A Randomized, Double-Blind Study of Larazotide Acetate to Prevent the Activation of Celiac Disease During Gluten Challenge

OBJECTIVES: In patients with celiac disease, enteropathy is caused by the entry of gluten peptides into the lamina propria of the intestine, in which their immunogenicity is potentiated by tissue transglutaminase (tTG) and T-helper type 1–mediated immune responses are triggered. Tight junction disassembly and paracellular permeability are believed to have an important role in the transport of gluten peptides to the lamina propria. Larazotide acetate is a tight-junction regulator peptide that, in vitro, prevents the opening of intestinal epithelial tight junctions. The aim of this study was to evaluate the efficacy and tolerability of larazotide acetate in protecting against gluten-induced intestinal permeability and gastrointestinal symptom severity in patients with celiac disease. METHODS: In this dose-ranging, placebo-controlled study, 86 patients with celiac disease controlled through diet were randomly assigned to larazotide acetate (0.25, 1, 4, or 8 mg) or placebo three times per day with or without gluten challenge (2.4 g/day) for 14 days. The primary efficacy outcome was the urinary lactulose/mannitol (LAMA) fractional excretion ratio. Secondary endpoints included gastrointestinal symptom severity, quality-of-life measures, and antibodies to tTG. RESULTS: LAMA measurements were highly variable in the outpatient setting. The increase in LAMA ratio associated with the gluten challenge was not statistically significantly greater than the increase in the gluten-free control. Among patients receiving the gluten challenge, the difference in the LAMA ratios for the larazotide acetate and placebo groups was not statistically significant. However, larazotide acetate appeared to limit gluten-induced worsening of gastrointestinal symptom severity as measured by the Gastrointestinal Symptom Rating Scale at some lower doses but not at the higher dose. Symptoms worsened significantly in the gluten challenge–placebo arm compared with the placebo–placebo arm, suggesting that 2.4 g of gluten per day is sufficient to induce reproducible gluten toxicity. Larazotide acetate was generally well tolerated. No serious adverse events were observed. The most common adverse events were headache and urinary tract infection. CONCLUSIONS: LAMA variability in the outpatient setting precluded accurate assessment of the effect of larazotide acetate on intestinal permeability. However, some lower doses of larazotide acetate appeared to prevent the increase in gastrointestinal symptom severity induced by gluten challenge

Remission and Relapse of Dyslipidemia After Vertical Sleeve Gastrectomy vs Roux-en-Y Gastric Bypass in a Racially and Ethnically Diverse Population.

IMPORTANCE: The comparative effectiveness of the most common operations in the long-term management of dyslipidemia is not clear. OBJECTIVE: To compare 4-year outcomes associated with vertical sleeve gastrectomy (VSG) vs Roux-en-Y gastric bypass (RYGB) for remission and relapse of dyslipidemia. DESIGN, SETTING, AND PARTICIPANTS: This retrospective comparative effectiveness study was conducted from January 1, 2009, to December 31, 2016, with follow-up until December 31, 2018. Participants included patients with dyslipidemia at the time of surgery who underwent VSG (4142 patients) or RYGB (2853 patients). Patients were part of a large integrated health care system in Southern California. Analysis was conducted from January 1, 2018, to December 31, 2021. EXPOSURES: RYGB and VSG. MAIN OUTCOMES AND MEASURES: Dyslipidemia remission and relapse were assessed in each year of follow-up for as long as 4 years after surgery. RESULTS: A total of 8265 patients were included, with a mean (SD) age of 46 (11) years; 6591 (79.8%) were women, 3545 (42.9%) were Hispanic, 1468 (17.8%) were non-Hispanic Black, 2985 (36.1%) were non-Hispanic White, 267 (3.2%) were of other non-Hispanic race, and the mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 44 (7) at the time of surgery. Dyslipidemia outcomes at 4 years were ascertained for 2168 patients (75.9%) undergoing RYGB and 3999 (73.9%) undergoing VSG. Remission was significantly higher for those who underwent RYGB (824 [38.0%]) compared with VSG (1120 [28.0%]) (difference in the probability of remission, 0.10; 95% CI, 0.01-0.19), with no differences in relapse (455 [21.0%] vs 960 [24.0%]). Without accounting for relapse, remission of dyslipidemia after 4 years was 58.9% (1279) for those who underwent RYGB and 51.9% (2079) for those who underwent VSG. Four-year differences between operations were most pronounced for patients 65 years or older (0.39; 95% CI, 0.27-0.51), those with cardiovascular disease (0.43; 95% CI, 0.24-0.62), or non-Hispanic Black patients (0.13; 95% CI, 0.01-0.25) and White patients (0.13; 95% CI, 0.03-0.22). CONCLUSIONS AND RELEVANCE: In this large, racially and ethnically diverse cohort of patients who underwent bariatric and metabolic surgery in clinical practices, RYGB was associated with higher rates of dyslipidemia remission after 4 years compared with VSG. However, almost one-quarter of all patients experienced relapse, suggesting that patients should be monitored closely throughout their postoperative course to maximize the benefits of these operations for treatment of dyslipidemia

Baseline Psychosocial, Environmental, Health, and Behavioral Correlates of 1- and 3-Year Weight Loss After Bariatric Surgery

PURPOSE: Weight loss surgery is an effective, long-term treatment for severe obesity but individual response to surgery varies widely. The purpose of this study was to test a comprehensive theoretical model of factors that may be correlated with the greatest surgical weight loss at 1-3 years following surgery. Such a model would help determine what predictive factors to measure when patients are preparing for surgery that may ensure the best weight outcomes. MATERIALS AND METHODS: The Bariatric Experience Long Term (BELONG) study collected self-reported and medical record-based baseline information as correlates of 1- and 3-year % total weight loss (TWL) in n = 1341 patients. Multiple linear regression was used to determine the associations between 120 baseline variables and %TWL. RESULTS: Participants were 43.4 ± 11.3 years old, Hispanic or Black (52%; n = 699), women (86%; n = 1149), and partnered (72%; n = 965) and had annual incomes of ≥ $51,000 (60%; n = 803). A total of 1006 (75%) had 3-year follow-up weight. Regression models accounted for 10.1% of the variance in %TWL at 1-year and 13.6% at 3 years. Only bariatric operation accounted for a clinically meaningful difference (~ 5%) in %TWL at 1-year. At 3 years after surgery, only bariatric operation, Black race, and BMI ≥ 50 kg/m CONCLUSIONS: Our findings combined with many others support a move away from extensive screening and selection of patients at the time of surgery to a focus on improving access to this treatment

Comparative Safety and Effectiveness of Roux-en-Y Gastric Bypass and Sleeve Gastrectomy for Weight Loss and Type 2 Diabetes Across Race and Ethnicity in the PCORnet Bariatric Study Cohort

IMPORTANCE: Bariatric surgery is the most effective treatment for severe obesity; yet it is unclear whether the long-term safety and comparative effectiveness of these operations differ across racial and ethnic groups. OBJECTIVE: To compare outcomes of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) across racial and ethnic groups in the National Patient-Centered Clinical Research Network (PCORnet) Bariatric Study. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective, observational, comparative effectiveness cohort study that comprised 25 health care systems in the PCORnet Bariatric Study. Patients were adults and adolescents aged 12 to 79 years who underwent a primary (first nonrevisional) RYGB or SG operation between January 1, 2005, and September 30, 2015, at participating health systems. Patient race and ethnicity included Black, Hispanic, White, other, and unrecorded. Data were analyzed from July 1, 2021, to January 17, 2022. EXPOSURE: RYGB or SG. OUTCOMES: Percentage total weight loss (%TWL); type 2 diabetes remission, relapse, and change in hemoglobin A1c (HbA1c) level; and postsurgical safety and utilization outcomes (operations, interventions, revisions/conversions, endoscopy, hospitalizations, mortality, 30-day major adverse events) at 1, 3, and 5 years after surgery. RESULTS: A total of 36 871 patients (mean [SE] age, 45.0 [11.7] years; 29 746 female patients [81%]) were included in the weight analysis. Patients identified with the following race and ethnic categories: 6891 Black (19%), 8756 Hispanic (24%), 19 645 White (53%), 826 other (2%), and 783 unrecorded (2%). Weight loss and mean reductions in HbA1c level were larger for RYGB than SG in all years for Black, Hispanic, and White patients (difference in 5-year weight loss: Black, -7.6%; 95% CI, -8.0 to -7.1; P \u3c .001; Hispanic, -6.2%; 95% CI, -6.6 to -5.9; P \u3c .001; White, -5.9%; 95% CI, -6.3 to -5.7; P \u3c .001; difference in change in year 5 HbA1c level: Black, -0.29; 95% CI, -0.51 to -0.08; P = .009; Hispanic, -0.45; 95% CI, -0.61 to -0.29; P \u3c .001; and White, -0.25; 95% CI, -0.40 to -0.11; P = .001.) The magnitude of these differences was small among racial and ethnic groups (1%-3% of %TWL). Black and Hispanic patients had higher risk of hospitalization when they had RYGB compared with SG (hazard ratio [HR], 1.45; 95% CI, 1.17-1.79; P = .001 and 1.48; 95% CI, 1.22-1.79; P \u3c .001, respectively). Hispanic patients had greater risk of all-cause mortality (HR, 2.41; 95% CI, 1.24-4.70; P = .01) and higher odds of a 30-day major adverse event (odds ratio, 1.92; 95% CI, 1.38-2.68; P \u3c .001) for RYGB compared with SG. There was no interaction between race and ethnicity and operation type for diabetes remission and relapse. CONCLUSIONS AND RELEVANCE: Variability of the comparative effectiveness of operations for %TWL and HbA1c level across race and ethnicity was clinically small; however, differences in safety and utilization outcomes were clinically and statistically significant for Black and Hispanic patients who had RYGB compared with SG. These findings can inform shared decision-making regarding bariatric operation choice for different racial and ethnic groups of patients

Fats and Factors: Lipid Profiles Associate with Personality Factors and Suicidal History in Bipolar Subjects

Polyunsaturated fatty acids (PUFA) have shown efficacy in the treatment of bipolar disorder, however their specific role in treating the illness is unclear. Serum PUFA and dietary intakes of PUFA associate with suicidal behavior in epidemiological studies. The objective of this study was to assess serum n-3 and n-6 PUFA levels in bipolar subjects and determine possible associations with suicidal risk, including suicidal history and relevant personality factors that have been associated with suicidality. We studied 27 bipolar subjects using the NEO-PI to assess the big five personality factors, structured interviews to verify diagnosis and assess suicidal history, and lipomics to quantify n-3 and n-6 PUFA in serum. We found positive associations between personality factors and ratios of n-3 PUFA, suggesting that conversion of short chain to long chain n-3s and the activity of enzymes in this pathway may associate with measures of personality. Thus, ratios of docosahexaenoic acid (DHA) to alpha linolenic acid (ALA) and the activity of fatty acid desaturase 2 (FADS2) involved in the conversion of ALA to DHA were positively associated with openness factor scores. Ratios of eicosapentaenoic acid (EPA) to ALA and ratios of EPA to DHA were positively associated with agreeableness factor scores. Finally, serum concentrations of the n-6, arachidonic acid (AA), were significantly lower in subjects with a history of suicide attempt compared to non-attempters. The data suggest that specific lipid profiles, which are controlled by an interaction between diet and genetics, correlate with suicidal history and personality factors related to suicidal risk. This study provides preliminary data for future studies to determine whether manipulation of PUFA profiles (through diet or supplementation) can affect personality measures and disease outcome in bipolar subjects and supports the need for further investigations into individualized specific modulations of lipid profiles to add adjunctive value to treatment paradigms

Acceptability of financial incentives and penalties for encouraging uptake of healthy behaviours: focus groups

BACKGROUND: There is evidence that financial incentive interventions, which include both financial rewards and also penalties, are effective in encouraging healthy behaviours. However, concerns about the acceptability of such interventions remain. We report on focus groups with a cross-section of adults from North East England exploring their acceptance of financial incentive interventions for encouraging healthy behaviours amongst adults. Such information should help guide the design and development of acceptable, and effective, financial incentive interventions. METHODS: Eight focus groups with a total of 74 adults were conducted between November 2013 and January 2014 in Newcastle upon Tyne, UK. Focus groups lasted approximately 60 minutes and explored factors that made financial incentives acceptable and unacceptable to participants, together with discussions on preferred formats for financial incentives. Verbatim transcripts were thematically coded and analysed in Nvivo 10. RESULTS: Participants largely distrusted health promoting financial incentives, with a concern that individuals may abuse such schemes. There was, however, evidence that health promoting financial incentives may be more acceptable if they are fair to all recipients and members of the public; if they are closely monitored and evaluated; if they are shown to be effective and cost-effective; and if clear health education is provided alongside health promoting financial incentives. There was also a preference for positive rewards rather than negative penalties, and for shopping vouchers rather than cash incentives. CONCLUSIONS: This qualitative empirical research has highlighted clear suggestions on how to design health promoting financial incentives to maximise acceptability to the general public. It will also be important to determine the acceptability of health promoting financial incentives in a range of stakeholders, and in particular, those who fund such schemes, and policy-makers who are likely to be involved with the design, implementation and evaluation of health promoting financial incentive schemes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-015-1409-y) contains supplementary material, which is available to authorized users

Intravenous mycophenolate mofetil: safety, tolerability, and pharmacokinetics

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72291/1/j.1399-0012.2000.140301.x.pd

Acceptability of financial incentives for breastfeeding: thematic analysis of readers' comments to UK online news reports.

BACKGROUND: Whilst it is recommended that babies are breastfed exclusively for the first six months, many mothers do not maintain breastfeeding for this length of time. Previous research confirms that women and midwives value financial incentives for breastfeeding, but limited research has explored the wider acceptability of these interventions to the general public. This paper examines opinion towards financial incentives for breastfeeding using reader responses to UK on-line media coverage of a study undertaken in this area. METHODS: This study used netnography to undertake a thematic analysis of 3,373 reader comments posted in response to thirteen articles, published in November 2013, which reported findings from a feasibility study of financial incentives for breastfeeding. All articles were published on one of six UK news websites that achieved a monthly audience of at least five million viewers across laptop and desktop computers and mobile devices during April-May 2013. RESULTS: Nine analytical themes were identified, with a majority view that financial incentives for breastfeeding are unacceptable. These themes cover a range of opinions: from negligent parents unable to take responsibility for their own actions; through to psychologically vulnerable members of society who should be protected from coercion and manipulation; to capable and responsible women who can, and should be allowed to, make their own decisions. Many views focused on the immediate costs of the intervention, concluding that this was something that was currently unaffordable to fund (e.g. by the NHS). Others contrasted the value of the incentive against other 'costs' of breastfeeding. There was some consideration of the issue of cost-effectiveness and cost-saving, where the potential future benefit from initial investment was identified. Many commenters identified that financial incentives do not address the many structural and cultural barriers to breastfeeding. CONCLUSIONS: Overall, those commenting on the on-line UK news articles viewed financial incentives for breastfeeding as unacceptable and that alternative, structural, interventions were likely to be more effective. Further consideration of how best to conduct internet-based qualitative research to elicit opinion towards public health issues is required