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BACKGROUND: Treatment in bipolar disorder (BD) is commonly applied as a multimodal therapy based on decision algorithms that lack an integrative understanding of molecular mechanisms or a biomarker associated clinical outcome measure. Pharmacogenetics/genomics study the individual genetic variation associated with drug response. This selective review of pharmacogenomics and pharmacogenomic testing (PGT) in BD will focus on candidate genes and genome wide association studies of pharmacokinetic drug metabolism and pharmacodynamic drug response/adverse event, and the potential role of decision support tools that incorporate multiple genotype/phenotype drug recommendations. MAIN BODY: We searched PubMed from January 2013 to May 2019, to identify studies reporting on BD and pharmacogenetics, pharmacogenomics and PGT. Studies were selected considering their contribution to the field. We summarize our findings in: targeted candidate genes of pharmacokinetic and pharmacodynamic pathways, genome-wide association studies and, PGT platforms, related to BD treatment. This field has grown from studies of metabolizing enzymes (i.e., pharmacokinetics) and drug transporters (i.e., pharmacodynamics), to untargeted investigations across the entire genome with the potential to merge genomic data with additional biological information. CONCLUSIONS: The complexity of BD genetics and, the heterogeneity in BD drug-related phenotypes, are important considerations for the design and interpretation of BD PGT. The clinical applicability of PGT in psychiatry is in its infancy and is far from reaching the robust impact it has in other medical disciplines. Nonetheless, promising findings are discovered with increasing frequency with remarkable relevance in neuroscience, pharmacology and biology.
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Introduction: Clinical and genetic study of psychiatric conditions has underscored the co-occurrence of complex phenotypes and the need to refine them. Bipolar Disorder (BD) and Binge Eating (BE) behavior are common psychiatric conditions that have high heritability and high co-occurrence, such that at least one quarter of BD patients have BE (BD + BE). Genetic studies of BD alone and of BE alone suggest complex polygenic risk models, with many genetic risk loci yet to be identified. Areas covered: We review studies of the epidemiology of BD+BE, its clinical features (cognitive traits, psychiatric comorbidity, and role of obesity), genomic studies (of BD, eating disorders (ED) defined by BE, and BD + BE), and therapeutic implications of BD + BE. Expert opinion: Subphenotyping of complex psychiatric disorders reduces heterogeneity and increases statistical power and effect size; thus, it enhances our capacity to find missing genetic (and other) risk factors. BD + BE has a severe clinical picture and genetic studies suggests a distinct genetic architecture. Differential therapeutic interventions may be needed for patients with BD + BE compared with BD patients without BE. Recognizing the BD + BE subphenotype is an example of moving towards more precise clinical and genetic entities.
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Trastorno por Atracón , Trastorno Bipolar , Comorbilidad , Trastorno por Atracón/epidemiología , Trastorno por Atracón/genética , Trastorno por Atracón/fisiopatología , Trastorno Bipolar/epidemiología , Trastorno Bipolar/genética , Trastorno Bipolar/fisiopatología , HumanosRESUMEN
IN BRIEF The national epidemic of diabetes and the exposure of Vietnam veterans to Agent Orange has led to insulin resistance requiring concentrated insulin (U-500 regular [U-500R] insulin) for glycemic control. Initiation of U-500R insulin is limited to endocrinology expertise housed at "hub" Veterans Health Administration locations hours away from smaller "spoke" facilities. To overcome potential health care disparities and improve patient safety, a program was developed ensuring that all clinicians could co-manage U-500R insulin. This program evaluation was undertaken to improve patient safety and access to U-500R insulin by improving spoke clinicians' knowledge of safe delivery and management of U-500R insulin.
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OBJECTIVE: To consider the Kidney Disease Outcomes Quality Initiative recommendation of using multiple nutritional measurements for patients on maintenance dialysis, we explored data for independent and joint associations of nutritional indicators with mortality risk among maintenance hemodialysis patients treated in 12 countries. SETTING: Dialysis units in seven European countries, the United States, Canada, Australia, New Zealand, and Japan. MAIN OUTCOME: Mortality risk. METHODS: We conducted a prospective cohort study of 40,950 patients from phases I to III of the Dialysis Outcomes and Practice Patterns Study (1996-2008). Independent and joint effects (interactions) of nutritional indicators (serum creatinine, serum albumin, normalized protein catabolic rate, body mass index [BMI]) on mortality risk were assessed by Cox regression with adjustments for demographics, years on dialysis, and comorbidities. RESULTS: Important variations in nutritional indicators were seen by country and patient characteristics. Poorer nutritional status assessed by each indicator was independently associated with higher mortality risk across regions. Significant multiplicative interactions (each p < or = 0.01) between indicators were also observed. For example, by using patients with serum creatinine 7.5-10.5 mg/dL and BMI 21-25 kg/m(2) as referent, BMI <21 kg/m(2) was associated with lower mortality risk among patients with creatinine >10.5 mg/dL (relative risk = 0.68) but with higher mortality risk among those with creatinine <7.5 mg/dL (relative risk = 1.38). The association of lower albumin concentration with higher mortality risk was stronger for patients with lower BMI or lower creatinine. CONCLUSION: The joint effects of nutritional indicators on mortality indicate the need to use multiple measurements when assessing the nutritional status of hemodialysis patients.
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Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/terapia , Desnutrición/mortalidad , Estado Nutricional , Diálisis Renal/mortalidad , Biomarcadores/sangre , Índice de Masa Corporal , Estudios de Cohortes , Comorbilidad , Creatinina/sangre , Femenino , Humanos , Modelos Logísticos , Masculino , Desnutrición/etiología , Persona de Mediana Edad , Análisis Multivariante , Estudios Prospectivos , Diálisis Renal/efectos adversos , Factores de Riesgo , Albúmina Sérica/metabolismo , Resultado del Tratamiento , Pérdida de PesoRESUMEN
BACKGROUND: Identification of haemodialysis patients with problems related to lack of appetite should help prevent adverse outcomes. We studied whether a single question about being bothered by lack of appetite within the prior 4 weeks is related to nutritional status, inflammation and risks of death and hospitalization. Additionally, we assessed associations of lack of appetite with depression, dialysis dose and length of haemodialysis. METHODS: This study is an analysis of baseline and longitudinal data from 14 406 patients enrolled in the Dialysis Outcomes and Practice Pattern Study. Cox regression was used to assess whether the degree (not, somewhat, moderately, very much, extremely) that patients were bothered by lack of appetite is an independent predictor of death and hospitalization. Logistic regression was used to identify baseline characteristics associated with being bothered by lack of appetite. RESULTS: The risk of death was more than 2-fold higher [relative risk (RR) = 2.23; 95% confidence interval (CI) = 1.90-2.62] and the risk of hospitalization 33% higher (RR = 1.33; 95% CI = 1.19-1.48) among patients extremely bothered, compared with not bothered, by lack of appetite. These associations followed a dose-response fashion and remained statistically significant after adjustments for 14 comorbidities. Depression, shorter haemodialysis session, hypoalbuminaemia, lower concentration of serum creatinine and normalized protein catabolic rate, lower body mass index and higher leucocyte and neutrophil counts were independently associated with higher odds of being bothered by lack of appetite. CONCLUSIONS: The data suggest that a single question about lack of appetite helps identify haemodialysis patients with poorer nutritional status, inflammation, depression and higher risks of hospitalization and death. The study calls attention to a possible beneficial effect of longer haemodialysis on appetite.
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Depresión/etiología , Trastornos de Alimentación y de la Ingestión de Alimentos/etiología , Estado Nutricional , Diálisis Renal/efectos adversos , Anciano , Depresión/epidemiología , Trastornos de Alimentación y de la Ingestión de Alimentos/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios ProspectivosRESUMEN
PURPOSE: This paper describes an international outreach program to support rebuilding Central America's health information infrastructure after several natural disasters in the region, including Hurricane Mitch in 1998 and two major earthquakes in 2001. SETTING, PARTICIPANTS, AND DESCRIPTION: The National Library of Medicine joined forces with the Pan American Health Organization/World Health Organization, the United Nations International Strategy for Disaster Reduction, and the Regional Center of Disaster Information for Latin America and the Caribbean (CRID) to strengthen libraries and information centers in Central America and improve the availability of and access to health and disaster information in the region by developing the Central American Network for Disaster and Health Information (CANDHI). Through CRID, the program created ten disaster health information centers in medical libraries and disaster-related organizations in six countries. RESULTS/OUTCOME: This project served as a catalyst for the modernization of several medical libraries in Central America. The resulting CANDHI provides much needed electronic access to public health "gray literature" on disasters, as well as access to numerous health information resources. CANDHI members assist their institutions and countries in a variety of disaster preparedness activities through collecting and disseminating information.