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2.
Psychiatr Serv ; 75(3): 268-274, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37855097

RESUMO

Certified community behavioral health centers (CCBHCs) were established under section 223 of the Protecting Access to Medicare Act of 2014. CCBHCs had the goal of expanding access to care for people with behavioral health needs "regardless of ability to pay and place of residence." The authors used descriptive tables and a heat map to compare the geographic distribution of CCBHCs with county-level rates of mental illness, poverty, and population density. Regression models were employed to determine which county-level characteristics are most strongly associated with the establishment of a CCBHC. The authors found that population density is a stronger predictor of CCBHC presence than are rates of poverty or serious mental illness. Holding all other local characteristics constant, the authors observed that going from the population density typical of the most rural counties to that of the most urban counties was associated with an approximately 28-percentage-point increase (from 7% to 35%) in the likelihood of being served by a CCBHC. Expanding CCBHC services to areas with lower population densities likely requires an approach that is different from the current method of allocation of grant funds by the Substance Abuse and Mental Health Services Administration (SAMHSA). Two features of the program might be modified. The first would build on flexibilities incorporated into the most recent round of SAMHSA grantmaking, which explicitly aim to build infrastructure and capacity to develop a CCBHC. A second modification might seek to identify which certification requirements are essential to supporting CCBHC quality and access and eliminate nonessential requirements.


Assuntos
Medicare , Transtornos Mentais , Idoso , Estados Unidos , Humanos , Certificação , Centros Comunitários de Saúde , Transtornos Mentais/epidemiologia , Transtornos Mentais/terapia , Pobreza
4.
Int J Mol Sci ; 22(22)2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34830323

RESUMO

Sporadic occurrence of inherited eye disorders has been reported in cattle but so far pathogenic variants were found only for rare forms of cataract but not for retinopathies. The aim of this study was to characterize the phenotype and the genetic aetiology of a recessive form of congenital day-blindness observed in several cases of purebred Original Braunvieh cattle. Electroretinography in an affected calf revealed absent cone-mediated function, whereas the rods continue to function normally. Brain areas involved in vision were morphologically normal. When targeting cones by immunofluorescence, a decrease in cone number and an accumulation of beta subunits of cone cyclic-nucleotide gated channel (CNGB3) in the outer plexiform layer of affected animals was obvious. Achromatopsia is a monogenic Mendelian disease characterized by the loss of cone photoreceptor function resulting in day-blindness, total color-blindness, and decreased central visual acuity. After SNP genotyping and subsequent homozygosity mapping with twelve affected cattle, we performed whole-genome sequencing and variant calling of three cases. We identified a single missense variant in the bovine CNGB3 gene situated in a ~2.5 Mb homozygous genome region on chromosome 14 shared between all cases. All affected cattle were homozygous carriers of the p.Asp251Asn mutation that was predicted to be deleterious, affecting an evolutionary conserved residue. In conclusion, we have evidence for the occurrence of a breed-specific novel CNGB3-related form of recessively inherited achromatopsia in Original Braunvieh cattle which we have designated OH1 showing an allele frequency of the deleterious allele of ~8%. The identification of carriers will enable selection against this inherited disorder. The studied cattle might serve as an animal model to further elucidate the function of CNGB3 in mammals.


Assuntos
Alelos , Defeitos da Visão Cromática/genética , Canais de Cátion Regulados por Nucleotídeos Cíclicos/genética , Mutação de Sentido Incorreto , Subunidades Proteicas/genética , Células Fotorreceptoras Retinianas Cones/metabolismo , Substituição de Aminoácidos , Animais , Asparagina/metabolismo , Ácido Aspártico/metabolismo , Bovinos , Defeitos da Visão Cromática/diagnóstico por imagem , Defeitos da Visão Cromática/metabolismo , Defeitos da Visão Cromática/patologia , Canais de Cátion Regulados por Nucleotídeos Cíclicos/deficiência , Eletrorretinografia , Feminino , Expressão Gênica , Frequência do Gene , Homozigoto , Masculino , Fenótipo , Subunidades Proteicas/deficiência , Células Fotorreceptoras Retinianas Cones/patologia , Células Fotorreceptoras Retinianas Bastonetes/citologia , Células Fotorreceptoras Retinianas Bastonetes/metabolismo , Sequenciamento Completo do Genoma
5.
Genes (Basel) ; 12(7)2021 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-34356054

RESUMO

Genodermatoses, such as heritable skin disorders, mostly represent Mendelian conditions. Congenital hypotrichosis (HY) characterize a condition of being born with less hair than normal. The purpose of this study was to characterize the clinicopathological phenotype of a breed-specific non-syndromic form of HY in Hereford cattle and to identify the causative genetic variant for this recessive disorder. Affected calves showed a very short, fine, wooly, kinky and curly coat over all parts of the body, with a major expression in the ears, the inner part of the limbs, and in the thoracic-abdominal region. Histopathology showed a severely altered morphology of the inner root sheath (IRS) of the hair follicle with abnormal Huxley and Henle's layers and severely dysplastic hair shafts. A genome-wide association study revealed an association signal on chromosome 5. Homozygosity mapping in a subset of cases refined the HY locus to a 690 kb critical interval encompassing a cluster of type II keratin encoding genes. Protein-coding exons of six positional candidate genes with known hair or hair follicle function were re-sequenced. This revealed a protein-changing variant in the KRT71 gene that encodes a type II keratin specifically expressed in the IRS of the hair follicle (c.281delTGTGCCCA; p.Met94AsnfsX14). Besides obvious phenocopies, a perfect concordance between the presence of this most likely pathogenic loss-of-function variant located in the head domain of KRT71 and the HY phenotype was found. This recessive KRT71-related form of hypotrichosis provides a novel large animal model for similar human conditions. The results have been incorporated in the Online Mendelian Inheritance in Animals (OMIA) database (OMIA 002114-9913).


Assuntos
Doenças dos Bovinos/genética , Folículo Piloso , Hipotricose/genética , Hipotricose/veterinária , Queratinas Específicas do Cabelo/genética , Animais , Bovinos , Éxons/genética , Feminino , Estudo de Associação Genômica Ampla/veterinária , Cabelo , Homozigoto , Hipotricose/metabolismo , Hipotricose/patologia , Masculino , Fenótipo , Medicina de Precisão
7.
Genes (Basel) ; 12(5)2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-33926013

RESUMO

Genodermatosis such as hair disorders mostly follow a monogenic mode of inheritance. Congenital hypotrichosis (HY) belong to this group of disorders and is characterized by abnormally reduced hair since birth. The purpose of this study was to characterize the clinical phenotype of a breed-specific non-syndromic form of HY in Belted Galloway cattle and to identify the causative genetic variant for this recessive disorder. An affected calf born in Switzerland presented with multiple small to large areas of alopecia on the limbs and on the dorsal part of the head, neck, and back. A genome-wide association study using Swiss and US Belted Galloway cattle encompassing 12 cases and 61 controls revealed an association signal on chromosome 29. Homozygosity mapping in a subset of cases refined the HY locus to a 1.5 Mb critical interval and subsequent Sanger sequencing of protein-coding exons of positional candidate genes revealed a stop gain variant in the HEPHL1 gene that encodes a multi-copper ferroxidase protein so-called hephaestin like 1 (c.1684A>T; p.Lys562*). A perfect concordance between the homozygous presence of this most likely pathogenic loss-of-function variant and the HY phenotype was found. Genotyping of more than 700 purebred Swiss and US Belted Galloway cattle showed the global spread of the mutation. This study provides a molecular test that will permit the avoidance of risk matings by systematic genotyping of relevant breeding animals. This rare recessive HEPHL1-related form of hypotrichosis provides a novel large animal model for similar human conditions. The results have been incorporated in the Online Mendelian Inheritance in Animals (OMIA) database (OMIA 002230-9913).


Assuntos
Doenças dos Bovinos/genética , Bovinos/genética , Hipotricose/veterinária , Oxirredutases/genética , Animais , Cromossomos/genética , Códon sem Sentido , Cabelo/metabolismo , Cabelo/patologia , Homozigoto , Hipotricose/genética , Mutação com Perda de Função
8.
Mol Biol Evol ; 38(6): 2260-2272, 2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-33528505

RESUMO

In the course of evolution, pecorans (i.e., higher ruminants) developed a remarkable diversity of osseous cranial appendages, collectively referred to as "headgear," which likely share the same origin and genetic basis. However, the nature and function of the genetic determinants underlying their number and position remain elusive. Jacob and other rare populations of sheep and goats are characterized by polyceraty, the presence of more than two horns. Here, we characterize distinct POLYCERATE alleles in each species, both associated with defective HOXD1 function. We show that haploinsufficiency at this locus results in the splitting of horn bud primordia, likely following the abnormal extension of an initial morphogenetic field. These results highlight the key role played by this gene in headgear patterning and illustrate the evolutionary co-option of a gene involved in the early development of bilateria to properly fix the position and number of these distinctive organs of Bovidae.


Assuntos
Evolução Biológica , Cabras/genética , Proteínas de Homeodomínio/genética , Cornos , Ovinos/genética , Animais , Biometria , Regulação da Expressão Gênica no Desenvolvimento , Cabras/embriologia , Cabras/metabolismo , Proteínas de Homeodomínio/metabolismo , Masculino , Camundongos Transgênicos , Mutação , Ovinos/embriologia , Ovinos/metabolismo
9.
Mol Genet Genomics ; 296(1): 235-242, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33159255

RESUMO

Sporadic occurrences of neurodegenerative disorders including neuroaxonal dystrophy (NAD) have been previously reported in sheep. However, so far no causative genetic variant has been found for ovine NAD. The aim of this study was to characterize the phenotype and the genetic aetiology of an early-onset neurodegenerative disorder observed in several lambs of purebred Swaledale sheep, a native English breed. Affected lambs showed progressive ataxia and stiff gait and subsequent histopathological analysis revealed the widespread presence of axonal spheroid indicating neuronal degeneration. Thus, the observed clinical phenotype could be explained by a novel form of NAD. After SNP genotyping and subsequent linkage mapping within a paternal half-sib pedigree with a total of five NAD-affected lambs, we identified two loss-of-function variants by whole-genome sequencing in the ovine PLA2G6 gene situated in a NAD-linked genome region on chromosome 3. All cases were carriers of a compound heterozygous splice site variant in intron 2 and a nonsense variant in exon 8. Herein we present evidence for the occurrence of a familial novel form of recessively inherited NAD in sheep due to allelic heterogeneity at PLA2G6. This study reports two pathogenic variants in PLA2G6 causing a novel form of NAD in Swaledale sheep which enables selection against this fatal disorder.


Assuntos
Precursor de Proteína beta-Amiloide/genética , Fosfolipases A2 do Grupo VI/genética , Distrofias Neuroaxonais/genética , Distrofias Neuroaxonais/veterinária , Polimorfismo de Nucleotídeo Único , Doenças dos Ovinos/genética , Processamento Alternativo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Sequência de Bases , Mapeamento Cromossômico , Cromossomos de Mamíferos/química , Éxons , Feminino , Expressão Gênica , Ligação Genética , Fosfolipases A2 do Grupo VI/deficiência , Heterozigoto , Íntrons , Masculino , Distrofias Neuroaxonais/metabolismo , Distrofias Neuroaxonais/patologia , Ovinos , Doenças dos Ovinos/metabolismo , Doenças dos Ovinos/patologia , Carneiro Doméstico , Sequenciamento Completo do Genoma
10.
Genes (Basel) ; 11(10)2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-33003365

RESUMO

Severe oxalate nephropathy has been previously reported in sheep and is mostly associated with excessive oxalate in the diet. However, a rare native Dutch breed (Zwartbles) seems to be predisposed to an inherited juvenile form of primary hyperoxaluria and no causative genetic variant has been described so far. This study aims to characterize the phenotype and genetic etiology of the inherited metabolic disease observed in several purebred Zwartbles sheep. Affected animals present with a wide range of clinical signs including condition loss, inappetence, malaise, and, occasionally, respiratory signs, as well as an apparent sudden unexpected death. Histopathology revealed widespread oxalate crystal deposition in kidneys of the cases. Whole-genome sequencing of two affected sheep identified a missense variant in the ovine AGXT gene (c.584G>A; p.Cys195Tyr). Variants in AGXT are known to cause type I primary hyperoxaluria in dogs and humans. Herein, we present evidence that the observed clinicopathological phenotype can be described as a form of ovine type I primary hyperoxaluria. This disorder is explained by a breed-specific recessively inherited pathogenic AGXT variant. Genetic testing enables selection against this fatal disorder in Zwartbles sheep as well as more precise diagnosis in animals with similar clinical phenotype. Our results have been incorporated in the Online Mendelian Inheritance in Animals (OMIA) database (OMIA 001672-9940).


Assuntos
Hiperoxalúria Primária/patologia , Mutação de Sentido Incorreto , Transaminases/genética , Animais , Animais Recém-Nascidos , Testes Genéticos , Hiperoxalúria Primária/etiologia , Ovinos
11.
Acta Vet Scand ; 62(1): 5, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31969185

RESUMO

BACKGROUND: Otocephaly is a rare lethal malformation of the first branchial arch. While the knowledge on the causes of otocephaly in animals is limited, different syndromic forms in man are associated with variants of the PRRX1 and OTX2 genes. CASE PRESENTATION: A stillborn male lamb of the Istrian Pramenka sheep breed showed several congenital craniofacial anomalies including microstomia, agnathia, aglossia, and synotia. In addition, the lamb had a cleft palate, a small opening in the ventral neck region, a cystic oesophagus and two hepatic cysts. The brain was normally developed despite the deformed shape of the head. Taken together the findings led to a diagnosis of otocephaly. Whole-genome sequencing was performed from DNA of the affected lamb and both parents revealing a heterozygous single nucleotide variant in the OTX2 gene (Chr7: 71478714G > A). The variant was absent in both parents and therefore due to a de novo mutation event. It was a nonsense variant, XM_015097088.2:c.265C > T; which leads to an early premature stop codon and is predicted to truncate more than 70% of the OTX2 open reading frame (p.Arg89*). CONCLUSIONS: The genetic findings were consistent with the diagnosis of the otocephaly and provide strong evidence that the identified loss-of-function variant is pathogenic due to OTX2 haploinsufficiency. The benefits of trio-based whole-genome sequencing as an emerging tool in veterinary pathology to confirm diagnosis are highlighted.


Assuntos
Anormalidades Craniofaciais/veterinária , Variação Genética , Mutação , Fatores de Transcrição Otx/genética , Doenças dos Ovinos/genética , Animais , Anormalidades Craniofaciais/genética , Ovinos
12.
J Oncol Pract ; 13(5): e431-e440, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28306372

RESUMO

PURPOSE: Hospitalized patients with advanced cancer have a high symptom burden and need for support. Integration of palliative care (PC) improves symptom control and decreases unwanted health care use, yet many patients are never offered these services. In 2016, ASCO called for incorporation of PC into oncologic care for all patients with metastatic cancer. To improve the quality of cancer care, we developed standardized criteria, or triggers, for PC consultation on the inpatient solid tumor service. METHODS: Patients were eligible for this prospective cohort study if they met at least one of the following eligibility criteria: had an advanced solid tumor; prior hospitalization within 30 days; hospitalization > 7 days; and active symptoms. During the intervention, patients who met the criteria received automatic PC consultation. RESULTS: When we compared patients in the intervention group with control subjects, there were increases in PC consultations (19 of 48 [39%] to 52 of 65 [80%]; P ≤ .001) and hospice referrals (seven of 48 [14%] to 17 of 65 [26%]; P = .03), and there were declines in 30-day readmission rates (17 of 48 [35%] to 13 of 65 [18%]; P = .04) and receipt of chemotherapy after discharge (21 of 48 [44%] to 12 of 65 [18%]; P = .03). There was an overall increase in support measures following discharge ( P = .004). Length of stay was unaffected. CONCLUSION: To our knowledge, this is the first study to demonstrate that among patients with advanced cancer admitted to an inpatient oncology service, the standardized use of triggers for PC consultation is associated with substantial impact on 30-day readmission rates, chemotherapy following discharge, hospice referrals, and use of support services following discharge. Expansion of this model to other hospitals and health systems should improve the value of cancer care.


Assuntos
Atenção à Saúde/normas , Oncologia/normas , Cuidados Paliativos/normas , Encaminhamento e Consulta , Adulto , Idoso , Atenção à Saúde/métodos , Feminino , Hospitalização , Humanos , Masculino , Oncologia/métodos , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/terapia , Avaliação de Resultados em Cuidados de Saúde , Cuidados Paliativos/métodos , Fatores Socioeconômicos
13.
Health Serv Res ; 49(5): 1701-20, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24779867

RESUMO

OBJECTIVES: To model the steps involved in preparing for and carrying out propensity score analyses by providing step-by-step guidance and Stata code applied to an empirical dataset. STUDY DESIGN: Guidance, Stata code, and empirical examples are given to illustrate (1) the process of choosing variables to include in the propensity score; (2) balance of propensity score across treatment and comparison groups; (3) balance of covariates across treatment and comparison groups within blocks of the propensity score; (4) choice of matching and weighting strategies; (5) balance of covariates after matching or weighting the sample; and (6) interpretation of treatment effect estimates. EMPIRICAL APPLICATION: We use data from the Palliative Care for Cancer Patients (PC4C) study, a multisite observational study of the effect of inpatient palliative care on patient health outcomes and health services use, to illustrate the development and use of a propensity score. CONCLUSIONS: Propensity scores are one useful tool for accounting for observed differences between treated and comparison groups. Careful testing of propensity scores is required before using them to estimate treatment effects.


Assuntos
Institutos de Câncer/estatística & dados numéricos , Modelos Estatísticos , Avaliação de Resultados em Cuidados de Saúde/métodos , Cuidados Paliativos/estatística & dados numéricos , Pontuação de Propensão , Adulto , Idoso , Idoso de 80 Anos ou mais , Fatores de Confusão Epidemiológicos , Interpretação Estatística de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , New York , Ohio , Pennsylvania , Projetos de Pesquisa , Resultado do Tratamento , Virginia , Wisconsin , Adulto Jovem
14.
J Oncol Pract ; 10(3): 174-7, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24839276

RESUMO

PURPOSE: Research has shown that patients with terminal illnesses prefer to die at home, yet more than 60% of patients with cancer are hospitalized in the last month of life. Less than half of these patients receive hospice care at the end of life. Inpatient palliative care consultations may serve as a bridge from hospitalization to receiving patient's preferred end-of-life care. GI tumors include some the deadliest cancers, and patients with these cancers may serve to benefit from palliative care services. METHODS: The objective of this study was to evaluate the role of palliative care versus usual care on postdischarge outcomes and hospice use for patients with advanced GI cancers. Two hundred one adults, 82 of whom received a palliative care consult, were followed for 6 months after hospital discharge. Propensity scores were used to match palliative care patients to usual care patients. Outcome measures included hospice use, place of death, subsequent emergency department visits, hospital readmission, and survival. RESULTS: Fifty-nine patients died in the 6 months postdischarge. Receiving a palliative care consult increased the odds of home death (odds ratio [OR] = 2.9; 95% CI, 1.02 to 8.44; P = .046) and decreased the odds of hospital death (OR = 0.159; 95% CI, 0.05 to 0.52; P = .002). At 2 and 4 months, more patients in the palliative care group were receiving hospice services at death, compared with the usual care group (75% v 18%, P = .001% and 93% v 30%, P = .000 respectively). There were no differences with respect to emergency department visits, hospital readmission, and survival. CONCLUSION: Palliative care consultation was associated with increased hospice utilization, decreased likelihood of dying in a hospital, and increased likelihood of dying at home.


Assuntos
Neoplasias Gastrointestinais/terapia , Cuidados Paliativos na Terminalidade da Vida/estatística & dados numéricos , Encaminhamento e Consulta , Feminino , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/patologia , Mortalidade Hospitalar , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Resultado do Tratamento
15.
Am J Obstet Gynecol ; 210(4): 338.e1-338.e8, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24211478

RESUMO

OBJECTIVE: Risk factors for the development of new-onset late postpartum preeclampsia (LPP) in women without any history of preeclampsia are not known. Because identification of women who are at risk may lead to an earlier diagnosis of disease and improved maternal outcomes, this study identified risk factors (associated patient characteristics) for new-onset LPP. STUDY DESIGN: A case-control study of 34 women with new-onset LPP and 68 women without new-onset LPP after normal delivery, who were matched on date of delivery, was conducted at Mount Sinai Hospital, New York, NY. Data were collected by chart review. Exact conditional logistic regression identified patient characteristics that were associated with new-onset LPP. RESULTS: New-onset LPP was associated with age ≥40 years (adjusted odds ratio, 24.83; 95% confidence interval [CI], 1.43-infinity; P = .03), black race (adjusted odds ratio, 78.35; 95% CI, 7.25-infinity; P < .001), Latino ethnicity (adjusted odds ratio, 19.08; 95% CI, 2.73-infinity; P = .001), final pregnancy body mass index of ≥30 kg/m(2) (adjusted odds ratio, 13.38; 95% CI, 1.87-infinity; P = .01), and gestational diabetes mellitus (adjusted odds ratio, 72.91; 95% CI, 5.52-infinity; P < .001). As predictive tests for new-onset LPP, the sensitivity and specificity of having ≥1 of these characteristics was 100% and 59%, respectively, and the sensitivity and specificity of having ≥2 was 56% and 93%, respectively. CONCLUSION: Older age, black race, Latino ethnicity, obesity, and a pregnancy complicated by gestational diabetes mellitus all are associated positively with the development of new-onset LPP. Closer observation may be warranted in these populations.


Assuntos
Pré-Eclâmpsia/epidemiologia , Transtornos Puerperais/epidemiologia , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Diabetes Gestacional/epidemiologia , Feminino , Humanos , Idade Materna , Análise Multivariada , Obesidade/epidemiologia , Readmissão do Paciente , Valor Preditivo dos Testes , Gravidez , Grupos Raciais/estatística & dados numéricos , Fatores de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença
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