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1.
Artigo em Inglês | MEDLINE | ID: mdl-38564795

RESUMO

BACKGROUND: Patients treated at a health safety-net hospital have increased medical complexity and social determinants of health that are associated with an increasing risk of complications after TKA and THA. Fast-track rapid recovery protocols (RRPs) are associated with reduced complications and length of stay in the general population; however, whether that is the case among patients who are socioeconomically disadvantaged in health safety-net hospitals remains poorly defined. QUESTIONS/PURPOSES: When an RRP protocol is implemented in a health safety-net hospital after TKA and THA: (1) Was there an associated change in complications, specifically infection, symptomatic deep venous thromboembolism (DVT), symptomatic pulmonary embolism (PE), myocardial infarction (MI), and mortality? (2) Was there an associated difference in inpatient opioid consumption? (3) Was there an associated difference in length of stay and 90-day readmission rate? (4) Was there an associated difference in discharge disposition? METHODS: An observational study with a historical control group was conducted in an urban, academic, tertiary-care health safety-net hospital. Between May 2022 and April 2023, an RRP consistent with current guidelines was implemented for patients undergoing TKA or THA for arthritis. We considered all patients aged 18 to 90 years presenting for primary TKA and THA as eligible. Based on these criteria, 562 patients with TKAs or THAs were eligible. Of these 33% (183) were excluded because they were lost before 90 days of follow-up and had incomplete datasets, leaving 67% (379) for evaluation. Patients in the historical control group (September 2014 to May 2022) met the same criteria, and 2897 were eligible. Of these, 31% (904) were excluded because they were lost before 90 days of follow-up and had incomplete datasets, leaving 69% (1993) for evaluation. The mean age in the historical control group was 61 ± 10 years and 63 ± 10 years in the RRP group. Both groups were 36% (725 of 1993 and 137 of 379) men. In the historical control group, 39% (770 of 1993) of patients were Black and 33% (658 of 1993) were White, compared with 38% (142 of 379) and 32% (121 of 379) in the RRP group, respectively. English was the most-spoken primary language, by 69% (1370 of 1993) and 68% (256 of 379) of the historical and RRP groups, respectively. A total of 65% (245 of 379) of patients in the RRP group had a peripheral nerve block compared with 54% (1070 of 1993) in the historical control group, and 39% (147 of 379) of them received spinal anesthesia, compared with 31% (615 of 1993) in the historical control group. The main elements of the RRP were standardization of preoperative visits, nutritional management, neuraxial anesthesia, accelerated physical therapy, and pain management. The primary outcomes were the proportions of patients with 90-day complications and opioid consumption. The secondary outcomes were length of stay, 90-day readmission, and discharge disposition. A multivariate analysis adjusting for age, BMI, gender, race, American Society of Anaesthesiologists class, and anesthesia type was performed by a staff biostatistician using R statistical programming. RESULTS: After controlling for the confounding variables as noted, patients in the RRP group had fewer complications after TKA than those in the historical control group (odds ratio 2.0 [95% confidence interval 1.3 to 3.3]; p = 0.005), and there was a trend toward fewer complications in THA (OR 1.8 [95% CI 1.0 to 3.5]; p = 0.06), decreased opioid consumption during admission (517 versus 676 morphine milligram equivalents; p = 0.004), decreased 90-day readmission (TKA: OR 1.9 [95% CI 1.3 to 2.9]; p = 0.002; THA: OR 2.0 [95% CI 1.6 to 3.8]; p = 0.03), and increased proportions of discharge to home (TKA: OR 2.4 [95% CI 1.6 to 3.6]; p = 0.01; THA: OR 2.5 [95% CI 1.5 to 4.6]; p = 0.002). Patients in the RRP group had no difference in the mean length of stay (TKA: 3.2 ± 2.6 days versus 3.1 ± 2.0 days; p = 0.64; THA: 3.2 ± 2.6 days versus 2.8 ± 1.9 days; p = 0.33). CONCLUSION: Surgeons should consider developing an RRP in health safety-net hospitals. Such protocols emphasize preparing patients for surgery and supporting them through the acute recovery phase. There are possible benefits of neuraxial and nonopioid perioperative anesthesia, with emphasis on early mobility, which should be further characterized in comparative studies. Continued analysis of opioid use trends after discharge would be a future area of interest. Analysis of RRPs with expanded inclusion criteria should be undertaken to better understand the role of these protocols in patients who undergo revision TKA and THA. LEVEL OF EVIDENCE: Level III, therapeutic study.

2.
Phys Sportsmed ; : 1-5, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37800896

RESUMO

OBJECTIVE: Despite an equal willingness to participate in clinical trials, there is evidence that several minority populations are systematically under-represented in studies. One potential cause and frequently used exclusionary criterion in orthopedic trials is patients with active workman's compensation (WC) insurance claims. The purpose of this study is to determine demographic differences in patients undergoing arthroscopic rotator cuff repair with commercial and government insurance vs workers compensation claims. METHODS: This was a retrospective review of patients who underwent primary arthroscopic rotator cuff repair at a single institution in the northeastern United States from 2018 to 2019. Patients undergoing revision cases were excluded. Chart review was used to extract demographic data such as age, gender, insurance, and reported race. RESULTS: A total of 4553 patient records were reviewed and included. There were 742 WC patients and 3811 non-WC patients. Two hundred and forty-four patients did not report their race. Overall, WC patients differed from non-WC with respect to race (P < 0.001). One hundred and eleven (15.0%) of WC and 293 (7.7%) non-WC patients reported being 'Black' or 'African American' (P = 0.002). This compares to 368 (49.6%) WC and 2788 (73.2%) non-WC patients who reported 'White' (P < 0.001). About 16.8% of WC patients were identified as 'Hispanic or Latino,' compared to 5.2% of non-WC (P < 0.001). CONCLUSION: African American and Hispanic/Latino patients are over-represented in workman's compensation patient populations relative to non-workman's compensation. Conversely, white patients are over-represented in non-WC patient populations, which serve as the basis for the majority of clinical study populations. Excluding workman's compensation patients from clinical trials may lead to an underrepresentation of African American and Hispanic/Latino patient populations in orthopedic clinical trials. In doing so, the generalizability of the results of rotator cuff repair clinical outcomes research to all races and ethnicities may be compromised.

3.
J Clin Transl Sci ; 7(1): e174, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37654777

RESUMO

Introduction: Midcareer is a critical transition point for biomedical research faculty and a common dropout point from an NIH-funded career. We report a study to assess the efficacy of a group peer mentoring program for diverse biomedical researchers in academic medicine, seeking to improve vitality, career advancement, and cross-cultural competence. Methods: We conducted a stratified randomized controlled trial with a waitlist control group involving 40 purposefully diverse early midcareer research faculty from 16 states who had a first-time NIH R01 (or equivalent) award, a K training grant, or a similar major grant. The yearlong intervention (2 to 3 days quarterly) consisted of facilitated, structured, group peer mentoring. Main study aims were to enhance faculty vitality, self-efficacy in achieving research success, career advancement, mentoring others, and cultural awareness and appreciation of diversity in the workplace. Results: Compared to the control group, the intervention group's increased vitality did not reach statistical significance (P = 0.20), but perceived change in vitality was 1.47 standard deviations higher (D = 1.47, P = 0.03). Self-efficacy for career advancement was higher in the intervention group (D = 0.41, P = 0.05) as was self-efficacy for research (D = 0.57, P = 0.02). The intervention group also valued diversity higher (D = 0.46, P = 0.02), had higher cognitive empathy (D = 0.85, P = 0.03), higher anti-sexism/racism skills (D = 0.71, P = 0.01), and higher self-efficacy in mentoring others (D = 1.14, P = 0.007). Conclusions: The mentoring intervention resulted in meaningful change in important dimensions and skills among a national sample of diverse early midcareer biomedical faculty. This mentoring program holds promise for addressing the urgencies of sustaining faculty vitality and cross-cultural competence.

4.
Arthroplast Today ; 23: 101194, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37745953

RESUMO

Background: Patients undergoing total joint arthroplasty (TJA) are at increased risk for venous thromboembolism (VTE). Prediction tools such as the Caprini Risk Assessment Model (RAM) have been developed to identify patients at higher risk. However, studies have reported heterogeneous results when assessing its efficacy for TJA. Patients treated in an urban health safety net hospital have increased medical complexity, advanced degenerative joint disease, and severe disability prior to TJA increasing the risk of VTE. We hypothesize that use of a tool designed to account for these conditions-the Boston Medical Center (BMC) VTE score-will more accurately predict VTE in this patient population. Methods: A retrospective case-control study was performed including subjects 18 years of age and older who underwent primary or revision TJA in an urban academic health safety net hospital. Patients with hemiarthroplasties, simultaneous bilateral TJA, and TJA after acute trauma were excluded. A total of 80 subjects were included: 40 who developed VTE after TJA (VTE+) and 40 who did not develop VTE (controls). Subjects were matched by age, gender, and surgical procedure. Results: There was a statistically significant difference between the mean BMC VTE score for VTE+ and controls (4.40 and 3.13, respectively, P = .036). Conversely, there was no statistical difference between the mean Caprini scores for VTE+ and controls (9.50 and 9.35, respectively, P = .797). Conclusions: In a health safety-net patient population, an institutional RAM-the BMC VTE score-was found to be more predictive of VTE than the modified Caprini RAM following TJA. The BMC-VTE score should be externally validated to confirm its reliability in VTE prediction in similar patient populations.

5.
Orthop J Sports Med ; 11(4): 23259671231157380, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37123993

RESUMO

Background: The coronavirus disease-2019 (COVID-19) pandemic led to disruptions in care for orthopaedic patients who underwent surgery just before the outbreak, rendering some unable to participate in standard postoperative care. Many of these patients underwent clinical follow-up and physical therapy via telehealth. Purpose: To evaluate the methods of postoperative care in patients who underwent arthroscopic rotator cuff repair (RCR) and had follow-ups during the height of the pandemic versus those who received prior standard of care. We aimed to compare the 1-year outcomes between these cohorts. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective chart review was used to identify patients who underwent primary RCR in February and March 2020 (COVID cohort) and the same period in 2019 (control cohort) at a single institution. Excluded were patients who underwent revision RCR, used workers' compensation, or were incarcerated or deceased. The included patients reported the postoperative care received, their satisfaction with care, physical therapy appointment type (in person, home based, telehealth, or self-guided), satisfaction with physical therapy, and minimum 1-year postoperative American Shoulder and Elbow Surgeons (ASES), Single Assessment Numeric Evaluation (SANE), and Penn Shoulder Score (PSS) outcomes. Results: Overall, 428 patients were included for final analysis--199 in the COVID cohort and 229 controls. Follow-up data were collected for 160 patients in the COVID group (80.4%) and 169 control patients (73.8%). In the COVID group, 110 patients (68.8%) had ≥1 clinical visit conducted via telehealth, compared with zero in the control group. There were no differences between the COVID and control groups in the ASES (84.2 ± 16.5 vs 86.5 ± 17; P = .27 ), SANE (83.9 ± 15.4 vs 84.8 ± 17.5; P = .66), PSS (84.8 ± 15.3 vs 87.1 ± 15.1; P = .22), or patient satisfaction with the care received (81.7 ± 22.6 vs 86.3 ± 23.5; P = .09). Satisfaction with physical therapy was significantly higher in the control group (88.3 ± 18.9 vs 81.9 ± 22.5; P = .01). Conclusion: Despite disruptions in care, RCR patients had comparable 1-year outcomes during the pandemic versus before the pandemic. Telehealth clinical follow-up appointments did not adversely affect patient-reported outcome measures and may be appropriate for RCR patients beyond the pandemic.

6.
J Clin Transl Sci ; 7(1): e105, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37251000

RESUMO

Introduction: Midcareer research faculty are a vital part of the advancement of science in U.S. medical schools, but there are troubling trends in recruitment, retention, and burnout rates. Methods: The primary sampling frame for this online survey was recipients of a single R01 or equivalent and/or K-award from 2013 to 2019. Inclusion criteria were 3-14 years at a U.S. medical school and rank of associate professor or two or more years as assistant professor. Forty physician investigators and Ph.D. scientists volunteered for a faculty development program, and 106 were propensity-matched controls. Survey items covered self-efficacy in career, research, work-life; vitality/burnout; relationships, inclusion, trust; diversity; and intention to leave academic medicine. Results: The majority (52%) reported receiving poor mentoring; 40% experienced high burnout and 41% low vitality, which, in turn, predicted leaving intention (P < 0.0005). Women were more likely to report high burnout (P = 0.01) and low self-efficacy managing work and personal life (P = 0.01) and to be seriously considering leaving academic medicine than men (P = 0.003). Mentoring quality (P < 0.0005) and poor relationships, inclusion, and trust (P < 0.0005) predicted leaving intention. Non-underrepresented men were very likely to report low identity self-awareness (65%) and valuing differences (24%) versus underrepresented men (25% and 0%; P < 0.0005). Ph.D.s had lower career advancement self-efficacy than M.D.s (P < .0005). Conclusions: Midcareer Ph.D. and physician investigators faced significant career challenges. Experiences diverged by underrepresentation, gender, and degree. Poor quality mentoring was an issue for most. Effective mentoring could address the concerns of this vital component of the biomedical workforce.

7.
Cureus ; 14(2): e22600, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35371739

RESUMO

Purpose This study aimed to determine whether prone cross-body adduction (superman stretch) improves range of motion (ROM) more than the sleeper stretch. Methods Collegiate overhead athletes were randomized to either a sleeper group or a superman stretch group. ROM measurements were collected before and after stretches by three orthopedic surgeons. Results We assessed a total of 212 shoulders. Both stretches demonstrated significant improvements in ROM, except horizontal adduction, which only improved in the superman stretch group. Conclusions The superman stretch may be superior in producing immediate improvements in horizontal adduction when compared to the traditional sleeper stretch.

8.
Phys Sportsmed ; 50(6): 515-521, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-34424824

RESUMO

OBJECTIVE: The SARS-COV2 pandemic led to massive disruptions of care for orthopedic patients. Although many elective procedures were put on hold, a cohort of patients who underwent surgery prior to the outbreak of the pandemic were rendered unable to participate in standard post-operative care. The purpose of this study was to determine the methods of post-operative care in arthroscopic anterior cruciate ligament reconstruction patients who received care during an early height of the pandemic to those who received standard of care in the prior year. We aimed to correlate those results with 1-year clinical outcomes in the form of subjective surveys. METHODS: Retrospective chart review was used to identify patients who underwent primary anterior cruciate ligament reconstruction in February and March of 2020 (case) and 2019 (control) at a single institution. Workman's compensation patients were excluded. Identified patients were asked to report post-operative care received, satisfaction with care, and complete the IKDC and Lysholm outcome measures. Surveys were conducted minimum 1-year post-operative. RESULTS: 236 patients were identified, including 103 in 2020 and 133 in 2019. Follow-up data was collected for 73 patients (70.9%) in 2020 and 97 patients (72.9%) in 2019. Fifty-one COVID cohort patients (69.9%) had at least one clinical visit conducted via telehealth, compared to zero in the control. There were no differences in IKDC (82.8 ± 13.2 vs 85.0 ± 12.0, P = 0.29) and Lysholm (89.2 ± 11.3 vs 89.6 ± 10.8, P = 0.82) between groups. There were no differences in patient satisfaction with the care received (82.9 ± 22.4 vs 81.9 ± 21.8, P = 0.79). CONCLUSION: Despite disruptions in care, anterior cruciate ligament reconstruction patients have excellent 1-year outcomes during the pandemic. Telehealth follow-up appointments may be appropriate for anterior cruciate ligament reconstruction patients beyond the pandemic and do not seem to adversely affect short-term patient reported outcome measures.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , COVID-19 , Humanos , Lesões do Ligamento Cruzado Anterior/epidemiologia , Lesões do Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/etiologia , RNA Viral , Estudos Retrospectivos , Pandemias , COVID-19/epidemiologia , SARS-CoV-2 , Reconstrução do Ligamento Cruzado Anterior/métodos
9.
Acad Med ; 94(9): 1276-1282, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31460915

RESUMO

Academic health centers (AHCs) play a significant role in educating the health care workforce, conducting innovative biomedical and clinical research, and delivering high-quality patient care. Much work remains, however, to adequately address the social determinants of health and equity that affect communities where patients live, work, and play. Doing so will help achieve the Quadruple Aim while addressing the unjust social structures that disproportionately impact communities of color and vulnerable populations. AHCs have a timely opportunity to focus their leading roles in education, research, and clinical care on social determinants, moving outside their walls to create academic-community health systems: a collection of academic-community partnerships advancing health equity through collaboration, power sharing, and cocreation.This Perspective proposes four strategies to start developing academic-community health systems. First, embark on all efforts through cocreation with communities. Second, address how future health care professionals are recruited. Third, build the right skills and opportunities for health care professionals to address health inequities. Finally, develop research agendas to evaluate programs addressing inequities. A fully realized vision of an academic-community health system will demonstrate interdependence between AHCs and the community. While considerable AHC resources are invested in building community capacity to improve health and health equity, health systems will also benefit in a multitude of ways, including increasing the diversity of ideas and experiences integrated into health systems. These strategies will support AHCs to embed across each arm of the tripartite mission a focus on partnering with communities to advance health equity together.


Assuntos
Centros Médicos Acadêmicos/organização & administração , Centros Comunitários de Saúde/organização & administração , Equidade em Saúde/organização & administração , Política de Saúde , Humanos , Estados Unidos
10.
Spine Deform ; 6(6): 662-668, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30348341

RESUMO

STUDY DESIGN: Prospective database review. OBJECTIVES: Determine if use of intraoperative 3D imaging of pedicle screw position provides clinical and cost benefit. SUMMARY OF BACKGROUND: Injury or reoperation from malpositioned pedicle screws in adolescent idiopathic scoliosis (AIS) surgery occurs but is increasingly considered to be a never-event. To avoid complications, intraoperative 3D imaging of screw position may be obtained. METHODS: A prospective, consecutive AIS database at a high-volume pediatric spine center was examined three years before and after implementation of an intraoperative low-dose computed tomographic (CT) scan protocol. All screws were placed via freehand technique and corrected if found to be outside optimal trajectory on the postplacement CT scan. Demographic and outcome data were compared between cohorts, along with number, location, and reason for screw change. Cost analysis was based on the average cost of revision surgery for screw malposition versus intraoperative CT use. RESULTS: There were 153 patients in the pre-CT and 153 in the post-CT cohorts with a minimum 2-year follow-up. Two reoperations were needed for revision of improper screw placement in the pre-CT group and none in the post-CT group. Number of patients needed to harm was 76 (absolute risk increase = 1.31% [-0.49%, 3.11%]). Of those who had intraoperative CT scans, 80 (52.3%) needed on average 1.75 screw trajectories/lengths changed. Forty-three percent were medial breaches; of these, 39% were in the concavity. There were no differences between patients who did and did not need screw repositioning with regard to body mass index (BMI), age, curve size, surgeon/trainee side, screw density, or preoperative and one-year postoperative Scoliosis Research Society-22 patient questionnaire (SRS-22) scores. The average cost of reoperation for malposition was $4,900, whereas the cost of a single intraoperative CT was $232. CONCLUSION: Intraoperative CT is an effective tool to prevent reoperation in AIS surgery for incorrect screw placement. Despite high volume, experience, and specialty training, incorrect trajectories occur and systems should be in place for preventable error. LEVEL OF EVIDENCE: Level II.


Assuntos
Parafusos Pediculares/estatística & dados numéricos , Reoperação/economia , Escoliose/cirurgia , Tomografia Computadorizada por Raios X/economia , Adolescente , Análise Custo-Benefício , Bases de Dados Factuais , Feminino , Humanos , Cuidados Intraoperatórios , Masculino , Escoliose/economia
11.
Biochem Biophys Res Commun ; 500(2): 256-260, 2018 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-29653101

RESUMO

Proper control of multipotent/stem cell number and fate is essential for ensuing organ formation during development. ß1-integrin, a subfamily of cell surface receptors, has a conserved role in maintenance of multipotent/stem cells, including renal progenitor cells, follicle stem cells, epidermal stem cells and neural stem cells. However, it remains unclear whether ß1-integrin has a role in cardiac progenitor cell (CPC) development. Here we show that a mesodermal deletion of ß1-integrin decreases Isl1+ cell number in the second pharyngeal arch (PA2), where CPCs undergo renewal and expansion. Mesp1 lineage-specific mosaicism revealed that ß1-integrin-deleted Isl1+ cells do not proliferate in the PA2. Consistently, ß1-integrin-deleted Isl1+ CPCs failed to expand in vitro, independent of PA2 cells. ß1-integrin co-localized and physically associated with Numb, a crucial regulator of CPC renewal and expansion. Importantly, Numb/Numbl-deleted CPCs showed dramatic reduction in ß1-integrin levels. These findings suggest that ß1-integrin is a key mediator of the Numb pathway in CPC maintenance.


Assuntos
Integrina beta1/metabolismo , Proteínas de Membrana/metabolismo , Miócitos Cardíacos/citologia , Proteínas do Tecido Nervoso/metabolismo , Transdução de Sinais , Células-Tronco/citologia , Células-Tronco/metabolismo , Animais , Linhagem Celular , Proliferação de Células , Embrião de Mamíferos/metabolismo , Deleção de Genes , Coração/embriologia , Peptídeos e Proteínas de Sinalização Intracelular , Camundongos Knockout , Ligação Proteica
12.
J Neurosurg Pediatr ; 21(6): 574-577, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29521606

RESUMO

Myelomeningocele and gastroschisis, on their own, are both relatively common entities encountered in pediatric surgical care. Coexistence of these pathologies, however, is exceedingly rare. The authors report on 2 patients who presented with myelomeningocele and gastroschisis at birth. They obtained blood for whole-exome analysis for one of the patients and identified 3 mutations that could be related to the underlying anomalies: homozygous mutations in FAM171B and ABCA1 and a hemizygous (X-linked) mutation in COL4A5. Of these, FAM171B and ABCA1 both have function that may be related to the underlying disease.


Assuntos
Gastrosquise/complicações , Meningomielocele/complicações , Adolescente , Adulto , Feminino , Gastrosquise/diagnóstico por imagem , Gastrosquise/cirurgia , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Meningomielocele/diagnóstico por imagem , Meningomielocele/cirurgia
13.
J Health Care Poor Underserved ; 29(1): 481-496, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29503313

RESUMO

As part of a cultural competence needs assessment study at a large academic health care system, we conducted a survey among 1,220 practicing physicians to assess their perceptions of the organization's cultural competence climate and their skills and behaviors targeting patient-centered care for culturally and socially diverse patients. Less than half of providers reported engaging in behaviors to address cultural and social barriers more than 75% of the time. In multivariable logistic regression models, providers who reported moderate or major structural problems were more likely to report low skillfulness in identifying patient mistrust (aOR: 2.01; 95% CI: 1.23-3.28, p<0.01), how well patients read and write English (aOR: 1.63; 95% CI: 1.03-2.57, p=0.03), and socioeconomic barriers (aOR: 2.14; 95% CI: 1.14-4.01, p=0.01), than providers who reported only small or no structural problems. Improved structural support for socially and culturally complex medical encounters is needed to enhance care for socially at-risk patients.


Assuntos
Atitude do Pessoal de Saúde , Competência Cultural/organização & administração , Pessoal de Saúde/psicologia , Assistência Centrada no Paciente/organização & administração , Populações Vulneráveis/estatística & dados numéricos , Adulto , Competência Clínica , Feminino , Pesquisas sobre Atenção à Saúde , Pessoal de Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Socioeconômicos
14.
Nat Genet ; 49(7): 1152-1159, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28530678

RESUMO

Congenital heart disease (CHD) affects up to 1% of live births. Although a genetic etiology is indicated by an increased recurrence risk, sporadic occurrence suggests that CHD genetics is complex. Here, we show that hypoplastic left heart syndrome (HLHS), a severe CHD, is multigenic and genetically heterogeneous. Using mouse forward genetics, we report what is, to our knowledge, the first isolation of HLHS mutant mice and identification of genes causing HLHS. Mutations from seven HLHS mouse lines showed multigenic enrichment in ten human chromosome regions linked to HLHS. Mutations in Sap130 and Pcdha9, genes not previously associated with CHD, were validated by CRISPR-Cas9 genome editing in mice as being digenic causes of HLHS. We also identified one subject with HLHS with SAP130 and PCDHA13 mutations. Mouse and zebrafish modeling showed that Sap130 mediates left ventricular hypoplasia, whereas Pcdha9 increases penetrance of aortic valve abnormalities, both signature HLHS defects. These findings show that HLHS can arise genetically in a combinatorial fashion, thus providing a new paradigm for the complex genetics of CHD.


Assuntos
Heterogeneidade Genética , Síndrome do Coração Esquerdo Hipoplásico/genética , Sequência de Aminoácidos , Animais , Aorta/embriologia , Sistemas CRISPR-Cas , Mapeamento Cromossômico , Cromossomos Humanos/genética , Modelos Animais de Doenças , Exoma , Feminino , Edição de Genes , Técnicas de Inativação de Genes , Ventrículos do Coração/embriologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Mutação , Mutação de Sentido Incorreto , Miócitos Cardíacos/patologia , Penetrância , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Obstrução do Fluxo Ventricular Externo/genética , Peixe-Zebra/genética
15.
Artigo em Inglês | MEDLINE | ID: mdl-28159874

RESUMO

A central role for cilia in congenital heart disease (CHD) was recently identified in a large-scale mouse mutagenesis screen. Although the screen was phenotype-driven, the majority of genes recovered were cilia-related, suggesting that cilia play a central role in CHD pathogenesis. This partly reflects the role of cilia as a hub for cell signaling pathways regulating cardiovascular development. Consistent with this, many cilia-transduced cell signaling genes were also recovered, and genes regulating vesicular trafficking, a pathway essential for ciliogenesis and cell signaling. Interestingly, among CHD-cilia genes recovered, some regulate left-right patterning, indicating cardiac left-right asymmetry disturbance may play significant roles in CHD pathogenesis. Clinically, CHD patients show a high prevalence of ciliary dysfunction and show enrichment for de novo mutations in cilia-related pathways. Combined with the mouse findings, this would suggest CHD may be a new class of ciliopathy.


Assuntos
Cílios/fisiologia , Ciliopatias/complicações , Cardiopatias Congênitas/etiologia , Animais , Humanos
16.
Biol Open ; 5(3): 323-35, 2016 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-26883626

RESUMO

Planar cell polarity (PCP) is controlled by a conserved pathway that regulates directional cell behavior. Here, we show that mutant mice harboring a newly described mutation termed Beetlejuice (Bj) in Prickle1 (Pk1), a PCP component, exhibit developmental phenotypes involving cell polarity defects, including skeletal, cochlear and congenital cardiac anomalies. Bj mutants die neonatally with cardiac outflow tract (OFT) malalignment. This is associated with OFT shortening due to loss of polarized cell orientation and failure of second heart field cell intercalation mediating OFT lengthening. OFT myocardialization was disrupted with cardiomyocytes failing to align with the direction of cell invasion into the outflow cushions. The expression of genes mediating Wnt signaling was altered. Also noted were shortened but widened bile ducts and disruption in canonical Wnt signaling. Using an in vitro wound closure assay, we showed Bj mutant fibroblasts cannot establish polarized cell morphology or engage in directional cell migration, and their actin cytoskeleton failed to align with the direction of wound closure. Unexpectedly, Pk1 mutants exhibited primary and motile cilia defects. Given Bj mutant phenotypes are reminiscent of ciliopathies, these findings suggest Pk1 may also regulate ciliogenesis. Together these findings show Pk1 plays an essential role in regulating cell polarity and directional cell migration during development.

17.
J Contin Educ Health Prof ; 36(4): 263-268, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28350307

RESUMO

INTRODUCTION: Despite the well-recognized benefits of mentoring in academic medicine, there is a lack of clarity regarding what constitutes effective mentoring. We developed a tool to assess mentoring activities experienced by faculty and evaluated evidence for its validity. METHODS: The National Initiative on Gender, Culture, and Leadership in Medicine-"C-Change"-previously developed the C-Change Faculty Survey to assess the culture of academic medicine. After intensive review, we added six items representing six components of mentoring to the survey-receiving help with career and personal goals, learning skills, sponsorship, and resources. We tested the items in four academic health centers during 2013 to 2014. We estimated reliability of the new items and tested the correlation of the new items with a mentoring composite variable representing faculty mentoring experiences as positive, neutral, or inadequate and with other C-Change dimensions of culture. RESULTS: Among the 1520 responding faculty (response rate 61-63%), there was a positive association between each of the six mentoring activities and satisfaction with both the amount and quality of mentoring received. There was no difference by sex. Cronbach α coefficients ranged from 0.89 to 0.95 across subgroups of faculty (by sex, race, and principal roles). The mentoring responses were associated most closely with dimensions of Institutional Support (r = 0.58, P < .001), Institutional Change Efforts for Faculty Support (r = 0.52, P < .001), Values Alignment (r = 0.58, P < .001), Self-efficacy (r = 0.43; P < .001), and Relationships/Inclusion/Trust (r = 0.41; P < .001). DISCUSSION: Data demonstrated that the Mentoring scale is a valid instrument to assess mentoring. Survey results could facilitate mentoring program development and evaluation.


Assuntos
Docentes de Medicina/psicologia , Tutoria/normas , Centros Médicos Acadêmicos/organização & administração , Adulto , Docentes de Medicina/normas , Feminino , Humanos , Liderança , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Autoeficácia , Inquéritos e Questionários , Confiança
18.
J Contin Educ Health Prof ; 35(3): 176-84, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26378423

RESUMO

INTRODUCTION: The aims of this study were to (1) describe the quantity and quality of mentoring faculty in US academic health centers (AHCs), (2) measure associations between mentoring and 12 dimensions that reflect the culture of AHCs, and (3) assess whether mentoring predicts seriously contemplating leaving one's institution. METHODS: During 2007-2009, our National Initiative on Gender, Culture and Leadership in Medicine (C - Change) conducted a cross-sectional study of faculty from 26 representative AHCs in the United States using the 74-item C - Change Faculty Survey to assess relationships of faculty characteristics and various aspects of the institutional culture (52% response rate). Among the 2178 eligible respondents (assistant, associate, and full professors), we classified their mentoring experience as either inadequate, neutral, or positive. RESULTS: In this national sample, 43% of the 2178 respondents had inadequate mentoring; only 30% had a positive assessment of mentoring. There was no statistical difference by sex, minority status, or rank. Inadequate mentoring was most strongly associated with less institutional support, lower self-efficacy in career advancement, and lower scores on the trust/relationship/inclusion scale. The percent of faculty who had seriously considered leaving their institution was highest among those who had inadequate mentoring (58%), compared to those who were neutral (28%) or had positive mentoring (14%) (all paired comparisons, p < .001). DISCUSSION: In a national survey of faculty of US AHCs, mentoring was frequently inadequate and this was associated with faculty contemplating leaving their institutions. Positive mentoring, although less prevalent, was associated with many other positive dimensions of AHCs.


Assuntos
Docentes de Medicina/educação , Tutoria/normas , Centros Médicos Acadêmicos/organização & administração , Adulto , Estudos Transversais , Docentes de Medicina/normas , Feminino , Humanos , Satisfação no Emprego , Masculino , Tutoria/métodos , Pessoa de Meia-Idade , Autoeficácia , Inquéritos e Questionários , Estados Unidos , Recursos Humanos
19.
Hum Mol Genet ; 24(14): 3994-4005, 2015 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-25877302

RESUMO

Recent studies identified a previously uncharacterized gene C5ORF42 (JBTS17) as a major cause of Joubert syndrome (JBTS), a ciliopathy associated with cerebellar abnormalities and other birth defects. Here we report the first Jbts17 mutant mouse model, Heart Under Glass (Hug), recovered from a forward genetic screen. Exome sequencing identified Hug as a S235P missense mutation in the mouse homolog of JBTS17 (2410089e03rik). Hug mutants exhibit multiple birth defects typical of ciliopathies, including skeletal dysplasia, polydactyly, craniofacial anomalies, kidney cysts and eye defects. Some Hug mutants exhibit congenital heart defects ranging from mild pulmonary stenosis to severe pulmonary atresia. Immunostaining showed JBTS17 is localized in the cilia transition zone. Fibroblasts from Hug mutant mice and a JBTS patient with a JBTS17 mutation showed ciliogenesis defects. Significantly, Hug mutant fibroblasts showed loss of not only JBTS17, but also NPHP1 and CEP290 from the cilia transition zone. Hug mutants exhibited reduced ciliation in the cerebellum. This was associated with reduction in cerebellar foliation. Using a fibroblast wound-healing assay, we showed Hug mutant cells cannot establish cell polarity required for directional cell migration. However, stereocilia patterning was grossly normal in the cochlea, indicating planar cell polarity is not markedly affected. Overall, we showed the JBTS pathophysiology is replicated in the Hug mutant mice harboring a Jbts17 mutation. Our findings demonstrate JBTS17 is a cilia transition zone component that acts upstream of other Joubert syndrome associated transition zone proteins NPHP1 and CEP290, indicating its importance in the pathogenesis of Joubert syndrome.


Assuntos
Doenças Cerebelares/genética , Cerebelo/anormalidades , Proteínas de Membrana/genética , Retina/anormalidades , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/patologia , Proteínas Adaptadoras de Transdução de Sinal , Sequência de Aminoácidos , Animais , Antígenos de Neoplasias , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Proteínas de Ciclo Celular , Polaridade Celular , Células Cultivadas , Doenças Cerebelares/patologia , Cerebelo/patologia , Cílios , Proteínas do Citoesqueleto , Modelos Animais de Doenças , Anormalidades do Olho/genética , Anormalidades do Olho/patologia , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Doenças Renais Císticas/genética , Doenças Renais Císticas/patologia , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Confocal , Dados de Sequência Molecular , Mutação , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Gravidez , Transporte Proteico/genética , Retina/patologia
20.
Acad Med ; 90(7): 930-6, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25692560

RESUMO

PURPOSE: Faculty with high vitality are essential to the missions of academic health centers (AHCs). Because little is known about how to measure or enhance faculty vitality, the authors assessed current faculty vitality and identified its predictors. METHOD: In a stratified random sample of 26 nationally representative U.S. AHCs, the authors surveyed 4,578 full-time faculty during 2007-2009. The validated survey measured detailed faculty perceptions of their professional experiences and organizational culture. Vitality was measured with a previously evaluated five-item scale. RESULTS: Of the faculty invited, 2,381 (52%) responded, with 2,218 eligible for analysis. Respondents included 512 (23%) underrepresented in medicine minority (URMM) faculty and 1,172 (53%) women. In a multivariable model including individual- and AHC-level factors, the strongest predictors of vitality were faculty members' perceptions of four dimensions of AHC culture: Relationships/inclusion, Values alignment, Work-life integration, and Institutional support (all P < .001). Weaker predictors were faculty age, institution type (public/private), and the AHC's National Institutes of Health funding rank (all P ≤ .03). Half of the respondents scored high on vitality, whereas 25% had low, or suboptimal, scores. Holding perceptions of culture constant, neither female nor URMM faculty had vitality scores that were different on average from male or nonminority faculty. CONCLUSIONS: A large percentage of faculty lack the vitality essential to meeting the AHC missions of discovery, education, and patient care. Enhancing faculty vitality, and AHC resilience, requires more attention to strengthening relationships, improving the misalignment between faculty and institutional values, and improving work-life integration.


Assuntos
Centros Médicos Acadêmicos , Atitude do Pessoal de Saúde , Docentes de Medicina , Satisfação no Emprego , Centros Médicos Acadêmicos/organização & administração , Adulto , Idoso , Mobilidade Ocupacional , Estudos Transversais , Docentes de Medicina/organização & administração , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Cultura Organizacional , Inquéritos e Questionários , Estados Unidos
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