control of BGV was achieved in 97–100% of patients treated by emergency or elective PCS, compared with 27–29% by ET. TIPS was even less effective, achieving long-term control of BGV in only 6%. Survival rates after PCS were greater at all time intervals and in all Child classes ( P < .001). Repeated episodes of PSE occurred in 50% of TIPS patients, 16-17% treated by ET, and 8-11% treated by PCS. Shunt stenosis or occlusion occurred in 67% of TIPS patients, in contrast with 0–2% of PCS patients. Conclusion These results support the conclusion that PCS is uniformly effective, whereas ET and TIPS are not very effective. [ABSTRACT FROM AUTHOR]

Study Objective To investigate whether endometrial ablation is associated with increased risk or delayed diagnosis of endometrial cancer compared with medical management of abnormal uterine bleeding. Design Multi-centered retrospective cohort study (Canadian Task Force classification II-2). Setting The study was performed using data from The Health Improvement Network, a representative population-based cohort of patients in 495 outpatient general practitioner practices in the United Kingdom. Patients Women aged >25 years with abnormal uterine bleeding diagnosed between June 1994 and September 2010. Interventions Endometrial ablation, medical management, or both. Measurements and Main Results A total of 234 721 women met study inclusion and exclusion criteria, 4776 of whom underwent endometrial ablation and the remaining 229 945 received medical management. Cox models compared endometrial cancer rates between ablation and medical management groups using hazard ratios. To investigate a possible diagnostic delay, the median time from bleeding diagnosis to endometrial cancer diagnosis in women in whom endometrial cancer developed was compared using the Mann-Whitney U test. All statistical tests were 2-tailed, with α = .05. During a median observation period of 4.07 years (interquartile range [IQR], 1.88–7.17), endometrial cancer developed in 3 women in the ablation group and 601 women in the medical management group (ablation hazard ratio, 0.45; 95% confidence interval, 0.15–1.40; p = .17). Median time to diagnosis was 237 in the ablation group, and 299 days in the medical management group (ablation IQR, 155–1350; medical management IQR, 144–1133.5; p = .99). Adjusted and sensitivity analyses did not change the results. Conclusions No difference was observed in endometrial cancer rates, and there was no delay in diagnosis when comparing endometrial ablation vs medical management. Further studies are needed to investigate the effect of previous ablation exposure on histology or cancer stage at manifestation of endometrial cancer. [ABSTRACT FROM AUTHOR]

Background: The incidence of malignancy in patients with chronic pruritus and nondiseased skin is unknown. Objective: We sought to assess the hazard ratio (HR) of incident overall malignancy and incident malignancy by subtype in patients with chronic pruritus during the 5 years after diagnosis. Methods: A population-based cohort study was performed in the Health Improvement Network. In all, 8744 patients with chronic pruritus were matched with 31,580 patients without chronic pruritus based on sex, age, and practice. Primary outcomes were HR of incident malignancy and HR of malignancy subtypes. Results: The fully adjusted HR for incident malignancy in patients with chronic pruritus was 1.14 (95% confidence interval 0.98-1.33). The fully adjusted HR for incident hematologic malignancy and incident bile duct malignancy in patients with chronic pruritus was 2.02 (95% confidence interval 1.48-2.75) and 3.73 (95% confidence interval 1.55-8.97), respectively. The incidence of hematologic malignancy and cholangiocarcinoma in patients with chronic pruritus was 0.0016 and 0.0003 per person-year, respectively. Limitations: Potential for misclassification and detection biases is a limitation. Conclusions: Chronic pruritus without concomitant skin changes is a risk factor for having undiagnosed hematologic and bile duct malignancies, but not other malignancies. The overall incidence of these malignancies in patients with chronic pruritus is very low. [Copyright &y& Elsevier]

Background: Emergency treatment of bleeding esophageal varices (BEV) in cirrhosis is of paramount importance because of the resultant high mortality rate. Emergency therapy today consists mainly of endoscopic and pharmacologic measures, with use of transjugular intrahepatic portosystemic shunt (TIPS) when bleeding is not controlled. Surgical portosystemic shunt has been relegated to last resort salvage when all other measures fail. Regrettably, no randomized controlled trials have been reported in which TIPS and surgical portosystemic shunt were compared in unselected patients with acute BEV, with long-term follow-up. This is a report of a long-term prospective randomized controlled trial (RCT) that compared TIPS with emergency portacaval shunt (EPCS) in patients with cirrhosis and acute BEV. Study Design: A total of 154 unselected, consecutive cirrhotic patients ('all comers') with acute BEV were randomized to TIPS ( n = 78) or EPCS ( n = 76), and the two treatments were compared with regard to effect on survival, control of bleeding, portal-systemic encephalopathy (PSE), and disability. Diagnostic workup was completed within 6 h and TIPS or EPCS was initiated within 24 h. Regular follow-up was accomplished in 100 % of patients and lasted for 5 to 10 years in 85 % and 3 to 4.5 years in the remainder. This report focuses on control of bleeding and survival. Results: The clinical characteristics of the two groups were similar, and the distribution of Child classes A, B, and C was almost identical. TIPS was successful in controlling BEV for 30 days in 80 % of patients but achieved long-term control of BEV in only 22 %. In contrast, EPCS controlled BEV immediately in all patients and permanently in 97 % ( p < 0.001). TIPS patients required almost twice as many units of blood transfusion as EPCS patients. Survival rate at all time intervals and in all Child classes was significantly greater following EPCS than after TIPS ( p < 0.001). Median survival was over 10 years following EPCS, compared to 1.99 years following TIPS. Stenosis or occlusion of TIPS was demonstrated in 84 % of patients who survived 21 days, 63 % of whom underwent TIPS revision, which failed in 80 %. In contrast, EPCS remained permanently patent in 97 % of patients. Recurrent PSE was threefold more frequent following TIPS than after EPCS (61 versus 21 %). Conclusions: EPCS was uniformly effective in the treatment of BEV, while TIPS was disappointing. EPCS accomplished long-term survival while TIPS resulted in a survival rate that was less than one fifth that of EPCS. The results of this RCT in unselected, consecutive patients justify the use of EPCS as a first-line emergency treatment of BEV in cirrhosis (clinicaltrials.gov #NCT00734227). [ABSTRACT FROM AUTHOR]

Background: Emergency treatment of bleeding esophageal varices in cirrhosis is of singular importance because of the high mortality rate. Emergency portacaval shunt is rarely used today because of the belief, unsubstantiated by long-term randomized trials, that it causes frequent portal-systemic encephalopathy and liver failure. Consequently, portacaval shunt has been relegated solely to salvage therapy when endoscopic and pharmacologic therapies have failed.Question: Is the regimen of endoscopic sclerotherapy with rescue portacaval shunt for failure to control bleeding varices superior to emergency portacaval shunt? A unique opportunity to answer this question was provided by a randomized controlled trial of endoscopic sclerotherapy versus emergency portacaval shunt conducted from 1988 to 2005.Methods: Unselected consecutive cirrhotic patients with acute bleeding esophageal varices were randomized to endoscopic sclerotherapy (n = 106) or emergency portacaval shunt (n = 105). Diagnostic workup was completed and treatment was initiated within 8 h. Failure of endoscopic sclerotherapy was defined by strict criteria and treated by rescue portacaval shunt (n = 50) whenever possible. Ninety-six percent of patients had more than 10 years of follow-up or until death.Results: Comparison of emergency portacaval shunt and endoscopic sclerotherapy followed by rescue portacaval shunt showed the following differences in measurements of outcomes: (1) survival after 5 years (72% versus 22%), 10 years (46% versus 16%), and 15 years (46% versus 0%); (2) median post-shunt survival (6.18 versus 1.99 years); (3) mean requirements of packed red blood cell units (17.85 versus 27.80); (4) incidence of recurrent portal-systemic encephalopathy (15% versus 43%); (5) 5-year change in Child's class showing improvement (59% versus 19%) or worsening (8% versus 44%); (6) mean quality of life points in which lower is better (13.89 versus 27.89); and (7) mean cost of care per year ($39,200 versus $216,700). These differences were highly significant in favor of emergency portacaval shunt (all p < 0.001).Conclusions: Emergency portacaval shunt was strikingly superior to endoscopic sclerotherapy as well as to the combination of endoscopic sclerotherapy and rescue portacaval shunt in regard to all outcome measures, specifically bleeding control, survival, incidence of portal-systemic encephalopathy, improvement in liver function, quality of life, and cost of care. These results strongly support the use of emergency portacaval shunt as the first line of emergency treatment of bleeding esophageal varices in cirrhosis. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate a mechanism designed to encourage pharmacy students to purse a PhD degree. Design: A model in use at Ohio Northern University (ONU)''s College of Pharmacy is described and provides research experiences and motivation for pharmacy students to pursue a PhD degree. The model described establishes a method for the recruitment and funding of undergraduate and pharmacy research students in a pharmacology laboratory. Assessment: Since 1997, the pharmacology laboratory has trained approximately 30 undergraduate and pharmacy students. These students have participated in research projects that led to more than 20 peer-reviewed publications. Former students from the laboratory were asked to fill out a web-based questionnaire of their research experience and its impact on career decisions. All respondents overwhelmingly agreed that the research experience aided in the learning of lecture material and in obtaining critical thinking skills in the practice of pharmacy. Furthermore, four of the students have earned a PhD degree and 10 students have other advanced degrees (e.g., MD, MSc). Conclusions: Although this model has been successfully used to encourage PharmD students to pursue a PhD degree in biomedical research, it can also be applied to any pharmacy discipline that offers a PhD degree program. Moreover, this model provides a template for encouraging pharmacy students to participate in biomedical research at liberal arts institutions with a primarily teaching focus. [Copyright &y& Elsevier]

Abstract: Objective: We sought to examine the validity of specific hospital discharge codes in identifying drug toxicity precipitating hospitalization, among elderly users of high-risk medications. Study Design and Setting: We conducted a cross-sectional evaluation assessing the diagnostic test characteristics of International Classification of Diseases-9 External-Cause-of-Injury codes (E-codes) compared with a reference standard of medical record review. This study was nested within a prospective cohort of elders using warfarin, digoxin, or phenytoin as identified in the Pharmaceutical Assistance Contract for the Elderly benefit program. Results: We identified 4,803 subjects contributing 11,409 person-years of exposure to at least one of three drug groups. Subjects experienced 8,756 hospitalizations, of which 304 were deemed, by expert review, to be a result of an adverse event of warfarin, digoxin, or phenytoin. The sensitivity, specificity, and positive (PPVs) and negative predictive values for drug-specific E-codes were warfarin—25.5%, 98.3%, 46.6%, and 95.7%; digoxin—84.0%, 99.1%, 56.8%, and 99.8%; and phenytoin—86.7%, 98.7%, 59.1%, and 99.7%. Conclusions: E-codes for digoxin and phenytoin have a high sensitivity, but E-codes for all three medications have poor PPVs, a result that might produce misclassification in studies based solely on discharge coding. Investigators should confirm such rare events via medical record review. [Copyright &y& Elsevier]

This ISPOR Good Practices report provides a framework for assessing the suitability of electronic health records data for use in health technology assessments (HTAs). Although electronic health record (EHR) data can fill evidence gaps and improve decisions, several important limitations can affect its validity and relevance. The ISPOR framework includes 2 components: data delineation and data fitness for purpose. Data delineation provides a complete understanding of the data and an assessment of its trustworthiness by describing (1) data characteristics; (2) data provenance; and (3) data governance. Fitness for purpose comprises (1) data reliability items, ie, how accurate and complete the estimates are for answering the question at hand and (2) data relevance items, which assess how well the data are suited to answer the particular question from a decision-making perspective. The report includes a checklist specific to EHR data reporting: the ISPOR SUITABILITY Checklist. It also provides recommendations for HTA agencies and policy makers to improve the use of EHR-derived data over time. The report concludes with a discussion of limitations and future directions in the field, including the potential impact from the substantial and rapid advances in the diffusion and capabilities of large language models and generative artificial intelligence. The report's immediate audiences are HTA evidence developers and users. We anticipate that it will also be useful to other stakeholders, particularly regulators and manufacturers, in the future. • This ISPOR Good Practices report proposes a framework for assessing the suitability of electronic health records data for use in health technology assessments (HTAs) and an accompanying ISPOR SUITABILITY Checklist. Although electronic health record (EHR) data can fill evidence gaps and improve decisions, several important limitations can affect their validity and relevance. The report describes the challenges faced when extracting and transforming structured and unstructured information into a reliable format for analysis. • This ISPOR Good Practices Report introduces a framework and the ISPOR SUITABILITY Checklist for assessing the suitability of EHR data in HTA. It contains 2 main elements. Data delineation provides a complete understanding of the data and an assessment of their trustworthiness by describing data characteristics, data provenance, and data governance. Data fitness for purpose examines the accuracy and completeness of items (data reliability) and the suitability of the data to answer the particular question at hand (data relevance). • This ISPOR Good Practices Report offers guidance to HTA agencies and policy makers on improving the suitability of EHR-derived data for decision making. Recommendations include developing or endorsing a common set of standards for EHR utilization, fostering multistakeholder collaborations to identify best practices, increasing the dissemination of exemplary case studies, and identifying resources to invest in the training of a workforce dedicated to this field. [ABSTRACT FROM AUTHOR]

Background & Aims Approximately 50% of all patients with pancreatic ductal adenocarcinoma (PDA) develop diabetes mellitus before their cancer diagnosis. Screening individuals with new-onset diabetes might allow earlier diagnosis of PDA. We sought to develop and validate a PDA risk prediction model to identify high-risk individuals among those with new-onset diabetes. Methods We conducted a retrospective cohort study in a population representative database from the United Kingdom. Individuals with incident diabetes after the age of 35 years and 3 or more years of follow-up after diagnosis of diabetes were eligible for inclusion. Candidate predictors consisted of epidemiologic and clinical characteristics available at the time of diabetes diagnosis. Variables with P values <.25 in the univariable analyses were evaluated using backward stepwise approach. Model discrimination was assessed using receiver operating characteristic curve analysis. Calibration was evaluated using the Hosmer−Lemeshow test. Results were internally validated using a bootstrapping procedure. Results We analyzed data from 109,385 patients with new-onset diabetes. Among them, 390 (0.4%) were diagnosed with PDA within 3 years. The final model (area under the curve, 0.82; 95% confidence interval, 0.75−0.89) included age, body mass index, change in body mass index, smoking, use of proton pump inhibitors, and anti-diabetic medications, as well as levels of hemoglobin A1C, cholesterol, hemoglobin, creatinine, and alkaline phosphatase. Bootstrapping validation showed negligible optimism. If the predicted risk threshold for definitive PDA screening was set at 1% over 3 years, only 6.19% of the new-onset diabetes population would undergo definitive screening, which would identify patients with PDA with 44.7% sensitivity, 94.0% specificity, and a positive predictive value of 2.6%. Conclusions We developed a risk model based on widely available clinical parameters to help identify patients with new-onset diabetes who might benefit from PDA screening. [ABSTRACT FROM AUTHOR]

Background & Aims Childhood obesity is increasing and is associated with adult obesity. Antibiotics have been used to promote weight gain in livestock for several decades. Antibiotics are commonly prescribed for children, but it is not clear how exposure to antibiotics early in life affects risk for obesity. We performed a population-based cohort study to assess the association between antibiotic exposure before age 2 years and obesity at age 4 years. Methods We performed a retrospective cohort study of 21,714 children in The Health Improvement Network—a population-representative dataset of >10 million individuals derived from electronic medical records from 1995 through 2013 in the United Kingdom. Eligible subjects were registered within 3 months of birth with complete follow-up and height and weight were recorded within 12 months of their 4th birthday. Antibiotic exposure was assessed before age 2 years, and classified based on anti-anaerobic activity. The primary outcome was obesity at age 4 years. We performed logistic regression analyses, adjusting for maternal and sibling obesity, maternal diabetes, mode of delivery, socioeconomic status, year and country of birth, and urban dwelling. Results In the cohort, 1306 of the children (6.4%) were obese at 4 years of age. Antibiotic exposure was associated with an increased risk of obesity at 4 years (odds ratio [OR] = 1.21; 95% confidence interval [CI]: 1.07–1.38). ORs increased with repeated exposures: for 1–2 prescriptions, OR = 1.07 (95% CI, 0.91–1.23); for 3–5 prescriptions, OR = 1.41 (95% CI, 1.20–1.65); and for 6 or more prescriptions, OR = 1.47 (95% CI, 1.19–1.82). Antifungal agents were not associated with obesity (OR = 0.81; 95% CI, 0.59–1.11). Conclusions Administration of 3 or more courses of antibiotics before children reach an age of 2 years is associated with an increased risk of early childhood obesity. [ABSTRACT FROM AUTHOR]

Background & Aims The benefit of continuing immunomodulators when “stepping up” to anti–tumor necrosis factor (anti-TNF) therapy for Crohn’s disease (CD) is uncertain. This study assessed the effectiveness and safety of immunomodulators with anti-TNF therapy in CD. Methods We conducted a retrospective cohort study of new users of anti-TNF therapy for CD in Medicare. Users of anti-TNF combination therapy with immunomodulators were matched to up to 3 users of anti-TNF monotherapy via propensity score and compared by using 3 metrics of effectiveness—surgery, hospitalization, and discontinuation of anti-TNF therapy or surgery—and 2 metrics of safety—serious infection and non- Candida opportunistic infection. Cox regression was used for all analyses. Results Among new users of infliximab, we matched 381 users of combination therapy to 912 users of monotherapy; among new users of adalimumab, we matched 196 users of combination therapy to 505 users of monotherapy. Combination therapy occurred predominantly as “step up” after thiopurine therapy. The rates of surgery (hazard ratio [HR], 1.20; 95% confidence interval, 0.73–1.96), hospitalization (HR, 0.82; 0.57–1.19), discontinuation of anti-TNF therapy or surgery (HR, 1.09; 0.88–1.34), and serious infection (HR, 0.93; 0.88–1.34) did not differ between users of anti-TNF combination therapy and monotherapy. However, the risks of opportunistic infection (HR, 2.64; 1.21–5.73) and herpes zoster (HR, 3.16; 1.25–7.97) were increased with combination therapy. Conclusions We found that continuation of immunomodulators after “stepping up” to anti-TNF therapy did not improve outcomes but was associated with an increased risk of opportunistic infection. [ABSTRACT FROM AUTHOR]

Background & Aims Medications are a major cause of acute liver failure (ALF) in the United States, but no population-based studies have evaluated the incidence of ALF from drug-induced liver injury. We aimed to determine the incidence and outcomes of drug-induced ALF in an integrated health care system that approximates a population-based cohort. Methods We performed a retrospective cohort study using data from the Kaiser Permanente Northern California (KPNC) health care system between January 1, 2004, and December 31, 2010. We included all KPNC members age 18 years and older with 6 months or more of membership and hospitalization for potential ALF. The primary outcome was drug-induced ALF (defined as coagulopathy and hepatic encephalopathy without underlying chronic liver disease), determined by hepatologists who reviewed medical records of all KPNC members with inpatient diagnostic and laboratory criteria suggesting potential ALF. Results Among 5,484,224 KPNC members between 2004 and 2010, 669 had inpatient diagnostic and laboratory criteria indicating potential ALF. After medical record review, 62 (9.3%) were categorized as having definite or possible ALF, and 32 (51.6%) had a drug-induced etiology (27 definite, 5 possible). Acetaminophen was implicated in 18 events (56.3%), dietary/herbal supplements in 6 events (18.8%), antimicrobials in 2 events (6.3%), and miscellaneous medications in 6 events (18.8%). One patient with acetaminophen-induced ALF died (5.6%; 0.06 events/1,000,000 person-years) compared with 3 patients with non–acetaminophen-induced ALF (21.4%; 0.18/1,000,000 person-years). Overall, 6 patients (18.8%) underwent liver transplantation, and 22 patients (68.8%) were discharged without transplantation. The incidence rates of any definite drug-induced ALF and acetaminophen-induced ALF were 1.61 events/1,000,000 person-years (95% confidence interval, 1.06–2.35) and 1.02 events/1,000,000 person-years (95% confidence interval, 0.59–1.63), respectively. Conclusions Drug-induced ALF is uncommon, but over-the-counter products and dietary/herbal supplements are its most common causes. [ABSTRACT FROM AUTHOR]

Background & Aims: Antibodies against tumor necrosis factor-α are widely used to treat patients with Crohn's disease (CD). This study compared the effectiveness of infliximab and adalimumab, the 2 most commonly used anti–tumor necrosis factor agents, in patients with CD. Methods: We conducted a retrospective cohort study by using U.S. Medicare data from 2006 through 2010. Patients with CD who were new users of infliximab (n = 1459) or adalimumab (n = 871) after January 31, 2007, were included. Patients older than age 85 and those with rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis were excluded. The primary outcome measures were disease persistence on therapy at week 26, surgery (including bowel resection, creation of an ostomy, or surgical treatment of a perforation or abscess), and hospitalization for CD. Propensity score-adjusted logistic and Cox regression were used to compute adjusted odds ratios or hazard ratios and 95% confidence intervals (CIs). Results: After 26 weeks of treatment, 49% of patients receiving infliximab remained on drug, compared with 47% of those receiving adalimumab (odds ratio, 0.98; 95% CI, 0.81–1.19). Fewer patients treated with infliximab underwent surgery than those treated with adalimumab, but this difference was not statistically significant (5.5 vs 6.9 surgeries per 100 person-years; hazard ratio, 0.79; 95% CI, 0.60–1.05). Rates of hospitalization did not differ between groups (hazard ratio, 0.88; 95% CI, 0.72–1.07). Conclusions: We observed similar effectiveness of infliximab and adalimumab for CD on the basis of 3 clinically important outcome measures. [Copyright &y& Elsevier]

Background: A pro-inflammatory gut microbiota was described in both Parkinson's disease and colorectal cancer (CRC) and recently α-synuclein was demonstrated in the enteric nervous system. We sought to evaluate the association between Parkinson's disease and CRC.Methods: We conducted a nested case-control study using a large primary-care database. Cases were defined as all individuals with CRC. Up to 4 controls were matched with each case based on age, sex, practice-site and duration of follow-up. The primary exposure of interest was diagnosis of Parkinson's disease prior to CRC as well as disease duration, and Parkinson's specific therapies. The primary analysis was a conditional logistic-regression to estimate odds ratios (ORs) and 95% confidence interval (95%CI).Results: The study included 22,093 CRC cases and 85,833 matched controls. Past medical history of Parkinson's disease >1 year before index-date was associated with lower CRC risk (OR 0.74, 95%CI 0.59-0.94). The inverse association was more prominent among females compared to males (0.64, 95%CI 0.42-0.96 and 0.8, 95%CI 0.60-1.07, respectively). While patients who received no therapy or therapy with dopamine agonists had a non-significant decrease in cancer risk, patients who were treated with dopamine had a non-significant elevated cancer risk.Conclusion: Parkinson's disease is inversely associated with CRC risk. [ABSTRACT FROM AUTHOR]

Background Bacterial dysbiosis was previously described in human malignancies. In a recent animal model, tumour susceptibility was transmitted using faecal transplantation. Our aim was to evaluate possible association between antibiotic exposure and cancer risk. Methods We conducted nested case–control studies for 15 common malignancies using a large population-based electronic medical record database. Cases were defined as those with any medical code for the specific malignancy. Individuals with familial cancer syndromes were excluded. For every case, four eligible controls matched on age, sex, practice site and duration of follow-up before index-date were selected using incidence-density sampling. Exposure of interest was antibiotic therapy >1 year before index-date. Adjusted odds-ratios (AORs) and 95% confidence intervals (CIs) were estimated for each antibiotic type using conditional logistic regression. Results 125,441 cases and 490,510 matched controls were analysed. For gastro-intestinal malignancies, the use of penicillin was associated with an elevated risk of oesophageal, gastric and pancreatic cancers. The association increased with the number of antibiotic courses and reached 1.4 for gastric cancers associated with >5 courses of penicillin (95% CI 1.2–1.8). Lung cancer risk increased with the use of penicillin, cephalosporins, or macrolides (AOR for >5 courses of penicillin: 1.4 95% CI 1.3–1.6). The risk of prostate cancer increased modestly with the use of penicillin, quinolones, sulphonamides and tetracyclines. The risk of breast cancer was modestly associated with exposure to sulphonamides. There was no association between the use of anti-virals and anti-fungals and cancer risk. Conclusion Recurrent exposure to certain antibiotics may be associated with cancer risk in specific organ sites. [ABSTRACT FROM AUTHOR]

Background Despite the lack of scientific data, many cancer patients hold the belief that glucose ‘feeds’ cancer and might affect disease outcome. We aimed to evaluate associations between glucose, hemoglobin A1C (HbA1C), and survival among individuals with diabetes and diabetes associated cancers. Methods Five retrospective cohort studies were conducted in a large population-representative database. The study population included all patients with diabetes and an incident diagnosis of colorectal, breast, bladder, pancreatic and prostate cancers. Exposure of interest was serum glucose or HbA1C levels within 6 months prior to cancer diagnosis. Cox regression model was used to calculate hazard-ratio (HR) and 95% confidence-interval (CI) for overall survival. Analyses were adjusted for cancer-specific confounders. A subgroup analysis was performed among insulin-treated patients. Results Study cohorts included 7916 individuals with incident cancers and concurrent diabetes. There was no association between HbA1C levels and overall survival in colorectal (HR 1.00, 95% CI 0.95–1.06), breast (HR 1.03, 95% CI 0.95–1.11), bladder (HR 0.94, 95% CI 0.86–1.01), pancreatic (HR 0.98, 95% CI 0.94–1.02), or prostate (HR 1.02, 95% CI 0.96–1.08) cancers. Among diabetes patients treated with insulin, there was increased survival with increasing serum glucose, most prominent for bladder cancer (HR 0.91, 95% CI 0.84–0.99, per 1 mmol/l increase). Conclusions Higher glucose and HbA1C levels in diabetes patients with incident cancer are not associated with worse overall survival following cancer diagnosis. Among insulin-treated patients, higher glucose levels may be associated with improved survival. [ABSTRACT FROM AUTHOR]

Abstract: Background: Disability has not been studied after emergency treatment of bleeding esophageal varices (BEV). We created a disability index (DI) in a randomized controlled trial comparing emergency endoscopic therapy (EST) versus emergency portacaval shunt (EPCS). Methods: There were 211 unselected, consecutive patients with cirrhosis and acute BEV who were randomized to EST (n = 106) or EPCS (n = 105). Diagnostic work-up and treatment were performed within 8 hours. Ninety-six percent underwent more than 10 years follow-up evaluation. Disability was measured by assessing 9 factors to create a DI. Results: Ten-year survival was 8% after EST versus 51% after EPCS (P < .001). EPCS had a significantly better DI. The EST and EPCS values were as follows: liver function improvement: not applicable and ++; worsening liver function, ++ and not applicable; portal-systemic encephalopathy (PSE) incidence, 36 and 15; PSE episodes, 179 and 94; packed red blood cell units, 1,005 and 320; hospital readmissions, 387 and 292; and number of readmission days, 9.6 and 4.7. All of the P values were less than .001. Conclusions: EPCS resulted in a markedly better DI than EST, a significantly higher survival rate, better control of bleeding, and a lower incidence of PSE. EPCS is an effective first-line emergency treatment of BEV. [Copyright &y& Elsevier]

Abstract: Background: Ninety percent of patients with hepatocellular carcinoma (HCC) have cirrhosis. Bleeding esophageal varices (BEV) is a frequent complication of cirrhosis. Detection of HCC in cirrhotic patients with BEV has not been studied. Methods: Two hundred eleven unselected patients with cirrhosis and BEV were randomized to endoscopic sclerotherapy (n = 106) or emergency portacaval shunt (n = 105). Diagnostic workup and treatment were initiated within 8 hours. Ninety-six percent had >10 years of follow-up. HCC screening involved serum α-fetoprotein (AFP) every 3 months, ultrasonography every 6 months, and selective computed tomography (CT). Results: HCC occurred in 15 patients, all incurable, a mean of 2.94 years after entry. They died a mean 1.33 years after discovery. Serial AFP and ultrasound examinations were unrevealing over a mean of 2.3 years. The mean model of end-stage liver disease score was 12.7 at entry and 17.4 at HCC diagnosis. Conclusions: Long-term screening by AFP and ultrasound plus selective CT failed to detect HCC at a curable stage. The detection of HCC in cirrhotic patients with BEV remains a serious, unsolved problem. The use of CT for routine screening warrants consideration despite increased costs. [Copyright &y& Elsevier]

Background: The mortality rate of bleeding esophageal varices in cirrhosis is highest during the period of acute bleeding. This is a report of a randomized trial that compared endoscopic sclerotherapy (EST) with emergency portacaval shunt (EPCS) in cirrhotic patients with acute variceal hemorrhage. Study Design: A total of 211 unselected consecutive patients with cirrhosis and acutely bleeding esophageal varices who required at least 2 U of blood transfusion were randomized to EST (n=106) or EPCS (n=105). Diagnostic workup was completed within 6 hours and EST or EPCS was initiated within 8 hours of initial contact. Longterm EST was performed according to a deliberate schedule. Ninety-six percent of patients underwent more than 10 years of followup, or until death. Results: The percent of patients in Child''s risk classes were A, 27.5; B, 45.0; and C, 27.5. EST achieved permanent control of bleeding in only 20% of patients; EPCS permanently controlled bleeding in every patient (p ≤0.001). Requirement for blood transfusions was greater in the EST group than in the EPCS patients. Compared with EST, survival after EPCS was significantly higher at all time intervals and in all Child''s classes (p ≤0.001). Recurrent episodes of portal-systemic encephalopathy developed in 35% of EST patients and 15% of EPCS patients (p ≤0.01). Conclusions: EPCS permanently stopped variceal bleeding, rarely became occluded, was accomplished with a low incidence of portal-systemic encephalopathy, and compared with EST, produced greater longterm survival. The widespread practice of using surgical procedures mainly as salvage for failure of endoscopic therapy is not supported by the results of this trial (clinicaltrials.gov #NCT00690027). [Copyright &y& Elsevier]