For Researchers on Obesity: Historical Review of Extra Body Weight Definitions

Rationale. The concept of obesity has been known since ancient world; however, the current standard definition of obesity was endorsed only about a decade ago. There is a need for researches to understand multiple approaches to defining obesity and how and why the standard definition was developed. The review will help to grasp the complexity of the problem and can lead to novel hypotheses in obesity research. Objective. This paper focuses on the objective to understand historical background on the development of “reference and standard tables” of weight as a platform for normal versus abnormal body weight definition. Methods. A systematic literature review was performed to chronologically summarize the definition of body weight from time of Hippocrates till the year of 2010. Conclusion. This paper presents the historical background on the development of “reference and standard tables” of weight as a platform for normal versus abnormal body weight definition. Knowledge of historical approaches to the concept of obesity can motivate researchers to find new hypotheses and utilize the appropriate obesity assessments to address their objectives

Subjective distress in a representative sample of outpatients with psychotic disorders

The affective burden of psychotic disorder has been increasingly recognised. However, subjective… reports of distress and its covariates, especially those related to service use, remain under-investigated in patients with psychosis. This study investigated subjective distress and its covariates in a representative sample of 401 outpatients with a confirmed diagnosis of psychotic disorders in Brazil. Distress was assessed using the corresponding domain of a standardised measure of need - the Camberwell Assessment of Need. Distress was reported as a need by 165 (41%) patients, being met in 78 (20%) and unmet in 87 (22%). Hierarchical logistic regression showed that the presence of distress as a need was predicted by attendance at psychotherapy (OR=3.49, CI=1.62-7.53), presence of suicidal ideation (OR=2.89, CI=1.75-4.79), non-attendance at psychosocial rehabilitation (OR=2.84, CI=1.31-6.19), and higher psychopathology (OR=1.09, CI=1.06-1.12). An unmet need was predicted by family not accompanying patients to treatment (OR=2.60, CI=1.05-6.44) and higher psychopathology (OR=1.05, CI=1.02-1.09). The use of a cross-sectional design and a single questionnaire domain to evaluate distress are the main limitations. Subjective distress is a common unmet need in psychosis, and can be treated. The main clinical implication is that subjective distress in psychosis may be impacted on by family engagement and psychosocial intervention

Weight Fluctuation and Postmenopausal Breast Cancer in the National Health and Nutrition Examination Survey I Epidemiologic Follow-Up Study

Objective. The aim of this study is to investigate if weight fluctuation is an independent risk factor for postmenopausal breast cancer (PBC) among women who gained weight in adult years. Methods. NHANES I Epidemiologic Follow-Up Study (NHEFS) database was used in the study. Women that were cancers-free at enrollment and diagnosed for the first time with breast cancer at age 50 or greater were considered cases. Controls were chosen from the subset of cancers-free women and matched to cases by years of follow-up and status of body mass index (BMI) at 25 years of age. Weight fluctuation was measured by the root-mean-square-error (RMSE) from a simple linear regression model for each woman with their body mass index (BMI) regressed on age (started at 25 years) while women with the positive slope from this regression were defined as weight gainers. Data were analyzed using conditional logistic regression models. Results. A total of 158 women were included into the study. The conditional logistic regression adjusted for weight gain demonstrated positive association between weight fluctuation in adult years and postmenopausal breast cancers (odds ratio/OR = 1.67; 95% confidence interval/CI: 1.06–2.66). Conclusions. The data suggested that long-term weight fluctuation was significant risk factor for PBC among women who gained weight in adult years. This finding underscores the importance of maintaining lost weight and avoiding weight fluctuation

Antihypertensive Medications and Change in Stages of Chronic Kidney Disease

Objectives. The goal of this study is to estimate the change in the relationships between use of five classes of antihypertensive medications and stages of Chronic Kidney Disease (CKD) in American adults treated for hypertension. Methods. The US National Health and Nutrition Examination Survey (NHANES) data sets 1999–2012 were used with the final analytical sample of 3,045 participants. Population prevalence estimates were calculated using the NHANES survey design weights. Inferential analyses were done with binomial logistic regression models. Results. The odds of advanced (3, 4, and 5 combined) versus early CKD stages (1 and 2 combined) were significantly higher among patients treated with Angiotensin Receptor Blockers (ARB) versus those not treated with ARB in 2009–2012 (adjusted odds ratio (95% confidence interval) = 2.52 (1.32–4.80)). From 1999 to 2012, the increase in this relationship was significant (p=0.0023) for users of ARB polytherapy and in users of ARB in patients with albuminuria (p=0.0031). Conclusion. Aggressive pharmacological management of hypertension with ARB as add-on therapy may have accelerated kidney damage in American adults. However, prospective longitudinal studies are needed to establish proper temporal sequence in this relationship

Pharmacokinetic Profile of the Asenapine Transdermal System (HP-3070)

PURPOSE/BACKGROUND: The asenapine transdermal system (HP-3070) is the first antipsychotic patch approved in the United States for treatment of adults with schizophrenia. METHODS/PROCEDURES: Three phase 1, open-label, randomized studies characterized the pharmacokinetic (PK) profile of HP-3070 by assessing its relative bioavailability compared with sublingual asenapine, its single-/multiple-dose PK and dose proportionality, and the effects of application site, ethnicity, and external heat on bioavailability. Two studies were conducted in healthy subjects, and 1 was conducted in adults with schizophrenia. FINDINGS/RESULTS: During single HP-3070 administration, asenapine concentrations increased gradually over approximately 12 hours and remained steady until the patch was removed 24 hours after application. Asenapine area under the curve values at HP-3070 3.8 and 7.6 mg/24 hours doses were similar to those for sublingual asenapine 5 and 10 mg twice-daily doses, respectively, whereas peak exposure (maximum observed plasma concentration) was significantly lower. During daily application of HP-3070, steady-state PK was reached within approximately 72 hours after initiating daily dosing and was characterized by peak-to-trough asenapine plasma concentration ratio of approximately 1.5. HP-3070 PK was dose proportional in the dose range studied, not affected by administration site, and similar across the studied ethnic groups. Application of external heat increased the rate of asenapine absorption (time to reach maximum observed plasma concentration) but did not significantly affect peak and total exposure. IMPLICATIONS/CONCLUSIONS: HP-3070 exhibited a dose-dependent PK profile unaffected by site of administration or ethnicity. HP-3070 showed a predictable absorption profile with limited variability, with an area under the curve similar to that of sublingual asenapine. Based on these PK metrics, HP-3070 steadily delivers asenapine with lower peaks and troughs than sublingual administration of asenapine

Efficacy of HP-3070, an Asenapine Transdermal System, on Symptoms of Hostility in Adults With Schizophrenia: A Post Hoc Analysis of a 6-Week Phase 3 Study

Patients with schizophrenia may exhibit symptoms of hostility. HP-3070 is the first antipsychotic patch approved by the US Food and Drug Administration (FDA) for adults with schizophrenia. Its efficacy was demonstrated in a phase 3 study. This post hoc analysis assessed the efficacy of HP-3070 in treating hostility in schizophrenia. In the pivotal phase 3 study, conducted between August 2016 and November 2017, adults with schizophrenia (per criteria) were randomized to HP-3070 3.8 mg/24 h, HP-3070 7.6 mg/24 h, or placebo. Least-squares mean (LSM) changes in Positive and Negative Syndrome Scale (PANSS) hostility item and PANSS-Excited Component (PANSS-EC) scores from baseline to week 6 were assessed post hoc using a mixed-effects model for repeated measures adjusted for selected PANSS-Positive symptoms and presence of somnolence or akathisia. Among 442 patients with baseline PANSS hostility item score \u3e 1 (n = 151, HP-3070 7.6 mg/24 h; n = 147, 3.8 mg/24 h; n = 144, placebo), week 6 LSM (95% CI) change from baseline (CFB) in hostility score was superior with HP-3070 versus placebo for 7.6 mg/24 h (-0.4 [-0.6 to -0.2];  \u3c .001) and 3.8 mg/24 h (-0.3 [-0.6 to -0.1];  \u3c .01), with similar results for 7.6 mg/24 h after adjusting for covariates ( \u3c .05). For all patients regardless of baseline PANSS hostility item score, PANSS-EC week 6 LSM CFB was greater for HP-3070 7.6 mg/24 h (-1.1 [-1.9 to -0.4]; n = 203;  \u3c .01) and 3.8 mg/24 h (-1.3 [-2.0 to -0.6]; n = 201;  \u3c .001) than for placebo (n = 203), with similar results observed in patients with baseline hostility item score \u3e 1. In this post hoc analysis, HP-3070 was superior to placebo in reducing schizophrenia-associated hostility, even after adjusting for covariates, suggesting these effects are at least partially independent of general antipsychotic effects or effects on sedation or akathisia. These findings suggest HP-3070 has a specific antihostility effect in patients with schizophrenia. ClinicalTrials.gov identifier: NCT02876900; EudraCT number: 2015-005134-21

Efficacy and Safety of HP-3070, an Asenapine Transdermal System, in Patients With Schizophrenia: A Phase 3, Randomized, Placebo-Controlled Study

OBJECTIVE: Asenapine is a second-generation antipsychotic used to treat individuals with schizophrenia. This phase 3 study assessed efficacy and safety of HP-3070, an asenapine transdermal system (patch), in adults with schizophrenia. METHODS: In this inpatient study, a 3- to 14-day screening/single-blind run-in washout period was followed by a 6-week double-blind period wherein patients with acutely exacerbated schizophrenia (DSM-5 criteria) were randomized 1:1:1 and received HP-3070 7.6 mg/24 h (n = 204), HP-3070 3.8 mg/24 h (n = 204), or placebo (n = 206). Primary endpoint was change from baseline (CFB) in week 6 Positive and Negative Syndrome Scale (PANSS) total score versus placebo; key secondary endpoint was CFB in week 6 Clinical Global Impression-Severity of Illness score versus placebo. Safety endpoints included treatment-emergent adverse events (TEAEs) and dermal assessments. RESULTS: Each of the HP-3070 doses demonstrated significant improvement versus placebo at week 6 for the primary and key secondary endpoints. Differences in the least-squares mean (LSM) (95% CI; adjusted P) of CFB for PANSS total scores were -4.8 (-8.06 to -1.64; adjusted P = .003) and -6.6 (-9.81 to -3.40; adjusted P \u3c .001) for 7.6 mg/24 h and 3.8 mg/24 h, respectively. HP-3070 was well tolerated, with a systemic safety profile consistent with sublingual asenapine. Incidence of application site TEAEs was higher for HP-3070 (14.2%, 7.6 mg/24 h; 15.2%, 3.8 mg/24 h) versus placebo (4.4%). Discontinuations due to application site reactions or skin disorders (urticaria, pruritus) were infrequent (≤ 0.5% per treatment group). CONCLUSIONS: HP-3070 7.6 mg/24 h and 3.8 mg/24 h doses were efficacious and well tolerated. As the first transdermal antipsychotic patch available in the US, HP-3070 offers a novel treatment option for people with schizophrenia. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02876900; EudraCT number: 2015-005134-21

An exploratory investigation of links between changes in adipokines and quality of life in individuals undergoing weight loss interventions: Possible implications for cancer research

Obesity has been linked to a wide spectrum of malignancies, with the strongest association demonstrated for endometrial cancer. Although the mechanisms are not yet entirely clear, a number of risk biomarkers have been proposed, including altered adipokines. Systemic levels of these adipose derived molecules have also been linked in prior research to self-reported quality of life (QOL). The study objective was to examine the hypothesis that adipokine changes during intentional weight loss may be associated with changes in QOL. Methods Fifty-two female participants were selected from two behavioral weight loss trials (SMART and PREFER) on the basis of achieving successful weight loss at 6 month assessment, availability of blood samples and completion of standard SF-36 QOL questionnaires. Levels of adiponectin, leptin, and resistin were measured using xMAP immunoassays. Changes in QOL were examined using linear regression models in relation to pre- and post-intervention changes in biomarker levels and BMI. Results Significant changes between pre- and post-intervention were observed for leptin. Controlling for baseline BMI, leptin was the only biomarker that predicted change in QOL (Physical Component Scale, PCS). Linear regression models demonstrated that leptin continued to be a significant predictor of change in PCS when other possible predictor variables were included in the model. Conclusions This study is among the first to demonstrate that changes in PCS may be regulated by levels of both metabolic variables and adipokines. An improved understanding of biological mechanisms associated with weight loss and the role of QOL may help guide preventive strategies for obesity-associated cancers. © 2014 Elsevier Inc