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1.
J Urol ; 210(1): 128-135, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37114615

RESUMO

PURPOSE: The ROCKS (Reducing Operative Complications from Kidney Stones) program in MUSIC (Michigan Urological Surgery Improvement Collaborative) was created to optimize ureteroscopy outcomes. Through data collection, distribution of reports, patient education, and standardization of medication, post-ureteroscopy emergency department visits in Michigan have declined. It is unclear whether this is because of statewide quality efforts or due to national trends. We therefore sought to understand emergency department visit rates in Michigan compared to a national data set. MATERIALS AND METHODS: We compared the MUSIC ROCKS clinical registry in Michigan against a national cohort, Optum's de-identified Clinformatics Data Mart, from 2016-2021 (excluding Michigan). We identified patients who underwent ureteroscopy and the proportion who had a postoperative emergency department visit within 30 days. Emergency department rates were modeled over time, adjusting for age, gender, comorbidity, and ureteral stenting. RESULTS: We identified 24,688 patients in MUSIC ROCKS and 99,340 in the Clinformatics Data Mart database who underwent ureteroscopy. The risk-adjusted emergency department visit rate in MUSIC ROCKS significantly declined over the study period (10.5% in 2016 to 6.9% in 2021, P < 0.001) while the mean emergency department visit rate in the Clinformatics Data Mart cohort was 9.9% and did not change over time (9.6% in 2016 to 10% in 2021). Comparing emergency department visits between the cohorts, the MUSIC ROCKS rate significantly declined relative to the Clinformatics Data Mart (P < 0.001) over the study period. CONCLUSIONS: Postoperative emergency department visit rates in Michigan have declined significantly after ureteroscopy since the establishment of MUSIC ROCKS. This decline outpaced national rates, providing evidence that systematic quality initiatives can improve urological care.


Assuntos
Cálculos Renais , Ureter , Cálculos Ureterais , Cálculos Urinários , Humanos , Ureteroscopia , Cálculos Renais/cirurgia , Serviço Hospitalar de Emergência , Cálculos Ureterais/cirurgia , Resultado do Tratamento
2.
Med Care ; 61(3): 137-144, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36729552

RESUMO

BACKGROUND AND OBJECTIVES: We examined transitional care management within 90 days and 1 year following discharge home among acute stroke and transient ischemic attack patients from the Comprehensive Post-Acute Stroke Services (COMPASS) Study, a cluster-randomized pragmatic trial of early supported discharge conducted in 41 hospitals (40 hospital units) in North Carolina, United States. METHODS: Data for 2262 of the total 6024 (37.6%; 1069 intervention and 1193 usual care) COMPASS patients were linked with the Centers for Medicare and Medicaid Services fee-for-service Medicare claims. Time to the first ambulatory care visit was examined using Cox proportional hazard models adjusted for patient characteristics not included in the randomization protocol. RESULTS: Only 6% of the patients [mean (SD) age 74.9 (10.2) years, 52.1% women, 80.3% White)] did not have an ambulatory care visit within 90 days postdischarge. Mean time (SD) to first ambulatory care visit was 12.0 (26.0) and 16.3 (35.1) days in intervention and usual care arms, respectively, with the majority of visits in both study arms to primary care providers. The COMPASS intervention resulted in a 27% greater use of ambulatory care services within 1 year postdischarge, relative to usual care [HR=1.27 (95% CI: 1.14-1.41)]. The use of transitional care billing codes was significantly greater in the intervention arm as compared with usual care [OR=1.87 (95% CI: 1.54-2.27)]. DISCUSSION: The COMPASS intervention, which was aimed at improving stroke post-acute care, was associated with an increase in the use of ambulatory care services by stroke and transient ischemic attack patients discharged home and an increased use of transitional care billing codes by ambulatory providers.


Assuntos
Ataque Isquêmico Transitório , Acidente Vascular Cerebral , Idoso , Feminino , Humanos , Masculino , Assistência ao Convalescente , Assistência Ambulatorial , Ataque Isquêmico Transitório/terapia , Medicare , Alta do Paciente , Acidente Vascular Cerebral/terapia , Cuidados Semi-Intensivos , Estados Unidos
3.
Arch Phys Med Rehabil ; 103(5): 882-890.e2, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34740596

RESUMO

OBJECTIVES: To examine the effect of a comprehensive transitional care model on the use of skilled nursing facility (SNF) and inpatient rehabilitation facility (IRF) care in the 12 months after acute care discharge home following stroke; and to identify predictors of experiencing a SNF or IRF admission following discharge home after stroke. DESIGN: Cluster randomized pragmatic trial SETTING: Forty-one acute care hospitals in North Carolina. PARTICIPANTS: 2262 Medicare fee-for-service beneficiaries with transient ischemic attack or stroke discharged home. The sample was 80.3% White and 52.1% female, with a mean (SD) age of 74.9 (10.2) years and a mean ± SD National Institutes of Health stroke scale score of 2.3 (3.7). INTERVENTION: Comprehensive transitional care model (COMPASS-TC), which consisted of a 2-day follow-up phone call from the postacute care coordinator and 14-day in-person visit with the postacute care coordinator and advanced practice provider. MAIN OUTCOME MEASURES: Time to first SNF or IRF and SNF or IRF admission (yes/no) in the 12 months following discharge home. All analyses utilized multivariable mixed models including a hospital-specific random effect to account for the non-independence of measures within hospital. Intent to treat analyses using Cox proportional hazards regression assessed the effect of COMPASS-TC on time to SNF/IRF admission. Logistic regression was used to identify clinical and non-clinical predictors of SNF/IRF admission. RESULTS: Only 34% of patients in the intervention arm received COMPASS-TC per protocol. COMPASS-TC was not associated with a reduced hazard of a SNF/ IRF admission in the 12 months post-discharge (hazard ratio, 1.20, with a range of 0.95-1.52) compared to usual care. This estimate was robust to additional covariate adjustment (hazard ratio, 1.23) (0.93-1.64). Both clinical and non-clinical factors (ie, insurance, geography) were predictors of SNF/IRF use. CONCLUSIONS: COMPASS-TC was not consistently incorporated into real-world clinical practice. The use of a comprehensive transitional care model for patients discharged home after stroke was not associated with SNF or IRF admissions in a 12-month follow-up period. Non-clinical factors predictive of SNF/IRF use suggest potential issues with access to this type of care.


Assuntos
Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Assistência ao Convalescente , Idoso , Feminino , Humanos , Pacientes Internados , Masculino , Medicare , Alta do Paciente , Centros de Reabilitação , Instituições de Cuidados Especializados de Enfermagem , Acidente Vascular Cerebral/terapia , Reabilitação do Acidente Vascular Cerebral/métodos , Estados Unidos
4.
Stroke ; 52(1): 385-393, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33349012

RESUMO

Worldwide, stroke is prevalent, costly, and disabling in >80 million survivors. The burden of stroke is increasing despite incredible progress and advancements in evidence-based acute care therapies and despite the substantial changes being made in acute care stroke systems, processes, and quality metrics. Although there has been increased global emphasis on the importance of postacute stroke care, stroke system changes have not expanded to include postacute care and outcome follow-up. Our objectives are to describe the gaps and challenges in postacute stroke care and suboptimal stroke outcomes; to report on stroke survivors' and caregivers' perceptions of current postacute stroke care and their call for improvements in follow-up services for recovery and secondary prevention; and, ultimately, to make the case that a paradigm shift is needed in the definition of comprehensive stroke care and the designation of Comprehensive Stroke Center. Three recommendations are made for a paradigm shift in comprehensive stroke care: (1) criteria should be established for designation of rehabilitation readiness for Comprehensive Stroke Centers, (2) The American Heart Association/American Stroke Association implement an expanded Get With The Guidelines-Stroke program and criteria for comprehensive stroke centers to be inclusive of rehabilitation readiness and measure outcomes at 90 days, and (3) a public health campaign should be launched to offer hopeful and actionable messaging for secondary prevention and recovery of function and health. Now is the time to honor the patients' and caregivers' strongest ask: better access and improved secondary prevention, stroke rehabilitation, and personalized care.


Assuntos
Acidente Vascular Cerebral/terapia , Fidelidade a Diretrizes , Humanos , Avaliação de Resultados em Cuidados de Saúde , Medicina de Precisão , Prevenção Secundária , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/prevenção & controle , Reabilitação do Acidente Vascular Cerebral , Cuidados Semi-Intensivos , Resultado do Tratamento , Estados Unidos/epidemiologia
5.
Med Care ; 59(Suppl 4): S344-S354, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34228016

RESUMO

BACKGROUND: Despite the well-documented risks to patient safety associated with transitions from one care setting to another, health care organizations struggle to identify which interventions to implement. Multiple strategies are often needed, and studying the effectiveness of these complex interventions is challenging. OBJECTIVE: The objective of this study was to present lessons learned in implementing and evaluating complex transitional care interventions in routine clinical care. RESEARCH DESIGN: Nine transitional care study teams share important common lessons in designing complex interventions with stakeholder engagement, implementation, and evaluation under pragmatic conditions (ie, using only existing resources), and disseminating findings in outlets that reach policy makers and the people who could ultimately benefit from the research. RESULTS: Lessons learned serve as a guide for future studies in 3 areas: (1) Delineating the function (intended purpose) versus form (prespecified modes of delivery of the intervention); (2) Evaluating both the processes supporting implementation and the impact of adaptations; and (3) Engaging stakeholders in the design and delivery of the intervention and dissemination of study results. CONCLUSION: These lessons can help guide future pragmatic studies of care transitions.


Assuntos
Pesquisa sobre Serviços de Saúde/métodos , Avaliação de Resultados da Assistência ao Paciente , Segurança do Paciente/normas , Garantia da Qualidade dos Cuidados de Saúde/métodos , Cuidado Transicional/normas , Academias e Institutos , Humanos , Ciência da Implementação
6.
Arch Phys Med Rehabil ; 102(3): 532-542, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33263286

RESUMO

The purpose of this Special Communication is to discuss the rationale and design of the Movement Matters Activity Program for Stroke (MMAP) and explore implementation successes and challenges in home health and outpatient therapy practices across the stroke belt state of North Carolina. MMAP is an interventional component of the Comprehensive Postacute Stroke Services Study, a randomized multicenter pragmatic trial of stroke transitional care. MMAP was designed to maximize survivor health, recovery, and functional independence in the community and to promote evidence-based rehabilitative care. MMAP provided training, tools, and resources to enable rehabilitation providers to (1) prescribe physical activity and exercise according to evidence-based guidelines and programs, (2) match service setting and parameters with survivor function and benefit coverage, and (3) align treatment with quality metric reporting to demonstrate value-based care. MMAP implementation strategies were aligned with the Expert Recommendations for Implementing Change project, and MMAP site champion and facilitator survey feedback were thematically organized into the Consolidated Framework for Implementation Research domains. MMAP implementation was challenging, required modification and was affected by provider- and system-level factors. Program and study participation were limited and affected by practice priorities, productivity standards, and stroke patient volume. Sites with successful implementation appeared to have empowered MMAP champions in vertically integrated systems that embraced innovation. Findings from this broad evaluation can serve as a road map for the design and implementation of other comprehensive, complex interventions that aim to bridge the currently disconnected realms of acute care, postacute care, and community resources.


Assuntos
Exercício Físico , Promoção da Saúde , Avaliação de Programas e Projetos de Saúde , Reabilitação do Acidente Vascular Cerebral/métodos , Cuidados Semi-Intensivos , Cuidado Transicional , Humanos , North Carolina , Recuperação de Função Fisiológica
7.
BMC Health Serv Res ; 19(1): 978, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31856808

RESUMO

BACKGROUND: The COMprehensive Post-Acute Stroke Services (COMPASS) pragmatic trial compared the effectiveness of comprehensive transitional care (COMPASS-TC) versus usual care among stroke and transient ischemic attack (TIA) patients discharged home from North Carolina hospitals. We evaluated implementation of COMPASS-TC in 20 hospitals randomized to the intervention using the RE-AIM framework. METHODS: We evaluated hospital-level Adoption of COMPASS-TC; patient Reach (meeting transitional care management requirements of timely telephone and face-to-face follow-up); Implementation using hospital quality measures (concurrent enrollment, two-day telephone follow-up, 14-day clinic visit scheduling); and hospital-level sustainability (Maintenance). Effectiveness compared 90-day physical function (Stroke Impact Scale-16), between patients receiving COMPASS-TC versus not. Associations between hospital and patient characteristics with Implementation and Reach measures were estimated with mixed logistic regression models. RESULTS: Adoption: Of 95 eligible hospitals, 41 (43%) participated in the trial. Of the 20 hospitals randomized to the intervention, 19 (95%) initiated COMPASS-TC. Reach: A total of 24% (656/2751) of patients enrolled received a billable TC intervention, ranging from 6 to 66% across hospitals. IMPLEMENTATION: Of eligible patients enrolled, 75.9% received two-day calls (or two attempts) and 77.5% were scheduled/offered clinic visits. Most completed visits (78% of 975) occurred within 14 days. Effectiveness: Physical function was better among patients who attended a 14-day visit versus those who did not (adjusted mean difference: 3.84, 95% CI 1.42-6.27, p = 0.002). Maintenance: Of the 19 adopting hospitals, 14 (74%) sustained COMPASS-TC. CONCLUSIONS: COMPASS-TC implementation varied widely. The greatest challenge was reaching patients because of system difficulties maintaining consistent delivery of follow-up visits and patient preferences to pursue alternate post-acute care. Receiving COMPASS-TC was associated with better functional status. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT02588664. Registered 28 October 2015.


Assuntos
Ataque Isquêmico Transitório/terapia , Acidente Vascular Cerebral/terapia , Cuidado Transicional/economia , Feminino , Hospitais/estatística & dados numéricos , Humanos , Ciência da Implementação , Ataque Isquêmico Transitório/economia , Masculino , Pessoa de Meia-Idade , North Carolina , Alta do Paciente/economia , Serviços Postais/economia , Acidente Vascular Cerebral/economia , Cuidados Semi-Intensivos/economia , Telefone/economia
8.
Prostate ; 78(5): 321-326, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29356034

RESUMO

BACKGROUND: African Americans have both a higher incidence of prostate cancer and greater disease-specific mortality compared with non-Hispanic whites. Historically, the investigation of the contribution of rare genetic variants to prostate cancer in African American men has been hampered by low participation in large genetic studies, particularly those focused on early-onset and familial disease. METHODS: We sequenced 160 genes purported to be involved in carcinogenic pathways in germline DNA samples collected from 96 African American men diagnosed with early-onset prostate cancer (≤55 years at diagnosis). REVEL software was used to determine the pathogenic potential of observed missense variants. RESULTS: We observed three protein-truncating mutations, one in BRCA2 and two in BRIP1 in three African American men diagnosed with early-onset prostate cancer. Furthermore, we observed five rare, mostly private, missense variants among four genes (BRCA1, BRCA2, PMS2, and ATM) that were predicted to be deleterious and hence likely pathogenic in our patient sample. CONCLUSIONS: Protein-truncating mutations in BRCA2 and BRIP1 were discovered in African American men diagnosed with early-onset prostate cancer. Further study is necessary to determine the role of rare, missense variants to prostate cancer incidence, and progression in this group of high-risk men.


Assuntos
Negro ou Afro-Americano/genética , Mutação em Linhagem Germinativa , Neoplasias da Próstata/genética , Adulto , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteína BRCA2/genética , DNA de Neoplasias/genética , Proteínas de Grupos de Complementação da Anemia de Fanconi/genética , Humanos , Masculino , Pessoa de Meia-Idade , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Mutação de Sentido Incorreto , Neoplasias da Próstata/etnologia , RNA Helicases/genética
10.
Arch Phys Med Rehabil ; 99(6): 1077-1089.e7, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-28389108

RESUMO

OBJECTIVE: To identify predictors of therapist use (any use, continuity of care, timing of care) in the acute care hospital and community (home or outpatient) for patients discharged home after stroke. DESIGN: Retrospective cohort analysis of Medicare claims (2010-2013) linked to hospital-level and county-level data. SETTING: Acute care hospital and community. PARTICIPANTS: Patients (N=23,413) who survived the first 30 days at home after being discharged from an acute care hospital after stroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Physical and occupational therapist use in acute care and community settings; continuity of care across the inpatient and home or the inpatient and outpatient settings; and early therapist use in the home or outpatient setting. Multivariate logistic and multinomial logistic regression analyses were conducted to identify hospital-level, county-level, and sociodemographic characteristics associated with therapist use, continuity, and timing, controlling for clinical characteristics. RESULTS: Seventy-eight percent of patients received therapy in the acute care hospital, but only 40.8% received care in the first 30 days after discharge. Hospital nurse staffing was positively associated with inpatient and outpatient therapist use and continuity of care across settings. Primary care provider supply was associated with inpatient and outpatient therapist use, continuity of care, and early therapist care in the home and outpatient setting. Therapist supply was associated with continuity of care and early therapist use in the community. There was consistent evidence of sociodemographic disparities in therapist use. CONCLUSIONS: Therapist use after stroke varies in the community and for specific sociodemographic subgroups and may be underused. Inpatient nurse staffing levels and primary care provider supply were the most consistent predictors of therapist use, continuity of care, and early therapist use.


Assuntos
Continuidade da Assistência ao Paciente/estatística & dados numéricos , Terapia Ocupacional/estatística & dados numéricos , Cooperação do Paciente/estatística & dados numéricos , Modalidades de Fisioterapia/estatística & dados numéricos , Reabilitação do Acidente Vascular Cerebral/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Avaliação da Deficiência , Feminino , Humanos , Modelos Logísticos , Masculino , Medicare/estatística & dados numéricos , Alta do Paciente/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Grupos Raciais , Características de Residência , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Estados Unidos
11.
Cancer ; 123(20): 3925-3932, 2017 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-28657667

RESUMO

BACKGROUND: Prostate cancer has a significant heritable component, and rare deleterious germline variants in certain genes can increase the risk of the disease. The aim of the current study was to describe the prevalence of pathogenic germline variants in cancer-predisposing genes in men with prostate cancer and at least 1 additional primary cancer. METHODS: Using a multigene panel, the authors sequenced germline DNA from 102 men with prostate cancer and at least 1 additional primary cancer who also met ≥1 of the following criteria: 1) age ≤55 years at the time of diagnosis of the first malignancy; 2) rare tumor type or atypical presentation of a common tumor; and/or 3) ≥3 primary malignancies. Cancer family history and clinicopathologic data were independently reviewed by a clinical genetic counselor to determine whether the patient met established criteria for testing for a hereditary cancer syndrome. RESULTS: Sequencing identified approximately 3500 variants. Nine protein-truncating deleterious mutations were found across 6 genes, including BRCA2, ataxia telangiectasia mutated (ATM), mutL homolog 1 (MLH1), BRCA1 interacting protein C-terminal helicase 1 (BRIP1), partner and localizer of BRCA2 (PALB2), and fibroblast growth factor receptor 3 (FGFR3). Likely pathogenic missense variants were identified in checkpoint kinase 2 (CHEK2) and homeobox protein Hox-B13 (HOXB13). In total, 11 of 102 patients (10.8%) were found to have pathogenic or likely pathogenic mutations in cancer-predisposing genes. The majority of these men (64%) did not meet current clinical criteria for germline testing. CONCLUSIONS: Men with prostate cancer and at least 1 additional primary cancer are enriched for harboring a germline deleterious mutation in a cancer-predisposing gene that may impact cancer prognosis and treatment, but the majority do not meet current criteria for clinical genetic testing. Cancer 2017;123:3925-32. © 2017 American Cancer Society.


Assuntos
Mutação em Linhagem Germinativa , Segunda Neoplasia Primária/genética , Síndromes Neoplásicas Hereditárias/genética , Neoplasias da Próstata/genética , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteína BRCA2/genética , Quinase do Ponto de Checagem 2/genética , Análise Mutacional de DNA , Proteínas de Ligação a DNA/genética , Proteína do Grupo de Complementação N da Anemia de Fanconi , Proteínas de Grupos de Complementação da Anemia de Fanconi , Predisposição Genética para Doença , Proteínas de Homeodomínio/genética , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL/genética , Mutação de Sentido Incorreto , Síndromes Neoplásicas Hereditárias/diagnóstico , Proteínas Nucleares/genética , RNA Helicases/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Análise de Sequência de DNA , Proteínas Supressoras de Tumor/genética
12.
BMC Neurol ; 17(1): 133, 2017 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-28716014

RESUMO

BACKGROUND: Patients discharged home after stroke face significant challenges managing residual neurological deficits, secondary prevention, and pre-existing chronic conditions. Post-discharge care is often fragmented leading to increased healthcare costs, readmissions, and sub-optimal utilization of rehabilitation and community services. The COMprehensive Post-Acute Stroke Services (COMPASS) Study is an ongoing cluster-randomized pragmatic trial to assess the effectiveness of a comprehensive, evidence-based, post-acute care model on patient-centered outcomes. METHODS: Forty-one hospitals in North Carolina were randomized (as 40 units) to either implement the COMPASS care model or continue their usual care. The recruitment goal is 6000 patients (3000 per arm). Hospital staff ascertain and enroll patients discharged home with a clinical diagnosis of stroke or transient ischemic attack. Patients discharged from intervention hospitals receive 2-day telephone follow-up; a comprehensive clinic visit within 2 weeks that includes a neurological evaluation, assessments of social and functional determinants of health, and an individualized COMPASS Care Plan™ integrated with a community-specific resource database; and additional follow-up calls at 30 and 60 days post-stroke discharge. This model is consistent with the Centers for Medicare and Medicaid Services transitional care management services provided by physicians or advanced practice providers with support from a nurse to conduct patient assessments and coordinate follow-up services. Patients discharged from usual care hospitals represent the control group and receive the standard of care in place at that hospital. Patient-centered outcomes are collected from telephone surveys administered at 90 days. The primary endpoint is patient-reported functional status as measured by the Stroke Impact Scale 16. Secondary outcomes are: caregiver strain, all-cause readmissions, mortality, healthcare utilization, and medication adherence. The study engages patients, caregivers, and other stakeholders (including policymakers, advocacy groups, payers, and local community coalitions) to advise and support the design, implementation, and sustainability of the COMPASS care model. DISCUSSION: Given the high societal and economic burden of stroke, identifying a care model to improve recovery, independence, and quality of life is critical for stroke survivors and their caregivers. The pragmatic trial design provides a real-world assessment of the COMPASS care model effectiveness and will facilitate rapid implementation into clinical practice if successful. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02588664 ; October 23, 2015.


Assuntos
Ataque Isquêmico Transitório/reabilitação , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/terapia , Cuidadores , Humanos , Avaliação de Resultados em Cuidados de Saúde , Alta do Paciente , Qualidade de Vida , Prevenção Secundária/métodos , Sobreviventes
13.
Prostate ; 74(9): 983-90, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24796539

RESUMO

BACKGROUND: Family history of prostate cancer is a well-recognized risk factor. Previous linkage studies have reported a putative prostate cancer susceptibility locus at chromosome 17q21-22. SPOP (Speckle-type POZ protein) maps to the 17q21-22 candidate linkage region and is one of the most frequently mutated genes in sporadic prostate cancers. METHODS: We performed targeted next generation sequencing to analyze 2009 exons from 202 genes in a candidate linkage region on chromosome 17q21-22 using 94 unrelated familial prostate cancer cases from the University of Michigan Prostate Cancer Genetics Project (n=54) and Johns Hopkins University (n=40) including the exons and UTRs of SPOP. RESULTS: We identified a novel SPOP missense mutation (N296I) in a man with prostate cancer diagnosed at age 43. This mutation completely segregates with prostate cancer affection status among the men in this family. The N296I mutation resides within the evolutionarily conserved Bric-a-brac, Tramtrack, Broad-complex (BTB) domain, involved in recruiting targets to Cul3 for degradation. Analysis of the prostate tumor from this individual verified the presence of heterozygous N296I as well as an ERG fusion. CONCLUSIONS: We have discovered a novel mutation in SPOP that tracks with prostate cancer within a family and is predicted to be deleterious. Taken together, our results implicate SPOP as a candidate gene for hereditary prostate cancer.


Assuntos
Cromossomos Humanos Par 17 , Mutação em Linhagem Germinativa , Proteínas Nucleares/genética , Neoplasias da Próstata/genética , Proteínas Repressoras/genética , Adulto , DNA de Neoplasias/química , DNA de Neoplasias/genética , Saúde da Família , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Masculino , Mutação de Sentido Incorreto , Linhagem , Neoplasias da Próstata/metabolismo
14.
Prostate ; 74(14): 1371-8, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25111073

RESUMO

BACKGROUND: Family history is a major risk factor for prostate cancer (PCa), suggesting a genetic component to the disease. However, traditional linkage and association studies have failed to fully elucidate the underlying genetic basis of familial PCa. METHODS: Here, we use a candidate gene approach to identify potential PCa susceptibility variants in whole exome sequencing data from familial PCa cases. Six hundred ninety-seven candidate genes were identified based on function, location near a known chromosome 17 linkage signal, and/or previous association with prostate or other cancers. Single nucleotide variants (SNVs) in these candidate genes were identified in whole exome sequence data from 33 PCa cases from 11 multiplex PCa families (3 cases/family). RESULTS: Overall, 4,856 candidate gene SNVs were identified, including 1,052 missense and 10 nonsense variants. Twenty missense variants were shared by all three family members in each family in which they were observed. Additionally, 15 missense variants were shared by two of three family members and predicted to be deleterious by five different algorithms. Four missense variants, BLM Gln123Arg, PARP2 Arg283Gln, LRCC46 Ala295Thr and KIF2B Pro91Leu, and one nonsense variant, CYP3A43 Arg441Ter, showed complete co-segregation with PCa status. Twelve additional variants displayed partial co-segregation with PCa. CONCLUSIONS: Forty-three nonsense and shared, missense variants were identified in our candidate genes. Further research is needed to determine the contribution of these variants to PCa susceptibility.


Assuntos
Códon sem Sentido , Mutação de Sentido Incorreto , Neoplasias da Próstata/genética , Idoso , Exoma , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade
15.
BJU Int ; 113(5): 830-5, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24148311

RESUMO

OBJECTIVE: To determine the prevalence and clinical correlates of the G84E mutation in the homeobox transcription factor, or HOXB13, gene using DNA samples from 9559 men with prostate cancer undergoing radical prostatectomy. PATIENTS AND METHODS: DNA samples from men treated with radical prostatectomy at the University of Michigan and John Hopkins University were genotyped for G84E and this was confirmed by Sanger sequencing. The frequency and distribution of this allele was determined according to specific patient characteristics (family history, age at diagnosis, pathological Gleason grade and stage). RESULTS: Of 9559 patients, 128 (1.3%) were heterozygous carriers of G84E. Patients who possessed the variant were more likely to have a family history of prostate cancer than those who did not (46.0 vs 35.4%; P = 0.006). G84E carriers were also more likely to be diagnosed at a younger age than non-carriers (55.2 years vs 58.1 years; P < 0.001). No difference in the proportion of patients diagnosed with high grade or advanced stage tumours according to carrier status was observed. CONCLUSIONS: In the present study, carriers of the rare G84E variant in HOXB13 were both younger at the time of diagnosis and more likely to have a family history of prostate cancer compared with homozygotes for the wild-type allele. No significant differences in allele frequency were detected according to selected clinical characteristics of prostate cancer. Further investigation is required to evaluate the role of HOXB13 in prostate carcinogenesis.


Assuntos
DNA/genética , Proteínas de Homeodomínio/genética , Mutação , Prostatectomia/métodos , Neoplasias da Próstata/genética , Adulto , Idoso , Alelos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Análise Mutacional de DNA , Seguimentos , Predisposição Genética para Doença , Genótipo , Proteínas de Homeodomínio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia
16.
Resusc Plus ; 17: 100554, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38317722

RESUMO

Importance: Out-of-hospital cardiac arrest (OHCA) is a leading cause of morbidity and mortality in the US and Europe (∼600,000 incident events annually) and around the world (∼3.8 million). With every minute that passes without cardiopulmonary resuscitation or defibrillation, the probability of survival decreases by 10%. Preliminary studies suggest that uncrewed aircraft systems, also known as drones, can deliver automated external defibrillators (AEDs) to OHCA victims faster than ground transport and potentially save lives. Objective: To date, the United States (US), Sweden, and Canada have made significant contributions to the knowledge base regarding AED-equipped drones. The purpose of this Special Communication is to explore the challenges and facilitators impacting the progress of AED-equipped drone integration into emergency medicine research and applications in the US, Sweden, and Canada. We also explore opportunities to propel this innovative and important research forward. Evidence review: In this narrative review, we summarize the AED-drone research to date from the US, Sweden, and Canada, including the first drone-assisted delivery of an AED to an OHCA. Further, we compare the research environment, emergency medical systems, and aviation regulatory environment in each country as they apply to OHCA, AEDs, and drones. Finally, we provide recommendations for advancing research and implementation of AED-drone technology into emergency care. Findings: The rates that drone technologies have been integrated into both research and real-life emergency care in each country varies considerably. Based on current research, there is significant potential in incorporating AED-equipped drones into the chain of survival for OHCA emergency response. Comparing the different environments and systems in each country revealed ways that each can serve as a facilitator or barrier to future AED-drone research. Conclusions and relevance: The US, Sweden, and Canada each offers different challenges and opportunities in this field of research. Together, the international community can learn from one another to optimize integration of AED-equipped drones into emergency systems of care.

17.
Circ Cardiovasc Qual Outcomes ; 17(1): e010026, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38189125

RESUMO

BACKGROUND: Few studies on care transitions following acute stroke have evaluated whether referral to community-based rehabilitation occurred as part of discharge planning. Our objectives were to describe the extent to which patients discharged home were referred to community-based rehabilitation and identify the patient, hospital, and community-level predictors of referral. METHODS: We examined data from 40 North Carolina hospitals that participated in the COMPASS (Comprehensive Post-Acute Stroke Services) cluster-randomized trial. Participants included adults discharged home following stroke or transient ischemic attack (N=10 702). In this observational analysis, COMPASS data were supplemented with hospital-level and county-level data from various sources. The primary outcome was referral to community-based rehabilitation (physical, occupational, or speech therapy) at discharge. Predictor variables included patient (demographic, stroke-related, medical history), hospital (structure, process), and community (therapist supply) measures. We used generalized linear mixed models with a hospital random effect and hierarchical backward model selection procedures to identify predictors of therapy referral. RESULTS: Approximately, one-third (36%) of stroke survivors (mean age, 66.8 [SD, 14.0] years; 49% female, 72% White race) were referred to community-based rehabilitation. Rates of referral to physical, occupational, and speech therapists were 31%, 18%, and 10%, respectively. Referral rates by hospital ranged from 3% to 78% with a median of 35%. Patient-level predictors included higher stroke severity, presence of medical comorbidities, and older age. Female sex (odds ratio, 1.24 [95% CI, 1.12-1.38]), non-White race (2.20 [2.01-2.44]), and having Medicare insurance (1.12 [1.02-1.23]) were also predictors of referral. Referral was higher for patients living in counties with greater physical therapist supply. Much of the variation in referral across hospitals remained unexplained. CONCLUSIONS: One-third of stroke survivors were referred to community-based rehabilitation. Patient-level factors predominated as predictors. Variation across hospitals was notable and presents an opportunity for further evaluation and possible targets for improved poststroke rehabilitative care. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02588664.


Assuntos
Ataque Isquêmico Transitório , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Adulto , Humanos , Feminino , Idoso , Estados Unidos , Masculino , Medicare , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Ataque Isquêmico Transitório/terapia , Alta do Paciente , Encaminhamento e Consulta
18.
Hum Genet ; 132(1): 5-14, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23064873

RESUMO

Prostate cancer has a strong familial component but uncovering the molecular basis for inherited susceptibility for this disease has been challenging. Recently, a rare, recurrent mutation (G84E) in HOXB13 was reported to be associated with prostate cancer risk. Confirmation and characterization of this finding is necessary to potentially translate this information to the clinic. To examine this finding in a large international sample of prostate cancer families, we genotyped this mutation and 14 other SNPs in or flanking HOXB13 in 2,443 prostate cancer families recruited by the International Consortium for Prostate Cancer Genetics (ICPCG). At least one mutation carrier was found in 112 prostate cancer families (4.6 %), all of European descent. Within carrier families, the G84E mutation was more common in men with a diagnosis of prostate cancer (194 of 382, 51 %) than those without (42 of 137, 30 %), P = 9.9 × 10(-8) [odds ratio 4.42 (95 % confidence interval 2.56-7.64)]. A family-based association test found G84E to be significantly over-transmitted from parents to affected offspring (P = 6.5 × 10(-6)). Analysis of markers flanking the G84E mutation indicates that it resides in the same haplotype in 95 % of carriers, consistent with a founder effect. Clinical characteristics of cancers in mutation carriers included features of high-risk disease. These findings demonstrate that the HOXB13 G84E mutation is present in ~5 % of prostate cancer families, predominantly of European descent, and confirm its association with prostate cancer risk. While future studies are needed to more fully define the clinical utility of this observation, this allele and others like it could form the basis for early, targeted screening of men at elevated risk for this common, clinically heterogeneous cancer.


Assuntos
Proteínas de Homeodomínio/genética , Neoplasias da Próstata/genética , Substituição de Aminoácidos , Estudos de Coortes , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Heterozigoto , Humanos , Agências Internacionais , Masculino , Mutação de Sentido Incorreto , Polimorfismo de Nucleotídeo Único , População Branca/genética
19.
Top Stroke Rehabil ; 30(5): 436-447, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-35603644

RESUMO

BACKGROUND: Stroke patients discharged home often require prolonged assistance from caregivers. Little is known about the real-world effectiveness of a comprehensive stroke transitional care intervention on relieving caregiver strain. OBJECTIVES: To describe the effect of the COMPASS transitional care (COMPASS-TC) intervention on caregiver strain and characterize the types, duration, and intensity of caregiving. METHODS: The cluster-randomized COMPASS pragmatic trial evaluated the effectiveness of COMPASS-TC versus usual care with patients with mild stroke and TIA at 40 hospitals in North Carolina, USA. Of 5882 patients enrolled, 4208 (71%) identified a familial caregiver. A follow-up Caregiver Questionnaire, including the Modified Caregiver Strain Index, was administered at approximately three months post-discharge. Demographics and frequency, duration, and intensity of caregiving were compared between groups. RESULTS: 1228 caregivers (29%) completed the questionnaire. Completion was positively associated with older patient age, white race, and spousal relationship. One-third of the caregivers provided ≥30 hours of care per week and 889 (79%) provided care ≥9 weeks. Average standardized caregiver strain was 21.9 (0-100), increasing with stroke severity and comorbidity burden. Women caregivers reported higher strain than men. Treatment allocation was not associated with caregiver strain. CONCLUSIONS: This sample of mild stroke and TIA survivors received significant assistance from familial caregivers. However, caregiver strain was relatively low. Findings support the importance of familial caregiving in stroke, the continued disproportionate burden on women within the family, and the need for future research on caregiver support.


Assuntos
Ataque Isquêmico Transitório , Acidente Vascular Cerebral , Cuidado Transicional , Feminino , Humanos , Masculino , Assistência ao Convalescente , Ataque Isquêmico Transitório/terapia , Alta do Paciente , Acidente Vascular Cerebral/terapia
20.
Curr HIV/AIDS Rep ; 9(4): 335-43, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22890780

RESUMO

Due to the co-occurrence of sexual risk behaviors and substance use among HIV-positive individuals, there is often a need for HIV prevention efforts to target multiple behaviors. Motivational Interviewing (MI), a widely disseminated behavior change intervention, has demonstrated effectiveness in promoting behavior change among persons with HIV and has been utilized to target these co-occurring risk behaviors. To identify the efficacy of MI in relation to sexual risk and substance use, we conducted a systematic review of research literature published before May 2012, which focused on treatment fidelity, study design, and findings. Results suggest that MI has the potential to reduce sexual risk behavior, but the effects on reducing substance use were less consistent. We identify opportunities for future research with HIV-positive individuals, including the development of interventions assessing the effects of MI on illicit drug use, utilizing higher fidelity standards in intervention implementation and studies of transportability and cost-effectiveness.


Assuntos
Síndrome da Imunodeficiência Adquirida , Soropositividade para HIV , Entrevista Motivacional , Comportamento de Redução do Risco , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/prevenção & controle , Síndrome da Imunodeficiência Adquirida/transmissão , Adulto , Feminino , Soropositividade para HIV/epidemiologia , Soropositividade para HIV/transmissão , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Comportamento Sexual , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
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