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Telo GH, Friedrich Fontoura L, Avila GO, Gheno V, Bertuzzo Brum MA, Teixeira JB, Erthal IN, Alessi J, Telo GH. Obesity bias: How can this underestimated problem affect medical decisions in healthcare? A systematic review. Obes Rev 2024; 25:e13696. [PMID: 38272850 DOI: 10.1111/obr.13696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 11/24/2023] [Accepted: 12/06/2023] [Indexed: 01/27/2024]
Abstract
INTRODUCTION Obesity is often labeled as a physical characteristic of a patient rather than a disease and it is subject to obesity bias by health providers, which harms the equality of healthcare in this population. OBJECTIVE Identifying whether obesity bias interferes in clinical decision-making in the treatment of patients with obesity. METHODS A systematic review of observational studies published between 1993 and 2023 in MEDLINE, Embase, and Cochrane Library on obesity bias and therapeutic decisions was carried out. The last search was conducted on June 30, 2023. The main outcome was the difference between clinical decisions in the treatment of individuals with and without obesity. The Newcastle-Ottawa scale for observational studies was used to assess for quality. After the selection process, articles were presented in narrative and thematic synthesis categories to better organize the descriptive analysis. RESULTS Of the 2546 records identified, 13 were included. The findings showed fewer screening exams for cancer in patients with obesity, who were also susceptible to less frequent pharmacological treatment intensification in the management of diabetes. Women with obesity received fewer pelvic exams and evidence of diminished visual contact and physician confidence in treatment adherence was reported. Some studies found no disparities in treatment for abdominal pain and tension headaches between patients presented with and without obesity. CONCLUSION The presence of obesity bias has negative effects on medical decision-making and on the quality of care provided to patients with obesity. These findings reveal the urgent necessity for reflection and development of strategies to mitigate its adverse impacts. (The protocol was registered with the international prospective register of systematic reviews, PROSPERO, under the number CRD42022307567).
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Affiliation(s)
- Guilherme Heiden Telo
- Medicine and Health Sciences Graduate Program, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil
- Cardiology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
| | - Lucas Friedrich Fontoura
- Medicine and Health Sciences Graduate Program, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil
| | - Georgia Oliveira Avila
- School of Medicine, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil
| | - Vicenzo Gheno
- School of Medicine, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil
| | | | - Julia Belato Teixeira
- School of Medicine, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil
| | - Isadora Nunes Erthal
- School of Medicine, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil
| | - Janine Alessi
- Medicine and Health Sciences Graduate Program, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil
- Endocrinology Division, Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil
- General Internal Medicine Division, Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil
| | - Gabriela Heiden Telo
- Medicine and Health Sciences Graduate Program, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil
- School of Medicine, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil
- General Internal Medicine Division, Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil
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Sachdeva P, Ghosh S, Ghosh S, Han S, Banerjee J, Bhaskar R, Sinha JK. Childhood Obesity: A Potential Key Factor in the Development of Glioblastoma Multiforme. LIFE (BASEL, SWITZERLAND) 2022; 12:life12101673. [PMID: 36295107 PMCID: PMC9605119 DOI: 10.3390/life12101673] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 10/15/2022] [Accepted: 10/18/2022] [Indexed: 12/04/2022]
Abstract
Glioblastoma multiforme (GBM) is a malignant primary tumor type of the central nervous system (CNS). This type of brain tumor is rare and is responsible for 12-15% of all brain tumors. The typical survival rate of GBM is only 12 to 14 months. GBM has a poor and unsatisfactory prognosis despite advances in research and therapeutic interventions via neurosurgery, radiation, and chemotherapy. The molecular heterogeneity, aggressive nature, and occurrence of drug-resistant cancer stem cells in GB restricts the therapeutic efficacy. Interestingly, the CNS tumors in children are the second most usual and persistent type of solid tumor. Since numerous research studies has shown the association between obesity and cancer, childhood obesity is one of the potential reasons behind the development of CNS tumors, including GBM. Obesity in children has almost reached epidemic rates in both developed and developing countries, harming children's physical and mental health. Obese children are more likely to face obesity as adults and develop non-communicable diseases such as diabetes and cardiovascular disease as compared to adults with normal weight. However, the actual origin and cause of obesity are difficult to be pointed out, as it is assumed to be a disorder with numerous causes such as environmental factors, lifestyle, and cultural background. In this narrative review article, we discuss the various molecular and genetic drivers of obesity that can be targeted as potential contributing factors to fight the development of GBM in children.
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Affiliation(s)
- Punya Sachdeva
- GloNeuro, Sector 107, Vishwakarma Road, Noida 201301, India
| | - Shampa Ghosh
- GloNeuro, Sector 107, Vishwakarma Road, Noida 201301, India
- ICMR—National Institute of Nutrition, Tarnaka, Hyderabad 500007, India
| | - Soumya Ghosh
- GloNeuro, Sector 107, Vishwakarma Road, Noida 201301, India
| | - Sungsoo Han
- School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Korea
| | - Juni Banerjee
- Department of Biotechnology and Bioengineering, Institute of Advanced Research, Gandhinagar 382426, India
- Correspondence: (J.B.); (R.B.); (J.K.S.)
| | - Rakesh Bhaskar
- School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Korea
- Correspondence: (J.B.); (R.B.); (J.K.S.)
| | - Jitendra Kumar Sinha
- GloNeuro, Sector 107, Vishwakarma Road, Noida 201301, India
- Correspondence: (J.B.); (R.B.); (J.K.S.)
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Ghusn W, Bouchard C, Frye MA, Acosta A. Weight-centric treatment of depression and chronic pain. OBESITY PILLARS 2022; 3:100025. [PMID: 37990725 PMCID: PMC10661995 DOI: 10.1016/j.obpill.2022.100025] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 06/20/2022] [Accepted: 06/20/2022] [Indexed: 11/23/2023]
Abstract
BACKGROUND Depression and chronic pain are two major chronic non-communicable diseases (CNCD). Considering the bidirectional relationship between obesity and CNCD, it is of the utmost importance to understand the effect of medications utilized to treat these diseases on body weight. METHODS This is a clinical review on the effect of medications for depression and chronic pain on body weight. We searched PubMed, Scopus, MEDLINE, and Google Scholar databases for studies on the topic from January 1, 1950 to April 1, 2022 in English language. Additionally, we present expert opinions in the fields of obesity, depression and chronic pain, providing a weight-centric approach to treat depression and chronic pain. RESULTS Several antidepressant and chronic pain medications are associated with weight gain. Selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, monoamine oxidases, mirtazapine and trazodone are common antidepressants that can increase body weight while bupropion is significantly associated with weight loss. Gabapentin and pregabalin are common chronic pain medications that are linked to weight gain. On the other hand, topiramate is associated with significant weight loss. Obesity, depression and chronic pain experts recommend avoiding medications that can increase body weight if another effective alternative is available. CONCLUSION By shifting prescribing practices toward a weight-conscious approach (i.e., switching from weight gain medications to weight loss/neutral), it is possible to mitigate the incidence of drug-induced weight gain.
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Affiliation(s)
- Wissam Ghusn
- Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | | | - Mark A. Frye
- Department of Psychiatry, Mayo Clinic, Rochester, MN, USA
| | - Andres Acosta
- Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
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Nappi RE, Chedraui P, Lambrinoudaki I, Simoncini T. Menopause: a cardiometabolic transition. Lancet Diabetes Endocrinol 2022; 10:442-456. [PMID: 35525259 DOI: 10.1016/s2213-8587(22)00076-6] [Citation(s) in RCA: 102] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 02/08/2022] [Accepted: 02/17/2022] [Indexed: 12/12/2022]
Abstract
Menopause is often a turning point for women's health worldwide. Increasing knowledge from experimental data and clinical studies indicates that cardiometabolic changes can manifest at the menopausal transition, superimposing the effect of ageing onto the risk of cardiovascular disease. The menopausal transition is associated with an increase in fat mass (predominantly in the truncal region), an increase in insulin resistance, dyslipidaemia, and endothelial dysfunction. Exposure to endogenous oestrogen during the reproductive years provides women with protection against cardiovascular disease, which is lost around 10 years after the onset of menopause. In particular, women with vasomotor symptoms during menopause seem to have an unfavourable cardiometabolic profile. Early management of the traditional risk factors of cardiovascular disease (ie, hypertension, obesity, diabetes, dyslipidaemia, and smoking) is essential; however, it is important to recognise in the reproductive history the female-specific conditions (ie, gestational hypertension or diabetes, premature ovarian insufficiency, some gynaecological diseases such as functional hypothalamic amenorrhoea, and probably others) that could enhance the risk of cardiovascular disease during and after the menopausal transition. In this Review, the first of a Series of two papers, we provide an overview of the literature for understanding cardiometabolic changes and the management of women at midlife (40-65 years) who are at higher risk, focusing on the identification of factors that can predict the occurrence of cardiovascular disease. We also summarise evidence about preventive non-hormonal strategies in the context of cardiometabolic health.
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Affiliation(s)
- Rossella E Nappi
- Research Center for Reproductive Medicine, Gynecological Endocrinology and Menopause, IRCCS San Matteo Foundation, Pavia, Italy; Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.
| | - Peter Chedraui
- Instituto de Investigación e Innovación en Salud Integral and Laboratorio de Biomedicina, Facultad de Ciencias Médicas, Universidad Católica de Santiago de Guayaquil, Guayaquil, Ecuador
| | - Irene Lambrinoudaki
- Menopause Unit, 2nd Department of Obstetrics and Gynecology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Tommaso Simoncini
- Division of Obstetrics and Gynecology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
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Dong X, Li H, Pei M, Tan J, Chen G, Li S, Xie Z, Wang Q, Wang G, Chen Y, Wang C. Analgesic effects of nerve growth factor-directed monoclonal antibody on diabetic neuralgia in an animal model. FEBS Open Bio 2022; 12:1325-1335. [PMID: 35417079 PMCID: PMC9249326 DOI: 10.1002/2211-5463.13410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 03/15/2022] [Accepted: 04/12/2022] [Indexed: 11/20/2022] Open
Abstract
Current treatment options for diabetic neuralgia are limited and unsatisfactory. Tanezumab, a monoclonal antibody that blocks nerve growth factor (NGF) signaling, has been shown to be effective in relieving the clinical symptoms of osteoarthritis pain, chronic low back pain, cancer pain induced by bone metastasis, and diabetic neuralgia. However, the clinical development of tanezumab has been terminated due to the risk of induction of rapidly progressive osteoarthritis (RPOA), and no other NGF antibodies have been examined for their ability to treat diabetic neuralgia in either animal models or clinical trials. In this study, a humanized high‐affinity NGF monoclonal antibody (mAb), huAb45 that could neutralize the interaction between NGF and its high‐affinity receptor TrkA. In a mouse diabetic neuralgia model, it effectively relieved neuropathic pain. This study may serve as the necessary foundation for future studies of huAb45 to potentially treat diabetic neuralgia.
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Affiliation(s)
- Xingchen Dong
- School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210000, China.,Shanghai Mabstone Biotechnology Ltd, Shanghai, 201203, China.,Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China
| | - Huanhuan Li
- Shanghai Mabstone Biotechnology Ltd, Shanghai, 201203, China
| | - Min Pei
- Shanghai Mabstone Biotechnology Ltd, Shanghai, 201203, China
| | - Jie Tan
- Shanghai Mabstone Biotechnology Ltd, Shanghai, 201203, China
| | - Ganjun Chen
- Shanghai Mabstone Biotechnology Ltd, Shanghai, 201203, China
| | - Santai Li
- Shanghai Mabstone Biotechnology Ltd, Shanghai, 201203, China
| | - Zuobin Xie
- Dartsbio Pharmaceuticals Ltd, Zhongshan, Guangdong, 528400, China
| | - Qi Wang
- Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China
| | - Guifeng Wang
- Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China
| | - Yili Chen
- Shanghai Mabstone Biotechnology Ltd, Shanghai, 201203, China.,Dartsbio Pharmaceuticals Ltd, Zhongshan, Guangdong, 528400, China
| | - Chunhe Wang
- School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210000, China.,Shanghai Mabstone Biotechnology Ltd, Shanghai, 201203, China.,Dartsbio Pharmaceuticals Ltd, Zhongshan, Guangdong, 528400, China.,Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China
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Müller TD, Blüher M, Tschöp MH, DiMarchi RD. Anti-obesity drug discovery: advances and challenges. Nat Rev Drug Discov 2022; 21:201-223. [PMID: 34815532 PMCID: PMC8609996 DOI: 10.1038/s41573-021-00337-8] [Citation(s) in RCA: 525] [Impact Index Per Article: 175.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/06/2021] [Indexed: 12/27/2022]
Abstract
Enormous progress has been made in the last half-century in the management of diseases closely integrated with excess body weight, such as hypertension, adult-onset diabetes and elevated cholesterol. However, the treatment of obesity itself has proven largely resistant to therapy, with anti-obesity medications (AOMs) often delivering insufficient efficacy and dubious safety. Here, we provide an overview of the history of AOM development, focusing on lessons learned and ongoing obstacles. Recent advances, including increased understanding of the molecular gut-brain communication, are inspiring the pursuit of next-generation AOMs that appear capable of safely achieving sizeable and sustained body weight loss.
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Affiliation(s)
- Timo D Müller
- Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, Neuherberg, Germany.
- German Center for Diabetes Research (DZD), Neuherberg, Germany.
| | - Matthias Blüher
- Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Leipzig, Germany
| | - Matthias H Tschöp
- Helmholtz Zentrum München, Neuherberg, Germany
- Division of Metabolic Diseases, Department of Medicine, Technische Universität München, München, Germany
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D’Alessandro C, Benedetti A, Di Paolo A, Giannese D, Cupisti A. Interactions between Food and Drugs, and Nutritional Status in Renal Patients: A Narrative Review. Nutrients 2022; 14:nu14010212. [PMID: 35011087 PMCID: PMC8747252 DOI: 10.3390/nu14010212] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Revised: 12/14/2021] [Accepted: 12/16/2021] [Indexed: 12/17/2022] Open
Abstract
Drugs and food interact mutually: drugs may affect the nutritional status of the body, acting on senses, appetite, resting energy expenditure, and food intake; conversely, food or one of its components may affect bioavailability and half-life, circulating plasma concentrations of drugs resulting in an increased risk of toxicity and its adverse effects, or therapeutic failure. Therefore, the knowledge of these possible interactions is fundamental for the implementation of a nutritional treatment in the presence of a pharmacological therapy. This is the case of chronic kidney disease (CKD), for which the medication burden could be a problem, and nutritional therapy plays an important role in the patient’s treatment. The aim of this paper was to review the interactions that take place between drugs and foods that can potentially be used in renal patients, and the changes in nutritional status induced by drugs. A proper definition of the amount of food/nutrient intake, an adequate definition of the timing of meal consumption, and a proper adjustment of the drug dosing schedule may avoid these interactions, safeguarding the quality of life of the patients and guaranteeing the effectiveness of drug therapy. Hence, a close collaboration between the nephrologist, the renal dietitian, and the patient is crucial. Dietitians should consider that food may interact with drugs and that drugs may affect nutritional status, in order to provide the patient with proper dietary suggestions, and to allow the maximum effectiveness and safety of drug therapy, while preserving/correcting the nutritional status.
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Zhang ZH, Li J, Li J, Ma Z, Huang XJ. Veratrilla baillonii Franch Ameliorates Diabetic Liver Injury by Alleviating Insulin Resistance in Rats. Front Pharmacol 2021; 12:775563. [PMID: 34899339 PMCID: PMC8662784 DOI: 10.3389/fphar.2021.775563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 10/27/2021] [Indexed: 11/13/2022] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a complex and polygenic disorder with diverse complications. Veratrilla baillonii Franch (V. baillonii) has been applied in the intervention and treatment a diverse range of diseases, including diabetes. In this study, we revealed that water extracts of V. baillonii (WVBF) can ameliorate liver injury and insulin resistance in T2DM rat model. To elucidate the anti-diabetic mechanisms of WVBF, we performed liver transcriptome analysis that displayed WVBF treatment significantly suppressed many gene expressions involved in insulin resistance. Furthermore, functional experiments showed that WVBF treatment reduced the pathological damages of liver and pancreas, which may be regulated by Foxo1, Sirt1, G6pc, c-Met, Irs1, Akt1, Pik3r1. These results indicated that WVBF improves diabetic liver injury and insulin resistance in diabetic rats. Therefore, this study demonstrated WVBF could be used as a promising therapeutic agent for intervention and treatment of diabetes.
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Affiliation(s)
- Zhi-Hao Zhang
- College of Pharmacy, South-Central University for Nationalities, Wuhan, China
| | - Juan Li
- Key Laboratory of Environmental Health, Ministry of Education, Department of Toxicology, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jun Li
- College of Pharmacy, South-Central University for Nationalities, Wuhan, China
| | - Zhaowu Ma
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, China
| | - Xian-Ju Huang
- College of Pharmacy, South-Central University for Nationalities, Wuhan, China
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9
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Prevalence of oropharyngeal dysphagia in geriatric patients and real-life associations with diseases and drugs. Sci Rep 2021; 11:21955. [PMID: 34754078 PMCID: PMC8578645 DOI: 10.1038/s41598-021-99858-w] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 09/27/2021] [Indexed: 12/19/2022] Open
Abstract
Risk factors for oropharyngeal dysphagia (OD) in elderly patients are mainly central nervous system (CNS) and structural organic diseases or presbyphagia. We analysed the OD prevalence and association of OD with multimorbidity and polypharmacy using real-life data to complete this spectrum, with a focus on further and iatrogenic risk. This was a cross-sectional retrospective study based on a random sample of 200 patients admitted to a geriatric hospital. Data analysis included diagnoses, the detailed list of drugs, and an intense clinical investigation of swallowing according to Stanschus to screen for OD in each patient. The mean patient age was 84 ± 6.5 years. The prevalence of OD was 29.0%, without an effect of age, but a higher rate was found in men and in nursing home residents and an elevated risk of pneumonia. OD risk was slight in diabetes mellitus and COPD, and pronounced in CNS diseases. A relevant OD association was found, even after adjusting for CNS diseases, with antipsychotics, benzodiazepines, anti-Parkinson drugs, antidepressants, and antiepileptics. Further risk of OD was found with beta-blockers, alpha-blockers, opioids, antiemetics, antivertiginosa or antihistamines, metoclopramide, domperidone, anticholinergics, loop diuretics, urologics, and ophthalmics. From real-life data in patients with and without CNS diseases, we identified drug groups associated with a risk of aggravating/inducing OD. Restrictive indications for these drugs may be a preventative contribution, requiring implementation in dysphagia guidelines and an integrative dysphagia risk scale that considers all associated and cumulative medication risks in addition to diseases.
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Löffler MC, Betz MJ, Blondin DP, Augustin R, Sharma AK, Tseng YH, Scheele C, Zimdahl H, Mark M, Hennige AM, Wolfrum C, Langhans W, Hamilton BS, Neubauer H. Challenges in tackling energy expenditure as obesity therapy: From preclinical models to clinical application. Mol Metab 2021; 51:101237. [PMID: 33878401 PMCID: PMC8122111 DOI: 10.1016/j.molmet.2021.101237] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 03/31/2021] [Accepted: 04/13/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND A chronic imbalance of energy intake and energy expenditure results in excess fat storage. The obesity often caused by this overweight is detrimental to the health of millions of people. Understanding both sides of the energy balance equation and their counter-regulatory mechanisms is critical to the development of effective therapies to treat this epidemic. SCOPE OF REVIEW Behaviors surrounding ingestion have been reviewed extensively. This review focuses more specifically on energy expenditure regarding bodyweight control, with a particular emphasis on the organs and attractive metabolic processes known to reduce bodyweight. Moreover, previous and current attempts at anti-obesity strategies focusing on energy expenditure are highlighted. Precise measurements of energy expenditure, which consist of cellular, animal, and human models, as well as measurements of their translatability, are required to provide the most effective therapies. MAJOR CONCLUSIONS A precise understanding of the components surrounding energy expenditure, including tailored approaches based on genetic, biomarker, or physical characteristics, must be integrated into future anti-obesity treatments. Further comprehensive investigations are required to define suitable treatments, especially because the complex nature of the human perspective remains poorly understood.
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Affiliation(s)
- Mona C Löffler
- Cardio Metabolic Diseases Research, Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany
| | - Matthias J Betz
- Department of Endocrinology, Diabetes and Metabolism, University Hospital Basel, Basel, Switzerland
| | - Denis P Blondin
- Department of Medicine, Division of Neurology, Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, QC, Canada
| | - Robert Augustin
- Cardio Metabolic Diseases Research, Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany
| | - Anand K Sharma
- Institute of Food, Nutrition and Health, ETH Zürich, Schwerzenbach, Switzerland
| | - Yu-Hua Tseng
- Joslin Diabetes Center, Section on Integrative Physiology and Metabolism, Harvard Medical School, Boston, MA, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA
| | - Camilla Scheele
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark
| | - Heike Zimdahl
- Cardio Metabolic Diseases Research, Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany
| | - Michael Mark
- Cardio Metabolic Diseases Research, Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany
| | - Anita M Hennige
- Therapeutic Area CardioMetabolism & Respiratory, Boehringer Ingelheim International GmbH, Biberach, Germany
| | - Christian Wolfrum
- Institute of Food, Nutrition and Health, ETH Zürich, Schwerzenbach, Switzerland
| | - Wolfgang Langhans
- Physiology and Behavior Laboratory, Department of Health Sciences and Technology, ETH Zürich, Switzerland
| | - Bradford S Hamilton
- Cardio Metabolic Diseases Research, Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany
| | - Heike Neubauer
- Cardio Metabolic Diseases Research, Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany.
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Luo H, Jiang ZL, Ren Y. Therapy Management of Metabolic Disorder Comorbidity With Depression. Front Psychol 2021; 12:683320. [PMID: 34408704 PMCID: PMC8366060 DOI: 10.3389/fpsyg.2021.683320] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Accepted: 06/29/2021] [Indexed: 11/29/2022] Open
Abstract
Depression is a common disease that seriously endangers the physical and mental health of human beings, and it often coexists with other metabolic disorders such as diabetes and cancer. There have been endless reports on the mechanism, prevention, and cure of comorbidity because of its high incidence and poor prognosis and the increased burden on the family and society. There may be a specific comorbid basis and causal relationship between depression and metabolic diseases. Depression in patients with metabolic disorders can be effectively alleviated through psychotherapy and medication. The timely and effective treatment of depression can significantly improve the quality of life of patients with metabolic disorders, reduce their psychological burden, and promote the effective treatment of metabolic diseases. This study reorganized the research progress on the management of metabolic disorder comorbidity with depression.
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Affiliation(s)
- Hua Luo
- Department of Orthopedics, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, China
| | - Zheng-Li Jiang
- Department of Pharmacy, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, China
| | - Yu Ren
- Department of Pharmacy, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, China
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12
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Adibi JJ, Layden AJ, Birru RL, Miragaia A, Xun X, Smith MC, Yin Q, Millenson ME, O’Connor TG, Barrett ES, Snyder NW, Peddada S, Mitchell RT. First trimester mechanisms of gestational sac placental and foetal teratogenicity: a framework for birth cohort studies. Hum Reprod Update 2021; 27:747-770. [PMID: 33675653 PMCID: PMC8222765 DOI: 10.1093/humupd/dmaa063] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Revised: 12/18/2020] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND The function of the gestational sac (GS) and the placenta in the closely related processes of embryogenesis and teratogenicity in the first trimester has been minimally described. The prevailing assumption is that direct teratogenic effects are mediated by the critical extraembryonic organ, the placenta, which either blocks or transfers exposures to the foetus. Placental transfer is a dominant mechanism, but there are other paradigms by which the placenta can mediate teratogenic effects. Knowledge of these paradigms and first trimester human developmental biology can be useful to the epidemiologist in the conduct of biomarker-based studies of both maternal and child health. OBJECTIVE AND RATIONALE Our aim is to provide a causal framework for modelling the teratogenic effects of first trimester exposures on child health outcomes mediated by the GS and placenta using biomarker data collected in the first trimester. We initially present first trimester human developmental biology for the sake of informing and strengthening epidemiologic approaches. We then propose analytic approaches of modelling placental mechanisms by way of causal diagrams using classical non-embryolethal teratogens (diethylstilboestrol [DES], folic acid deficiency and cytomegalovirus [CMV]) as illustrative examples. We extend this framework to two chronic exposures of particular current interest, phthalates and maternal adiposity. SEARCH METHODS Information on teratogens was identified by a non-systematic, narrative review. For each teratogen, we included papers that answered the five following questions: (i) why were these exposures declared teratogens? (ii) is there a consensus on biologic mechanism? (iii) is there reported evidence of a placental mechanism? (iv) can we construct a theoretical model of a placental mechanism? and (v) can this knowledge inform future work on measurement and modelling of placental-foetal teratogenesis? We prioritized literature specific to human development, the organogenesis window in the first trimester and non-embryolethal mechanisms. OUTCOMES As a result of our review of the literature on five exposures considered harmful in the first trimester, we developed four analytic strategies to address first trimester placental mechanisms in birth cohort studies: placental transfer and direct effects on the foetus (DES and maternal adiposity), indirect effects through targeted placental molecular pathways (DES and phthalates), pre-placental effects through disruptions in embryonic and extraembryonic tissue layer differentiation (folic acid deficiency), and multi-step mechanisms that involve maternal, placental and foetal immune function and inflammation (DES and CMV). WIDER IMPLICATIONS The significance of this review is to offer a causal approach to classify the large number of potentially harmful exposures in pregnancy when the exposure occurs in the first trimester. Our review will facilitate future research by advancing knowledge of the first trimester mechanisms necessary for researchers to effectively associate environmental exposures with child health outcomes.
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Affiliation(s)
- Jennifer J Adibi
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA
| | - Alexander J Layden
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA
| | - Rahel L Birru
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | - Alexandra Miragaia
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | - Xiaoshuang Xun
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | - Megan C Smith
- Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, USA
| | - Qing Yin
- Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | | | - Thomas G O’Connor
- Department of Psychiatry, University of Rochester Medical Center, Rochester, NY, USA
- Department of Neuroscience, University of Rochester Medical Center, Rochester, NY, USA
- Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, NY, USA
| | - Emily S Barrett
- Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ, USA
| | - Nathaniel W Snyder
- Department of Microbiology and Immunology, Center for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
| | - Shyamal Peddada
- Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | - Rod T Mitchell
- MRC Centre for Reproductive Health, The University of Edinburgh, Queens Medical Research Institute, Edinburgh, UK
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Bessell E, Markovic TP, Fuller NR. How to provide a structured clinical assessment of a patient with overweight or obesity. Diabetes Obes Metab 2021; 23 Suppl 1:36-49. [PMID: 33621413 DOI: 10.1111/dom.14230] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2020] [Revised: 09/28/2020] [Accepted: 10/09/2020] [Indexed: 12/27/2022]
Abstract
With the increasing prevalence of overweight and obesity worldwide, there is a reciprocal increase in the global economic burden and ill-health from obesity-related chronic diseases. Primary healthcare services have a role to play in ensuring early detection of weight issues and in directing patients towards evidence-based care to slow this progression. Research shows that many people with obesity are motivated to lose weight and want their clinician to initiate a conversation about weight management and treatment options. However, this conversation rarely occurs and there is a significant delay in treatment, resulting in an increased burden on the individual, healthcare system and society. In this paper, the components and rationale for the clinical assessment of adult patients with overweight or obesity, including anthropometric measurements and pathology tests, are described. Recommendations to ascertain the potential factors influencing the development of obesity in the patient, such as lifestyle factors (diet and physical activity) and mental health, are also provided. The potential sequelae of obesity that may be present and the necessary assessments for diagnosis are also addressed. These assessments are vital to ensure the patient is referred to the appropriate allied health services and/or specialists.
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Affiliation(s)
- Erica Bessell
- Boden Collaboration, Charles Perkins Centre, Faculty of Medicine and Health University of Sydney, Sydney, New South Wales, Australia
| | - Tania P Markovic
- Boden Collaboration, Charles Perkins Centre, Faculty of Medicine and Health University of Sydney, Sydney, New South Wales, Australia
- Metabolism and Obesity Services, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
| | - Nicholas R Fuller
- Boden Collaboration, Charles Perkins Centre, Faculty of Medicine and Health University of Sydney, Sydney, New South Wales, Australia
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Wolff LS, Flynn A, Xuan Z, Errichetti KS, Tapia Walker S, Brodesky MK. The Effect of Integrating Primary Care and Mental Health Services on Diabetes and Depression: A Multi-site Impact Evaluation on the US-Mexico Border. Med Care 2021; 59:67-76. [PMID: 33017341 DOI: 10.1097/mlr.0000000000001429] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
BACKGROUND Health care delivery systems are increasingly integrating physical and mental health services to address patients' complex needs, contain costs, and improve satisfaction. Therefore, it is critical to understand whether adoption of integrated care models is effective in diverse settings. OBJECTIVE This study examined the effect of integrated care on physical and mental health outcomes among low-income Latino participants on the US-Mexico border. RESEARCH DESIGN In this quasi-experimental multisite study, individual-level data were pooled from 8 studies of locally adapted integrated care models. SUBJECTS Participants were 18 years or older and had 1 or more chronic conditions: diabetes, depression, hypertension, or obesity. The study enrolled 4226 participants with 2254 participants in the intervention group and 1972 in the comparison group. MEASURES Primary outcomes were depressive symptoms as measured by the Patient Health Questionnaire-9 score and blood glucose measured by hemoglobin A1c (HbA1c). Blood pressure, body mass index, and quality of life were secondary outcomes. RESULTS Multivariable linear regression analyses indicated intervention participants had significantly lower Patient Health Questionnaire-9 scores (β=-0.39, P=0.03) and HbA1c (β=-0.14, P=0.02) at 12 months compared with comparison group participants. Stratified analyses showed improvements in HbA1c were even greater among intervention participants who had diabetes, depression, severe and persistent mental illness, were older or female compared with their counterparts in the comparison group. CONCLUSIONS Health care is constantly transforming, making it critical to study these changes across populations and settings. Findings from this study indicate that integrated care can significantly improve mental and physical health in an underserved Latino population.
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Kim TN. Barriers to Obesity Management: Patient and Physician Factors. J Obes Metab Syndr 2020; 29:244-247. [PMID: 33342768 PMCID: PMC7789016 DOI: 10.7570/jomes20124] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 12/03/2020] [Accepted: 12/15/2020] [Indexed: 01/24/2023] Open
Affiliation(s)
- Tae Nyun Kim
- Department of Internal Medicine, Cardiovascular and Metabolic Disease Center, Inje University College of Medicine, Busan, Korea
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16
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The association between weight-promoting medication use and weight gain in postmenopausal women: findings from the Women's Health Initiative. ACTA ACUST UNITED AC 2020; 27:1117-1125. [DOI: 10.1097/gme.0000000000001589] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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González-Maciel A, Romero-Velázquez RM, Alfaro-Rodríguez A, Sanchez Aparicio P, Reynoso-Robles R. Prenatal exposure to oxcarbazepine increases hippocampal apoptosis in rat offspring. J Chem Neuroanat 2019; 103:101729. [PMID: 31794794 DOI: 10.1016/j.jchemneu.2019.101729] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Revised: 11/29/2019] [Accepted: 11/29/2019] [Indexed: 01/18/2023]
Abstract
This study assessed apoptosis in the offspring of rats exposed to oxcarbazepine (OXC) from day 7 to 15 of gestation. Three groups of pregnant Wistar rats were used: 1) Control, treated with saline solution; 2) treated with 100 mg/kg OXC; 3) treated with 100 mg/kg of carbamazepine (CBZ, as a positive control for apoptosis); the route of administration was intragastric. Apoptosis was detected at three postnatal ages using the TUNEL technique in the CA1, and CA3 regions of the hippocampus and in the dentate gyrus (DG); neurogenesis was assessed in the DG using an antibody against doublecortin. The litter characteristics were recorded. OXC increased apoptosis in all regions (p < 0.01) at the three ages evaluated. Lamination disruption occurred in CA1 and CA3 due to the neuron absence and to ectopic neurons; there were also malformations in the dorsal lamina of the DG in 38% and 25% of the pups born from rats treated with OXC and CBZ respectively. CBZ also increased apoptosis. No clear effect on neurogenesis in the DG was observed. The size of the litter was smaller (p < 0.01) in the experimental groups. Nineteen-day OXC fetuses had low weight (p < 0.01), but 21 and 30 postnatal days old CBZ and OXC pups were overweight (p < 0.01). The results demonstrate that OXC administered during gestation is pro-apoptotic, alters the cytoarchitecture of the hippocampus, reduces litter size, and probably influences postnatal weight. We provide evidence of the proapoptotic effect of CBZ when administered early in gestation.
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Affiliation(s)
- A González-Maciel
- Laboratory of Cell and Tissue Morphology, Instituto Nacional de Pediatría, Secretaría de Salud, Insurgentes Sur No. 3700-C, Mexico City, C. P. 04530, Mexico.
| | - R M Romero-Velázquez
- Laboratory of Cell and Tissue Morphology, Instituto Nacional de Pediatría, Secretaría de Salud, Insurgentes Sur No. 3700-C, Mexico City, C. P. 04530, Mexico.
| | - A Alfaro-Rodríguez
- Division of Neurosciences, Instituto Nacional de Rehabilitación, "Luis Guillermo Ibarra Ibarra", Secretaría de Salud, Col. Arenal de Guadalupe, Mexico City, C.P. 14389, Mexico.
| | - P Sanchez Aparicio
- Faculty of Veterinary Medicine, Department of Pharmacology, Universidad Autónoma del Estado de México, Mexico
| | - R Reynoso-Robles
- Laboratory of Cell and Tissue Morphology, Instituto Nacional de Pediatría, Secretaría de Salud, Insurgentes Sur No. 3700-C, Mexico City, C. P. 04530, Mexico.
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Desalermos A, Russell B, Leggett C, Parnell A, Ober K, Hagerich K, Gerlan C, Ganji G, Lee E, Proudfoot JA, Grunvald E, Gupta S, Ho SB, Zarrinpar A. Effect of Obesogenic Medications on Weight-Loss Outcomes in a Behavioral Weight-Management Program. Obesity (Silver Spring) 2019; 27:716-723. [PMID: 31012292 PMCID: PMC6544176 DOI: 10.1002/oby.22444] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Accepted: 01/17/2019] [Indexed: 01/06/2023]
Abstract
OBJECTIVE This study aimed to evaluate a possible association between the use of obesogenic medications and inadequate weight loss in a behavioral weight-management program. METHODS This is a case-control, single-center study of 666 adult patients within a Veterans Health Administration health system who participated in the MOVE! behavioral weight-loss program. The cohort was divided into responders (n = 150), patients who achieved ≥ 5% total weight loss by the end of the MOVE! program, and nonresponders (n = 516), those who achieved < 5% total weight loss. We reviewed each patient's medical records for exposure to obesogenic medication during the time of treatment. RESULTS Approximately 62% (n = 411) of patients entering MOVE! had a prescription for obesogenic medications. Obesogenic medication use was associated with worse weight-loss outcomes, and participants were 37% less likely to achieve a clinically meaningful (≥ 5% total weight loss) outcome at the end of the MOVE! program (odds ratio, 0.633; 95% CI: 0.427-0.937; adjusted P = 0.022). Patients who received three or more medications (n = 72) had the greatest difficulty achieving 5% weight loss compared with the control group (odds ratio, 0.265; 95% CI: 0.108-0.646; adjusted P = 0.003). CONCLUSIONS The use of provider-prescribed obesogenic medications was associated with worse weight-loss outcomes in a behavioral weight-loss program. Closer scrutiny of patient medications is necessary to help improve outcomes of weight-loss treatments.
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Affiliation(s)
- Athanasios Desalermos
- Veterans Affairs San Diego Healthcare System, San Diego, California, USA
- Division of Gastroenterology. University of California, San Diego, La Jolla, California, USA
- School of Medicine, University of California, San Diego, La Jolla, California, USA
| | - Baylee Russell
- Division of Gastroenterology. University of California, San Diego, La Jolla, California, USA
- School of Medicine, University of California, San Diego, La Jolla, California, USA
| | - Cecilia Leggett
- School of Medicine, University of California, San Diego, La Jolla, California, USA
| | - Amelia Parnell
- Veterans Affairs San Diego Healthcare System, San Diego, California, USA
| | - Kathleen Ober
- Veterans Affairs San Diego Healthcare System, San Diego, California, USA
| | - Kelley Hagerich
- Veterans Affairs San Diego Healthcare System, San Diego, California, USA
| | - Cindy Gerlan
- Veterans Affairs San Diego Healthcare System, San Diego, California, USA
| | - Gelareh Ganji
- Veterans Affairs San Diego Healthcare System, San Diego, California, USA
| | - Euyhyun Lee
- Clinical and Translational Research Institute, University of California, San Diego, La Jolla, California, USA
| | - James A. Proudfoot
- Clinical and Translational Research Institute, University of California, San Diego, La Jolla, California, USA
| | - Eduardo Grunvald
- School of Medicine, University of California, San Diego, La Jolla, California, USA
- Bariatric and Metabolic Institute, University of California, San Diego, La Jolla, California, USA
- Division of General Internal Medicine, University of California, San Diego, La Jolla, California, USA
- Institute of Diabetes and Metabolic Health, University of California, San Diego, La Jolla, California, USA
| | - Samir Gupta
- Veterans Affairs San Diego Healthcare System, San Diego, California, USA
- Division of Gastroenterology. University of California, San Diego, La Jolla, California, USA
- School of Medicine, University of California, San Diego, La Jolla, California, USA
| | - Samuel B. Ho
- Veterans Affairs San Diego Healthcare System, San Diego, California, USA
- Division of Gastroenterology. University of California, San Diego, La Jolla, California, USA
- School of Medicine, University of California, San Diego, La Jolla, California, USA
| | - Amir Zarrinpar
- Veterans Affairs San Diego Healthcare System, San Diego, California, USA
- Division of Gastroenterology. University of California, San Diego, La Jolla, California, USA
- School of Medicine, University of California, San Diego, La Jolla, California, USA
- Clinical and Translational Research Institute, University of California, San Diego, La Jolla, California, USA
- Institute of Diabetes and Metabolic Health, University of California, San Diego, La Jolla, California, USA
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Behl S, Adem A, Hussain A, Singh J. Effects of rilpivirine, 17β-estradiol and β-naphthoflavone on the inflammatory status of release of adipocytokines in 3T3-L1 adipocytes in vitro. Mol Biol Rep 2019; 46:2643-2655. [DOI: 10.1007/s11033-019-04671-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2018] [Accepted: 02/05/2019] [Indexed: 12/22/2022]
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Park EG, Lee J, Lee J. Use of the Modified Atkins Diet in Intractable Pediatric Epilepsy. J Epilepsy Res 2018; 8:20-26. [PMID: 30090758 PMCID: PMC6066692 DOI: 10.14581/jer.18004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2018] [Accepted: 05/18/2018] [Indexed: 11/13/2022] Open
Abstract
Background and Purpose The modified Atkins diet is a less restrictive alternative to the ketogenic diet (KD), allowing unlimited protein, fat, calories, and fluid intake. Moreover, it can be started on an outpatient basis without requiring a fast. This study evaluated the efficacy, tolerability, and compliance of the modified Atkins diet in intractable pediatric epilepsy. Methods We retrospectively reviewed the medical records of 26 pediatric patients (10 males and 16 females) with intractable epilepsy who were treated using the modified Atkins diet at Samsung Medical Center from January 2011 to March 2017. Results The mean age at initiation of the modified Atkins diet was 10.9 (range, 2–21) years. The diet was continued for a mean duration of 5.9 (range, 1–16) months. After 6 months, 10 (38.5%) remained on the diet, of whom six (60%) had > 50% seizure reduction and two (20%) became seizure free. Four of 26 patients (15.4%) reported side effects of the diet, including constipation (n = 2) and lipid profile elevations (n = 2). Mean body mass index (BMI) was reduced from 22.6 to 20.9 kg/m2 (p < 0.05) in 13 patients who continued the diet for ≥ 3 months. Four of these patients (30.8%) were overweight (BMI > 25 kg/m2) before initiating the diet and were satisfied with their BMI changes from a mean of 30.3 to 27 kg/m2 (p < 0.05). Food refusal (n = 3) and poor parental compliance (n = 3) were the common reasons cited for cessation. Conclusions The modified Atkins diet may be an alternative treatment option for children with intractable epilepsy who are unable to tolerate KD because of food intake-related restrictiveness or adverse effects. The continuous support of healthcare professionals and families plays a key role in diet maintenance.
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Affiliation(s)
- Eu Gene Park
- Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jiwon Lee
- Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jeehun Lee
- Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Abstract
As a leading cause of morbidity and mortality in the United States and worldwide, obesity is a disease that is frequently encountered in clinical practice today and requires a range of medical interventions. While obesity affects both men and women across all ages, multiple issues are particularly germane to women's health, particularly as obesity is more prevalent among women than men in the United States and obesity among women of reproductive health relates to the growing issue of childhood obesity. Discussed herein are the epidemiology and pathophysiology of obesity along with the impact of perinatal obesity on fetal programming. Guidance on screening and management of obesity through lifestyle intervention, pharmacologic therapy, and bariatric surgery, as well as avoidance of weight-promoting medications wherever possible, is elaborated. Particular attention is paid to the contribution of these modalities to weight loss as well as their impact on obesity-related comorbidities that affect a woman's overall health, such as type 2 diabetes and hypertension, and her reproductive and gynecologic health. With modest weight loss, women with obesity can achieve notable improvements in chronic medical conditions, fertility, pregnancy outcomes, and symptoms of pelvic floor disorders. Moreover, as children born to women after bariatric surgery-induced weight loss show improved metabolic outcomes, this demonstrates a role for maternal weight loss in reducing risk of development of metabolic disturbances in children. In light of the immense cost burden and mortality from obesity, it is important to emphasize the role of lifestyle intervention, pharmacologic management, and bariatric surgery for weight loss in clinical practice to mitigate the impact of obesity on women's health.
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Affiliation(s)
| | - Gricelda Gomez
- Harvard Medical School, Boston, Massachusetts
- Department of Surgery-Urology, Brigham and Women's Hospital, Boston, Massachusetts
| | - Fatima Cody Stanford
- Division of Gastroenterology and Endocrinology, Department of Internal Medicine and Pediatrics, Massachusetts General Hospital Weight Center, Boston, Massachusetts
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A cross-continental analysis of weight gain, psychiatric diagnoses and medication use during inpatient psychiatric treatment. The international study on physical illness in mentally ill. Eur Psychiatry 2018; 48:65-70. [PMID: 29331602 DOI: 10.1016/j.eurpsy.2017.11.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2017] [Revised: 11/07/2017] [Accepted: 11/08/2017] [Indexed: 11/23/2022] Open
Abstract
Weight gain among psychiatric inpatients is a widespread phenomenon. This change in body mass index (BMI) can be caused by several factors. Based on recent research, we assume the following factors are related to weight gain during psychiatric inpatient treatment: psychiatric medication, psychiatric diagnosis, sex, age, weight on admission and geographic region of treatment. 876 of originally recruited 2328 patients met the criteria for our analysis. Patients were recruited and examined in mental health care centres in Nigeria (N = 265), Japan (N = 145) and Western-Europe (Denmark, Germany and Switzerland; N = 466). There was a significant effect of psychiatric medication, psychiatric diagnoses and geographic region, but not age and sex, on BMI changes. Geographic region had a significant effect on BMI change, with Nigerian patients gaining significantly more weight than Japanese and Western European patients. Moreover, geographic region influenced the type of psychiatric medication prescribed and the psychiatric diagnoses. The diagnoses and psychiatric medication prescribed had a significant effect on BMI change. In conclusion, we consider weight gain as a multifactorial phenomenon that is influenced by several factors. One can discuss a number of explanations for our findings, such as different clinical practices in the geographical regions (prescribing or admission strategies and access-to-care aspects), as well as socio-economic and cultural differences.
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Ge T, Yang W, Fan J, Li B. Preclinical evidence of ghrelin as a therapeutic target in epilepsy. Oncotarget 2017; 8:59929-59939. [PMID: 28938694 PMCID: PMC5601790 DOI: 10.18632/oncotarget.18349] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2017] [Accepted: 05/22/2017] [Indexed: 12/17/2022] Open
Abstract
Ghrelin, an orexigenic peptide synthesized by endocrine cells of the gastric mucosa, plays a major role in inhibiting seizures. However, the underlying mechanism of ghrelin's anticonvulsant action is still unclear. Nowadays, there are considerable evidences showing that ghrelin is implicated in various neurophysiological processes, including learning and memory, neuroprotection, neurogenesis, and inflammatory effects. In this review, we will summarize the effects of ghrelin on epilepsy. It may provide a comprehensive picture of the role of ghrelin in epilepsy.
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Affiliation(s)
- Tongtong Ge
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun 130041, PR China
| | - Wei Yang
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun 130041, PR China
| | - Jie Fan
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun 130041, PR China
| | - Bingjin Li
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun 130041, PR China
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Henwood J, Rössner S, Binns A. Medicines. LIFESTYLE MEDICINE 2017. [DOI: 10.1016/b978-0-12-810401-9.00024-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
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Bingsohn L, Knorr E, Vilcinskas A. The model beetle Tribolium castaneum can be used as an early warning system for transgenerational epigenetic side effects caused by pharmaceuticals. Comp Biochem Physiol C Toxicol Pharmacol 2016; 185-186:57-64. [PMID: 26972758 DOI: 10.1016/j.cbpc.2016.03.002] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2015] [Revised: 02/25/2016] [Accepted: 03/09/2016] [Indexed: 11/24/2022]
Abstract
Pharmaceuticals are not currently tested for transgenerational and epigenetic side effects. The use of vertebrates as preclinical research models is limited by their long generation times, low numbers of progeny and ethical concerns. In contrast, invertebrates such as insects breed rapidly, produce many offspring and are more ethically acceptable, allowing them to be used for high-throughput screening. Here, we established Tribolium castaneum as a model to screen for the effect of drugs on complex fitness parameters and the expression of epigenetic regulatory genes. We tested diets supplemented with the psychoactive drug valproic acid (VPA), which is a histone deacetylase inhibitor, or the antioxidant curcumin, which is a histone acetyltransferase inhibitor. We found that VPA delayed development, reduced longevity, and increased female body weight compared to a control diet. Fertility and fecundity declined and the expression of epigenetic regulatory genes was induced in the untreated F1 generation. In contrast, curcumin did not affect development or body weight, but it increased longevity, caused a significant reduction in fertility, and induced the expression of epigenetic regulatory genes mostly in the treated F0 generation. VPA and curcumin administered to vertebrate models have similar effects to those we observed in T. castaneum, confirming that this beetle is potentially useful as an alternative model to screen for the epigenetic effect of drugs. T. castaneum also provides a valuable early warning system for transgenerational epigenetic risk factors that are difficult to detect in mammals.
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Affiliation(s)
- Linda Bingsohn
- Fraunhofer Institute for Molecular Biology and Applied Ecology, Department of Bioresources, Winchester Str. 2, 35394 Giessen, Germany
| | - Eileen Knorr
- Fraunhofer Institute for Molecular Biology and Applied Ecology, Department of Bioresources, Winchester Str. 2, 35394 Giessen, Germany
| | - Andreas Vilcinskas
- Fraunhofer Institute for Molecular Biology and Applied Ecology, Department of Bioresources, Winchester Str. 2, 35394 Giessen, Germany; Institute for Insect Biotechnology, Heinrich-Buff-Ring 26-32, 35392 Giessen, Germany.
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Dinkelacker V. Obstructive sleep apnea in drug-resistant epilepsy: A significant comorbidity warranting diagnosis and treatment. Rev Neurol (Paris) 2016; 172:361-70. [DOI: 10.1016/j.neurol.2016.03.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2016] [Accepted: 03/18/2016] [Indexed: 11/08/2022]
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Factors Related to Early Clinical Effects of Quetiapine Extended-Release: A Multinational, Prospective, Observational Study. Clin Drug Investig 2016; 36:491-7. [DOI: 10.1007/s40261-016-0395-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Chakraborti CK. New-found link between microbiota and obesity. World J Gastrointest Pathophysiol 2015; 6:110-119. [PMID: 26600968 PMCID: PMC4644874 DOI: 10.4291/wjgp.v6.i4.110] [Citation(s) in RCA: 260] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2015] [Accepted: 10/27/2015] [Indexed: 02/06/2023] Open
Abstract
Due to the grave pathological role of obesity, worldwide research is being continued to find out the causative factors involved in it. Recent advances in this field reveal a possible relationship between the compositional pattern of gut microbiota and genesis of obesity. Several study results have shown that short-chain fatty acids (SCFAs, microbiota-induced fermentation products) and lipopolysaccharides (LPS, an integral component of Gram negative microorganisms) play the key role in linking the two. Though several SCFAs are produced as microbiota-fermentation products, three of them, i.e., butyrate, propionate and acetate have been found to be definitely involved in obesity; though individually they are neither purely obesogenic nor antiobesogenic. Out of these, butyrate and propionate are predominantly antiobesogenic. Butyrate, though a major energy source for colonocytes, has been found to increase mitochondrial activity, prevent metabolic endotoxemia, improve insulin sensitivity, possess anti-inflammatory potential, increase intestinal barrier function and protect against diet-induced obesity without causing hypophagia. Propionate has been found to inhibit cholesterol synthesis, thereby antagonizing the cholesterol increasing action of acetate, and to inhibit the expression of resistin in adipocytes. Moreover, both these SCFAs have been found to cause weight regulation through their stimulatory effect on anorexigenic gut hormones and to increase the synthesis of leptin. Unlike butyrate and propionate, acetate, which is substantially absorbed, shows more obesogenic potential, as it acts as a substrate for hepatic and adipocyte lipogenesis. High fat diet increases the absorption of LPS, which, in turn, has been found to be associated with metabolic endotoxemia and to induce inflammation resulting in obesity. Multiple independent and interrelated mechanisms have been found to be involved in such linking processes which are discussed in this review work along with some possible remedial measures for prevention of weight gain and obesity.
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Osunlana AM, Asselin J, Anderson R, Ogunleye AA, Cave A, Sharma AM, Campbell-Scherer DL. 5As Team obesity intervention in primary care: development and evaluation of shared decision-making weight management tools. Clin Obes 2015; 5:219-25. [PMID: 26129630 PMCID: PMC4755160 DOI: 10.1111/cob.12105] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2014] [Revised: 04/13/2015] [Accepted: 05/18/2015] [Indexed: 11/28/2022]
Abstract
Despite several clinical practice guidelines, there remains a considerable gap in prevention and management of obesity in primary care. To address the need for changing provider behaviour, a randomized controlled trial with convergent mixed method evaluation, the 5As Team (5AsT) study, was conducted. As part of the 5AsT intervention, the 5AsT tool kit was developed. This paper describes the development process and evaluation of these tools. Tools were co-developed by the multidisciplinary research team and the 5AsT, which included registered nurses/nurse practitioners (n = 15), mental health workers (n = 7) and registered dieticians (n = 7), who were previously randomized to the 5AsT intervention group at a primary care network in Edmonton, Alberta, Canada. The 5AsT tool development occurred through a practice/implementation-oriented, need-based, iterative process during learning collaborative sessions of the 5AsT intervention. Feedback during tool development was received through field notes and final provider evaluation was carried out through anonymous questionnaires. Twelve tools were co-developed with 5AsT. All tools were evaluated as either 'most useful' or 'moderately useful' in primary care practice by the 5AsT. Four key findings during 5AsT tool development were the need for: tools that were adaptive, tools to facilitate interdisciplinary practice, tools to help patients understand realistic expectations for weight loss and shared decision-making tools for goal setting and relapse prevention. The 5AsT tools are primary care tools which extend the utility of the 5As of obesity management framework in clinical practice.
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Affiliation(s)
- A M Osunlana
- Department of Medicine, Obesity Research and Management, University of Alberta, Edmonton, AB, Canada
| | - J Asselin
- Department of Medicine, Obesity Research and Management, University of Alberta, Edmonton, AB, Canada
- Department of Family Medicine, University of Alberta, Edmonton, AB, Canada
| | - R Anderson
- Edmonton Southside Primary Care Network, Edmonton, AB, Canada
| | - A A Ogunleye
- Department of Medicine, Obesity Research and Management, University of Alberta, Edmonton, AB, Canada
- Department of Family Medicine, University of Alberta, Edmonton, AB, Canada
| | - A Cave
- Department of Family Medicine, University of Alberta, Edmonton, AB, Canada
| | - A M Sharma
- Department of Medicine, Obesity Research and Management, University of Alberta, Edmonton, AB, Canada
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Fang M, Webster TF, Ferguson PL, Stapleton HM. Characterizing the peroxisome proliferator-activated receptor (PPARγ) ligand binding potential of several major flame retardants, their metabolites, and chemical mixtures in house dust. ENVIRONMENTAL HEALTH PERSPECTIVES 2015; 123:166-72. [PMID: 25314719 PMCID: PMC4314249 DOI: 10.1289/ehp.1408522] [Citation(s) in RCA: 98] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/07/2014] [Accepted: 10/09/2014] [Indexed: 05/18/2023]
Abstract
BACKGROUND Accumulating evidence has shown that some environmental contaminants can alter adipogenesis and act as obesogens. Many of these contaminants act via the activation of the peroxisome proliferator-activated receptor γ (PPARγ) nuclear receptor. OBJECTIVES Our goal was to determine the PPARγ ligand binding potency of several major flame retardants, including polybrominated diphenyl ethers (PBDEs), halogenated phenols and bisphenols, and their metabolites. Ligand binding activity of indoor dust and its bioactivated extracts were also investigated. METHODS We used a commercially available fluorescence polarization ligand binding assay to investigate the binding potency of flame retardants and dust extracts to human PPARγ ligand-binding domain. Rosiglitazone was used as a positive control. RESULTS Most of the tested compounds exhibited dose-dependent binding to PPARγ. Mono(2-ethylhexyl) tetrabromophthalate, halogenated bisphenols and phenols, and hydroxylated PBDEs were found to be potent PPARγ ligands. The most potent compound was 3-OH-BDE-47, with an IC50 (concentration required to reduce effect by 50%) of 0.24 μM. The extent of halogenation and the position of the hydroxyl group strongly affected binding. In the dust samples, 21 of the 24 samples tested showed significant binding potency at a concentration of 3 mg dust equivalent (DEQ)/mL. A 3-16% increase in PPARγ binding potency was observed following bioactivation of the dust using rat hepatic S9 fractions. CONCLUSION Our results suggest that several flame retardants are potential PPARγ ligands and that metabolism may lead to increased binding affinity. The PPARγ binding activity of house dust extracts at levels comparable to human exposure warrants further studies into agonistic or antagonistic activities and their potential health effects.
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Affiliation(s)
- Mingliang Fang
- Nicholas School of the Environment, Duke University, Durham, North Carolina, USA
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Chen B, Choi H, Hirsch LJ, Moeller J, Javed A, Kato K, Legge A, Buchsbaum R, Detyniecki K. Cosmetic side effects of antiepileptic drugs in adults with epilepsy. Epilepsy Behav 2015; 42:129-37. [PMID: 25513768 DOI: 10.1016/j.yebeh.2014.10.021] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2014] [Revised: 10/15/2014] [Accepted: 10/17/2014] [Indexed: 10/24/2022]
Abstract
OBJECTIVE Cosmetic side effects (CSEs) such as weight gain and alopecia are common, undesirable effects associated with several AEDs. The objective of the study was to compare the CSE profiles in a large specialty practice-based sample of patients taking both older and newer AEDs. METHODS As part of the Columbia and Yale AED Database Project, we reviewed patient records including demographics, medical history, AED use, and side effects for 1903 adult patients (≥16years of age) newly started on an AED. Cosmetic side effects were determined by patient or physician report in the medical record and included acne, gingival hyperplasia, hair loss, hirsutism, and weight gain. We compared the overall rate of CSEs and intolerable CSEs (ICSEs-CSEs that led to dosage reduction or discontinuation) between different AEDs in both monotherapy and polytherapy. RESULTS Overall, CSEs occurred in 110/1903 (5.8%) patients and led to intolerability in 70/1903 (3.7%) patients. Weight gain was the most commonly reported CSE (68/1903, 3.6%) and led to intolerability in 63 (3.3%) patients. Alopecia was the second most common patient-reported CSE (36/1903, 1.9%) and was intolerable in 33/1903 (1.7%) patients. Risk factors for CSEs included female sex (7.0% vs. 4.3% in males; p<0.05) and any prior CSE (37% vs. 2.9% in patients without prior CSE; p<0.001). Significantly more CSEs were attributed to valproic acid (59/270; 21.9%; p<0.001) and pregabalin (14/143; 9.8%; p<0.001) than to all other AEDs. Significantly less CSEs were attributed to levetiracetam (7/524; 1.3%; p=0.002). Weight gain was most frequently associated with valproic acid (35/270; 13.0%; p<0.001) and pregabalin (12/143; 8.4%; p<0.001). Hair loss was most commonly reported among patients taking valproic acid (24/270; 8.9%; p<0.001). Finally, gingival hyperplasia was most commonly reported in patients taking phenytoin (10/404; 2.5%; p<0.001). Cosmetic side effects leading to dosage change or discontinuation occurred most frequently with pregabalin and valproic acid compared with all other AEDs (13.3 and 5.6% vs. 2.3%; p<0.001). For patients who had been on an AED in monotherapy (n=677), CSEs and ICSEs were still more likely to be attributed to valproic acid (30.2% and 17.1%, respectively) than to any other AED (both p<0.001). SIGNIFICANCE Weight gain and alopecia were the most common patient-reported CSEs in this study, and weight gain was the most likely cosmetic side effect to result in dosage adjustment or medication discontinuation. Particular attention should be paid to pregabalin, phenytoin, and valproic acid when considering cosmetic side effects. Female patients and patients who have had prior CSE(s) to AED(s) were more likely to report CSEs. Knowledge of specific CSE rates for each AED found in this study may be useful in clinical practice.
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Affiliation(s)
- B Chen
- Comprehensive Epilepsy Center, Dept. of Neurology, Yale University, New Haven, CT, USA.
| | - H Choi
- Comprehensive Epilepsy Center, Dept. of Neurology, Columbia University, New York, NY, USA
| | - L J Hirsch
- Comprehensive Epilepsy Center, Dept. of Neurology, Yale University, New Haven, CT, USA
| | - J Moeller
- Comprehensive Epilepsy Center, Dept. of Neurology, Yale University, New Haven, CT, USA
| | - A Javed
- Comprehensive Epilepsy Center, Dept. of Neurology, Columbia University, New York, NY, USA
| | - K Kato
- Comprehensive Epilepsy Center, Dept. of Neurology, Columbia University, New York, NY, USA
| | - A Legge
- Comprehensive Epilepsy Center, Dept. of Neurology, Columbia University, New York, NY, USA
| | - R Buchsbaum
- Comprehensive Epilepsy Center, Dept. of Neurology, Columbia University, New York, NY, USA
| | - K Detyniecki
- Comprehensive Epilepsy Center, Dept. of Neurology, Yale University, New Haven, CT, USA
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Abstract
Data from clinical trials, retrospective and cross-sectional studies have quantified the metabolic changes associated with long-term use of antiepileptic drugs (AEDs). AEDs can be associated with weight gain or weight loss, although most are weight neutral. Weight gain is not only a cosmetic problem but also a risk for obesity-related vascular disorders. Weight loss may compromise growth in children/adolescents. This review discusses the possible contribution of peripheral and central hormones/neuropeptides (as leptin, insulin, adiponectin, neuropeptide-Y, ghrelin and galanin) and pathways that influence energy balance in the pathogenesis of weight changes with AEDs. As AEDs may influence weight, physicians have to properly select and characterize the suitable AED as an initial step or modify the existing AED if it compromises patient's health.
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Affiliation(s)
- Sherifa Ahmed Hamed
- Department of Neurology and Psychiatry, Faculty of Medicine, Assiut University Hospital, Floor # 4, Room # 4, P.O.Box 71516, Assiut, Egypt
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Belcastro V, D'Egidio C, Striano P, Verrotti A. Metabolic and endocrine effects of valproic acid chronic treatment. Epilepsy Res 2013; 107:1-8. [PMID: 24076030 DOI: 10.1016/j.eplepsyres.2013.08.016] [Citation(s) in RCA: 95] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2013] [Revised: 07/23/2013] [Accepted: 08/14/2013] [Indexed: 12/30/2022]
Abstract
Treatment of epileptic patients with valproic acid (VPA) may be associated with substantial weight changes that may increase morbidity and impair adherence to the treatment regimen. VPA-induced weight gain seems to be associated with many metabolic disturbances; the most frequent are hyperinsulinemia and insulin resistance, hyperleptinemia and leptin resistance. Patients who gain weight during VPA therapy can develop dyslipidemia and metabolic syndrome that are associated with long-term vascular complications such as hypertension and atherosclerosis. Moreover, an elevation in the levels of uric acid and homocysteine, together with oxidative stress, may contribute to atherosclerotic risk in patients under long-term therapy with VPA. The aim of this review is to discuss the metabolic and endocrine effects of VPA chronic treatment in patients with epilepsy.
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Affiliation(s)
- Vincenzo Belcastro
- Neurology Unit, Department of Neuroscience, Sant'Anna Hospital, Como, Italy.
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Elvert R, Wille A, Wandschneider J, Werner U, Glombik H, Herling AW. Energy loss via urine and faeces--a combustive analysis in diabetic rats and the impact of antidiabetic treatment on body weight. Diabetes Obes Metab 2013; 15:324-34. [PMID: 23121319 DOI: 10.1111/dom.12030] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2012] [Revised: 09/25/2012] [Accepted: 10/24/2012] [Indexed: 01/10/2023]
Abstract
AIMS Intensive glycaemic control in type 2 diabetes achieved by insulin is generally accompanied by body weight gain. This study was performed to emphasize the meaning of caloric analysis of urine and faeces for energy balance. METHODS We measured energetic loss via urine and faeces during antihyperglycaemic treatment in male obese Zucker diabetic fatty (ZDF) rats. Rats were treated for 10 days with the sodium-glucose-linked transporter-2 (SGLT2) inhibitor AVE2268, with insulin glargine, with the GLP-1 receptor agonist lixisenatide and with the combination of insulin glargine and lixisenatide. Each study was accompanied by one lean (Fa/?) and one obese (fa/fa) untreated non-diabetic and diabetic control group, respectively. Blood glucose, body weight alterations and food assimilation efficiency were monitored. RESULTS In control ZDF rats, more than 12 g/day of pure glucose was urinarily excreted. In total, the energetic loss via urine exceeded 30% from total energy uptake. Insulin glargine treatment decreased urinary energetic loss, leading to a body weight gain of approximately 3 g/day. An almost body weight-neutral antihyperglycaemic treatment could be achieved with AVE2268 and lixisenatide. While lixisenatide reduced body weight gain via reduction of energy uptake, the SGLT2 inhibitor even increased urinary glucose and thus energy excretion. Combining insulin glargine with lixisenatide attenuated the anabolic effect of insulin resulting in weight neutrality. CONCLUSIONS Our data clearly show renal contribution to the body's energy control by urinary glucose excretion (UGE) during antidiabetic treatment. The undesired retained energy could be reduced via additional UGE or via simultaneous reduction of energy uptake and/or energy retention.
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Affiliation(s)
- R Elvert
- R&D Diabetes Division, Translational Medicine, Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany.
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Hasnain M, Vieweg WVR, Hollett B. Weight gain and glucose dysregulation with second-generation antipsychotics and antidepressants: a review for primary care physicians. Postgrad Med 2012; 124:154-67. [PMID: 22913904 DOI: 10.3810/pgm.2012.07.2577] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Second-generation antipsychotics (SGAPs) and second-generation antidepressants (SGADs) have multiple US Food and Drug Administration-approved indications and are frequently prescribed by primary care physicians. We review the relative potential of these drugs to cause weight gain and glucose dysregulation, and offer clinical guidance to minimize and manage this risk. Among SGAPs, clozapine and olanzapine have a high risk for causing weight gain and glucose dysregulation; iloperidone, paliperidone, quetiapine, and risperidone have a medium risk; and aripiprazole, asenapine, lurasidone, and ziprasidone have a low risk. Young, drug-naïve patients are particularly vulnerable to weight gain associated with SGAPs. With the exception of clozapine, SGAPs have modest differences in their efficacy; however, their side effect profiles may influence selection. Using SGAPs with high metabolic liability conservatively and limiting their off-label use are important means to minimize risk. Patients should be screened before initiating any SGAP (or any antipsychotic medication) and monitored subsequently following standard guidelines, such as those provided by the American Diabetes Association. Healthy lifestyle counseling should be offered to all patients. Patients showing evidence of significant weight gain should be switched to an SGAP with a lower metabolic liability. Metformin may have some utility in young patients with limited exposure to antipsychotic drugs if lifestyle interventions fail and switching the SGAP is not an option. This option should be tried sooner than later for the best possible result. For SGADs, paroxetine and mirtazapine are associated with weight gain, and bupropion may cause modest weight loss. Other SGADs are mostly weight neutral, but individual variations may occur. Depression is associated with weight change and is a risk factor for glucose dysregulation. Treatment of depression improves glucose metabolism. We recommend that all patients taking SGADs be screened using anthropometric measures and metabolic assessment at baseline. Monitoring should be guided individually based on weight gain and other risk factors.
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Affiliation(s)
- Mehrul Hasnain
- Department of Psychiatry, Memorial University, St John's, Newfoundland, Canada.
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Arnold LM, Palmer RH, Hufford MR, Chen W. Effect of milnacipran on body weight in patients with fibromyalgia. Int J Gen Med 2012; 5:879-87. [PMID: 23109813 PMCID: PMC3479947 DOI: 10.2147/ijgm.s36444] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The purpose of this study was to evaluate the effects of milnacipran on body weight in patients with fibromyalgia. METHODS ANALYSES WERE CONDUCTED IN THE FOLLOWING GROUPS: patients from three double-blind, placebo-controlled milnacipran trials (3 months, n = 2096; 6 months, n = 1008); 354 patients receiving milnacipran in placebo-controlled trials and double-blind extension studies (total ≥ 12 months of treatment); and 1227 patients in a long-term (up to 3.25 years) open-label milnacipran study. RESULTS In placebo-controlled trials, 77% of patients were overweight or obese at baseline (body mass index ≥ 25 kg/m(2)). Mean weight loss was found with milnacipran at 3 months (100 mg/day, -1.14 kg; 200 mg/day, -0.97 kg; placebo, -0.06 kg; P < 0.001) and 6 months (100 mg/day, -1.01 kg; 200 mg/day, -0.71 kg; placebo, -0.04 kg; P < 0.05). Approximately twice as many milnacipran-treated patients had ≥5% weight loss from baseline compared with placebo (3 and 6 months, P < 0.01). In extension studies, mean weight loss in patients receiving ≥12 months of milnacipran was -1.06 kg. In patients receiving ≥3 years of treatment in the open-label study, mean changes at 12, 24, 30, and 36-38 months were -1.16, -0.76, -0.19, and +0.11 kg, respectively. Among milnacipran-treated patients, rates of nausea (the most common adverse event) were lower among patients who lost weight than among those who did not (3 months, P = 0.02). CONCLUSION The majority of patients with fibromyalgia in the milnacipran studies were overweight or obese. Milnacipran was associated with mean weight loss at 3 and 6 months (P < 0.05 versus placebo) and at 12 and 24 months of treatment, with mean changes drifting back to baseline at 30 months (-0.19 kg) and 36-38 months (+0.11 kg, no placebo comparison).
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Affiliation(s)
- Lesley M Arnold
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Robert H Palmer
- Medical Affairs, Forest Research Institute Inc, Jersey City, NJ
| | | | - Wei Chen
- Medical Affairs, Forest Research Institute Inc, Jersey City, NJ
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Toledo E, Lebel A, Becerra L, Minster A, Linnman C, Maleki N, Dodick DW, Borsook D. The young brain and concussion: imaging as a biomarker for diagnosis and prognosis. Neurosci Biobehav Rev 2012; 36:1510-31. [PMID: 22476089 PMCID: PMC3372677 DOI: 10.1016/j.neubiorev.2012.03.007] [Citation(s) in RCA: 86] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2011] [Revised: 02/15/2012] [Accepted: 03/21/2012] [Indexed: 01/20/2023]
Abstract
Concussion (mild traumatic brain injury (mTBI)) is a significant pediatric public health concern. Despite increased awareness, a comprehensive understanding of the acute and chronic effects of concussion on central nervous system structure and function remains incomplete. Here we review the definition, epidemiology, and sequelae of concussion within the developing brain, during childhood and adolescence, with current data derived from studies of pathophysiology and neuroimaging. These findings may contribute to a better understanding of the neurological consequences of traumatic brain injuries, which in turn, may lead to the development of brain biomarkers to improve identification, management and prognosis of pediatric patients suffering from concussion.
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Affiliation(s)
- Esteban Toledo
- Center for Pain and the Brain, Children's Hospital Boston, Harvard Medical School, United States
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Chien IC, Wu EL, Lin CH, Chou YJ, Chou P. Prevalence of diabetes in patients with major depressive disorder: a population-based study. Compr Psychiatry 2012; 53:569-75. [PMID: 21821237 DOI: 10.1016/j.comppsych.2011.06.004] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2011] [Revised: 06/14/2011] [Accepted: 06/18/2011] [Indexed: 11/16/2022] Open
Abstract
OBJECTIVE We conducted this population-based study to detect the prevalence and associated factors of diabetes in patients with major depressive disorder (MDD) in Taiwan. METHODS The National Health Research Institute provided a database of 1,000,000 random subjects for health service study. We obtained a random sample of 766,427 subjects 18 years or older, in 2005. Study subjects who had at least one service claim during 2005 for either outpatient or inpatient care, with a primary diagnosis of MDD or with a primary or secondary diagnosis of diabetes, were identified. RESULTS The 1-year prevalence of diabetes in patients with MDD was higher than that in the general population (11.65% vs 6.53%; odds ratio, 1.53; 95% confidence interval, 1.39-1.69) in 2005. Compared with the general population, patients with MDD had a higher prevalence of diabetes in all age groups, except age 18 to 29 years; among men and women; among all insurance amount groups; among those living in the northern and southern regions; and among residents living in urban, suburban, and rural areas. A higher prevalence of diabetes in patients with MDD was associated with increased age, use of antipsychotic agents, use of mood stabilizers, and residence in suburban areas. CONCLUSIONS Patients with MDD had a much higher prevalence of diabetes in young adult age group and in men than in the general population. Consequently, we must emphasize prevention, early detection, and adequate treatment of diabetes in patients with MDD.
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Affiliation(s)
- I-Chia Chien
- Department of Health, Taoyuan Mental Hospital, Taoyuan, Taiwan.
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Cabrera J, Emir B, Dills D, Murphy TK, Whalen E, Clair A. Characterizing and understanding body weight patterns in patients treated with pregabalin. Curr Med Res Opin 2012; 28:1027-37. [PMID: 22494020 DOI: 10.1185/03007995.2012.684044] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVE We examined patterns of weight change among patients treated with pregabalin for up to 1 year. METHODS Patients with ≥1 pre-treatment weight measurement, ≥2 measurements in Period 1 (day 2-56), and ≥2 during Period 2 (day 57-356) were identified from pooled data of 106 studies including 43,525 patients. Seven patterns were developed and used for exploratory 'change point' analyses (day on-treatment when weight-change trend changed from initial trajectory) and to assess patterns of weight change by baseline weight/body mass index (BMI). RESULTS A total of 3187 patients (from 41 studies) were eligible. 98.9% of patients were described by three of the seven patterns. The majority of patients (2607/3187 [81.8%]) remained within ±7% of baseline weight ('Pattern 4'). Fewer patients (463/3187 [14.5%]) were 'delayed weight gainers' (exceeded 7% weight gain in Period 2 but not Period 1 ['Pattern 6']), fewer still (82/3187 [2.6%]) were 'early weight gainers' (exceeded ≥7% baseline weight in Period 1 and remained above 7% or continued to gain weight in Period 2 ['Pattern 7']). Overall weight gainers (Patterns 6, 7) experienced 1-year weight gain (median [% change]) of +6.20 kg [+9.12%] and 5.46 kg [+13.9%] vs. 2.22 kg [+2.10%] for non-weight gainers (Pattern 4). Average baseline weight/BMI was lower for weight gainers (Patterns 6, 7) versus other patterns. Early weight gainers (Pattern 7) had change point day at day 40 versus day 54 for Pattern 4 and day 69 for Pattern 6. Use of concomitant medications and influence of comorbid conditions on weight should be considered as inherent variables when interpreting the study. CONCLUSIONS The majority of patients treated with pregabalin (150-600 mg/day) for 1 year maintained weight within ±7% baseline weight. One in six patients gained ≥7% weight from baseline, and generally exceeded 7%, 2-12 months after treatment onset.
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Affiliation(s)
- George A Bray
- Pennington Biomedical Research Center, 6400 Perkins Rd, Baton Rouge, LA 70808, USA.
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Abstract
Tricyclic antidepressants (TCAs) are among the most effective antidepressants available, although their poor tolerance at usual recommended doses and toxicity in overdose make them difficult to use. While selective serotonin reuptake inhibitors (SSRIs) are better tolerated than TCAs, they have their own specific problems, such as the aggravation of sexual dysfunction, interaction with coadministered drugs, and for many, a discontinuation syndrome. In addition, some of them appear to be less effective than TCAs in more severely depressed patients. Increasing evidence of the importance of norepinephrine in the etiology of depression has led to the development of a new generation of antidepressants, the serotonin and norepinephrine reuptake inhibitors (SNRIs). Milnacipran, one of the pioneer SNRIs, was designed from theoretic considerations to be more effective than SSRIs and better tolerated than TCAs, and with a simple pharmacokinetic profile. Milnacipran has the most balanced potency ratio for reuptake inhibition of the two neurotransmitters compared with other SNRIs (1:1.6 for milnacipran, 1:10 for duloxetine, and 1:30 for venlafaxine), and in some studies milnacipran has been shown to inhibit norepinephrine uptake with greater potency than serotonin (2.2:1). Clinical studies have shown that milnacipran has efficacy comparable with the TCAs and is superior to SSRIs in severe depression. In addition, milnacipran is well tolerated, with a low potential for pharmacokinetic drug-drug interactions. Milnacipran is a first-line therapy suitable for most depressed patients. It is frequently successful when other treatments fail for reasons of efficacy or tolerability.
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Affiliation(s)
- Siegfried Kasper
- Department of Psychiatry and Psychotherapy, Medical, University of Vienna, Austria
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42
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Assessment and Treatment of the Burden of Migraine. Neurologist 2010; 16:254-61. [DOI: 10.1097/nrl.0b013e3181a74c17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Kim JH, Lee JO, Lee SK, Jung JH, You GY, Park SH, Park M, Kim SD, Kim HS. Clozapine activates AMP-activated protein kinase (AMPK) in C2C12 myotube cells and stimulates glucose uptake. Life Sci 2010; 87:42-8. [DOI: 10.1016/j.lfs.2010.05.017] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2010] [Revised: 04/20/2010] [Accepted: 05/15/2010] [Indexed: 11/15/2022]
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Hum KM, Megna S, Burnham WM. Lack of laterality in the effects of right and left amygdala kindling on weight gain in female rats. Epilepsy Res 2009; 87:40-6. [DOI: 10.1016/j.eplepsyres.2009.07.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2009] [Revised: 07/18/2009] [Accepted: 07/21/2009] [Indexed: 10/20/2022]
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Bigal ME, Lipton RB, Biondi DM, Xiang J, Hulihan J. Weight Change and Clinical Markers of Cardiovascular Disease Risk During Preventive Treatment of Migraine. Cephalalgia 2009; 29:1188-96. [DOI: 10.1111/j.1468-2982.2009.01853.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Migraine, particularly migraine with aura, and increased body weight are independent risk factors for cardiovascular disease (CVD). The association of weight change and clinical markers of CVD risk was evaluated in subjects participating in a randomized double-blind, parallel-group study of migraine-preventive treatment comparing 100 mg/day of topiramate and amitriptyline. Individuals from both treatment groups were pooled and stratified into three groups. The ‘major weight gain’ group gained ≥ 5% of their baseline body weight at the conclusion of the study; the ‘major weight loss’ group lost ≥ 5% of their baseline body weight. The third group had < 5% of weight change. The influence of weight change in headache outcomes, as well as in markers of CVD (blood pressure, cholesterol, C-reactive protein), was assessed using analysis of covariance. Of 331 subjects, 52 (16%) experienced major weight gain and 56 (17%) experienced major weight loss. Weight change was not associated with differential efficacy for the treatment of headache. However, contrasted with those with major weight loss, those who gained weight experienced elevations in mean diastolic blood pressure (+2.5 vs. -1.2 mmHg), heart rate (+7.6 vs. -1.3 beats per minute), glycosylated haemoglobin (+0.09% vs. -0.04%), total cholesterol (+6.4 vs. -6.3 mg/dl), low-density lipoprotein cholesterol (+7.0 vs. -4.4 mg/ dl) and triglycerides (+15.3 vs. -10.4 mg/dl) and an increase in high-sensitivity C-reactive protein (+1.8 vs. -1.9 mg/l). Both groups experienced decreases in systolic blood pressure (-4.0 vs. -1.3 mmHg) and high-density lipoprotein cholesterol (-3.7 vs. -0.8 mg/dl). Increased weight during migraine treatment is not associated with poor headache treatment outcomes, but is associated with deterioration of CVD risk markers.
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Affiliation(s)
- ME Bigal
- Global Center for Scientific Affairs, Merck Research Laboratories, Whitehouse Station
- Department of Neurology, Albert Einstein College of Medicine
| | - RB Lipton
- Department of Neurology, Albert Einstein College of Medicine
- Montefiore Headache Center
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA
| | - DM Biondi
- Ortho-McNeil Janssen Scientific Affairs, LLC, Titusville, NJ
| | - J Xiang
- Ortho-McNeil Janssen Scientific Affairs, LLC, Titusville, NJ
| | - J Hulihan
- Ortho-McNeil Janssen Scientific Affairs, LLC, Titusville, NJ
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46
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Uludag IF, Kulu U, Sener U, Kose S, Zorlu Y. The effect of carbamazepine treatment on serum leptin levels. Epilepsy Res 2009; 86:48-53. [DOI: 10.1016/j.eplepsyres.2009.04.005] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2009] [Revised: 04/19/2009] [Accepted: 04/27/2009] [Indexed: 11/25/2022]
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47
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Ettinger AB, Baker GA. Best clinical and research practice in epilepsy of older people: Focus on antiepileptic drug adherence. Epilepsy Behav 2009; 15 Suppl 1:S60-3. [PMID: 19303055 DOI: 10.1016/j.yebeh.2009.03.010] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2009] [Accepted: 03/06/2009] [Indexed: 01/08/2023]
Abstract
Few studies have examined the issues that are specific to the older person with epilepsy, a population of increasing prominence in epilepsy management. Our understanding of the impact of epilepsy in the older person is based predominantly on what is inferred from studies of younger adults. Consequently, there is relatively little documented about the impact of epilepsy on the everyday lives of older people. In this article, we focus on adherence and its consequences for the physical, social, and psychological well-being of the older person. A number of strategies are proposed to improve adherence, including patient education through better communication between physician and patient; simplification of the medical regime; and use of extended-release formulations. This issue highlights that to ameliorate the impact of epilepsy for the older person with epilepsy, a greater understanding is required so that appropriate interventions can be tailored.
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Affiliation(s)
- Alan B Ettinger
- North Shore-LIJ Comprehensive Epilepsy Centers, EEG Lab LIJMC, 270-05 76th Avenue, New Hyde Park, NY 11040, USA.
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Abstract
Clinicians have long used lithium to treat manic depression. They have also observed that lithium causes granulocytosis and lymphopenia while it enhances immunological activities of monocytes and lymphocytes. In fact, clinicians have long used lithium to treat granulocytopenia resulting from radiation and chemotherapy, to boost immunoglobulins after vaccination, and to enhance natural killer activity. Recent studies revealed a mechanism that ties together these disparate effects of lithium. Lithium acts through multiple pathways to inhibit glycogen synthetase kinase-3beta (GSK3 beta). This enzyme phosphorylates and inhibits nuclear factors that turn on cell growth and protection programs, including the nuclear factor of activated T cells (NFAT) and WNT/beta-catenin. In animals, lithium upregulates neurotrophins, including brain-derived neurotrophic factor (BDNF), nerve growth factor, neurotrophin-3 (NT3), as well as receptors to these growth factors in brain. Lithium also stimulates proliferation of stem cells, including bone marrow and neural stem cells in the subventricular zone, striatum, and forebrain. The stimulation of endogenous neural stem cells may explain why lithium increases brain cell density and volume in patients with bipolar disorders. Lithium also increases brain concentrations of the neuronal markers n-acetyl-aspartate and myoinositol. Lithium also remarkably protects neurons against glutamate, seizures, and apoptosis due to a wide variety of neurotoxins. The effective dose range for lithium is 0.6-1.0 mM in serum and >1.5 mM may be toxic. Serum lithium levels of 1.5-2.0 mM may have mild and reversible toxic effects on kidney, liver, heart, and glands. Serum levels of >2 mM may be associated with neurological symptoms, including cerebellar dysfunction. Prolonged lithium intoxication >2 mM can cause permanent brain damage. Lithium has low mutagenic and carcinogenic risk. Lithium is still the most effective therapy for depression. It "cures" a third of the patients with manic depression, improves the lives of about a third, and is ineffective in about a third. Recent studies suggest that some anticonvulsants (i.e., valproate, carbamapazine, and lamotrigene) may be useful in patients that do not respond to lithium. Lithium has been reported to be beneficial in animal models of brain injury, stroke, Alzheimer's, Huntington's, and Parkinson's diseases, amyotrophic lateral sclerosis (ALS), spinal cord injury, and other conditions. Clinical trials assessing the effects of lithium are under way. A recent clinical trial suggests that lithium stops the progression of ALS.
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Affiliation(s)
- Wise Young
- W. M. Keck Center for Collaborative Neuroscience, Rutgers, State University of New Jersey, Piscataway, NJ 08854, USA.
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Emerson MH, Glovsky E, Amaro H, Nieves R. Unhealthy weight gain during treatment for alcohol and drug use in four residential programs for Latina and African American women. Subst Use Misuse 2009; 44:1553-65. [PMID: 19938931 DOI: 10.1080/10826080802494750] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Weight gain in women (n = 52) in four alcohol and drug user residential treatment programs in Boston, Massachusetts, was studied in 2004 through focus groups (n = 52) and weekly weights (n = 10). Focus group theme analyses revealed that weight gain was primarily attributed to availability of food and lack of exercise. Participants were very interested in improving nutrition, diet, and exercise in the programs. Weight gain (mean = 6.4 pounds) occurred in nine women (n = 10) in the first 12 weeks of treatment. The two-dimensional Food Model Chart and the Yale Physical Activity Survey were used. Limitations are noted and future research is suggested.
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Affiliation(s)
- Margaret H Emerson
- Northeastern University, Bouvé College of Health Sciences, School of Nursing, Boston, Massachusetts 02115, USA.
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Grosso S, Mostardini R, Piccini B, Balestri P. Body Mass Index and Serum Lipid Changes During Treatment with Valproic Acid in Children with Epilepsy. Ann Pharmacother 2009; 43:45-50. [DOI: 10.1345/aph.1l414] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND Valproic acid is the drug of choice for a wide variety of epileptic seizures and syndromes because of its broad spectrum of activity and because, in most patients, it is well tolerated. Although weight gain is a well-known adverse effect of valproic acid therapy, only a few studies have addressed weight gain associated with it in children aged 2–8 years. OBJECTIVE To evaluate valproic acid–associated changes in the body mass index (BMI) z-scores and to assess changes in serum triglyceride, cholesterol, and fasting glucose levels in young children receiving valproic acid treatment. METHODS Eighty-seven patients (39 females, 48 males) receiving valproic acid therapy for at least 3 months were included in the retrospective longitudinal study. Mean ± SD age at initiation of therapy was 4.8 ± 0.8 years. Changes in BMI z-scores as well as serum triglyceride, total cholesterol, and fasting glucose levels were evaluated as continuous variables and analyzed by longitudinal methods for all patients. RESULTS The average change from baseline in BMI z-scores was 0.80 (p = 0.001) at 3.1 years of follow-up. No significant change in triglyceride, cholesterol, and serum fasting glucose levels was observed over the same period. The percentage of overweight children at baseline was 6.9% and rose to 16% by the final visit (p = 0.081). CONCLUSIONS Valproic acid–associated weight gain may occur in young children. However, only 16% of patients were categorized as overweight at the end of the study; this percentage overlaps the percentage of overweight healthy young Italian children. The BMI z-scores significantly increased during the first 16 months of therapy, then appeared to level off. These observations may influence clinical practice and decision-making regarding suspending the drug due to weight gain in children in whom seizure control has been achieved. A For Our Patients summary of this article is available at www.ForOurPatients.info
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Affiliation(s)
- Salvatore Grosso
- Salvatore Grosso MD PhD, Clinical Researcher, Pediatric Neurology Section, Department of Pediatrics, Obstetrics, Gynecology and Reproductive Medicine, University of Siena, Siena, Italy
| | - Rosa Mostardini
- Rosa Mostardini MD, Clinical Assistant, “Santa Maria alle Scotte” Hospital, Azienda Ospedaliera Universitaria Senese, Siena
| | - Barbara Piccini
- Barbara Piccini MD, Clinical Assistant, Department of Pediatrics, Obstetrics, Gynecology and Reproductive Medicine, University of Siena
| | - Paolo Balestri
- Paolo Balestri MD, Assistant Professor, Head of Pediatric Section, Head of Pediatric Neurology Section, Pediatric Neurology Section, Department of Pediatrics, University of Siena
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