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1.
BMC Public Health ; 24(1): 1072, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38632603

RESUMEN

BACKGROUND: Regular HIV and STI testing remain a cornerstone of comprehensive sexual health care. In this study, we examine the efficacy of Get Connected, a WebApp that combines test locators with personalized educational resources, in motivating young men who have sex with men (YMSM) to undergo regular HIV and STI testing. METHODS: Participants were randomly placed in one of two conditions. The first condition included the full version of GC (GC-PLUS), which included content tailored to users' psychosocial characteristics (e.g., age, race/ethnicity, relationship status, HIV/STI testing history). The second condition served as our attention-control and only included the testing locator (GC-TLO) for HIV/STI testing services. Participants were recruited from three cities (Houston, Philadelphia, and Atlanta) characterized by high HIV incidence. Assessments were collected at 1, 3-, 6-, 9- and 12-month follow-ups. RESULTS: Both versions of GC were acceptable and efficacious in increasing routine HIV and STI testing over a 12-month period. 40% of the sample reported testing at least twice, with no main effects observed across the two intervention arms (OR = 1.11; 95% CI: 0.69, 1.80), p =.66). Greater intervention effects were observed among YMSM who engaged more frequently with the intervention, with regional differences observed. CONCLUSIONS: Our findings underscore the need to cater to the diverse needs of YMSM through multilevel approaches. Broadly, mHealth HIV/STI testing interventions, such as Get Connected, would benefit from matching technologies to the local context to have the greatest impact. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov (NCT03132415).


Asunto(s)
Infecciones por VIH , Minorías Sexuales y de Género , Enfermedades de Transmisión Sexual , Masculino , Humanos , Homosexualidad Masculina , Enfermedades de Transmisión Sexual/epidemiología , Infecciones por VIH/epidemiología , Conducta Sexual
2.
Acute Med ; 21(2): 74-79, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35681180

RESUMEN

INTRODUCTION: The SAM Quality Improvement Committee (SAM-QI), set up in 2016, has worked over the last year to determine the priority Acute Medicine QI topics. They have also discussed and put forward proposals to improve QI training for Acute Medicine professionals. METHODS: A modified Delphi process was completed over four rounds to determine priority QI topics. Online meetings were also used to develop proposals for QI training. RESULTS: Same Day Emergency Care (SDEC) was chosen as the priority topic for QI work within Acute Medicine. CONCLUSION: The SAM-QI group settled on SDEC being the priority topic for Acute Medicine QI development. Throughout the Delphi process SAM-QI has also developed proposals for QI training that will help Acute Medicine professionals deliver coordinated meaningful improvements in care.


Asunto(s)
Medicina , Mejoramiento de la Calidad , Consenso , Técnica Delphi , Humanos
3.
J Intern Med ; 290(3): 602-620, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34213793

RESUMEN

The fields of human genetics and genomics have generated considerable knowledge about the mechanistic basis of many diseases. Genomic approaches to diagnosis, prognostication, prevention and treatment - genomic-driven precision medicine (GDPM) - may help optimize medical practice. Here, we provide a comprehensive review of GDPM of complex diseases across major medical specialties. We focus on technological readiness: how rapidly a test can be implemented into health care. Although these areas of medicine are diverse, key similarities exist across almost all areas. Many medical areas have, within their standards of care, at least one GDPM test for a genetic variant of strong effect that aids the identification/diagnosis of a more homogeneous subset within a larger disease group or identifies a subset with different therapeutic requirements. However, for almost all complex diseases, the majority of patients do not carry established single-gene mutations with large effects. Thus, research is underway that seeks to determine the polygenic basis of many complex diseases. Nevertheless, most complex diseases are caused by the interplay of genetic, behavioural and environmental risk factors, which will likely necessitate models for prediction and diagnosis that incorporate genetic and non-genetic data.


Asunto(s)
Genómica , Medicina de Precisión , Atención a la Salud , Enfermedad , Humanos
4.
Clin Exp Immunol ; 203(1): 125-136, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33006758

RESUMEN

Pattern recognition receptors, such as Toll-like receptors (TLRs), play an important role in the host defense against invading microbial pathogens. Their activation must be precisely regulated, as inappropriate activation or overactivation of TLR signaling pathways may result in inflammatory disorders, such as septic shock or autoimmune diseases. TMEM106A is a type II transmembrane protein constitutively expressed in macrophages. Our current study demonstrated that TMEM106A levels were increased in macrophages upon lipopolysaccharide (LPS) stimulation, as well as in the peripheral monocytes of patients with sepsis. Tmem106a knockout mice were more sensitive to lipopolysaccharide (LPS)-induced septic shock than wild-type mice. Further experiments indicated that Tmem106a ablation enhanced the expression of CD80, CD86 and major histocompatibility complex (MHC)-II in mouse macrophages upon LPS stimulation, accompanied with up-regulation of tumor necrosis factor (TNF)-α, interleukin (IL)-6, interferon (IFN)-ß and inducible nitric oxide synthase (iNOS), indicating the activation of macrophages and polarization towards the M1 inflammatory phenotype. Moreover, elevated mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling were found to be involved in the LPS-induced inflammatory response in Tmem106a-/- macrophages. However, this effect was largely abrogated by macrophage deletion in Tmem106a-/- mice. Therefore, deficiency of Tmem106a in macrophages may enhance the M1 polarization in mice, resulting in inflammation. This suggests that TMEM106A plays an important regulatory role in maintaining macrophage homeostasis.


Asunto(s)
Quinasas MAP Reguladas por Señal Extracelular/inmunología , Lipopolisacáridos/toxicidad , Sistema de Señalización de MAP Quinasas/inmunología , Macrófagos Peritoneales/inmunología , FN-kappa B/inmunología , Proteínas Supresoras de Tumor/inmunología , Animales , Quinasas MAP Reguladas por Señal Extracelular/genética , Inflamación/inducido químicamente , Inflamación/genética , Inflamación/inmunología , Inflamación/patología , Sistema de Señalización de MAP Quinasas/genética , Macrófagos Peritoneales/patología , Ratones , Ratones Noqueados , FN-kappa B/genética , Proteínas Supresoras de Tumor/genética
5.
AIDS Behav ; 25(5): 1464-1473, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-32749626

RESUMEN

In the United States, HIV infection rate inequities persist, with new infections highest among young, Black men who have sex with men (YBMSM) in the South. We conducted 23 in-depth interviews with YBMSM newly diagnosed with HIV to explore awareness of and barriers to uptake of HIV pre-exposure prophylaxis (PrEP). Participants were recruited from two university-based HIV Clinics in Alabama and were: (1) 16-29 years of age, (2) diagnosed with HIV within the prior 365 days, (3) Black race, (4) self-identified as a cis-gender male reporting sex with men AND (5) did not report prior PrEP use. Interview guides were grounded in Anderson's Behavioral Healthcare Utilization Model (ABM), with embedded constructs from the situated Information, Motivation and Behavioral Skills theoretical framework. Coding was conducted by three independent coders using thematic analysis methods. Participants (N = 23) median age was 24, more than two-thirds reported annual incomes less than $15,000 and the majority (84%) identified as gay. Major themes that emerged as barriers to accessing PrEP included low prioritization and interests in using PrEP; low perceived HIV risk due to feelings of invincibility and trust in sex partners; lack of information about accessing PrEP; negative beliefs around PrEP; and the suggestion to change PrEP messaging from only targeting YBMSM. These findings indicate that there are important missed opportunities for HIV prevention with PrEP among YBMSM in the South. In these high-risk young men, tailored interventions are needed to better inform and frame perceptions around risk, knowledge, access and prioritization of PrEP.


En Estados Unidos, desigualdades en la tasa de infección por VIH persisten, y en el sur del pais, la tasa de nuevas infecciones hombres jóvenes Afro-americanos que tienen sexo con hombres son más altas. Realizamos veintitrés entrevistas en profundidad con YBMSM recién diagnosticado con VIH para explorar la conciencia y las barreras para la adopción de la profilaxis previa a la exposición al VIH (PrEP). Los participantes fueron reclutados de dos clínicas de VIH en centros medicos academicos en el estado de Alabama con los siguientes criterios: 1) 16-29 años de edad, 2) diagnostico VIH dentro de los 365 días, 3) raza afro-americana, 4) autoidentificados como un género cis-hombres que tienen sexo con hombres, y 5) no informaron el uso previo de PrEP. Las guías de la entrevista se basaron en el Modelo conductual de utilización de la salud (ABM) de Anderson, con construcciones integradas del marco teórico de Información, motivación y habilidades conductuales. Tres codificadores independientes codificaron utilizando métodos de análisis temáticos. La edad mediana de los participantes (N = 23) era de 24 años, más de dos tercios informaron ingresos anuales de menos de $15,000 (USD) y la mayoría (84%) se identificó como gay. Los temas principales que surgieron como barreras para acceder a PrEP incluyeron una baja priorización e interes en su; bajo riesgo percibido de VIH debido a sentimientos de invencibilidad y confianza en las parejas sexuales; falta de información sobre el acceso a PrEP; creencias negativas sobre PrEP; y la sugerencia de enfocar los mensajes sobre PreP no solo ha jovenes afro-americanos que tienen sexo con hombres. Estos hallazgos indican que hay importantes oportunidades perdidas para la prevención del VIH con PrEP entre esto jovenes en el Sur de EEUU. En estos hombres jóvenes de alto riesgo, se necesitan intervenciones personalizadas para mejor informar y enmarcar las percepciones sobre el riesgo, el conocimiento, el acceso y la priorización de PrEP.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Adulto , Negro o Afroamericano , Alabama , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Humanos , Masculino , Estados Unidos , Adulto Joven
6.
Acute Med ; 20(2): 125-130, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34190739

RESUMEN

Acute Medicine is a specialty that is not defined by a single organ system and sits at the interface between primary and secondary care. In order to document improvements in the quality of care delivered a system of metrics is required. A number of frameworks for measurements exist to quantify quality of care at the level of patients, teams and organisations, such as measures of population health, patient satisfaction and cost per patient. Measures can capture whether care is safe, effective, patient-centred, timely, efficient and equitable. Measurement in Acute Medicine is challenged by the often-transient nature of the contact between Acute Medicine clinicians and patients, the lack of diagnostic labels, a low degree of standardisation and difficulties in capturing the patient experience in the context. In a time of increasing ecological and financial constraints, reflecting about the most appropriate metrics to document the impact of Acute Medicine is required.


Asunto(s)
Medicina , Satisfacción del Paciente , Humanos
7.
J Asthma ; 57(3): 271-285, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-30732486

RESUMEN

Objective: Certain populations suffer disproportionately from asthma and asthma morbidity. The objective was to provide a national descriptive profile of asthma control and treatment patterns among school-aged children (SAC: aged 6-17) in the U.S. Methods: This was a cross-sectional analysis using the nationally representative 2007-2014 Medical Expenditure Panel Survey. Among SAC with asthma, indicators of poor control included: exacerbation/asthma attack; >3 canisters short-acting beta agonist (SABA)/3 months; and asthma-specific Emergency Department or inpatient visits (ED/IP). Results: Non-Hispanic black, non-Hispanic multiple races, Puerto Rican, obese, Medicaid, poor, ≥2 non-asthma chronic comorbidities (CC), and family average CC ≥ 2 were associated with higher odds of having asthma. The following had significantly higher odds ratios (OR) of excessive SABA use compared to non-Hispanic whites [OR; CI; p < 0.05]: Puerto Rican (3.8; 2.1-6.9), Mexican (3.6; 2.0-6.4), Central/South American (3.0; 1.2-7.7), Hispanic-other (3.1; 1.1-9.0), non-Hispanic black (2.5; 1.6-3.9), and non-Hispanic Asian (4.0; 1.7-9.2). SABA OR were also significant for Spanish spoken at home (2.5; 1.6-3.8), obese (2.1; 1.3-3.3), Medicaid (2.9; 2.0-4.1), no medical insurance (2.1; 1.1-4.1), no prescription insurance (2.5; 1.8-3.5), poor (2.8; 1.7-4.7), CC ≥ 2 (2.1; 1.6-2.8), parent-without high-school degree (2.5; 1.8-3.6), parent-SF-12 Physical Component Scale <50 (1.6; 1.2-2.1) and Mental Component Scale <50 (1.5; 1.1-2.0). Significant differences also existed across subgroups for ED/IP visits. Conclusions: There are disparities in asthma control and prevalence among certain populations in the U.S. These results provide national data on disparities in several indicators of poor asthma control beyond the standard race/ethnicity groupings.


Asunto(s)
Antiasmáticos/uso terapéutico , Asma/epidemiología , Disparidades en el Estado de Salud , Adolescente , Negro o Afroamericano/estadística & datos numéricos , Asma/tratamiento farmacológico , Niño , Estudios Transversales , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Masculino , Prevalencia , Estados Unidos/epidemiología , Población Blanca/estadística & datos numéricos
8.
Psychol Med ; 49(16): 2646-2656, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31559935

RESUMEN

To identify genetic risk loci for major depressive disorder (MDD), two broad study design approaches have been applied: (1) to maximize sample size by combining data from different phenotype assessment modalities (e.g. clinical interview, self-report questionnaires) and (2) to reduce phenotypic heterogeneity through selecting more homogenous MDD subtypes. The value of these strategies has been debated. In this review, we summarize the most recent findings of large genomic studies that applied these approaches, and we highlight the merits and pitfalls of both approaches with particular attention to methodological and psychometric issues. We also discuss the results of analyses that investigated the heterogeneity of MDD. We conclude that both study designs are essential for further research. So far, increasing sample size has led to the identification of a relatively high number of genomic loci linked to depression. However, part of the identified variants may be related to a phenotype common to internalizing disorders and related traits. As such, samples containing detailed clinical information are needed to dissect depression heterogeneity and enable the potential identification of variants specific to a more restricted MDD phenotype. A balanced portfolio reconciling both study design approaches is the optimal approach to progress further in unraveling the genetic architecture of depression.


Asunto(s)
Depresión/genética , Trastorno Depresivo Mayor/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Sitios Genéticos , Humanos , Herencia Multifactorial , Fenotipo , Polimorfismo de Nucleótido Simple , Factores de Riesgo
9.
Psychol Med ; 49(7): 1166-1173, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30221610

RESUMEN

BACKGROUND: Most studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic instruments, and study designs that each has its inherent assumptions, strengths, and biases. We aim to test the homogeneity in heritability estimates between two powerful, and state of the art study designs for eight psychiatric disorders. METHODS: We assessed heritability based on data of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on summary data of eight samples with measured genotypes (N = 125 533 cases and 208 215 controls). All data were based on standard diagnostic criteria. Eight psychiatric disorders were studied: (1) alcohol dependence (AD), (2) anorexia nervosa, (3) attention deficit/hyperactivity disorder (ADHD), (4) autism spectrum disorder, (5) bipolar disorder, (6) major depressive disorder, (7) obsessive-compulsive disorder (OCD), and (8) schizophrenia. RESULTS: Heritability estimates from sibling data varied from 0.30 for Major Depression to 0.80 for ADHD. The estimates based on the measured genotypes were lower, ranging from 0.10 for AD to 0.28 for OCD, but were significant, and correlated positively (0.19) with national sibling-based estimates. When removing OCD from the data the correlation increased to 0.50. CONCLUSIONS: Given the unique character of each study design, the convergent findings for these eight psychiatric conditions suggest that heritability estimates are robust across different methods. The findings also highlight large differences in genetic and environmental influences between psychiatric disorders, providing future directions for etiological psychiatric research.


Asunto(s)
Familia/psicología , Trastornos Mentales/genética , Trastornos Mentales/psicología , Hermanos/psicología , Adulto , Alcoholismo/genética , Alcoholismo/psicología , Anorexia Nerviosa/genética , Anorexia Nerviosa/psicología , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno por Déficit de Atención con Hiperactividad/psicología , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/psicología , Trastorno Bipolar/genética , Trastorno Bipolar/psicología , Estudios de Casos y Controles , Estudios de Cohortes , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/psicología , Femenino , Interacción Gen-Ambiente , Genotipo , Humanos , Masculino , Trastorno Obsesivo Compulsivo/genética , Trastorno Obsesivo Compulsivo/psicología , Carácter Cuantitativo Heredable , Esquizofrenia/genética , Psicología del Esquizofrénico , Suecia
10.
Mol Psychiatry ; 23(1): 15-23, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29158581

RESUMEN

There is an emerging consensus that genomic researchers should, at a minimum, offer to return to individual participants clinically valid, medically important and medically actionable genomic findings (for example, pathogenic variants in BRCA1) identified in the course of research. However, this is not a common practice in psychiatric genetics research. Furthermore, psychiatry researchers often generate findings that do not meet all of these criteria, yet there may be ethically compelling arguments to offer selected results. Here, we review the return of results debate in genomics research and propose that, as for genomic studies of other medical conditions, psychiatric genomics researchers should offer findings that meet the minimum criteria stated above. Additionally, if resources allow, psychiatry researchers could consider offering to return pre-specified 'clinically valuable' findings even if not medically actionable-for instance, findings that help corroborate a psychiatric diagnosis, and findings that indicate important health risks. Similarly, we propose offering 'likely clinically valuable' findings, specifically, variants of uncertain significance potentially related to a participant's symptoms. The goal of this Perspective is to initiate a discussion that can help identify optimal ways of managing the return of results from psychiatric genomics research.


Asunto(s)
Comités de Ética en Investigación/normas , Investigación Genética/ética , Genómica/métodos , Guías como Asunto , Trastornos Mentales/genética , Femenino , Predisposición Genética a la Enfermedad , Variación Genética , Genómica/ética , Humanos , Masculino , Trastornos Mentales/diagnóstico
11.
Mol Psychiatry ; 23(3): 708-712, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-28555076

RESUMEN

Genome-wide association studies (GWAS) for schizophrenia have identified over 100 loci encoding >500 genes. It is unclear whether any of these genes, other than dopamine receptor D2, are immediately relevant to antipsychotic effects or represent novel antipsychotic targets. We applied an in vivo molecular approach to this question by performing RNA sequencing of brain tissue from mice chronically treated with the antipsychotic haloperidol or vehicle. We observed significant enrichments of haloperidol-regulated genes in schizophrenia GWAS loci and in schizophrenia-associated biological pathways. Our findings provide empirical support for overlap between genetic variation underlying the pathophysiology of schizophrenia and the molecular effects of a prototypical antipsychotic.


Asunto(s)
Cuerpo Estriado/efectos de los fármacos , Haloperidol/metabolismo , Esquizofrenia/genética , Animales , Antipsicóticos/uso terapéutico , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Cuerpo Estriado/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo , Genómica/métodos , Haloperidol/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Factores de Riesgo , Psicología del Esquizofrénico , Análisis de Secuencia de ARN
13.
Psychol Med ; 48(7): 1190-1200, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-28950923

RESUMEN

BACKGROUND: Race, psychiatric history, and adverse life events have all been independently associated with postpartum depression (PPD). However, the role these play together in Black and Latina women remains inadequately studied. Therefore, we performed a case-control study of PPD, including comprehensive assessments of symptoms and biomarkers, while examining the effects of genetic ancestry. METHODS: We recruited our sample (549 cases, 968 controls) at 6 weeks postpartum from obstetrical clinics in North Carolina. PPD status was determined using the MINI-plus. Psychiatric history was extracted from medical records. Participants were administered self-report instruments to assess depression (Edinburgh Postnatal Depression Scale) and adverse life events. Levels of estradiol, progesterone, brain-derived neurotrophic factor, oxytocin, and allopregnanalone were assayed. Principal components from genotype data were used to estimate genetic ancestry and logistic regression was used to identify predictors of PPD. RESULTS: This population was racially diverse (68% Black, 13% Latina, 18% European). Genetic ancestry was not a predictor of PPD. Case status was predicted by a history of major depression (p = 4.01E-14), lifetime anxiety disorder diagnosis (p = 1.25E-34), and adverse life events (p = 6.06E-06). There were no significant differences between groups in any hormones or neurosteroids. CONCLUSIONS: Psychiatric history and multiple exposures to adverse life events were significant predictors of PPD in a population of minority and low-income women. Genetic ancestry and hormone levels were not predictive of case status. Increased genetic vulnerability in conjunction with risk factors may predict the onset of PPD, whereas genetic ancestry does not appear predictive.


Asunto(s)
Depresión Posparto/epidemiología , Etnicidad/estadística & datos numéricos , Acontecimientos que Cambian la Vida , Anamnesis , Periodo Posparto/psicología , Estrés Psicológico/epidemiología , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Modelos Logísticos , North Carolina/epidemiología , Pobreza , Escalas de Valoración Psiquiátrica , Factores de Riesgo , Apoyo Social
14.
Psychol Med ; 48(7): 1201-1208, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-28942743

RESUMEN

BACKGROUND: Family history is a long-standing and readily obtainable risk factor for schizophrenia (SCZ). Low-cost genotyping technologies have enabled large genetic studies of SCZ, and the results suggest the utility of genetic risk scores (GRS, direct assessments of inherited common variant risk). Few studies have evaluated family history and GRS simultaneously to ask whether one can explain away the other. METHODS: We studied 5959 SCZ cases and 8717 controls from four Nordic countries. All subjects had family history data from national registers and genome-wide genotypes that were processed through the quality control procedures used by the Psychiatric Genomics Consortium. Using external training data, GRS were estimated for SCZ, bipolar disorder (BIP), major depression, autism, educational attainment, and body mass index. Multivariable modeling was used to estimate effect sizes. RESULTS: Using harmonized genomic and national register data from Denmark, Estonia, Norway, and Sweden, we confirmed that family history of SCZ and GRS for SCZ and BIP were risk factors for SCZ. In a joint model, the effects of GRS for SCZ and BIP were essentially unchanged, and the effect of family history was attenuated but remained significant. The predictive capacity of a model including GRS and family history neared the minimum for clinical utility. CONCLUSIONS: Combining national register data with measured genetic risk factors represents an important investigative approach for psychotic disorders. Our findings suggest the potential clinical utility of combining GRS and family history for early prediction and diagnostic improvements.


Asunto(s)
Predisposición Genética a la Enfermedad , Anamnesis , Medición de Riesgo/métodos , Esquizofrenia/genética , Adulto , Estudios de Casos y Controles , Estonia , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Sistema de Registros , Factores de Riesgo , Países Escandinavos y Nórdicos
15.
Mol Psychiatry ; 22(10): 1502-1508, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-27400856

RESUMEN

The antipsychotic clozapine is uniquely effective in the management of schizophrenia; however, its use is limited by its potential to induce agranulocytosis. The causes of this, and of its precursor neutropenia, are largely unknown, although genetic factors have an important role. We sought risk alleles for clozapine-associated neutropenia in a sample of 66 cases and 5583 clozapine-treated controls, through a genome-wide association study (GWAS), imputed human leukocyte antigen (HLA) alleles, exome array and copy-number variation (CNV) analyses. We then combined associated variants in a meta-analysis with data from the Clozapine-Induced Agranulocytosis Consortium (up to 163 cases and 7970 controls). In the largest combined sample to date, we identified a novel association with rs149104283 (odds ratio (OR)=4.32, P=1.79 × 10-8), intronic to transcripts of SLCO1B3 and SLCO1B7, members of a family of hepatic transporter genes previously implicated in adverse drug reactions including simvastatin-induced myopathy and docetaxel-induced neutropenia. Exome array analysis identified gene-wide associations of uncommon non-synonymous variants within UBAP2 and STARD9. We additionally provide independent replication of a previously identified variant in HLA-DQB1 (OR=15.6, P=0.015, positive predictive value=35.1%). These results implicate biological pathways through which clozapine may act to cause this serious adverse effect.


Asunto(s)
Clozapina/efectos adversos , Neutropenia/inducido químicamente , Neutropenia/genética , Proteínas Portadoras/genética , Estudios de Casos y Controles , Clozapina/uso terapéutico , Exoma , Femenino , Estudio de Asociación del Genoma Completo , Cadenas beta de HLA-DQ/genética , Humanos , Masculino , Neutropenia/metabolismo , Oportunidad Relativa , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/genética , Miembro 1B3 de la Familia de los Transportadores de Solutos de Aniones Orgánicos/genética
17.
Depress Anxiety ; 35(2): 160-167, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29172228

RESUMEN

BACKGROUND: Trauma histories may increase risk of perinatal psychiatric episodes. We designed an epidemiological population-based cohort study to explore if adverse childhood experiences (ACE) in girls increases risk of later postpartum psychiatric episodes. METHODS: Using Danish registers, we identified women born in Denmark between January 1980 and December 1998 (129,439 childbirths). Exposure variables were ACE between ages 0 and 15 including: (1) family disruption, (2) parental somatic illness, (3) parental labor market exclusion, (4) parental criminality, (5) parental death, (6) placement in out-of-home care, (7) parental psychopathology excluding substance use, and (8) parental substance use disorder. Primary outcome was first occurrence of in- or outpatient contact 0-6 months postpartum at a psychiatric treatment facility with any psychiatric diagnoses, ICD-10, F00-F99 (N = 651). We conducted survival analyses using Cox proportional hazard regressions of postpartum psychiatric episodes. RESULTS: Approximately 52% of the sample experienced ACE, significantly increasing risk of any postpartum psychiatric diagnosis. Highest risks were observed among women who experienced out-of-home placement, hazard ratio (HR) 2.57 (95% CI: 1.90-3.48). Women experiencing two adverse life events had higher risks of postpartum psychiatric diagnosis HR: 1.88 (95% CI: 1.51-2.36), compared to those with one ACE, HR: 1.24 (95% CI: 1.03-49) and no ACE, HR: 1.00 (reference group). CONCLUSIONS: ACE primarily due to parental psychopathology and disability contributes to increased risk of postpartum psychiatric episodes; and greater numbers of ACE increases risk for postpartum psychiatric illness with an observed dose-response effect. Future work should explore genetic and environmental factors that increase risk and/or confer resilience.


Asunto(s)
Adultos Sobrevivientes de Eventos Adversos Infantiles/estadística & datos numéricos , Depresión Posparto/epidemiología , Trastornos Psicóticos/epidemiología , Trastornos Puerperales/epidemiología , Sistema de Registros/estadística & datos numéricos , Trastornos de Estrés Traumático Agudo/epidemiología , Adulto , Estudios de Cohortes , Dinamarca/epidemiología , Femenino , Humanos , Embarazo , Riesgo , Adulto Joven
18.
J Asthma ; 55(6): 659-667, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-28981368

RESUMEN

OBJECTIVE: The degree of poorly controlled asthma and its association with missed school days and parental missed work days is not well understood. METHODS: This was a retrospective analysis of missed school days and missed work days for school-aged children (SAC; aged 6-17) and their caregivers in the nationally representative 2007-2013 Medical Expenditure Panel Survey (MEPS). Indicators of poor asthma control included: exacerbation in previous 12 months; use of >3 canisters of short-acting beta agonist (SABA) in 3 months; and annual asthma-specific (AS) Emergency Department (ED) or inpatient (IP) visits. Negative binomial regression was used for missed school days, and a Heckman two-step selection model was used for missed work days. All analyses controlled for sociodemographics and other covariates. RESULTS: There were 44,320 SAC in MEPS, of whom 5,890 had asthma. SAC with asthma and an indicator of poor control missed more school days than SAC without asthma: exacerbation (1.8 times more; p < 0.001); >3 canisters SABA (2.7 times more; p < 0.001) and ED/IP visit (3.8 times more; p < 0.001). The parents/caregivers of SAC with asthma and an exacerbation missed 1.2 times more work days (p < 0.05), while those with SAC with asthma and an ED/IP visit missed 1.8 times more work days (p < 0.01) than the parents of SAC without asthma. CONCLUSIONS: This study provides evidence of the significant national burden of poorly controlled asthma due to missed school and work days in the United States. More effective and creative asthma management strategies, with collaboration across clinical, community and school-based outreach, may help address this burden.


Asunto(s)
Absentismo , Asma/epidemiología , Cuidadores/estadística & datos numéricos , Costo de Enfermedad , Padres , Adolescente , Agonistas Adrenérgicos beta/uso terapéutico , Asma/tratamiento farmacológico , Niño , Estudios Transversales , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Calidad de Vida , Estudios Retrospectivos , Instituciones Académicas/estadística & datos numéricos , Desempleo/estadística & datos numéricos , Estados Unidos/epidemiología
19.
Nature ; 488(7411): 349-52, 2012 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-22895340

RESUMEN

In the cores of some clusters of galaxies the hot intracluster plasma is dense enough that it should cool radiatively in the cluster's lifetime, leading to continuous 'cooling flows' of gas sinking towards the cluster centre, yet no such cooling flow has been observed. The low observed star-formation rates and cool gas masses for these 'cool-core' clusters suggest that much of the cooling must be offset by feedback to prevent the formation of a runaway cooling flow. Here we report X-ray, optical and infrared observations of the galaxy cluster SPT-CLJ2344-4243 (ref. 11) at redshift z = 0.596. These observations reveal an exceptionally luminous (8.2 × 10(45) erg s(-1)) galaxy cluster that hosts an extremely strong cooling flow (around 3,820 solar masses a year). Further, the central galaxy in this cluster appears to be experiencing a massive starburst (formation of around 740 solar masses a year), which suggests that the feedback source responsible for preventing runaway cooling in nearby cool-core clusters may not yet be fully established in SPT-CLJ2344-4243. This large star-formation rate implies that a significant fraction of the stars in the central galaxy of this cluster may form through accretion of the intracluster medium, rather than (as is currently thought) assembling entirely via mergers.

20.
Psychol Med ; 47(8): 1427-1441, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28112056

RESUMEN

BACKGROUND: Childbirth is a potent trigger for the onset of psychiatric illness in women including postpartum depression (PPD) and postpartum psychosis (PP). Medical complications occurring during pregnancy and/or childbirth have been linked to postpartum psychiatric illness and sociodemographic factors. We evaluated if pregnancy and obstetrical predictors have similar effects on different types of postpartum psychiatric disorders. METHOD: A population-based cohort study using Danish registers was conducted in 392 458 primiparous women with a singleton delivery between 1995 and 2012 and no previous psychiatric history. The main outcome was first-onset postpartum psychiatric episodes. Incidence rate ratios (IRRs) were calculated for any psychiatric contact in four quarters for the first year postpartum. RESULTS: PPD and postpartum acute stress reactions were associated with pregnancy and obstetrical complications. For PPD, hyperemesis gravidarum [IRR 2.69, 95% confidence interval (CI) 1.93-3.73], gestational hypertension (IRR 1.84, 95% CI 1.33-2.55), pre-eclampsia (IRR 1.45, 95% CI 1.14-1.84) and Cesarean section (C-section) (IRR 1.32, 95% CI 1.13-1.53) were associated with increased risk. For postpartum acute stress, hyperemesis gravidarum (IRR 1.93, 95% CI 1.38-2.71), preterm birth (IRR 1.51, 95% CI 1.30-1.75), gestational diabetes (IRR 1.42, 95% CI 1.03-1.97) and C-section (IRR 1.36, 95% CI 1.20-1.55) were associated with increased risk. In contrast, risk of PP was not associated with pregnancy or obstetrical complications. CONCLUSIONS: Pregnancy and obstetrical complications can increase the risk for PPD and acute stress reactions but not PP. Identification of postpartum women requiring secondary care is needed to develop targeted approaches for screening and treatment. Future work should focus on understanding the contributions of psychological stressors and underlying biology on the development of postpartum psychiatric illness.


Asunto(s)
Complicaciones del Trabajo de Parto/epidemiología , Trastornos Psicóticos/epidemiología , Trastornos Puerperales/epidemiología , Sistema de Registros/estadística & datos numéricos , Trastornos de Estrés Traumático Agudo/epidemiología , Adulto , Dinamarca/epidemiología , Depresión Posparto/epidemiología , Femenino , Humanos , Paridad , Embarazo , Factores de Riesgo , Adulto Joven
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