The APB study: apixaban pharmacokinetics in bariatric patients before to 1 year after vertical sleeve gastrectomy or Roux-en-Y gastric bypass.

BACKGROUND: The optimal regimen for prevention and treatment of venous thromboembolism in bariatric surgical patients remains controversial. Direct oral anticoagulants are potentially advantageous over other agents, but inadequate evidence exists regarding their effects in bariatric surgical patients. OBJECTIVES: To investigate single-dose pharmacokinetic (PK) and pharmacodynamic (PD) parameters of apixaban when administered to patients undergoing vertical sleeve gastrectomy (VSG) or Roux-en-Y gastric bypass (RYGB) and to determine whether the PK and PD parameters are affected by type of bariatric surgery and weight loss in the immediate and postoperative period up to 12 months. SETTING: University Hospital and A Bariatric Center of Excellence, Baltimore, Maryland. METHODS: Adults with a body mass index ≥35 kg/m2 approved for bariatric surgery were enrolled in a single-center, open-label, nonrandomized, single-dose clinical study (NCT No. 02406885; www. CLINICALTRIALS: gov). Apixaban PK and PD parameters were measured after a single 5 mg dose of the drug was given preoperatively and at 1, 6, and 12 months postoperatively in patients undergoing VSG and RYGB. Change in PK parameters was assessed as maximum concentration, time to maximum concentration, elimination half-life, and area under the concentration-time curve from 0-72 hours and change in PD parameters were assessed by chromogenic factor X activity. RESULTS: Of 33 patients enrolled, 28 (14 VSG, 14 RYGB) completed all visits and were analyzed. Most patients (89%) were female, with a mean age of 43.8 years and a body mass index of 48.7 kg/m2. Area under the concentration-time curve from 0-72 hours increased from baseline to 1 month (1009.1 to 1232.9 ng/mL/hr, P = .002), returned to baseline at 6 months (1000.9 ng/mL/hr, P = .88), and decreased significantly at 12 months (841.8 ng/mL/hr, P = .001). Maximum concentration did not change significantly. Predose factor X activity dropped significantly from 113% preoperatively to 89.8 % at 12 months postoperatively (P < .0001). Three-hour postdose factor X activity was significantly lower at 1, 6, and 12 months postoperatively versus preoperatively. However, the magnitude of the decrease from predose to 3-hour postdose was not significantly altered by surgery. CONCLUSION: The effect of either VSG or RYGB on apixaban PK and PD parameters is minimal. Factor X activity after 5 mg apixaban was lower in postoperative versus preoperative bariatric patients, but this effect appears to be primarily the result of a decrease in factor X activity from bariatric surgery itself and not a postoperative change in apixaban PK and PD parameters. Future studies should investigate the safety, efficacy, and clinical outcomes of apixaban and other direct oral anticoagulants perioperatively and beyond 12 months following bariatric surgery.

Incidence of and risk factors associated with care fragmentation following bariatric surgery.

BACKGROUND: Current readmission rates do not account for readmissions to nonindex hospitals and may underestimate the actual burden of readmissions. OBJECTIVE: Using a nationally representative database, we sought to characterize nonindex readmissions following bariatric surgery and identify risk factors associated with readmission to a nonindex hospital. SETTING: Patients in the United States undergoing elective bariatric surgery. METHODS: The Nationwide Readmissions Database was used to identify a weighted sample of 545,377 patients undergoing elective bariatric surgery between 2010 and 2014. Multivariable logistic regression analysis was used to identify factors associated with readmission to a nonindex hospital. RESULTS: Among all patients, 5.6% were readmitted at least once within 30 days. Within the subgroup of patients who were readmitted, 17.6% were readmitted to a different hospital than the index admission hospital. Factors independently associated with higher odds of readmission to a nonindex hospital were primary payor (Medicare: odds ratio [OR] = 1.48, 95% confidence interval [CI]: 1.24-1.75; Medicaid: OR = 1.56, 95% CI: 1.26-1.95), All Patients Refined Diagnosis Related Group severity of illness score (extreme versus minor: OR = 1.48; 95% CI: 1.04-2.09), primary procedure (laparoscopic sleeve gastrectomy versus laparoscopic gastric bypass: OR = 1.23; 95% CI: 1.05-1.44), hospital bed size (reference: small hospital, medium: OR = .52, 95% CI: .39-.70; large: OR = .47, 95% CI: .35-.63), hospital ownership (reference: private, nonprofit hospital, government: OR = 1.77, 95% CI: 1.32-2.37; private, investor-owned: OR = 1.33, 95% CI: 1.07-1.64), and hospital location (reference: metropolitan area >1 million population, metropolitan <1 million population: OR = .44, 95% CI: .34-.56; micropolitan/rural: OR = .44, 95% CI: .27-.73). CONCLUSION: Failure to account for readmissions to different hospitals may underestimate readmission rates by approximately 18%.

The reported validity and reliability of methods for evaluating continuing medical education: a systematic review.

PURPOSE: To appraise the reported validity and reliability of evaluation methods used in high-quality trials of continuing medical education (CME). METHOD: The authors conducted a systematic review (1981 to February 2006) by hand-searching key journals and searching electronic databases. Eligible articles studied CME effectiveness using randomized controlled trials or historic/concurrent comparison designs, were conducted in the United States or Canada, were written in English, and involved at least 15 physicians. Sequential double review was conducted for data abstraction, using a traditional approach to validity and reliability. RESULTS: Of 136 eligible articles, 47 (34.6%) reported the validity or reliability of at least one evaluation method, for a total of 62 methods; 31 methods were drawn from previous sources. The most common targeted outcome was practice behavior (21 methods). Validity was reported for 31 evaluation methods, including content (16), concurrent criterion (8), predictive criterion (1), and construct (5) validity. Reliability was reported for 44 evaluation methods, including internal consistency (20), interrater (16), intrarater (2), equivalence (4), and test-retest (5) reliability. When reported, statistical tests yielded modest evidence of validity and reliability. Translated to the contemporary classification approach, our data indicate that reporting about internal structure validity exceeded reporting about other categories of validity evidence. CONCLUSIONS: The evidence for CME effectiveness is limited by weaknesses in the reported validity and reliability of evaluation methods. Educators should devote more attention to the development and reporting of high-quality CME evaluation methods and to emerging guidelines for establishing the validity of CME evaluation methods.

Prevalence and predictors of postoperative thiamine deficiency after vertical sleeve gastrectomy.

BACKGROUND: As the vertical sleeve gastrectomy (VSG) becomes increasingly popular, its effect on postoperative micronutrient levels, such as thiamine, becomes more important. We previously found a 1.8% prevalence of thiamine deficiency in bariatric patients before surgery. OBJECTIVE: The aims of this study were to determine the prevalence of thiamine deficiency at our center after VSG and to explore possible predictors of postoperative thiamine levels. SETTING: University hospital, United States. METHODS: A retrospective chart review was performed on 147 bariatric patients between 18- and 65-years old who underwent VSG between April 2011 and February 2015. Demographic characteristics, preoperative body mass index (BMI), obesity-associated co-morbidities, alcohol intake, smoking habits, insurance type, calendar year of the procedure, occurrence of postoperative complications, and compliance with postoperative nutrition and follow-up appointment guidelines were extracted from clinical charts. We defined thiamine deficiency as<78 nM on any lab draw within 1 year after the VSG. The χ2, Fisher exact, and Mann-Whitney U tests, and multivariate logistic regression models were created to analyze the association of the above factors with thiamine deficiency after a VSG. RESULTS: Of 147 patients, 105 met inclusion criteria and were analyzed, of whom 27 (25.7%) had thiamine deficiency. Overall median age was 42 years (interquartile ratio: 36, 49). The majority of patients were either African Americans or Caucasian (47.6% and 44.8%, respectively), female (77.1%), and compliant with vitamins (81.0%). The overall mean preoperative BMI was 46.4 kg/m2. Patients with thiamine deficiency were more likely to be African American (66.7%, P = .024), have a larger preoperative BMI (P = .026), and to report repetitive episodes of nausea (59.3%, P = .002) and vomiting (44.4%, P = .001) at any of their postoperative appointments within 1 year after surgery. Compliance with vitamins did not differ between those with or without thiamine deficiency (70.4%, 84.6%, P = .10). After controlling for all factors, African American race (odds ratio [OR] 3.9, P = .019), higher preoperative BMI (OR 1.13, P = .001), nausea (OR 3.81, P = .02), and vomiting (OR 3.49, P = .032) were independent risk factors for the development of thiamine deficiency. CONCLUSIONS: We found an alarmingly high prevalence of thiamine deficiency in postoperative SG patients. This disorder may have serious consequences including Wernicke encephalopathy; hence, it is important to identify predictive demographic, postoperative, and behavioral factors so that appropriate measures can be taken to prevent thiamine deficiency in VSG patients.

Current evidence for the use of emerging radiologic technologies for disease screening.

Recent technologic advances in the field of radiology have resulted in the availability of several new tests with potential applications for disease screening. Presently, these tests are being marketed directly to patients as noninvasive means to provide peace of mind that they are disease free. Such assurance is appealing to many individuals, and some are willing to spend up to 1500 dollars to choose from a menu of available diagnostic options. Given that a physician's referral is unnecessary, many healthcare providers are unaware that such testing has taken place until their patients present to them with abnormal test results. In this review, we examine the evidence supporting the use of electron beam computed tomography for coronary artery disease screening, spiral computed tomography of the chest for lung cancer screening, computed tomographic colonography for colon cancer screening, and total-body computed tomography for general screening. Although some of these modalities show promise for the future, there is insufficient evidence to support the use of any of these testing methods for secondary prevention. The potential for harm associated with false-positive test results, false-negative test results, undue anxiety, and radiation exposure exists but requires further study to quantify actual risk.

A multi-level system quality improvement intervention to reduce racial disparities in hypertension care and control: study protocol.

BACKGROUND: Racial disparities in blood pressure control have been well documented in the United States. Research suggests that many factors contribute to this disparity, including barriers to care at patient, clinician, healthcare system, and community levels. To date, few interventions aimed at reducing hypertension disparities have addressed factors at all of these levels. This paper describes the design of Project ReD CHiP (Reducing Disparities and Controlling Hypertension in Primary Care), a multi-level system quality improvement project. By intervening on multiple levels, this project aims to reduce disparities in blood pressure control and improve guideline concordant hypertension care. METHODS: Using a pragmatic trial design, we are implementing three complementary multi-level interventions designed to improve blood pressure measurement, provide patient care management services and offer expanded provider education resources in six primary care clinics in Baltimore, Maryland. We are staggering the introduction of the interventions and will use Statistical Process Control (SPC) charting to determine if there are changes in outcomes at each clinic after implementation of each intervention. The main hypothesis is that each intervention will have an additive effect on improvements in guideline concordant care and reductions in hypertension disparities, but the combination of all three interventions will result in the greatest impact, followed by blood pressure measurement with care management support, blood pressure measurement with provider education, and blood pressure measurement only. This study also examines how organizational functioning and cultural competence affect the success of the interventions. DISCUSSION: As a quality improvement project, Project ReD CHiP employs a novel study design that specifically targets multi-level factors known to contribute to hypertension disparities. To facilitate its implementation and improve its sustainability, we have incorporated stakeholder input and tailored components of the interventions to meet the specific needs of the involved clinics and communities. Results from this study will provide knowledge about how integrated multi-level interventions can improve hypertension care and reduce disparities. TRIAL REGISTRATION: ClinicalTrials.gov NCT01566864.

Risk of complications after bariatric surgery among individuals with and without type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus is highly prevalent in obese individuals. Bariatric surgery, promoted for reducing the medical problems of morbid obesity, has been increasingly recognized for its particular efficacy in treating diabetes. However, before bariatric surgery can be recommended for the treatment of diabetes, its safety in the diabetic population must be known. We assessed the odds of complications after bariatric surgery in patients with and without diabetes. METHODS: This was a retrospective cohort study. Using an administrative database from 7 Blue Cross/Blue Shield plans, we identified 22,288 subjects who had undergone bariatric surgery from 2002 to 2008. From this cohort, we selected 6754 pairs of surgical patients (1 with and 1 without diabetes) matched by age, gender, health plan, and year of surgery. With conditional logistic regression analysis, we determined the relative odds of postoperative complications for ≤ 12 months after surgery in the 2 groups. RESULTS: The mean age of the surgical patients was 46 years, and 79% were women. Postoperative complications were rare and comparable in those with and without diabetes. The most common complications were nausea, vomiting, and abdominal pain (8.8%), the need for a gastric revision procedure (5.0%), and upper endoscopy (2.3%). Select cardiac, infectious, and renal complications occurred more frequently in the diabetic group. The incidence of cardiac complications was greater in the 2-3-month and 4-6-month postoperative periods (odds ratio [OR] 1.7, P < .001), the incidence of infectious complications was greater in the 0-1-month (OR 1.3, P < .02) and 4-6-month (OR 1.8, P < .001) periods, and the incidence of renal complications was greater in the 2-3-month postoperative period (OR 4.6, P = .01). CONCLUSIONS: Our findings support the safety of bariatric surgery in obese individuals with diabetes, although management strategies to avert postoperative cardiac, infectious, and renal complications in this population might be warranted.

Alterations of central dopamine receptors before and after gastric bypass surgery.

BACKGROUND: While bariatric surgery has proved highly successful at producing sustained weight loss, variability in treatment response persists. A better understanding of the pathophysiology of appetite and obesity may improve patient selection and management. Research into feeding behavior and satiety has focused on the role of dopamine in reward-based behaviors. Specifically, positron-emission computed tomography (PET) has demonstrated reduced brain dopamine receptor availability in obese subjects compared to controls. This may be due to a primary deficiency in dopamine receptors or to secondary dopamine receptor downregulation. We performed a preliminary study to investigate dopamine D2 receptor activity in obese subjects before and after laparoscopic Roux-en Y gastric bypass (LGBP). METHODS: Five female subjects, ages 20 to 38 years old with a mean body mass index of 45, underwent PET with [C-11] raclopride injection. Five regions of interest were studied: ventral striatum, anterior and posterior putamen, and anterior and posterior caudate nucleus. Repeat PET was performed at 6 weeks following LGBP. D2 receptor binding was compared within subjects pre- and post-surgery. Baseline D2 binding was also compared to historical nonobese controls. RESULTS: D2 receptor availability increased 6 weeks after gastric bypass surgery. The increase in receptor availability appeared roughly proportional to the amount of weight lost. No significant difference in D2 binding was seen between the obese subjects and historical nonobese controls. CONCLUSIONS: Brain available dopamine D2 binding appears to increase following GBP. This preliminary finding needs to be replicated in a larger population but suggests that diminished D2 binding in the obese may be due to D2 receptor downregulation. Changes in available dopamine receptor binding may play an important role in centrally mediated appetite suppression and resultant weight loss after LGBP.

Effectiveness of continuing medical education.

OBJECTIVES: Despite the broad range of continuing medical education (CME) offerings aimed at educating practicing physicians through the provision of up-to-date clinical information, physicians commonly overuse, under-use, and misuse therapeutic and diagnostic interventions. It has been suggested that the ineffective nature of CME either accounts for the discrepancy between evidence and practice or at a minimum contributes to this gap. Understanding what CME tools and techniques are most effective in disseminating and retaining medical knowledge is critical to improving CME and thus diminishing the gap between evidence and practice. The purpose of this review was to comprehensively and systematically synthesize evidence regarding the effectiveness of CME and differing instructional designs in terms of knowledge, attitudes, skills, practice behavior, and clinical practice outcomes. REVIEW METHODS: We formulated specific questions with input from external experts and representatives of the Agency for Healthcare Research and Quality (AHRQ) and the American College of Chest Physicians (ACCP) which nominated this topic. We systematically searched the literature using specific eligibility criteria, hand searching of selected journals, and electronic databases including: MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, The Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Database of Abstracts of Reviews of Effects (DARE), PsycINFO, and the Educational Resource Information Center (ERIC). Two independent reviewers conducted title scans, abstract reviews, and then full article reviews to identify eligible articles. Each eligible article underwent double review for data abstraction and assessment of study quality. RESULTS: Of the 68,000 citations identified by literature searching, 136 articles and 9 systematic reviews ultimately met our eligibility criteria. The overall quality of the literature was low and consequently firm conclusions were not possible. Despite this, the literature overall supported the concept that CME was effective, at least to some degree, in achieving and maintaining the objectives studied, including knowledge (22 of 28 studies), attitudes (22 of 26), skills (12 of 15), practice behavior (61 of 105), and clinical practice outcomes (14 of 33). Common themes included that live media was more effective than print, multimedia was more effective than single media interventions, and multiple exposures were more effective than a single exposure. The number of articles that addressed internal and/or external characteristics of CME activities was too small and the studies too heterogeneous to determine if any of these are crucial for CME success. Evidence was limited on the reliability and validity of the tools that have been used to assess CME effectiveness. Based on previous reviews, the evidence indicates that simulation methods in medical education are effective in the dissemination of psychomotor and procedural skills. CONCLUSIONS: Despite the low quality of the evidence, CME appears to be effective at the acquisition and retention of knowledge, attitudes, skills, behaviors and clinical outcomes. More research is needed to determine with any degree of certainty which types of media, techniques, and exposure volumes as well as what internal and external audience characteristics are associated with improvements in outcomes.