RESUMO
Weight discrimination has adverse effects on health that include increasing the risk factors for developing type 2 diabetes. Preliminary evidence suggests a positive association between weight discrimination and diagnosed diabetes; however, it is unknown whether psychosocial resources may buffer this association. In logistic regressions stratified by gender, we examined links between weight discrimination and diabetes among a nationally representative sample of U.S. adults (the National Social Life, Health, and Aging Project; N = 2,794 adults age 50 and older in 2015-16). We also tested the extent to which trait-resilience and social support from a spouse/partner, family, and friends buffered any observed association. We adjusted for known predictors of diabetes (age, race/ethnicity, Body Mass Index) and conducted sensitivity analyses restricted to men and women with obesity. Net of covariates, in the overall sample, weight discrimination was associated with significantly greater odds of having ever had diabetes among women (OR = 2.00, 95% CI [1.15, 3.47]), but not men. Among women with obesity, weight discrimination was only significantly associated with greater odds of diabetes for those with low resilience (OR = 1.84, 95% CI [1.01, 3.35]). Among men overall, weight discrimination was associated with lower odds of diabetes for those with high family support (OR = 0.03, 95% CI [0.003, 0.25]) as well as those with high friend support (OR = 0.34, 95% CI [0.13, 0.91]); similar effects were observed in men with obesity. These novel findings evince a role for psychosocial resources in buffering associations between weight discrimination and diabetes.
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Diabetes Mellitus Tipo 2 , Adulto , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Obesidade/psicologia , Índice de Massa Corporal , Etnicidade , Fatores de RiscoRESUMO
OBJECTIVE: Perianal Crohn's disease (pCD) occurs in up to 40% of patients with CD and is associated with poor quality of life, limited treatment responses and poorly understood aetiology. We performed a genetic association study comparing CD subjects with and without perianal disease and subsequently performed functional follow-up studies for a pCD associated SNP in Complement Factor B (CFB). DESIGN: Immunochip-based meta-analysis on 4056 pCD and 11 088 patients with CD from three independent cohorts was performed. Serological and clinical variables were analysed by regression analyses. Risk allele of rs4151651 was introduced into human CFB plasmid by site-directed mutagenesis. Binding of recombinant G252 or S252 CFB to C3b and its cleavage was determined in cell-free assays. Macrophage phagocytosis in presence of recombinant CFB or serum from CFB risk, or protective CD or healthy subjects was assessed by flow cytometry. RESULTS: Perianal complications were associated with colonic involvement, OmpC and ASCA serology, and serology quartile sum score. We identified a genetic association for pCD (rs4151651), a non-synonymous SNP (G252S) in CFB, in all three cohorts. Recombinant S252 CFB had reduced binding to C3b, its cleavage was impaired, and complement-driven phagocytosis and cytokine secretion were reduced compared with G252 CFB. Serine 252 generates a de novo glycosylation site in CFB. Serum from homozygous risk patients displayed significantly decreased macrophage phagocytosis compared with non-risk serum. CONCLUSION: pCD-associated rs4151651 in CFB is a loss-of-function mutation that impairs its cleavage, activation of alternative complement pathway, and pathogen phagocytosis thus implicating the alternative complement pathway and CFB in pCD aetiology.
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Fator B do Complemento , Doença de Crohn , Humanos , Fator B do Complemento/genética , Doença de Crohn/complicações , Qualidade de Vida , Seguimentos , FagocitoseRESUMO
BACKGROUND & AIMS: Recent literature has implicated a key role for mast cells in murine models of colonic inflammation, but their role in human ulcerative colitis (UC) is not well established. A major advance has been the identification of mrgprb2 (human orthologue, MRGPX2) as mediating IgE-independent mast cell activation. We sought to define mechanisms of mast cell activation and MRGPRX2 in human UC. METHODS: Colon tissues were collected from patients with UC for bulk RNA sequencing and lamina propria cells were isolated for MRGPRX2 activation studies and single-cell RNA sequencing. Genetic association of all protein-altering G-protein coupled receptor single-nucleotide polymorphism was performed in an Ashkenazi Jewish UC case-control cohort. Variants of MRGPRX2 were transfected into Chinese hamster ovary (CHO) and human mast cell (HMC) 1.1 cells to detect genotype-dependent effects on ß-arrestin recruitment, IP-1 accumulation, and phosphorylated extracellular signal-regulated kinase. RESULTS: Mast cell-specific mediators and adrenomedullin (proteolytic precursor of PAMP-12, an MRGPRX2 agonist) are up-regulated in inflamed compared to uninflamed UC. MRGPRX2 stimulation induces carboxypeptidase secretion from inflamed UC. Of all protein-altering GPCR alleles, a unique variant of MRGPRX2, Asn62Ser, was most associated with and was bioinformatically predicted to alter arrestin recruitment. We validated that the UC protective serine allele enhances ß-arrestin recruitment, decreases IP-1, and increases phosphorylated extracellular signal-regulated kinase with MRGPRX2 agonists. Single-cell RNA sequencing defines that adrenomedullin is expressed by activated fibroblasts and epithelial cells and that interferon gamma is a key upstream regulator of mast cell gene expression. CONCLUSION: Inflamed UC regions are distinguished by MRGPRX2-mediated activation of mast cells, with decreased activation observed with a UC-protective genetic variant. These results define cell modules of UC activation and a new therapeutic target.
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Degranulação Celular , Colite Ulcerativa/metabolismo , Colo/metabolismo , Mastócitos/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Neuropeptídeos/metabolismo , Adrenomedulina/genética , Adrenomedulina/metabolismo , Animais , Células CHO , Estudos de Casos e Controles , Colite Ulcerativa/genética , Colite Ulcerativa/imunologia , Colo/imunologia , Cricetulus , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Variação Genética , Humanos , Fosfatos de Inositol/metabolismo , Ligantes , Mastócitos/imunologia , Proteínas do Tecido Nervoso/genética , Fosforilação , Receptores Acoplados a Proteínas G/genética , Receptores de Neuropeptídeos/genética , beta-Arrestina 2/genética , beta-Arrestina 2/metabolismoRESUMO
Multisensory, physical, and cognitive dysfunction share age-related physiologic disturbances and may have common health effects. We determined whether the effect of multisensory impairment on physical activity (PA) is explained by physical (timed up and go) or cognitive (Short Portable Mental Status Questionnaire) dysfunction. A National Social Life, Health, and Aging Project participant subset (n = 507) underwent objective sensory testing in 2005-2006 and wrist accelerometry in 2010-2011. We related multisensory impairment to PA using multivariate mixed-effects linear regression and compared the effect magnitude after adjusting for physical then cognitive dysfunction. Worse multisensory impairment predicted lower PA across three scales (Global Sensory Impairment: ß = -0.04, 95% confidence interval [-0.07, -0.02]; Total Sensory Burden: ß = -0.01, 95% confidence interval [-0.03, -0.003]; and Number of Impaired Senses: ß = -0.02, 95% confidence interval [-0.04, -0.004]). Effects were similar after accounting for physical and cognitive dysfunction. Findings suggest that sensory, physical, and cognitive dysfunction have unique mechanisms underlying their PA effects.
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Disfunção Cognitiva , Exercício Físico , Acelerometria , Envelhecimento , HumanosRESUMO
OBJECTIVES: To test the effect of CommunityRx, a scalable, low-intensity intervention that matches patients to community resources, on mental health-related quality of life (HRQOL) (primary outcome), physical HRQOL, and confidence in finding resources. METHODS: A real-world trial assigned publicly insured residents of Chicago, Illinois, aged 45 to 74 years to an intervention (n = 209) or control (n = 202) group by alternating calendar week, December 2015 to August 2016. Intervention group participants received usual care and an electronic medical record-generated, personalized list of community resources. Surveys (baseline, 1-week, 1- and 3-months) measured HRQOL and confidence in finding community resources to manage health. RESULTS: At 3 months, there was no difference between groups in mental (-1.03; 95% confidence interval [CI] = -3.02, 0.96) or physical HRQOL (0.59; 95% CI = -0.98, 2.16). Confidence in finding resources was higher in the intervention group (odds ratio = 2.08; 95% CI = 1.18, 3.63); the effect increased at each successive time point. Among intervention group participants, 65% recalled receiving the intervention; 48% shared community resource information with others. CONCLUSIONS: CommunityRx did not increase HRQOL, but its positive effect on confidence in finding resources for self-care suggests that this low-intensity intervention may have a role in population health promotion. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02435511.
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Centros Comunitários de Saúde/organização & administração , Registros Eletrônicos de Saúde , Promoção da Saúde , Encaminhamento e Consulta , Idoso , Chicago , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Saúde da População , Pobreza , Qualidade de Vida/psicologiaRESUMO
BACKGROUND & AIMS: The role of tobacco smoke in the etiology of inflammatory bowel disease (IBD) is unclear. We investigated interactions between genes and smoking (gene-smoking interactions) that affect risk for Crohn's disease (CD) and ulcerative colitis (UC) in a case-only study of patients and in mouse models of IBD. METHODS: We used 55 Immunochip-wide datasets that included 19,735 IBD cases (10,856 CD cases and 8879 UC cases) of known smoking status. We performed 3 meta-analyses each for CD, UC, and IBD (CD and UC combined), comparing data for never vs ever smokers, never vs current smokers, and never vs former smokers. We studied the effects of exposure to cigarette smoke in Il10-/- and Nod2-/- mice, as well as in Balb/c mice without disruption of these genes (wild-type mice). Mice were exposed to the smoke of 5 cigarettes per day, 5 days a week, for 8 weeks, in a ventilated smoking chamber, or ambient air (controls). Intestines were collected and analyzed histologically and by reverse transcription polymerase chain reaction. RESULTS: We identified 64 single nucleotide polymorphisms (SNPs) for which the association between the SNP and IBD were modified by smoking behavior (meta-analysis Wald test P < 5.0 × 10-5; heterogeneity Cochrane Q test P > .05). Twenty of these variants were located within the HLA region at 6p21. Analysis of classical HLA alleles (imputed from SNP genotypes) revealed an interaction with smoking. We replicated the interaction of a variant in NOD2 with current smoking in relation to the risk for CD (frameshift variant fs1007insC; rs5743293). We identified 2 variants in the same genomic region (rs2270368 and rs17221417) that interact with smoking in relation to CD risk. Approximately 45% of the SNPs that interact with smoking were in close vicinity (≤1 Mb) to SNPs previously associated with IBD; many were located near or within genes that regulate mucosal barrier function and immune tolerance. Smoking modified the disease risk of some variants in opposite directions for CD vs UC. Exposure of Interleukin 10 (il10)-deficient mice to cigarette smoke accelerated development of colitis and increased expression of interferon gamma in the small intestine compared to wild-type mice exposed to smoke. NOD2-deficient mice exposed to cigarette smoke developed ileitis, characterized by increased expression of interferon gamma, compared to wild-type mice exposed to smoke. CONCLUSIONS: In an analysis of 55 Immunochip-wide datasets, we identified 64 SNPs whose association with risk for IBD is modified by tobacco smoking. Gene-smoking interactions were confirmed in mice with disruption of Il10 and Nod2-variants of these genes have been associated with risk for IBD. Our findings from mice and humans revealed that the effects of smoking on risk for IBD depend on genetic variants.
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Colite Ulcerativa/genética , Doença de Crohn/genética , Fumar/genética , Alelos , Animais , Estudos de Casos e Controles , Modelos Animais de Doenças , Feminino , Frequência do Gene , Interação Gene-Ambiente , Genótipo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Fumar/efeitos adversos , Poluição por Fumaça de Tabaco/efeitos adversosRESUMO
BACKGROUND: The Montreal Cognitive Assessment (MoCA) has not been administered to a representative national sample, precluding comparison of patient scores to the general population and for risk factor identification. METHODS: A validated survey-based adaptation of the MoCA (MoCA-SA) was administered to a probability sample of home-dwelling US adults aged 62 to 90, using the National Social Life, Health, and Aging Project (n=3129), yielding estimates of prevalence in the United States. The association between MoCA-SA scores and sociodemographic and health-related risk factors were determined. RESULTS: MoCA-SA scores decreased with age, and there were substantial differences among sex, education, and race/ethnicity groups. Poor physical health, functional status, and depression were also associated with lower cognitive performance; current health behaviors were not. Using the recommended MoCA cut-point score for Mild Cognitive Impairment (MoCA score <26; MoCA-SA score <17), 72% (95% confidence interval, 69% to 74%) of older US adults would be classified as having some degree of cognitive impairment. CONCLUSIONS: Our results provide an important national estimate for interpreting MoCA scores from individual patients, and establish wide variability in cognition among older home-dwelling US adults. Care should be taken in applying previously-established MoCA cut-points to the general population, especially when evaluating individuals from educationally and ethnically diverse groups.
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Cognição/fisiologia , Avaliação Geriátrica/estatística & dados numéricos , Vida Independente , Atividades Cotidianas , Idoso , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome-wide association studies and subsequent meta-analyses of these two diseases as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases. Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.
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Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Interações Hospedeiro-Patógeno , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/microbiologia , Mycobacterium/imunologia , Colite Ulcerativa/genética , Colite Ulcerativa/imunologia , Colite Ulcerativa/microbiologia , Colite Ulcerativa/fisiopatologia , Doença de Crohn/genética , Doença de Crohn/imunologia , Doença de Crohn/microbiologia , Doença de Crohn/fisiopatologia , Genoma Humano/genética , Haplótipos/genética , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/fisiopatologia , Mycobacterium/patogenicidade , Infecções por Mycobacterium/genética , Infecções por Mycobacterium/microbiologia , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/patogenicidade , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases. METHODS: This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34,819 patients (19,713 with Crohn's disease, 14,683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype-phenotype associations across 156,154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile. FINDINGS: After quality control, the primary analysis included 29,838 patients (16,902 with Crohn's disease, 12,597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for inflammatory bowel disease showed strong association with disease subphenotype (p=1·65â×â10(-78)), even after exclusion of NOD2, MHC, and 3p21 (p=9·23â×â10(-18)). Predictive models based on the genetic risk score strongly distinguished colonic from ileal Crohn's disease. Our genetic risk score could also identify a small number of patients with discrepant genetic risk profiles who were significantly more likely to have a revised diagnosis after follow-up (p=6·8â×â10(-4)). INTERPRETATION: Our data support a continuum of disorders within inflammatory bowel disease, much better explained by three groups (ileal Crohn's disease, colonic Crohn's disease, and ulcerative colitis) than by Crohn's disease and ulcerative colitis as currently defined. Disease location is an intrinsic aspect of a patient's disease, in part genetically determined, and the major driver to changes in disease behaviour over time. FUNDING: International Inflammatory Bowel Disease Genetics Consortium members funding sources (see Acknowledgments for full list).
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Colite Ulcerativa/genética , Doença de Crohn/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Adulto , Alelos , Feminino , Genótipo , Cadeias HLA-DRB1/genética , Fator de Crescimento de Hepatócito/genética , Humanos , Imunoensaio , Complexo Principal de Histocompatibilidade/genética , Masculino , Proteína Adaptadora de Sinalização NOD2/genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas/genética , Medição de Risco , Adulto JovemRESUMO
BACKGROUND & AIMS: Genome-wide association studies have identified 200 inflammatory bowel disease (IBD) loci, but the genetic architecture of Crohn's disease (CD) and ulcerative colitis remain incompletely defined. Here, we aimed to identify novel associations between IBD and functional genetic variants using the Illumina ExomeChip (San Diego, CA). METHODS: Genotyping was performed in 10,523 IBD cases and 5726 non-IBD controls. There were 91,713 functional single-nucleotide polymorphism loci in coding regions analyzed. A novel identified association was replicated further in 2 independent cohorts. We further examined the association of the identified single-nucleotide polymorphism with microbiota from 338 mucosal lavage samples in the Mucosal Luminal Interface cohort measured using 16S sequencing. RESULTS: We identified an association between CD and a missense variant encoding alanine or threonine at position 391 in the zinc transporter solute carrier family 39, member 8 protein (SLC39A8 alanine 391 threonine, rs13107325) and replicated the association with CD in 2 replication cohorts (combined meta-analysis P = 5.55 × 10(-13)). This variant has been associated previously with distinct phenotypes including obesity, lipid levels, blood pressure, and schizophrenia. We subsequently determined that the CD risk allele was associated with altered colonic mucosal microbiome composition in both healthy controls (P = .009) and CD cases (P = .0009). Moreover, microbes depleted in healthy carriers strongly overlap with those reduced in CD patients (P = 9.24 × 10(-16)) and overweight individuals (P = 6.73 × 10(-16)). CONCLUSIONS: Our results suggest that an SLC39A8-dependent shift in the gut microbiome could explain its pleiotropic effects on multiple complex diseases including CD.
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Proteínas de Transporte de Cátions/genética , Colite Ulcerativa/genética , Doença de Crohn/genética , Microbioma Gastrointestinal/genética , Mutação de Sentido Incorreto , Alelos , Estudos de Casos e Controles , Colite Ulcerativa/microbiologia , Doença de Crohn/microbiologia , Feminino , Pleiotropia Genética , Genótipo , Humanos , Masculino , Fatores de RiscoRESUMO
BACKGROUND: Sleep and olfaction are both critical physiological processes that tend to worsen with age. Decline in olfaction can be an early indicator of neurodegenerative diseases, whereas poor sleep quality is associated with reduced physical and mental health. Given associations with aging-related health declines, we explored whether variations in sleep were associated with olfactory function among older adults. METHODS: We assessed the relationship between sleep characteristics and olfaction among 354 community-dwelling older adults. Olfaction was measured using a validated field and survey research tool. Sleep characteristics were measured using wrist actigraphy and with self-report of sleep problems. We fit structural equation models of latent constructs of olfaction based on olfactory task items and let this be a function of each sleep characteristic. RESULTS: Actigraph sleep quality measures were associated with odor identification, but not with odor sensitivity. Longer duration sleepers had worse odor sensitivity compared to medium (58 h) sleepers, but sleep duration was not associated with odor identification. Reported sleep problems and reported usual duration were not associated with olfaction. CONCLUSIONS: Diminished sleep quality was associated with reduced capacity to identify odors. Determining whether this is a causal association will require further study and longitudinal data.
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Envelhecimento , Sono , Olfato , Actigrafia , Idoso , Feminino , Humanos , Masculino , AutorrelatoRESUMO
OBJECTIVES: The olfactory nerve is anatomically susceptible to injury from pollution in inspired air, but there are no large-scale epidemiologic studies investigating this relationship. METHODS: Cross-sectional study using data from the National Social Life, Health, and Aging Project, a representative sample of home-dwelling US adults age 57-85 years. Olfactory function was tested using a validated 5-item odor identification test (Sniffin' Sticks). Exposure to fine particulate matter (PM2.5) at each respondent's home was estimated as 1-12 month moving averages prior to olfactory assessment using validated spatio-temporal models. RESULTS: Olfactory dysfunction was significantly associated with PM2.5 exposures averaged over 3-12 months in urban-dwelling respondents. The strongest effect was for 6 month average exposure (per 1-IQR increase in PM2.5: OR 1.28, 95% CI 1.05, 1.55) adjusting for age, gender, race/ethnicity, education, cognition, comorbidity, smoking, and the season. Interestingly, the most deleterious effects were observed among the youngest respondents, 57-64 years old, and those living in the northeast and south. CONCLUSIONS: We show for the first time that air pollution exposure is associated with poor olfaction among urban-living, older US adults.
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Poluentes Atmosféricos/toxicidade , Poluição do Ar em Ambientes Fechados/análise , Exposição Ambiental/análise , Transtornos do Olfato/induzido quimicamente , Material Particulado/toxicidade , População Urbana , Idoso , Idoso de 80 Anos ou mais , Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/efeitos adversos , Estudos Transversais , Exposição Ambiental/efeitos adversos , Feminino , Sistemas de Informação Geográfica , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/epidemiologia , Material Particulado/análise , Análise Espaço-Temporal , Inquéritos e Questionários , Estados UnidosRESUMO
We present a genome-wide association study of ileal Crohn disease and two independent replication studies that identify several new regions of association to Crohn disease. Specifically, in addition to the previously established CARD15 and IL23R associations, we identified strong and significantly replicated associations (combined P < 10(-10)) with an intergenic region on 10q21.1 and a coding variant in ATG16L1, the latter of which was also recently reported by another group. We also report strong associations with independent replication to variation in the genomic regions encoding PHOX2B, NCF4 and a predicted gene on 16q24.1 (FAM92B). Finally, we demonstrate that ATG16L1 is expressed in intestinal epithelial cell lines and that functional knockdown of this gene abrogates autophagy of Salmonella typhimurium. Together, these findings suggest that autophagy and host cell responses to intracellular microbes are involved in the pathogenesis of Crohn disease.
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Autofagia/fisiologia , Proteínas de Transporte/genética , Cromossomos Humanos Par 10/genética , Doença de Crohn/genética , Doença de Crohn/fisiopatologia , Predisposição Genética para Doença/genética , Animais , Proteínas Relacionadas à Autofagia , Proteínas de Transporte/metabolismo , Perfilação da Expressão Gênica , Células HeLa , Proteínas de Homeodomínio/genética , Humanos , Imuno-Histoquímica , Camundongos , NADPH Oxidases/genética , América do Norte , Polimorfismo de Nucleotídeo Único , Interferência de RNA , Fatores de Transcrição/genéticaRESUMO
BACKGROUND AND PURPOSE: Hemicraniectomy and Durotomy Upon Deterioration From Infarction-Related Swelling Trial (HeADDFIRST) was a randomized pilot study to obtain information necessary to design a Phase III trial to evaluate the benefit of surgical decompression for brain swelling from large supratentorial cerebral hemispheric infarction. METHODS: All patients with stroke were screened for eligibility (age 18-75 years, National Institutes of Health Stroke Scale≥18 with Item 1a<2 [responsive to minor stimulation], and CT demonstrating unilateral, complete middle cerebral artery territory infarction by specific imaging criteria). All enrolled patients were treated using a standardized medical treatment protocol. Those with both≥4 mm of pineal shift and deterioration in level of arousal or ≥7.5 mm of anteroseptal shift within 96 hours of stroke onset were randomized to continued medical treatment only or medical treatment plus surgery. Death at 21 days was the primary outcome measure. RESULTS: Among 4909 screened patients, only 66 (1.3%) patients were eligible for HeADDFIRST. Forty patients were enrolled, and 26 patients developed the requisite brain swelling for randomization. All who failed to meet randomization criteria were alive at 21 days. Mortality at 21 and 180 days was 40% (4/10) in the medical treatment only and 21% (3/14) and 36% (5/14) in the medical treatment plus surgery arms, respectively. CONCLUSIONS: HeADDFIRST randomization criteria effectively distinguished low from high risk of death from large supratentorial cerebral hemispheric infarction. Lower mortality in the medical treatment only group than in other published trials suggests a possible benefit to standardizing medical management. These results can inform the interpretation of recently completed European trials concerning patient selection and medical management. CLINICAL TRIAL REGISTRATION: This trial was not registered because enrollment began before July 1, 2005.
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Edema Encefálico/cirurgia , Infarto Cerebral/cirurgia , Craniectomia Descompressiva/métodos , Dura-Máter/cirurgia , Adulto , Idoso , Edema Encefálico/complicações , Edema Encefálico/mortalidade , Infarto Cerebral/complicações , Infarto Cerebral/mortalidade , Protocolos Clínicos , Cuidados Críticos , Interpretação Estatística de Dados , Feminino , Humanos , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/cirurgia , Pressão Intracraniana/fisiologia , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Seleção de Pacientes , Projetos Piloto , Tamanho da Amostra , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/cirurgia , Acidente Vascular Cerebral/terapia , Resultado do TratamentoRESUMO
OBJECTIVES: Scholarly, clinical, and policy interest in cognitive function has grown over the last several decades in part due to large increases in Alzheimer's Disease and related dementias as populations age. However, adequate measures of cognitive function have not been available in many research data sets. We argue that a wealth of previously unexploited survey data exists to model cognition and cognitive decline. METHODS: We use metadata of the time it takes older respondents in the National Social Life, Health and Aging Survey, which we label response times (RT), to answer questions in a standard cognitive assessment. We compare several measures of RT to a survey-adapted form of the Montreal Cognitive Assessment (MoCA). RESULTS: We show that RT predict both concurrent and future MoCA scores. Our results show that longer and more varied RT at baseline predict lower MoCA scores five year later, net of baseline scores and controls. We also show that the effect of RT measures on predicting current MoCA differ for individuals of different races and ages, but are not different by gender. DISCUSSION: Our paper demonstrates that RT constitute a separate powerful measure of cognitive functioning. RT may be remarkably useful both to clinicians and social scientists because they can increase accuracy of cognitive assessment without increasing the time it takes to administer the assessment.
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OBJECTIVES: We investigate the impact of data collection mode on responses to variables in NSHAP Round 4 and discuss how potential mode differences should (and should not) be addressed in substantive analyses. METHODS: Among the set of respondents who were eligible to be contacted remotely in Round 4, we randomly selected 398 to be contacted instead for an in-person interview. We compare response rates and the distributions of selected key outcomes among those 398 respondents to those among the control group who were initially approached remotely. As a contrast, we compare all R4 respondents according to the mode in which they completed the interview, including those not part of the randomized experiment. RESULTS: Among those included in the experiment, there was no evidence of systematic differences in responses to physical and mental health questions between remote and in-person modes, nor in responses to number recall measures. In-person respondents scored moderately lower on cognitive function measures requiring careful attention to a figure and/or task, though this difference became less with each similar item. Remote respondents named fewer social network members. Comparing all respondents according to their final mode yielded substantially different results in all cases. DISCUSSION: Mode did not appear to affect reports of physical and mental health based on a randomized comparison, though it did moderately affect other items in predictable ways. Naïve estimates of mode effects based on comparing all respondents according to mode yielded misleading results, and should not be used to adjust for mode differences in analyses.
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OBJECTIVES: We examined the impact of Catholic hospital delivery on short interval pregnancy in the California 2010-2014 Medicaid population. STUDY DESIGN: We used Cox regression to estimate the association between hospital affiliation and short interval pregnancy, adjusting for patient factors. RESULTS: Catholic hospital delivery had increased the risk of pregnancy within 6 months for Black (hazard ratio [HR] 1.11, 95% CI 1.06, 1.17) and Hispanic (HR 1.07, 95% CI 1.05, 1.09) but not for White women (HR 1.02, 95% CI 0.98, 1.05). CONCLUSIONS: Among California women with Medicaid, Catholic hospital delivery was associated with short interval pregnancy only among women of color.
Assuntos
Intervalo entre Nascimentos , Catolicismo , Hospitais Religiosos , Medicaid , Feminino , Humanos , Gravidez , California , Disparidades em Assistência à Saúde , Estados Unidos , Grupos Raciais , EtnicidadeRESUMO
BACKGROUND AND OBJECTIVES: The role of social factors in diabetes onset has been obscured by wide variation in their conceptualization and operationalization. We apply three theoretical frameworks to categorize social relationship variables along several dimensions and identify which dimension(s) are robustly associated with incident diabetes in the older adult population. RESEARCH DESIGN AND METHODS: The National Social Life, Health, and Aging Project (n=2,365) and the Health and Retirement Study (n=11,824) provided longitudinal data from 57-90 year-old respondents over a 4- to 5-year period. Logistic regression models were used to test associations of 15 social variables measured identically in both datasets with diabetes onset measured as respondents' first report of a physician's diagnosis. RESULTS: In both studies, not being married, experiencing strain in a spousal relationship, and feeling lonely were associated with increased risk for diabetes onset at follow-up. Inconsistent or null findings were observed for social support, social activity, network size, number of friends and relatives, living alone, and closeness to network members. DISCUSSION AND IMPLICATIONS: Robust findings in two large-scale surveys support the importance of the valence dimension (i.e., positive and negative); specifically, alleviating negative aspects of social life might more effectively reduce risk for diabetes than augmenting positive ones. Findings were not aligned with social variables differing on the subjectivity dimension (i.e., structural, functional, and qualitative aspects of social connections). Future work needs consistent conceptualization and measurement of social factors to correctly identify and categorize risk factors for diabetes onset and other health conditions in older adults.
RESUMO
OBJECTIVES: While depression has been associated with physical function decline and worsening frailty in older adults, the impact of other mental health symptoms on physical function and frailty is unknown. The study objective was to determine whether depression, perceived stress, loneliness, and anxiety symptoms affect 5-year physical function and frailty trajectories of older adults. METHODS: The National Social Life, Health, and Aging Project (NSHAP) is a nationally-representative study of adults born between 1920 and 1947. The analysis included data collected in 2010-11 and 2015-16. Mental health symptoms were quantified using NSHAP's measures of anxiety (range:0-21), perceived stress (0-8), depression (0-22), and loneliness (0-6); higher scores indicated worse symptoms. We regressed 2015-16 3 m usual walk time, five-repeated chair stand time or an adapted frailty phenotype scale (0-4) separately on each 2010-11 mental health scale, adjusting for baseline physical function or frailty, demographics, and comorbidities. RESULTS: In separate models, every one-point increase on the depression or perceived stress scales was associated with, respectively, a 0.06 s slower (95 % CI: 0.03, 0.10) or 0.09 s slower (95 % CI: 0.01, 0.16) 5-year walk time. Every one-point increase on the depression or perceived stress scales was associated with a 0.15 s slower (95 % CI: 0.06, 0.23) or 0.16 s slower (95 % CI: 0.02, 0.29) 5-year chair stand time. Every one-point increase on the depression scale predicted 0.06 higher log odds of having a worse frailty score 5 years later. Only depression's association with 3 m walk time and chair stands remained significant in models including all four mental health scales. DISCUSSION: Older adults with more depression and to a lesser extent stress symptoms may experience faster physical function decline and worsening frailty. Future work exploring and addressing the mechanisms underlying these relationships are warranted.
Assuntos
Fragilidade , Transtornos Mentais , Humanos , Idoso , Solidão/psicologia , Depressão/epidemiologia , Depressão/psicologia , Fragilidade/epidemiologia , Ansiedade/epidemiologia , Ansiedade/psicologiaRESUMO
The objective of this study is to compare self-reported preconception care utilization (PCU) among Medicaid-covered births to Medicaid claims. We identified all Medicaid-covered births to women ages 15-45 in 26 states in the year 2012 among the Pregnancy Risk Assessment and Monitoring System (PRAMS) survey and Medicaid Analytic eXtract (MAX) claims data, and identified preconception services in the latter using diagnosis codes published by Health and Human Services' Office of Population Affairs. We fit mixed-effects logistic regression models for the probability of PCU on sociodemographic factors (age, race, and ethnicity) and clinical diagnoses (depression, diabetes, or hypertension), separately for each dataset. Among 652,929 women delivering in MAX, 28.1% received at least one claims-based preconception service while an estimated 23.6% (95% CI 22.1-25.3) of PRAMS respondents reported receiving preconception care. Adjusting for age, chronic diseases, and state, PCU rates in both MAX and PRAMS were higher for non-Hispanic Black versus non-Hispanic White women (OR 1.51, 95% CI 1.49-1.54 and OR 2.05, 95% CI 1.60-2.62, respectively). Adjusting for differences in age, race and ethnicity, and state, PCU rates were higher for patients with diabetes (OR 1.34, 95% CI 1.29-1.40 and OR 1.82, 95% CI 1.16-2.85) or hypertension (OR 1.22, 95% CI 1.18-1.27 and OR 1.85, 95% CI 1.41-2.44). While Hispanic and Asian women were also more likely to report PCU than their non-Hispanic White counterparts (OR 2.07, 95% CI 1.53-2.80 and OR 3.37, 95% CI 2.28-4.98), they were less likely to have received it (OR 0.74, 95% CI 0.73-0.75 and OR 0.65, 95% CI 0.63-0.67). In conclusion, comparing self-report to claims measures of PCU, we found similar trends in the differences between non-Hispanic Black and White women, and between those with vs. without diabetes and hypertension. However, the two data sources differed in trends in other racial/ethnic groups (differences between Hispanic vs. non-Hispanic White women, and between Asian vs. non-Hispanic White women), and in those with vs. without depression. This suggests that while Medicaid claims can be a useful tool for studying preconception care, they may miss certain types of care among some sub-groups of the population or be subject to reporting differences that are hard to surmise. Both data sets have potential benefits and drawbacks as research tools.