RESUMO
PURPOSE: To explore how boxed warning (BW) information fits within the context of prescribers' overall treatment decision-making and communication with patients. METHODS: In-depth interviews (N = 52) were conducted with primary care providers and specialists. Participants were presented with one of two prescribing scenarios: (1) estrogen vaginal inserts to treat vulvovaginal atrophy (VVA) associated with menopause; or (2) direct-acting antivirals (DAA) to treat chronic hepatitis C virus infection (HCV). The semi-structured interviews explored participants' treatment decision-making within the scenario, reactions to current prescribing information for a product within the FDA-approved drug class, as well as their perceptions of BWs generally. RESULTS: Across scenarios, providers described that the BW is only one of several factors that influence treatment decision-making. In the VVA scenario, symptom severity, family history, and experience with nonprescription drugs were raised as common factors that influence prescribing considerations; compared to comorbid infections, viral load, and HCV genotype in the HCV scenario. Perceptions of the DAA BW were generally positive or neutral, as many participants found the information important and appropriate. The VVA BW was viewed less favorably, with many participants stating the BW overstates the risk for this drug. CONCLUSIONS: Findings suggest that BWs are one of several factors that influence providers' treatment decisions, and BW influence largely depends on context. Providers across scenarios expressed notable differences in their perceptions of the risk information provided in the presented BWs; however, across scenarios participants expressed consideration of how patients may perceive the BW.
Assuntos
Antivirais , Hepatite C Crônica , Feminino , Humanos , Estados Unidos , Rotulagem de Medicamentos , Hepatite C Crônica/tratamento farmacológico , Pesquisa Qualitativa , United States Food and Drug AdministrationRESUMO
Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behaviour. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used â¼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, P = 5.87 × 10 - 9; odds ratio (OR) = 1.12) and markers within ERBB2 (rs2517959, P = 4.53 × 10 - 9; OR = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
Assuntos
Transtorno Bipolar/genética , Cromossomos Humanos X/genética , Estudo de Associação Genômica Ampla , Receptor ErbB-2/genética , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: Lithium is a first-line treatment in bipolar disorder, but individual response is variable. Previous studies have suggested that lithium response is a heritable trait. However, no genetic markers of treatment response have been reproducibly identified. METHODS: Here, we report the results of a genome-wide association study of lithium response in 2563 patients collected by 22 participating sites from the International Consortium on Lithium Genetics (ConLiGen). Data from common single nucleotide polymorphisms (SNPs) were tested for association with categorical and continuous ratings of lithium response. Lithium response was measured using a well established scale (Alda scale). Genotyped SNPs were used to generate data at more than 6 million sites, using standard genomic imputation methods. Traits were regressed against genotype dosage. Results were combined across two batches by meta-analysis. FINDINGS: A single locus of four linked SNPs on chromosome 21 met genome-wide significance criteria for association with lithium response (rs79663003, p=1·37â×â10(-8); rs78015114, p=1·31â×â10(-8); rs74795342, p=3·31â×â10(-9); and rs75222709, p=3·50â×â10(-9)). In an independent, prospective study of 73 patients treated with lithium monotherapy for a period of up to 2 years, carriers of the response-associated alleles had a significantly lower rate of relapse than carriers of the alternate alleles (p=0·03268, hazard ratio 3·8, 95% CI 1·1-13·0). INTERPRETATION: The response-associated region contains two genes for long, non-coding RNAs (lncRNAs), AL157359.3 and AL157359.4. LncRNAs are increasingly appreciated as important regulators of gene expression, particularly in the CNS. Confirmed biomarkers of lithium response would constitute an important step forward in the clinical management of bipolar disorder. Further studies are needed to establish the biological context and potential clinical utility of these findings. FUNDING: Deutsche Forschungsgemeinschaft, National Institute of Mental Health Intramural Research Program.
Assuntos
Transtorno Bipolar/genética , Compostos de Lítio/uso terapêutico , Polimorfismo de Nucleotídeo Único/genética , Transtorno Bipolar/tratamento farmacológico , Feminino , Variação Genética , Estudo de Associação Genômica Ampla , Genótipo , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Prospectivos , Resultado do TratamentoRESUMO
For more than half a decade, lithium has been successfully used to treat bipolar disorder. Worldwide, it is considered the first-line mood stabilizer. Apart from its proven antimanic and prophylactic effects, considerable evidence also suggests an antisuicidal effect in affective disorders. Lithium is also effectively used to augment antidepressant drugs in the treatment of refractory major depressive episodes and prevent relapses in recurrent unipolar depression. In contrast to many psychiatric drugs, lithium has outlasted various pharmacotherapeutic 'fashions', and remains an indispensable element in contemporary psychopharmacology. Nevertheless, data from pharmacogenetic studies of lithium are comparatively sparse, and these studies are generally characterized by small sample sizes and varying definitions of response. Here, we present an international effort to elucidate the genetic underpinnings of lithium response in bipolar disorder. Following an initiative by the International Group for the Study of Lithium-Treated Patients (www.IGSLI.org) and the Unit on the Genetic Basis of Mood and Anxiety Disorders at the National Institute of Mental Health,lithium researchers from around the world have formed the Consortium on Lithium Genetics (www.ConLiGen.org) to establish the largest sample to date for genome-wide studies of lithium response in bipolar disorder, currently comprising more than 1,200 patients characterized for response to lithium treatment. A stringent phenotype definition of response is one of the hallmarks of this collaboration. ConLiGen invites all lithium researchers to join its efforts.
Assuntos
Antimaníacos/farmacologia , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/genética , Compostos de Lítio/farmacologia , National Institute of Mental Health (U.S.) , Antimaníacos/efeitos adversos , Antimaníacos/uso terapêutico , Humanos , Cooperação Internacional , Compostos de Lítio/efeitos adversos , Compostos de Lítio/uso terapêutico , Farmacogenética , Fenótipo , Estados UnidosRESUMO
OBJECTIVE: Evaluative conditioning (EC), the pairing of objects (conditioned stimuli; CS) with positive and negative unconditioned stimuli (US) in order to induce attitude change, has proven to be a viable method of changing attitudes toward foods and corresponding eating behaviors. Positively conditioning healthy foods and negatively conditioning unhealthy foods should result in healthier food choices. Of interest in the current research is the extent to which EC can generalize beyond the conditioned foods to entire dimensions underlying food judgment, such as health and taste. METHOD: The current research included 2 EC experiments configured in accord with the Implicit Misattribution Model (IMM; Jones, Fazio, & Olson, 2009). Four healthy CS foods were paired with positive US and 4 unhealthy CS foods were paired with negative US. Participants then reported eating intentions for a variety of foods, including non-CS foods. RESULTS: Experiment 1 demonstrated that conditioning a few exemplar food items increased sensitivity to health and decreased sensitivity to taste when judging a variety of additional foods. Experiment 2 replicated the generalization effect with regard to health sensitivity, but only when a task that preceded the EC procedure promoted, rather than interfered with, categorization of the CS foods by health. CONCLUSIONS: This research shows that EC can generalize to an entire dimension underlying food judgment and that this effect is facilitated by accessibility of the health dimension at the time of exposure to the EC pairings. (PsycINFO Database Record
Assuntos
Atitude , Ingestão de Alimentos/psicologia , Comportamento Alimentar/psicologia , Intenção , Adulto , Condicionamento Psicológico , Feminino , Preferências Alimentares/psicologia , Humanos , Masculino , Modelos Psicológicos , Adulto JovemRESUMO
OBJECTIVE: As large-scale genome sequencing technology advances, concerns surrounding the reporting of individual findings to study volunteers have grown and fueled controversy. This is especially true in mental health research, where the clinical importance of sequencing results is particularly unclear. The ethical, legal, and social issues are being widely debated, but less is known about the attitudes of actual study volunteers toward sequencing studies or what they wish to learn about their DNA sequence and its health implications. This study provides information on psychiatric research volunteers' attitudes, beliefs, and concerns with respect to participation in DNA sequencing studies and reporting of individual results. METHOD: We conducted a pilot study using a questionnaire that we developed to assess what information volunteers in an ongoing family study of bipolar disorder would like to receive if they underwent genome sequencing, what they would do with that information, and what concerns they may have. RESULTS: Almost all of the respondents were willing to participate in genome sequencing. Most respondents wished to be informed about all their health-related genetic risks, including risks for diseases without known prevention or treatment. However, few respondents felt well informed about the nature of genome sequencing or its implications for their health, insurability, or offspring. CONCLUSIONS: Despite generally positive attitudes toward genome sequencing among study volunteers, most are not fully aware of the special issues raised by genome sequencing. The attitudes of study volunteers should be considered in the debate about the reporting of individual findings from genome sequencing.