Lower Baseline Weight Research Articles

Association between variants in TCF7L2, CTRB1/2, and GLP-1R genes and response to therapy with glucagon-like peptide-1 receptor agonists

ABSTRACT Objectives The factors determining the response to treatment with glucagon-like peptide-1 receptor agonists (GLP-1- RAs) have not been clarified. The present study investigated the association between polymorphisms in TCF7L2, CTRB1/2, and GLP-1 R genes and response to GLP-1 RAs regarding glycemic control and weight loss among Greek patients with type 2 diabetes mellitus (T2DM). Methods Patients (n = 191) treated with GLP-1 RAs for at least 6 months were included. Participants were genotyped for TCF7L2 rs7903146 (C>T), CTRB1/2 rs7202877 (T>G) and GLP-1 R rs367543060 (C>T) polymorphisms. Clinical and laboratory parameters were measured before, 3, and 6 months after treatment initiation. The patients were classified into responders and non-responders according to specific criteria. Results Carriers of at least one rs7903146 ‘T’ allele and rs7202877 ‘G’ allele presented similar glucose control and weight loss response to GLP-1 RAs with the respective homozygous wild-type genotypes [odds ratio (OR): 1.08, 95% confidence interval (CI): 0.5, 2.31, p = 0.85 and OR: 1.35, 95% CI: 0.66, 2.76, p = 0.42; OR: 1.4, 95% CI: 0.56, 3.47, p = 0.47 and OR: 1.28, 95% CI: 0.55, 2.98, p = 0.57, respectively]. Regarding the GLP-1 R polymorphism, all participants were homozygous for the wild-type allele; thus, no comparisons were feasible. Female sex (p = 0.03) and lower baseline weight (p = 0.024) were associated with an improved glycemic and weight loss response, respectively. Conclusion There is no evidence suggesting a role for the variants studied in response to GLP-1 RA therapy in people with T2DM. However, specific demographic and clinical factors may be related to a better response to treatment with these agents.

Body mass index and weight loss as risk factors for poor outcomes in patients with idiopathic pulmonary fibrosis: a systematic review and meta-analysis

Objective The association between nutritional status and prognosis of idiopathic pulmonary fibrosis (IPF) remains unclear. This systematic review and meta-analysis aimed to explore the effect of body mass index (BMI) and weight loss on the prognosis of IPF patients. Methods We accumulated studies on IPF, BMI, and weight loss from databases including PubMed, Embase, Web of science, Scopus, Ovid and Cochrane Library up to 4 August 2023. Using Cox proportional hazard regression model for subgroup analysis, hazard ratio (HR) and 95% confidence intervals (CI) for BMI in relation to mortality, acute exacerbation (AE), and hospitalization in IPF patients were calculated, and HR, odds ratio (OR), and 95% CI for weight loss corresponding to IPF patient mortality were assessed. Sensitivity analysis was peformed by eliminating every study one by one, and publication bias was judged by Egger’s test and trim-and-fill method. Results A total of 34 eligible studies involving 18,343 IPF patients were included in the meta-analysis. The pooled results by univariate Cox regression analysis showed that baseline BMI was a predictive factor for IPF mortality (HR = 0.93, 95%CI = [0.91, 0.94]). Furthermore, the results by the multivariable regression model indicated that baseline BMI was an independent risk factor for predicting IPF mortality (HR = 0.94, 95%CI = [0.91, 0.98]). Weight loss was identified as a risk factor for IPF mortality (HR = 2.74, 95% CI = [2.12, 3.54]; OR = 4.51, 95% CI = [1.72, 11.82]) and there was no predictive value of BMI for acute exacerbation (HR = 1.00, 95% CI= [0.93, 1.07]) or hospitalization (HR = 0.95, 95% CI = [0.89, 1.02]). Conclusion Low baseline BMI and weight loss in the course of IPF may indicate a high risk of mortality in patients with IPF, so it is meaningful to monitor and manage the nutritional status of IPF patients, and early intervention should be conducted for low BMI and weight loss.

GRADUATE I AND II: Factors that may influence participant response to subcutaneous gantenerumab

AbstractBackgroundGRADUATE I (NCT03444870) and GRADUATE II (NCT03443973) were two Phase III trials that investigated the efficacy and safety of gantenerumab, a subcutaneous fully human monoclonal antibody that binds aggregated forms of amyloid‐beta, in participants with early Alzheimer’s disease (AD). Although the studies did not meet their primary endpoints, participant characteristics that might influence response to gantenerumab were evaluated.MethodEligible participants with early AD (mild cognitive impairment [MCI] due to AD or mild AD dementia) were randomized 1:1 to receive gantenerumab or placebo. Gantenerumab‐treated participants were up‐titrated to 510 mg subcutaneous gantenerumab every 2 weeks. The primary endpoint was change from baseline to Week 116 in Clinical Dementia Rating‐Sum of Boxes (CDR‐SB). Secondary endpoints of cognition (ADAS‐Cog13) and function (ADCS‐ADL, FAQ) were assessed. Pre‐specified and exploratory post‐hoc subgroup analyses on these endpoints were performed.ResultAcross endpoints, there were consistent trends towards larger point estimates of gantenerumab treatment effect compared with placebo at Week 116 in males (using CDR‐SB as representative example: GRADUATE I: 16% relative reduction (RR); GRADUATE II: 17% RR) vs females (GRADUATE I: 3% RR; GRADUATE II: –2% RR) and participants with MCI (GRADUATE I:15% RR; GRADUATE II:10% RR) vs mild AD (GRADUATE I: 4% RR; GRADUATE II: 2% RR). This pattern was not consistently seen when using CDR‐Global Score (0.5 vs >0.5) to define disease stage. Compliers, defined as participants who received ≥90% of the intended cumulative dose, had an increased point estimate of treatment effect (CDR‐SB: GRADUATE I: 17% RR; GRADUATE II: 18% RR) vs non‐compliers (CDR‐SB: GRADUATE I: –1% RR; GRADUATE II: –3% RR). In a pooled analysis, a larger point estimate of treatment effect vs placebo was observed in East‐Asian vs Non‐East‐Asian countries (CDR‐SB: RR 38% vs 5%). The East‐Asian population had lower baseline weight, greater treatment compliance, and accordingly higher plasma exposure, than the Non‐East‐Asian population, suggesting this observation is not driven by racial differences in treatment response.ConclusionSubgroup analyses in the GRADUATE studies provide insights into participant characteristics that may influence the degree of clinical response to gantenerumab treatment. Higher gantenerumab exposure may result in greater clinical efficacy.

Are Different Modes of Weight Loss Associated with Survival in Oropharyngeal Cancer?

Patients with oropharyngeal squamous cell carcinomas (OPSCC) often lose weight during radical radiotherapy (RT). Nutritional intervention is required in case of severe weight loss. However, weight loss does not provide full insight into body composition changes. Muscle mass is emerging as an important prognostic factor in cancer patients. We employed on-treatment cone-beam CT (CBCT) scans to monitor muscle mass and weight loss under the hypothesis that different modes of weight loss exist and may impact overall survival (OS). A retrospective analysis of 197 OPSCC patients treated with definitive or adjuvant (chemo)RT. Weekly weight measurements & CBCTs were collected. Patients were included if at least two time-points were available and the interval between the first and last was between 15-50 days. CBCTs were normalized to account for calibration differences between treatment machines. An in-house deep-learning model automatically segmented the skeletal muscle compartment at C3 on all CBCTs. Segmentations were visually checked and failures removed. Skeletal muscle volume (SMV, in mm3) was extracted after thresholding for intra-muscular fat. Relative changes in weight & SMV were then calculated. Linear models were fitted to each trajectory for every patient and slopes were estimated. The following weight & SMV categories were defined to generate equal groups: lost (more than 0.4 standard deviations (SDs) below the mean (M)), maintained (within +/- 0.4 SDs of M) or gained (more than 0.4 SDs above the M). Table 1 highlights the nine modes of body composition change. The prognostic value of these was investigated in multivariable Cox models accounting for age, sex, disease stage, oropharynx subsite, smoking status, performance status (PS), tumor p16 status, baseline weight & SMV, and treatment prescribed. The primary endpoint was OS. Mean weight & SMV changes during treatment were -0.047±0.001% & -0.044±0.019% per day. In multivariable analysis, gaining weight & losing SMV was identified as a significant risk factor for OS (p = 0.01, hazard ratio [95% CI]: 4.59 [1.40-15.10]). In this sub-group, mean weight & SMV change were +0.054±0.008% & -0.396±0.030% per day. PS>2 (p<0.001) & lower baseline weight (p = 0.02) were also significantly associated with OS. Patients losing substantial SMV but mildly gaining weight have significantly worse OS than others. This suggests there exists a group of patients where nutritional support is needed, but not offered because they maintain weight during treatment. Although our results need validation, continual monitoring of muscle condition during RT would allow these patients to be identified and promptly targeted for nutritional support.

Changes in body mass index, weight, and waist-to-hip ratio over five years in HIV-positive individuals in the HIV Heart Aging Study compared to the general population

PurposeOverweight and obesity have increased in people living with HIV (PLH). Our study evaluated weight, body-mass-index (BMI), and waist-to-hip ratio (WHR) change over 5 years of follow-up in PLH compared to the general population.MethodsHIV-positive participants in the HIV Heart Aging (HIVH) study were matched 1:2 by age and sex with HIV-negative controls of the population-based Heinz Nixdorf Recall (HNR) study. Both studies were recruited in the German Ruhr area. The association between HIV and weight, BMI, and WHR changes was examined using linear regression. Regression models were adjusted for parameters potentially affecting weight gain.ResultsThe matched HIVH and HNR participants (N = 585 and N = 1170, respectively; 14.7% females) had a mean age of 55 years at baseline. Despite the lower baseline weight (− 6 kg, 95% CI − 7.46 to − 4.59), the linear regression showed greater absolute and relative weight and BMI increases after 5 years in HIVH compared to HNR. Adjusting the linear regression models for smoking amplified that HIVH had a higher absolute and relative weight difference of 0.7 kg or ~ 1% compared to HNR after 5 years (95% Cl 0.1 to 1.3 and 0.2 to 1.6, respectively). Adjusting for HDL, LDL, systolic blood pressure, and diabetes mellitus did not affect the results.ConclusionsPLH had lower weight than the general population at baseline and after 5 years, but experienced greater increases in body weight after 5 years. WHR change after 5 years was lower in PLH compared to the general population, despite a higher WHR at baseline.

Clinical and Genetic Predictors of Glycemic Control and Weight Loss Response to Liraglutide in Patients with Type 2 Diabetes.

Background: Evidence suggests a heterogeneous response to therapy with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes mellitus (T2DM). The aim of this study is to identify the genetic and clinical factors that relate to glycemic control and weight loss response to liraglutide among patients with T2DM. Methods: The medical records of 116 adults with T2DM (51% female, mean body mass index 35.4 ± 6.4 kg/m2), who had been on treatment with liraglutide for at least 6 months and were genotyped for CTRB1/2 rs7202877 (T > G) polymorphism, were evaluated. Clinical and laboratory parameters were measured at baseline, 3, and 6 months after initiating liraglutide treatment. The good glycemic response was defined as one of the following: (i) achievement of glycated hemoglobin (HbA1c) < 7% (ii) reduction of the baseline HbA1c by ≥1%, and (iii) maintenance of HbA1c < 7% that a patient already had before switching to liraglutide. Weight loss responders were defined as subjects who lost ≥3% of their baseline weight. Results: Minor allele frequency was 16%. Individuals were classified as glycemic control and weight loss responders (81 (70%) and 77 (66%), respectively). Carriers of the rs7202877 polymorphic allele had similar responses to liraglutide treatment in terms of glycemic control (odds ratio (OR): 1.25, 95% confidence interval (CI): 0.4, 3.8, p = 0.69) and weight loss (OR: 1.12, 95% CI: 0.4, 3.2, p = 0.84). In the multivariable analysis, higher baseline HbA1c (adjusted OR: 1.45, 95% CI: 1.05, 2.1, p = 0.04) and lower baseline weight (adjusted OR: 0.97, 95% CI: 0.94, 0.99, p = 0.01) were associated with better glycemic response to liraglutide, while higher baseline weight was associated with worse weight response (adjusted OR: 0.97, 95% CI: 0.95, 0.99, p = 0.02). Conclusions: Specific patient features can predict glycemic and weight loss response to liraglutide in individuals with T2DM.

Detrimental Effects of Online Pro-Eating Disorder Communities on Weight Loss and Desired Weight: Longitudinal Observational Study.

BackgroundOnline pro–eating disorder (pro-ED) communities are considered harmful because of their detrimental effects on their users’ body dissatisfaction, dieting, and help seeking. To date, it is unknown to which extent participation in pro-ED communities affects users’ body weight and desired weight loss.ObjectiveThis study aims to investigate the changes in the current and desired body weight of users of a pro-ED community (r/proed) on the social media website Reddit over time.MethodsData on 1170 users and the unsolicited weight information they shared with the pro-ED community were collected over a period of 15 months. Linear growth models were used to model changes in the users’ current and desired BMI over time.ResultsBoth current and desired BMI decreased over time, with a predicted rate of 0.087 and 0.015 BMI points per week, respectively. Weight loss was moderated by the users’ activity level in the community, with more active users losing more weight. Users with a higher baseline BMI experienced greater weight loss, but even users with a very low baseline weight (BMI <17 kg/m2) lost weight during their participation. In addition, users decreased their desired weight over time, with many pursuing extremely low, unrealistic weight goals. Changes in the desired weight were moderated by the baseline current BMI and baseline desired BMI. Users with higher desired weight and lower body weight at baseline decreased their desired weight more over time.ConclusionsThis is the first study to demonstrate the detrimental effects of pro-ED communities in a longitudinal study based on a large data set of user-generated online data. The results extend the literature detailing the harmful effects of online pro-ED communities by showing users’ weight loss, decreases in desired weight, and that higher activity levels lead to greater weight loss. Users could be driven to pursue very low, unrealistic weight loss goals by images of very thin bodies presented in these communities.

Maternal weight and birth outcomes among women on antiretroviral treatment from conception in a birth surveillance study in Botswana.

IntroductionAntiretrovirals such as dolutegravir (DTG) and tenofovir alafenamide (TAF) have been associated with excessive weight gain. The objective of this study was to understand the potential impact of ART‐associated weight gain on pregnancy outcomes among women living with HIV.MethodsUsing data from the Tsepamo birth outcomes surveillance study in Botswana, we evaluated the relationship between maternal weight (and weight gain) and severe birth outcomes (very preterm delivery <32 weeks, very small for gestational age (SGA) <3rd percentile, perinatal death), macrosomia (birthweight > 4000 g) and maternal hypertension. We estimated the relative risk of each outcome by baseline weight (first weight in pregnancy <24 weeks) and second trimester average weekly weight gain (kg/week from 12 ± 2 to 24 ± 2 weeks) using log binomial regression and evaluated effect modification by ART regimen (DTG vs. Efavirenz (EFV)).ResultsOf 22,828 women on ART at conception with singleton deliveries between August 2014 and April 2020, 16,300 (71.4%) had a weight measured <24 weeks’ gestation (baseline weight) and 4437 (19.2%) had weight measured both at 12 (±2) weeks and 24 (±2) weeks, allowing second trimester weight gain calculation. Compared to women with baseline weight 60 to 70 kg, low baseline weight (<50 kg) was associated with increased risk of very preterm delivery (aRR 1.30, 95% CI 1.03, 1.65) and very SGA (aRR1.96, 95% CI 1.69, 2.28). High baseline weight (>90 kg) was associated with increased risk of macrosomia (aRR 3.24, 95% CI 2.36, 4.44) and maternal hypertension (aRR 1.79, 95% CI 1.62, 1.97). Baseline weight was not associated with stillbirth or early neonatal death. For all outcomes, second trimester weight gain showed weaker associations than did baseline weight. Duration of pre‐pregnancy ART (years) was associated with higher baseline weight for DTG but not for EFV, and the risk of maternal hypertension by baseline weight category was higher for DTG than EFV for all strata.ConclusionsART regimens associated with weight gain may reduce the number of women at risk for certain severe adverse pregnancy outcomes associated with low weight but increase the number at risk of macrosomia and maternal hypertension. Further research could determine whether weight‐based ART treatment strategies improve maternal and child health.

Prévalence et facteurs de risque associés à l’hypotension intradialytique en Afrique subsaharienne : cas du Burkina Faso

AimThe aim of our study was to determine the prevalence and factors associated with intradialytic hypotension in our cohort of chronic hemodialysis patients. MethodsThis was a prospective monocentric study over a six-month period. Intradialytic hypotension was defined as a decrease in systolic blood pressure ≥ 20mmHg or a decrease in mean arterial pressure of 10mmHg associated with clinical events and the need for nursing interventions. The groups were compared using univariate analysis of variance. ResultsWe included 48 patients and counted 3014 hemodialysis sessions. The mean age was 44.7±15 years. The prevalence of intradialytic hypotension was 12.4%, with cramps 20 (41.7%) as the main symptom. Factors associated with frequent intradialytic hypotension compared to the groups without intradialytic hypotension and with infrequent intradialytic hypotension were age (61±13 years, p=0.018), diabetes (33.3%, p=0.019), high body mass index (27, 3±7.8kg/m2, p=0.002), interdialytic weight gain ≥ 5% of baseline weight (66.7%, p=0.033), hourly ultrafiltration (800±275ml/h, p=0.037) and perdialytic feeding (33.3%, p=0.016). Low pre-dialysis diastolic blood pressure (72±13mmHg, p=0.012) and high baseline weight (73.9±17.5kg, p=0.028) were associated with frequent versus infrequent intradialytic hypotension. ConclusionIntradialytic hypotension is common in our context. Its prevention in at-risk patients is critical to reducing morbidity and mortality and improving quality of life.

ASSOCIATION BETWEEN CLINICAL OUTCOMES AND BASELINE BMI OR ANNUALIZED WEIGHT LOSS IN PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS ENROLLED IN THE PULMONARY FIBROSIS FOUNDATION PATIENT REGISTRY

SESSION TITLE: Diffuse Lung Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Low baseline body mass index (BMI) and weight loss have been linked with poor outcomes in patients with idiopathic pulmonary fibrosis (IPF). This analysis investigated the association between clinical outcomes and baseline BMI or annualized change in body weight in patients with IPF enrolled in the Pulmonary Fibrosis Foundation Patient Registry (PFF-PR). METHODS: This analysis examined the relationship between (a) BMI group at enrollment (<25 kg/m2, 25 to <30 kg/m2 or ≥30 kg/m2) or annualized percent change in body weight group (no loss, >0% to <5% or ≥5%) and patient baseline characteristics, (b) BMI group at enrollment and clinical outcomes and (c) annualized percent change in body weight group and clinical outcomes. Outcomes included all-cause mortality at 24 months as well as changes from baseline to 24 months in lung function and exercise capacity, as assessed by percent predicted forced vital capacity (%FVC) and percent predicted diffusing capacity for carbon monoxide (%DLCO). Regression analyses were conducted with adjustment for age, sex, smoking history, oxygen use during exertion, pulmonary function, significant comorbidities and medications (pirfenidone, nintedanib and corticosteroids). RESULTS: As of February 14, 2020, 696 patients with IPF from the PFF-PR were eligible for the analysis. At enrollment, pulmonary arterial hypertension (PAH) was the only comorbidity that varied across weight-change categories (P=0.026), with 34 of 36 patients with PAH in the >0% to <5% annualized weight loss category. Logistic regression models did not indicate any difference in all-cause mortality between baseline BMI groups. Compared with patients with no weight loss, increased all-cause mortality was observed in patients with >0% to <5% and with ≥5% weight loss (odds ratios [95% CI], 5.4 [1.5, 34.4] and 5.4 [1.3, 36.9]). In the longitudinal analysis of %FVC and %DLCO, patients with baseline BMI <25 kg/m2 had a greater estimated annualized decline in %FVC than patients with baseline BMI ≥30 kg/m2 (difference [95% CI], 1.74% [0.47%, 3.0%]). A similar trend was also observed with %DLCO. There was no significant difference in annualized change of %FVC or %DLCO between groups defined by annualized percentage change in weight. CONCLUSIONS: Lower all-cause mortality was observed in patients with IPF with no annualized weight loss. Higher baseline BMI was associated with a lesser decline in lung function but not with lower all-cause mortality. CLINICAL IMPLICATIONS: Baseline BMI and annualized weight loss may be associated with clinical outcomes in patients with IPF. DISCLOSURES: Employee relationship with Genentech Please note: >$100000 Added 04/07/2020 by Cindy Burg, source=Web Response, value=Salary No relevant relationships by Elizabeth Freiheit, source=Web Response Consultant relationship with Boehringer Ingelheim Please note: $1001 - $5000 Added 04/07/2020 by Joyce Lee, source=Web Response, value=Consulting fee Consultant relationship with Genentech Please note: $1001 - $5000 Added 04/07/2020 by Joyce Lee, source=Web Response, value=Consulting fee Consultant relationship with Celgene Please note: $1001 - $5000 Added 04/07/2020 by Joyce Lee, source=Web Response, value=Consulting fee Consultant relationship with Galapagos Please note: $1001 - $5000 Added 04/07/2020 by Joyce Lee, source=Web Response, value=Consulting fee Consultant relationship with Eleven P15 Please note: $1001 - $5000 Added 04/07/2020 by Joyce Lee, source=Web Response, value=Consulting fee No relevant relationships by Adam Martin-Schwarze, source=Web Response Employee relationship with Genentech, Inc. Please note: >$100000 Added 04/07/2020 by Ming Yang, source=Web Response, value=Salary

Analysis of patient-specific factors contributing to effectiveness of glucagon-like peptide-1 receptor agonists

BackgroundGlucagon-like peptide-1 receptor (GLP-1) agonists are antidiabetic medications used to improve hemoglobin A1c (HbA1c) and promote weight loss. Per the Veterans Affairs/Department of Defense guidelines for the management of type 2 diabetes, GLP-1 agonists are expected to lower HbA1c by 1%-1.5%. The clinical pharmacy specialist in the women’s health primary care clinic at the Louis A. Johnson Veterans Affairs Medical Center noted cases of women started on GLP-1 agonists achieving greater than expected HbA1c reduction. ObjectivesThe primary objective of this study was to determine if there are any patient-specific factors that may increase the effectiveness of GLP-1 agonists. Secondary objectives included an analysis of average weight and HbA1c, use of the Pearson rank correlation test to determine if there is a correlation between weight change and HbA1c reduction, and an analysis of HbA1c reduction associated with each GLP-1 agonist prescribed. MethodsA retrospective chart review was conducted. Data collected from the charts included age, sex, height, GLP-1 agonist prescribed, and HbA1c and weight before and after GLP-1 agonist initiation. For primary outcomes, statistical analyses were run between 2 groups: patients who had an HbA1c reduction of greater than 1.5% and patients who had an HbA1c reduction less than or equal to 1.5%. ResultsWomen were more likely to have an HbA1c reduction of greater than 1.5% (P = 0.001). Patients with a lower baseline weight were more likely to attain an HbA1c reduction greater than 1.5% (P = 0.045). Higher baseline HbA1c was correlated with an increased likelihood of HbA1c reduction greater than 1.5% (P = 0.001). ConclusionGLP-1 agonists may be more effective at reducing HbA1c in female patients, those with a lower baseline weight, and those with a higher baseline HbA1c.

M201. MODERATORS OF WEIGHT GAIN IN RANDOMIZED CONTROLLED TRIALS OF SCHIZOPHRENIA – A META-REGRESSION ANALYSIS

BackgroundWeight gain is an important side effect of antipsychotics. Meta-analyses of randomized controlled trials indicate differences between the multiple antipsychotics in propensity to cause weight gain. However, antipsychotic-associated weight gain, in randomized controlled trials as well as in real life situations, might also depend on population characteristics and treatment-related factors.As a preparatory work for a systematic review and network-meta-analysis on metabolic side effects of antipsychotics (presented in another poster at this conference), we conducted a meta-regression analysis of potential moderators of weight gain.MethodsWe selected acute phase short-term, acute phase long-term as well as relapse prevention studies (all found by systematic reviews conducted by our group in the past) from our database of randomized controlled trials of antipsychotics in schizophrenia.We conductedi) meta-regression-analyses based on pairwise meta-analysis of the mean difference (MD) in change in weight (kg) between patients exposed to antipsychotics and placebo, andii) meta-regression-analyses based on single-arm meta-analysis of the change in weight (kg).We examined the moderators baseline weight, study duration, percentage women, and publication year.We conducted the analyses for all drugs pooled, placebo and per individual drug. For presentation of the results we focus on the drugs aripiprazole, haloperidol, quetiapine, olanzapine, and risperidone, because these are popular drugs in clinical practice, they differ in their receptor-binding profiles and multiple studies are available for these drugs.We conducted the analysis in R using the commands metacont, metagen and metareg from the package meta.ResultsThe dataset comprises 603 randomized controlled trials with 141 584 patients that examined 40 different antipsychotics. Trial duration varied between 3 and 156 weeks (median 8 weeks). 168 studies with 49 670 patients reported on change in body weight.We found no effect of baseline weight on antipsychotic-associated weight gain, however on placebo, lower baseline weight was associated with more weight loss.Moreover, on antipsychotics, higher percentage of women was associated with less weight gain, and, on placebo, higher percentage of women was associated with more weight loss.Longer study duration was not associated with increased weight gain. On placebo, longer studies were associated with more weight loss.There was no effect of publication year.DiscussionSurprisingly, we found no moderating effect of baseline weight and study duration on weight gain. However, our data suggests that men and women could have different risk of weight gain. Moreover, weight loss after switching to placebo might be higher in women and patients with less baseline weight. For interpretation, it must be noted that meta-regressions are observational evidence and thus prone to confounding. In addition, the scatter plots, presented on the poster, need to be considered to judge the robustness and magnitude of the moderated effects. Additional meta-regressions (planned to present on the poster) should address further potential moderators, such as antipsychotic dose, ethnicity, previous antipsychotic exposure and dropout rates.

Nativity, Neighborhoods, and Body Composition in the Sacramento Area Latino Study on Aging.

Globally, obesity influences the risk of many major chronic diseases. Our study examines the association between individual nativity and neighborhood level concentration of immigrants with 10-year changes in weight, body mass index (BMI), and waist circumference (WC) among older Latinos. The Sacramento Area Latino Study on Aging (SALSA) is a population-based prospective study of community-dwelling older adults of Mexican origin (baseline ages 58-101 years). The primary outcome was repeated measures of weight over a 10-year period for 1,628 respondents. Nativity was defined by participants' reported place of birth (US-born or Latin American foreign born). Neighborhood immigrant concentration was measured as the percentage of foreign born at census tract level (2000 US Census). We used linear mixed models with repeated measures of weight, height, BMI, and WC as dependent variables (level 1), clustered within individuals (level 2) and neighborhood migrant concentration (level 3). Foreign born (FB) respondents had lower baseline weight than the US-born (mean, 160 vs. 171 lbs, p < .0001). Over time, weight differences between the FB and the US-born decreased by 1.7 lbs/5 years as US-born weight decreased more rapidly. We observed a significant interaction between individual nativity and neighborhood immigrant concentration (p = .012). We found similar patterns for BMI, but did not find statistically significant differences in WC trajectories. Our study observed significant differences by foreign born vs. US nativity in baseline weight/BMI and in their trajectories over time. Additionally, we found weight/BMI differences in neighborhood immigrant concentration for the FB, but not for the US-born.

Phenotypic factors associated with amisulpride‐induced weight gain in first‐episode psychosis patients (from the OPTiMiSE cohort)

ObjectiveAntipsychotic‐induced weight gain (AiWG) is a debilitating adverse effect of most antipsychotics. First‐episode psychosis patients are particularly vulnerable to the detrimental consequences of AiWG. Amisulpride has good efficacy and tolerability. We here aimed to identify the phenotypic factors associated with amisulpride‐induced weight gain in first‐episode psychosis patients.MethodData were collected from the Optimization of Treatment and Management of Schizophrenia in Europe trial. Multivariable regression models with various phenotypic variables (N = 305) were performed with absolute AiWG and clinically relevant AiWG (≥7% AiWG) as outcomes.ResultsFour weeks of amisulpride treatment increased body weight from 69.7 to 72.4 kg (P < 0.001). In the regression model of absolute AiWG, unemployment (β = 0.94, P = 0.016), younger age (β = −0.07, P = 0.031) and absence of current comorbid major depression disorder (β = −1.61, P = 0.034) were positively associated with absolute AiWG. In the regression model of clinically relevant AiWG, unemployment (OR = 2.83, P = 0.001), schizophreniform disorder (OR = 2.00, P = 0.025) and low baseline weight (OR = 0.97, P = 0.032) increased the likelihood of clinically relevant AiWG.ConclusionsClinicians prescribing amisulpride should consider the relatively high susceptibility to AiWG in unemployed first‐episode patients with psychosis, in particular young subjects with a diagnosis of schizophreniform disorder. We advise to carefully monitor these patients and, when needed, implement weight‐reducing strategies.

Sex-differential effects of olanzapine vs. aripiprazole on glucose and lipid metabolism in first-episode schizophrenia

Abstract Objective To compare sex difference in metabolic effect of olanzapine versus aripiprazole on schizophrenia. Methods A twelve-week prospective open-label cohort study to compare four subgroups according to first-episode schizophrenia patients’ type of drug usage and sex: female aripiprazole (n = 11), male aripiprazole (n = 11), female olanzapine (n = 10), and male olanzapine (n = 11) for body mass index, fasting serum triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and fasting glucose. Results Aripiprazole may be associated with weight gain in female patients with low-baseline weight. Aripiprazole may have an adverse effect of weight and favorable effects of circulating glucose and lipid on female over male schizophrenia patients. The aripiprazole–induced changes in glucose and lipid may be independent of body fat storage, especially for female schizophrenia patients. Olanzapine may have adverse effects of weight, glucose and lipid profiles on female over male schizophrenic patients. Discussion Our findings fill the gap in knowledge and provide a sex-specific guidance to psychiatrist better tailoring treatment to individual sex-differential characteristics and a key clue to understand the sex-differential mechanism of antipsychotics-induced metabolic dysfunction.

Abstract P143: Late Success in Weight Loss Trials: Do Participants Start Losing Weight After 6 Months?

Background: Weight loss programs often start with an initial phase of intensive lifestyle coaching to facilitate early weight loss, with a typical weight loss goal of ≥ 5%. While early weight loss is associated with long-term weight loss success, less is known about those who do not lose weight in the initial phase. This study examines those without initial weight loss success, but lose weight later. Methods: Analyses included 346 obese adults from the POWER Hopkins weight loss trial and 673 overweight to obese adults from the PREMIER hypertension control trial. Mutually exclusive categories are based on weight loss success (≥ 5% reduction from baseline) at 6m and 12m: continued success (success 6m and 12m); regainer (success 6m then regained 12m); no success (no success 6m or 12m); and late success (12m success only). Results: No success (NS) was the most common category among control and intervention participants in both studies (see table). There were low rates of late success (LS) in POWER (intervention 5%, control 7%, p=.25) and PREMIER (intervention 5%, control 8%, p=.75). Within the POWER intervention, LS and NS were similar in age, sex, race, and baseline weight. Coaching contact rates were similar at 1-6m (LS 64%, NS 57%, p=.49) and 7-12m (LS 45%, NS 46%, p=.89). Within the PREMIER intervention LS had a lower baseline weight than NS (89 vs 99 kg, p=.01), but were similar in age, sex, and race. Coaching contact rates are similar at 1-6m (LS 77%, NS 72%, p=.23) and 7-12m (LS 66%, NS 62%, p=.58). Conclusion: Given the small fraction of intervention participants with late success (only 5%), alternative strategies are needed to address the large fraction of persons without initial weight loss success.

Addressing health disparities in survivors of breast cancer through lifestyle modifications and group support.

177 Background: Obesity and inactivity have been shown to adversely affect outcomes in survivors of breast cancer. These factors may contribute to poorer outcomes in women of black and Hispanic populations, and those from lower socioeconomic backgrounds. We sought to improve overall well-being and limit weight gain in patients from these underserved populations through a group lifestyle intervention in a public hospital setting. Methods: 46 women were recruited and gave informed consent after completion of adjuvant chemotherapy for stage I-III breast cancer to participate in this feasibility pilot program. Blood work, body measurements, diet, two-minute walk tests, and PHQ9 depression scores were collected at the first and last of six monthly sessions. The group classes were led by a registered dietician and included diet and light exercise instruction at each visit. Results: Patient demographics and results are in the table below. Trends for non-completers included younger age, ethnicity, no hormonal therapy, lower baseline weight, lower HOMA IR, and dropout after two sessions. Among the 40% who completed all six sessions, there was a trend toward greater well-being (lower PHQ) with slight weight gain and increased insulin resistance. Completers tended to start in the same cohort and were more likely to complete if they attended more than two visits. Conclusions: Greater well-being may be an important outcome for group lifestyle improvement programs in populations with disparities. Motivations for better attendance may include group bonding. Participants will continue to be followed to obtain information on long-term weight change and cancer recurrence.[Table: see text]

Retrospective Analysis of Cisplatin Nephrotoxicity in Patients With Head and Neck Cancer Receiving Outpatient Treatment With Concurrent High-dose Cisplatin and Radiotherapy.

Cisplatin remains the pivotal chemotherapy in squamous cell carcinoma of the head and neck (SCCHN), with nephrotoxicity considered the dose-limiting toxicity. The purpose of our study was to propose an outpatient high-dose cisplatin protocol aimed at preventing nephrotoxicity and to analyze the results of its utilization in patients with SCCHN treated with concurrent radiotherapy. We retrospectively evaluated 82 SCCHN patients treated with outpatient high-dose cisplatin concurrent with radiotherapy at our institution. Acute kidney injury (AKI) and chronic kidney disease were defined by Kidney Disease Improving Global Outcomes criteria. Associated factors were identified using analysis of covariance models for categorical variables and adjusted Pearson correlations for continuous variables. The incidence of AKI during treatment was 34.2%. With a median follow-up of 25.7 months, the average decrease in estimated glomerular filtration rate was 12.57 mL/min/1.73 m (SD=18.58). At 1 year and at last follow-up, 5.4% and 4.4% of patients had estimated glomerular filtration rate <60 mL/min/1.73 m. Predictors associated with AKI and chronic kidney disease were: lower baseline weight and creatinine, higher baseline creatinine clearance, smoking, female sex, African American race, hypertension, and increased hydration and magnesium replacement requirements. We encountered limited early and late nephrotoxicity. Importantly, nephrotoxicity was not the main dose-limiting toxicity. Our results emphasize the importance of close monitoring and additional replacement of water and electrolytes as needed. A consistent method of measuring and reporting chemotherapy-induced nephrotoxicity would be a valuable contribution to the literature.

Does Gastrostomy Tube Improve the Long-term Nutritional Outcome in Patients With Head and Neck Cancer?

Introduction: Maintaining nutrition in patients with head and neck cancer receiving radiation therapy (RT) and/or chemotherapy (CT) remains a challenge. Previous studies have shown that gastrostomy for tube feedings has an important role in reducing nutritional compromise during and after treatment and hence often placed prophylactically. Research question: The aim of this study is to compare the nutritional benefits in patients with head and neck cancer who received tube feedings via gastrostomy with the patients who did not receive gastrostomy tube (GT). Methods: A retrospective chart review was conducted on patients with head and neck cancer from January 1, 2005 to March 31, 2014. Nutritional parameters (weight, BMI, albumin and total protein) were collected at baseline, 3 months, 6 months and 12 months after gastrostomy and in the no-gastrostomy group the data were collected at the same intervals after the cancer diagnosis. Results: There were 304 total patients, of whom 123 (40.5%) had gastrostomy tubes. Those who received tubes were older (78.4 vs. 66.7 years of age), had greater then T1N0M0 disease (99.1% vs. 67.3%), were more likely to undergo CT (79.7% vs. 26.8%) and were more likely to have RT (99.1% vs. 66.7%) than those without GT. Looking only those with greater than T1N0M0 disease, 113/222 (50.9%) received GT. The values of the nutritional variables over time declined in both those with and without GT. Those with GT at baseline had lower values in all four variables, but the time course did not differ between groups (change in weight depicted in fig 1). In linear regression, the net change over 12 months in weight and BMI depended only on whether CT was received. Use of GT was not predictive of any of these net changes. No variables predicted change in albumin or total protein. In those who had GT placed, neither duration or frequency of tube usage predicted any of these nutritional 12 month changes. Conclusion: Our study found no significant difference in the nutritional outcome between those with and without GT at the end of 1 year. However, patients in the GT group had lower baseline weight, BMI, albumin and total protein. Age, CT and stage of the tumor positively predicted the placement of the GT, which suggests that patients who have advanced disease or nutritionally compromised tend to get gastrostomy. Based on the above findings, we propose the GT should be placed on-demand rather than prophylactically to minimize the morbidity and mortality associated with GT placement.Figure: Change in weight with time between the two groups.

Abstract TP293: Errors in Estimation of Body Weight in Thrombolysis for Acute Ischemic Stroke

Introduction: Intravenous tissue plasminogen activator (IVtPA) is a proven treatment in acute ischemic stroke but relies on weight-based dosing in a time sensitive manner. Errors in body weight estimation are common and may result in over or under-dosing of IVtPA. Methods: With IRB approval, we prospectively screened 99 consecutive patients who received IVtPA for suspected acute ischemic stroke from November 1, 2015 to July 1, 2016 as part of a prospective IVtPA study. Patients were included in this analysis who had complete data. Data was collected on patient demographics, National Institutes of Health Stroke Scale (NIHSS), body weight, and times of last known normal (LKN) and IVtPA administration. A significant error in IVtPA dosing was defined as a &gt;10% difference in actual versus calculated IVtPA dose. Results: Among 42 patients prospectively enrolled, the mean age was 65.8 years (range, 32 to 89) and 30 (79%) of patients were transfers from outside Emergency Rooms. Mean time from LKN to IVtPA administration was 2.4 hours (range. 0.7 to 4.8). Initial pre-IVtPA mean NIHSS was 14 (range, 3 to 26). The mean % error in IVtPA dose was +1.9% (range, -29% to + 21%). Ten patients (24%) had a significant error in IVtPA dosing of &gt; 10% of the dose, and 8 (80%) were over-doses. Patients with significant IVtPA dosing error did not differ in terms of age (65.8 vs 65.8, p 0.99), sex (female 55.6% vs 38.9%, p 0.45), race (white 70% vs 47%, p 0.28), height (164.8 vs 171.0 cm, p 0.1), or time from LKN to IVtPA (2.8 vs 2.3, p 0.15). Patients with significant IVtPA dosing errors had significantly lower baseline weight (70.3 vs 90.0 kilograms, p 0.029) and higher NIHSS (18.7 vs 12.6, p 0.018). Conclusion: Dosing errors of &gt; 10% of the calculated IVtPA dose occur in nearly one-quarter of acute stroke patients treated in the community, and patients with lower weight and higher NIHSS were at higher risk of dosing errors.