Weight loss differences seen between glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors for treatment of type 2 diabetes.

BACKGROUND: Weight loss is an advantageous quality for diabetic medications because it can improve insulin sensitivity and glucose control and reduce cardiovascular risk factors and comorbidities. Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors are both preferred agents for use after metformin therapy, and both cause modest weight loss. OBJECTIVE: The aim of this study was to evaluate the difference in weight loss between GLP-1 receptor agonists and SGLT-2 inhibitors in patients with type 2 diabetes (T2D). METHODS: This was a retrospective study that was conducted at a level 3 patient-centered medical home in Buffalo, NY. The participants were adults with T2D treated with either a GLP-1 receptor agonist or an SGLT-2 inhibitor, in addition to background diabetes medications, between January 1, 2012, and September 20, 2017. The outcome measures included the median weight loss after 6 months of consecutive therapy compared between the 2 antidiabetic classes and the median differences in blood pressure, glycosylated hemoglobin (A1C) levels, and renal function markers compared between the 2 classes. RESULTS: A total of 73 patients were included in the final analysis, with 31 receiving SGLT-2 inhibitors and 42 receiving therapy with GLP-1 receptor agonists. The SGLT-2 inhibitor cohort presented a median weight loss of -2.80 kg (interquartile range [IQR] -5.40 to -1.50), and the GLP-1 receptor agonist cohort presented a median weight loss of -1.15 kg (IQR -3.38 to 0.975) (P = 0.014). There were no statistically significant differences in A1C levels, blood pressure, or renal function markers. CONCLUSION: SGLT-2 inhibitors, when used in combination with background diabetes regimens, can lead to more statistically significant weight loss than GLP-1 receptor agonists without compromising renal function.

Reduction in Opiate Use, Pain, Nausea, and Length of Stay After Implementation of a Bariatric Enhanced Recovery After Surgery Protocol.

PURPOSE: Evaluate adherence to bariatric surgery enhanced recovery after surgery (ERAS) protocols in pre-operative, operative, and post-operative phases, and to compare opiate use, nausea control, and length of stay (LOS) versus historical controls. MATERIALS AND METHODS: A retrospective, observational cohort study was conducted to evaluate adherence to ERAS protocols and compare opiate and antiemetic use, pain intensity, and LOS versus those of traditional care (TC) patients preceding protocol implementation at Erie County Medical Center, a community-based hospital in Buffalo, NY, USA. RESULTS: One hundred ERAS and TC patients were compared. Patients were similar in age (42.5 years), gender (female, ~ 80%), race (~ 80 white), and BMI (47 kg/m2). The primary procedure performed was sleeve gastrectomy (89% ERAS, 86% TC). Protocol adherence was high for ERAS phases: prior to admission (85-98%), pre-operative (96-100%), operative (93-99%), post-anesthesia care unit (PACU) (55-61%), and floor (86-98%). Opiate morphine milligram equivalent (MME) was reduced in ERAS vs. TC in hospital by 73% (43.5 ± 42.4 vs. 160 ± 116; p < 0.001), discharge prescribing by 53% (34.8 ± 38.2 vs. 74 ± 125 MME; p = 0.003), and in total by 69% (78.3 ± 67.5 vs. 252 ± 160; p < 0.001). Despite lower opiate use, ERAS had lower pain intensity entering PACU (1.1 ± 1.8 vs. 1.9 ± 2.6; p < 0.011), leaving PACU (1.7 ± 1.5 vs. 2.9 ± 1.5; p < 0.001), and floor day 0 (5.0 ± 2.1 vs. 5.9 ± 1.8; p < 0.001). Fewer ERAS required antiemetic day 0 (63% vs. 94%; p < 0.001). ERAS were discharged in fewer hours than TC (41.1 ± 15.5 vs. 52.1 ± 18.9 h; p < 0.001). CONCLUSIONS: Bariatric surgery ERAS protocols were implemented with a high rate of adherence and yielded profound reduction in operative and post-operative opiate use while improving pain control and nausea management in hospital and decreasing LOS.

Knowledge and Attitudes of Student Pharmacists Regarding Polypharmacy and Deprescribing: A Cross-Sectional Study.

Pharmacists play a key role in deprescribing medications. Incorporation of this concept into pharmacy school curricula is important in ensuring that graduates can address the complex needs of an aging population. The aims of this study were to assess if and how student pharmacists were exposed to deprescribing within their curriculum, to assess students' perceptions regarding their attitudes, ability and confidence in deprescribing, and to assess if reported curricular exposure to this topic resulted in improved perceptions or objective knowledge assessment scores. An electronic survey was distributed to third- and fourth-year pharmacy students at 132 schools of pharmacy. The survey included three sections including: (i) demographics and questions on their exposure to deprescribing and other experiences within their curriculum; (ii) questions regarding their attitudes, ability, and confidence regarding deprescribing on a 5-point Likert-scale; (iii) a knowledge assessment on polypharmacy and deprescribing in the form of 12 multiple-choice questions. Likert-scale questions were analyzed as scales utilizing the mean score for items measuring student perceptions regarding deprescribing attitudes, ability, and confidence. Comparisons were made on each variable between students with and without curricular exposure to deprescribing using t-tests. Ninety-one responses were included in the analysis. Only 59.3% of respondents reported exposure to deprescribing in their didactic coursework. The mean scores on the polypharmacy and deprescribing knowledge assessments were 61.0% and 64.5%, respectively. Those with exposure to deprescribing concepts within their curriculum were more likely to agree that their school's curriculum prepared them to deprescribe in clinical practice (t(89) = -2.26, p = 0.03). Pharmacy schools should evaluate their curricula and consider the addition of specific deprescribing objectives and outcome measures for didactic and experiential training.

Student Pharmacist Perceptions of the Utility of a Medication Therapy Management-Based, Medication-Related, Falls Risk-Assessment Tool.

OBJECTIVE: To evaluate student pharmacists' perceptions of the Medication Fall Risk-Assessment Tool (MFRAT), a novel medication therapy management (MTM)-based clinical decision support tool.
DESIGN: A cross-sectional study
SETTING: One school of pharmacy
PARTICIPANTS: Participants were eligible if they had used the MFRAT as part of a wellness clinic or as part of required coursework prior to April 2016.
INTERVENTIONS: An online, author developed survey was distributed to assess previous MFRAT use, perceptions of the tool on a 5-point Likert-type scale, and qualitative feedback related in the areas of pharmacy workflow, clinical utility, and perceived patient acceptance.
MAIN OUTCOME MEASURE(S): Positive agreement to survey items served as the main outcome measure. A chi-square test was used to test for a difference in positive response between naive and experienced MFRAT users. Cronbach's alpha was calculated to assess internal consistency of items in each domain.
RESULTS: Of the 127 potential participants surveyed, 110 completed the survey for an overall response rate of 87%. Greater than 85% of participants found the MFRAT's report clinically useful. Eighty-seven percent of respondents agreed or strongly agreed that the information provided by the tool could easily be understood by patients. The most significant limitation to the use if the MFRAT in existing workflow was time required to enter a patient's medication profile.
CONCLUSION: The MFRAT was viewed positively in terms of clinical utility and perceived patient acceptance. Improvements will need to be made to make using the tool more time efficient in pharmacy MTM workflow.

Opportunities and Recommendations for Improving Medication Safety: Understanding the Medication Management System in Primary Care Through an Abstraction Hierarchy.

BACKGROUND: Despite making great strides in improving the treatment of diseases, the minimization of unintended harm by medication therapy continues to be a major hurdle facing the health care system. Medication error and prescription of potentially inappropriate medications (PIMs) represent a prevalent source of harm to patients and are associated with increased rates of adverse events, hospitalizations, and increased health care costs. Attempts to improve medication management systems in primary care have had mixed results. Implementation of new interventions is difficult because of complex contextual factors within the health care system. Abstraction hierarchy (AH), the first step in cognitive work analysis (CWA), is used by human factors practitioners to describe complex sociotechnical systems. Although initially intended for the nuclear power domain and interface design, AH has been used successfully to aid the redesign of numerous health care systems such as the design of decision support tools, mobile patient monitoring apps, and a telephone triage system. OBJECTIVE: This paper aims to refine our understanding of the primary care office in relation to a patient's medication through the development of an AH. Emphasis was placed on the elements related to medication safety to provide guidance for the design of a safer medication management system in primary care. METHODS: The AH development was guided by the methodology used by seminal CWA literature. It was initially developed by 2 authors and later fine-tuned by an expert panel of clinicians, social scientists, and a human factors engineer. It was subsequently refined until an agreement was reached. A means-ends analysis was performed and described for the nodes of interest. The model represents the primary care office space through functional purposes, values and priorities, function-related purposes, object-related processes, and physical objects. RESULTS: This model depicts the medication management system at various levels of abstraction. The resulting components must be balanced and coordinated to provide medical treatment with limited health care resources. Understanding the physical and informational constraints on activities that occur in a primary care office depicted in the AH defines areas in which medication safety can be improved. CONCLUSIONS: Numerous means-ends relationships were identified and analyzed. These can be further evaluated depending on the specific needs of the user. Recommendations for optimizing a medication management system in a primary care facility were made. Individual practices can use AH for clinical redesign to improve prescribing and deprescribing practices.

Bariatric Surgery: Remission of Inflammation, Cardiometabolic Benefits, and Common Adverse Effects.

Obesity is associated with increased mortality as a result of several comorbidities which occur in tandem with the obese state. Chronic inflammation is well documented in obesity, and evidence from numerous studies support the notion that the increased inflammation in individuals with obesity accentuates the comorbidities seen in this condition. The remission of comorbidities such as metabolic, cardiovascular, and neurological complications occurs following bariatric procedures. Bariatric surgery significantly reduces mortality and results in remarkable weight loss and reversal in several obesity-related comorbidities. There is indisputable evidence that the resolution of inflammation that occurs after bariatric surgery mitigates some of these comorbidities. With the increasing use of bariatric surgery for the treatment of severe obesity, it is pivotal to elucidate the underlying mechanisms responsible for the notable improvements seen after the procedure. This review summarizes underlying mechanisms responsible for the remission of obesity-related abnormalities and discusses the common adverse effects of bariatric surgery. Well-stratified, large-scale studies are still needed for a proper evaluation of these underlying mechanisms.

Interventions to deprescribe potentially inappropriate medications in the elderly: Lost in translation?

WHAT IS KNOWN AND OBJECTIVE: Use of potentially inappropriate medications (PIMs) remains common in older adults, despite the easy availability of screening tools such as the Beers and Screening Tool of Older Person's Prescriptions (STOPP) criteria. Multiple published studies have implemented these screening tools to encourage deprescribing of PIMs, with mixed results. Little is known about the reasons behind the success or failure of these interventions, or what could be done to improve their impact. Implementation science (IS) provides a set of theories, models and frameworks to address these questions. The goal of this study was to conduct a focused narrative review of the deprescribing literature through an IS lens-to determine the extent to which implementation factors were identified and the intermediate steps in the intervention were measured. A better understanding of the existing literature, including its gaps, may provide a roadmap for future research. METHODS: PubMed search from 2000-2019 using appropriate MeSH headings. INCLUSION CRITERIA: controlled trials or prospective cohort studies intended to reduce PIMs in the elderly that used hospitalizations and/or emergency department visits as outcome measures. Studies were reviewed to identify potential implementation factors (known as determinants), using the Consolidated Framework for Implementation Research (CFIR) as a guide. In addition, intermediate outcomes were extracted. RESULTS AND DISCUSSION: Of the 548 reviewed abstracts, 14 studies met the inclusion criteria and underwent detailed analysis. Of the 14 studies, 10 acknowledged potential implementation determinants that could be mapped onto CFIR. The most commonly identified determinant was the degree of pharmacist integration into the medical team (seven of 14 studies), which mapped onto the CFIR construct of 'networks and communication'. Several important CFIR constructs were absent in the reviewed literature. Intermediate measures were captured by 12 of the 14 reviewed papers, but the choice of measures was inconsistent across studies. WHAT IS NEW AND CONCLUSION: In recent high-quality studies of deprescribing interventions, we found limited acknowledgement of factors known to be important to successful implementation and inconsistent reporting of intermediate outcomes. These findings indicate missed opportunities to understand the factors underlying study outcomes. As a result, we run the risk of rejecting worthwhile interventions due to negative results, when the correct interpretation might be that they failed in implementation. In other words, they were 'lost in translation'. Studies that rigorously examine and report on the implementation process are needed to tease apart this important distinction.

A pharmacist-led pilot program to facilitate deprescribing in a primary care clinic.

OBJECTIVE: To develop and pilot-test a model in which a community-based clinical pharmacist was incorporated as part of a Medicare Annual Wellness Visit (AWV) to make deprescribing recommendations targeted at potentially inappropriate medications (PIMs) in seniors. SETTING: A family medicine patient-centered medical home (PCMH) clinic in Buffalo, NY. PRACTICE DESCRIPTION: Implementation and evaluation of a pilot program incorporating a pharmacist-provided medication review targeting PIMs in seniors as part of a Medicare AWV. PRACTICE INNOVATION: A community pharmacy-based clinical pharmacist provided face-to-face medication reviews for patients older than 65 years as part of their AWV with a focus on deprescribing PIMs. No clinical pharmacy service existed at the practice when this program was implemented. EVALUATION: Identified PIMs, pharmacist recommendations, recommendation acceptance rate, time spent on intervention, health care utilization at 6 months postvisit, and barriers to implementation. RESULTS: Of the 21 patients enrolled, 13 unique patients received a total of 20 deprescribing recommendations from the pharmacist. The overall acceptance rate for pharmacist recommendations was 20%. The pharmacist spent a mean (± SD) of 34 (± 6) minutes per patient encounter. One patient in the intervention group was hospitalized, and 1 was seen in the emergency department (ED) during the 6-month follow-up period compared with 1 patient in the control group who had an ED visit. We identified multiple logistical and organizational barriers to the implementation of the intervention. CONCLUSION: In this prospective pilot study, a workflow to include a pharmacist medication review to facilitate deprescribing in the primary care setting was tested. We encountered several barriers to integrating the pharmacist into the AWV workflow to deliver the intervention. Future pragmatic clinical trials are warranted to improve provider awareness and comfort with deprescribing PIMs in seniors.

Impact of Sleeve Gastrectomy on Psychiatric Medication Use and Symptoms.

Background: Sleeve gastrectomy (SG) has become the primary bariatric surgery procedure in the U.S. Over 50% of people presenting for surgery have psychiatric diagnoses. The study purpose was to evaluate change in anxiety and depression symptoms and medication use after SG. Methods: Subjects completing SG with a diagnosis of anxiety and/or depression treated with medication were retrospectively identified from the electronic medical record (EMR) of Synergy Bariatrics, a department of the Erie County Medical Center. Phone outreach was made to complete seven-point global impression of change scale classifying symptom improvement or worsening in the 3- to 6-month postoperative period. Improvement or worsening was defined as either all reported symptoms improving or worsening or ≥1 improving or worsening while remaining unchanged. If ≥1 symptom improved and worsened, it was classified as mixed. No change required the same profile before and after surgery. Medication, dose, and changes were identified by EMR, verified during interview and classified as no change, discontinued, decreased, or increased. Results: 59 subjects completed the interview. 21 subjects were diagnosed with anxiety. 13 (62%) had no change in therapy and 5 (24%) decreased. Symptoms improved in 12 (57%), worsened in 3 (14%), and mixed in 5 (24%). When symptoms improved, the same dose was present in 7/12 (58%) and dose decreased in 3 (25%). 51 subjects were diagnosed with depression. 32 (63%) had no change in therapy, 11 (21%) discontinued, and 4 (8%) decreased. Symptoms improved in 34 (67%), mixed in 10 (20%), worsened in 4 (8%), and unchanged in 3 (6%). When symptoms improved, the same regimen and dose was present in 21/34 cases (62%) and discontinued in 9 (26%). Conclusion: Anxiety symptoms improved in >50% of subjects at predominantly the same or reduced dosage. Depression symptoms improved in 67% and commonly without therapy change. These data suggest evidence that patients undergoing SG while on medication for anxiety or depression may have early symptom improvement on the same or lessened dosage.

Aspirin responsiveness changes in obese patients following bariatric surgery.

AIMS: Bariatric surgery has emerged as a promising treatment option for weight loss and to counter the metabolic consequences of obesity. Obesity has been linked to a hyperaggregable state, as well as a blunted response to aspirin. This pilot study assessed the hypothesis that bariatric surgery would lead to an improvement in aspirin-induced platelet inhibition and a reduction in platelet aggregability. METHODS: Fifteen patients scheduled to undergo bariatric surgery were administered two 7-day courses of aspirin 81 mg: the first course administered before surgery and the second was 3 months following surgery. Platelet aggregation was measured before and after each aspirin course using VerifyNow-Aspirin. The primary endpoint was the change in on-treatment aspirin reactive units (ARU) pre- and postsurgery. Data from bariatric surgery study patients were compared to data of normal weighted subjects gathered in a previous study. RESULTS: Roux-en-Y gastric bypass was performed in 80%, and 20% underwent sleeve gastrectomy. The mean starting body mass index (BMI) was 46.9 kg/m2 . Patients lost on average 24.5 kg, resulting in a postsurgical BMI of 38.5 kg/m2 . Postbariatric surgery, off-treatment ARU was significantly reduced from presurgery levels (602±59 vs 531±78; P=.035). On-aspirin platelet reactivity was also significantly reduced following surgery (469±60 vs 432±143, P=.03). There was a significant correlation between the extent of weight loss and the degree of improvement in on-aspirin platelet reactivity (r2 =.49, P=.024). Presurgery on-aspirin platelet reactivity was significantly higher in obese patients compared to normal weighted subjects (469±60 vs 419±52; P=.016) and reduced to the baseline after the surgery (432±63 vs 419±52; P=.54). CONCLUSION: Aspirin-induced platelet inhibition may be more potent following bariatric surgery. The mechanisms behind this improvement require further investigation.

Obesity and Inflammation and Altered Clopidogrel Pharmacokinetics and Pharmacodynamics.

BACKGROUND: Clopidogrel is a key antiplatelet drug that has substantial interpatient variability in pharmacodynamic response. Patients with lesser degrees of platelet inhibition in response to clopidogrel appear to be at increased risk of cardiovascular events. Obesity is an independent risk factor for cardiovascular morbidity and mortality due to atherothrombotic events and represents a group of patients who are in need of optimized antithrombotic therapy. Central to the obesity-related risk of atherothrombosis is a pro-thrombotic state characterized by increased levels of coagulation factors, impaired fibrinolysis and platelet hyper-reactivity, which results from the interaction among the features clustering in obesity: insulin resistance, inflammation, oxidative stress, and endothelial dysfunction. RESULTS: A number of reports have demonstrated that obesity is a risk factor for a reduced clopidogrel pharmacodynamic response. The inflammatory state associated with obesity, particularly a metabolic endotoxemia, may set in motion, a number of mechanisms that increase platelet reactivity, suppress cytochrome P450 enzyme activity, and increase platelet turnover, all contributing to a poor clopidogrel response. CONCLUSION: Comprehensive understanding of the mechanisms underlying obesity-related high onclopidogrel platelet reactivity will help in the optimization of antithrombotic therapy in this patient population.

Statin Adherence Rates in Patients Utilizing a Patient-Centered Medical Home-Based Pharmacy.

BACKGROUND: Medication nonadherence contributes to approximately US$290 billion per year in avoidable health-care spending. Statins are of particular interest because of their importance to patient outcomes, costs of treatment failure, and categorization as a Medicare star measure linked to financial reimbursement. OBJECTIVE: To evaluate statin adherence as defined by the proportion of days covered (PDC) among patients who use an embedded dispensing pharmacy in a patient-centered medical home (PCMH). METHODS: This study is a retrospective chart review of Lifetime Health Medical Group's electronic health record and third-party prescription claims data of statin therapy. Statin adherence is reported using PDC, with 0.8 or greater considered adherent for statin therapy. Statistics used include 2-sample unpaired t test to compare PDC between gender and age, and analysis of variance was used to determine differences in PDC among different insurance types. RESULTS: One hundred ninety-three patients were included, and 917 statin prescriptions were filled. PDC for statin medications in the population was 0.92 ± 0.20. Eighty-six percent of patients were considered adherent, with a PDC ≥80%. The average insurance and patient costs for brand prescriptions (n = 106) were US$233 ± US$143 and US$31 ± US$27, respectively, and costs for generic prescriptions (n = 811) were US$8 ± US$13 and US$7 ± US$6, respectively. CONCLUSION: Statin adherence rates for patients utilizing a dispensing pharmacy embedded in a large PCMH exceed the national average of 40% to 50% adherence.

Provider Perception of Pharmacy Services in the Patient-Centered Medical Home.

BACKGROUND: Despite the positive data on clinical outcomes, cost savings, and provider experience, no study has surveyed providers to evaluate what pharmacy services they find to be worthwhile. OBJECTIVE: To determine what clinical, cost/access, and educational pharmacy services providers in a patient-centered medical home (PCMH) consider worthwhile and the perceived barriers to successful pharmacist incorporation. METHODS: A cross-sectional online survey was distributed to primary care physicians, nurse practitioners, and physician assistants in a PCMH physician group. RESULTS: The survey response rate was 78%. Top-tier clinical services were identified as medication counseling, reconciliation, adherence assessment, polypharmacy assessment, and drug information. Formulary review was the only top-tier cost- or access-related service. Top-tier educational services included new black-boxed warnings, drug market withdrawals, and new drug reviews. Ninety-one percent of providers were comfortable referring to a pharmacist for diabetes medication selection and dose titration, but no other disease state eclipsed 75%. More than twice as many providers found the pharmacy service to be very or extremely valuable when the pharmacist is physically located in the office versus virtual interactions (70% vs 34%). CONCLUSION: Top-tier clinical, cost/access, and educational services considered worthwhile by providers in a PCMH have been identified. In addition to these services, when developing or evaluating a pharmacy service, special attention should be paid to provider preference for physical location in the office and perceived barriers to the pharmacist availability, concern over complex disease management competency and patient confusion as to the role of the pharmacist.

Pharmacist home visits: A 1-year experience from a community pharmacy.

OBJECTIVE: To provide experience on the methods and costs for delivering a large-scale community pharmacist home visit service. SETTING: Independent urban community pharmacy, Buffalo, NY. PRACTICE DESCRIPTION: Mobile Pharmacy Solutions provides traditional community pharmacy walk-in service and a suite of clinically oriented services, including outbound adherence calls linked to home delivery, payment planning, medication refill synchronization, adherence packaging, and pharmacist home visits. Pharmacist daily staffing included three dispensing pharmacists, one residency-trained pharmacist, and two postgraduate year 1 community pharmacy residents. PRACTICE INNOVATION: A large-scale community pharmacy home visit service delivered over a 1-year period. EVALUATION: Pharmacist time and cost to administer the home visit service as well as home visit request sources and description of patient demographics. RESULTS: A total of 172 visits were conducted (137 initial, 35 follow-up). Patients who received a home visit averaged 9.8 ± 5.2 medications and 3.0 ± 1.6 chronic disease states. On average, a home visit required 2.0 ± 0.8 hours, which included travel time. The percentages of visits completed by pharmacists and residents were 60% and 40%, respectively. The amounts of time to complete a visit were similar. Average home visit cost including pharmacist time and travel was $119 ($147 for a pharmacist, $77 for a resident). CONCLUSION: In this community pharmacy-based home visit service, costs are an important factor, with each pharmacist visit requiring 2 hours to complete. This experience provides a blueprint and real-world perspective for community pharmacies endeavoring to implement a home visit service and sets a foundation for future prospective trials to evaluate the impact of the service on important indicators of health and cost.

Distal small bowel bypass for weight regain after gastric bypass: safety and efficacy threshold occurs at <70% bypass.

BACKGROUND: For patients with poor weight loss (WL) after Roux-en-Y gastric bypass (RYGB) there are few well-tolerated and effective surgical options. Revision to distal bypass by shortening of the common channel (CC) induces significant WL but often produces protein calorie malnutrition (PCM) and severe diarrhea. OBJECTIVE: The aim of this study was to identify a safe and effective threshold for distal small bowel bypass when done for revision of gastric bypass. SETTING: Academic Institution, United States. METHODS: We performed revision of RYGB for WL in 20 patients by shortening the CC to a new length of 120-300 cm. The Roux limb length was unchanged. WL and PCM were monitored. A threshold for percent of small bowel bypassed at which PCM was avoided was retrospectively determined. WL was then compared in patients above and below this threshold. Five patients completed a 250-kcal mixed meal challenge before and 3 months after revision to determine selected gut hormone responses. RESULTS: Bypassing ≥70% small bowel resulted in PCM in 4 of 10 patients but in none of 10 patients below that threshold. PCM was observed as late as 2 years after revision and necessitated rerevision by lengthening of the CC in 3 patients. Additionally, nocturnal diarrhea was more common and more intractable when ≥70% bypass was done. Both groups had significant excess body WL over 2 years, but it was greater in patients with ≥70% bypass (47±19 versus 26±17; P<.05). A favorable gut hormone response was observed with 3-hour decrease in glucose-dependent insulinotropic peptide (GIP) by 25% and increase in glucagon-like peptide-1 (GLP-1) by 25%, whereas fasting peptide-YY (PYY) increased by 71% (P<.05 for all). CONCLUSIONS: Revision of RYGB to distal bypass when it is <70% of a patient's small bowel length results in an acceptable balance of WL and a positive safety profile. WL may be mediated through an enhanced gut hormone effect, an aversion to ingested fat, and possibly other mechanisms.

Increase in the mediators of asthma in obesity and obesity with type 2 diabetes: reduction with weight loss.

OBJECTIVE: To determine whether the expression of key asthma related genes, IL-4, LIGHT, LTBR, MMP-9, CCR-2, and ADAM-33 in mononuclear cells and the plasma concentration of nitric oxide metabolites (NOM) and MMP-9 are increased in the obese, obese type 2 diabetics (T2DM) and in morbidly obese patients prior to and after gastric bypass surgery (RYGB). DESIGN AND METHODS: The expression of these genes in MNC and plasma concentrations of these indices was measured in healthy lean and in obese with and without T2DM and following RYGB in obese T2DM. RESULTS: The expression of IL-4, MMP-9, LIGHT and CCR-2 and plasma NOM concentrations was significantly higher in the obese subjects and in obese T2DM patients than in normal subjects. The expression of IL-4, LIGHT, MMP-9, and CCR-2 expression was related to BMI and HOMA-IR. The expression of IL-4, LIGHT, LTBR, ADAM-33, MMP-9, and CCR-2 fell after RYGB surgery as did plasma concentrations of MMP-9 and NOM. CONCLUSIONS: Obesity with and without T2DM is associated with an increase in the expression of IL-4, LIGHT, MMP-9 and CCR-2; plasma NOM and MMP-9 concentrations are also increased. Following RYGB surgery and weight loss, the expression of these factors in MNC and plasma concentrations falls significantly.

Reduction in inflammation and the expression of amyloid precursor protein and other proteins related to Alzheimer's disease following gastric bypass surgery.

OBJECTIVE: Obesity and type 2 diabetes are associated with an increase in the incidence and prevalence of Alzheimer's disease (AD) and an impaired cognitive function. Because peripheral blood mononuclear cells (MNC) express amyloid precursor protein (APP), the precursor of ß-amyloid, which forms the pathognomonic plaques in the brain, we hypothesized that APP expression diminishes after the marked caloric restriction and weight loss associated with Roux-en-Y gastric bypass (RYGB) surgery. RESEARCH DESIGN AND METHODS: Fifteen type 2 diabetic patients with morbid obesity (body mass index, 52.1 ± 13 kg/m(2)) underwent RYGB, and the expression of inflammatory and AD-related genes was examined before and after 6 months in plasma and in MNC. RESULTS: Body mass index fell to 40.4 ± 11.1 kg/m(2) at 6 months after RYGB. There was a significant fall in plasma concentrations of glucose and insulin and in homeostasis model of assessment for insulin resistance. The expression of APP mRNA fell by 31 ± 9%, and that of protein fell by 36 ± 14%. In addition, there was a reduction in the expression of other AD-related genes including presinilin-2, ADAM-9, GSK-3ß, PICALM, SORL-1, and clusterin (P < 0.05 for all). Additionally, the expression of c-Fos, a subunit of the proinflammatory transcription factor AP-1, was also suppressed after RYGB. These changes occurred in parallel with reductions in other proinflammatory mediators including C-reactive protein and monocyte chemoattractant protein-1. CONCLUSIONS: Thus, the reversal of the proinflammatory state of obesity is associated with a concomitant reduction in the expression of APP and other AD-related genes in MNC. We conclude that obesity and caloric intake modulate the expression of APP in MNC. If indeed, this effect also occurs in the brain, this may have implications for the pathogenesis and the treatment of AD. It is relevant that cognitive function has been shown to improve with weight loss following bariatric surgery.

A national survey of hospice administrator and pharmacist perspectives on pharmacist services and the impact on medication requirements and cost.

Symptom management at the end of life relies heavily on medications. For this reason, pharmacists are an ideal addition to the interdisciplinary hospice team (IDT). The aim of this study is to characterize the utilization of pharmacists in hospices from the hospice administrator and pharmacist perspectives and to determine the impact utilization has on per diem medication requirement and costs. Surveys were sent to 2824 hospice administrators and 658 pharmacists to obtain their perceptions on what clinical, administrative, and dispensing services were being performed. Responses were returned by 9.4% of administrators and 12.6% of pharmacists. The majority of administrators and pharmacists reported a mix of clinical, administrative, and dispensing responsibilities. Medication requirements and costs were not significantly impacted as the administrator's perception of pharmacist clinical, administrative, or dispensing time increased from 0% to 100%.

Reduction in endotoxemia, oxidative and inflammatory stress, and insulin resistance after Roux-en-Y gastric bypass surgery in patients with morbid obesity and type 2 diabetes mellitus.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) results in profound weight loss and resolution of type 2 diabetes mellitus (T2DM). The mechanism of this remarkable transition remains poorly defined. It has been proposed that endotoxin (lipopolysaccharide [LPS]) sets inflammatory tone, triggers weight gain, and initiates T2DM. Because RYGB may diminish LPS from endogenous and exogenous sources, we hypothesized that LPS and the associated cascade of oxidative and inflammatory stress would diminish after RYGB. METHODS: Fifteen adults with morbid obesity and T2DM undergoing RYGB were studied. After an overnight fast, a baseline blood sample was collected the morning of surgery and at 180 days to assess changes in glycemia, insulin resistance, LPS, mononuclear cell nuclear factor (NF)-κB binding and mRNA expression of CD14, TLR-2, TLR-4, and markers of inflammatory stress. RESULTS: At 180 days after RYGB, subjects had a significant decrease in body mass index (52.1 ± 13.0 to 40.4 ± 11.1), plasma glucose (148 ± 8 to 101 ± 4 mg/dL), insulin (18.5 ± 2.2 mµU/mL to 8.6 ± 1.0 mµU/mL) and HOMA-IR (7.1 ± 1.1 to 2.1 ± 0.3). Plasma LPS significantly reduced by 20 ± 5% (0.567 ± 0.033 U/mL to 0.443 ± 0.022 E U/mL). NF-κB DNA binding decreased significantly by 21 ± 8%, whereas TLR-4, TLR-2, and CD-14 expression decreased significantly by 25 ± 9%, 42 ± 8%, and 27 ± 10%, respectively. Inflammatory mediators CRP, MMP-9, and MCP-1 decreased significantly by 47 ± 7% (10.7 ± 1.6 mg/L to 5.8 ± 1.0 mg/L), 15 ± 6% (492 ± 42 ng/mL to 356 ± 26 ng/mL) and 11 ± 4% (522 ± 35 ng/mL to 466 ± 35 ng/mL), respectively. CONCLUSION: LPS, NF-κB DNA binding, TLR-4, TLR-2, and CD14 expression, CRP, MMP-9, and MCP-1 decreased significantly after RYGB. The mechanism underlying resolution of insulin resistance and T2DM after RYGB may be attributable, at least in part, to the reduction of endotoxemia and associated proinflammatory mediators.