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BACKGROUND: There is concern regarding potential long-term cardiotoxicity with systemic distribution of metals in total joint arthroplasty (TJA) patients. AIM: To determine the association of commonly used implant metals with echocardiographic measures in TJA patients. METHODS: The study comprised 110 TJA patients who had a recent history of high chromium, cobalt or titanium concentrations. Patients underwent two-dimensional, three-dimensional, Doppler and speckle-strain transthoracic echocardiography and a blood draw to measure metal concentrations. Age and sex-adjusted linear and logistic regression models were used to examine the association of metal concentrations (exposure) with echocardiographic measures (outcome). RESULTS: Higher cobalt concentrations were associated with increased left ventricular end-diastolic volume (estimate 5.09; 95%CI: 0.02-10.17) as well as left atrial and right ventricular dilation, particularly in men but no changes in cardiac function. Higher titanium concentrations were associated with a reduction in left ventricle global longitudinal strain (estimate 0.38; 95%CI: 0.70 to 0.06) and cardiac index (estimate 0.08; 95%CI, -0.15 to -0.01). CONCLUSION: Elevated cobalt and titanium concentrations may be associated with structural and functional cardiac changes in some patients. Longitudinal studies are warranted to better understand the systemic effects of metals in TJA patients.
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OBJECTIVE: To evaluate the impact of methotrexate and rituximab therapy on highly recurrent idiopathic subglottic stenosis (iSGS) patients with a negative antineutrophil cytoplasmic antibody titer cANCA(-). METHODS: This was a retrospective cohort study of highly recurrent iSGS patients who recurred within 1 year or less and were treated with methotrexate (MTX), and rituximab (RTX), or a combination of both at different time points (MTX/RTX). Average surgical durations before and after drug treatment were summarized, and the differences were calculated. RESULTS: A total of 21 female patients with median age of 62 years were included. Fifteen patients were treated with MTX, three were treated with RTX, and five treated with both. Patients treated with immunosuppressants showed a trend toward longer intervals between operations (mean pre-drug interval: 338; mean post-drug interval: 697 days) (p-value = 0.25). Three patients did not recur following drug initiation with median follow-up of 1265 days. All three treatment groups demonstrated a trend toward increased post-drug recurrence intervals (MTX: 444 days, RTX: 374 days, MTX/RTX: 55 days), that was not statistically significant. Patients with prior dilations demonstrated longer post-drug recurrence intervals (mean pre-drug interval: 341 days, mean post-drug interval 978 days) (p-value = 0.17). Four patients in the cohort with the highest recurring disease improved from mean 129 days between operations to 509 days with drug therapy. The most common drug side effect was nausea (16%). CONCLUSION: MTX and RTX may be treatment options for some highly recurrent iSGS patients. Initial results are variable and demonstrate a need for further research on drug candidacy. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.
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OBJECTIVES: Acinic cell carcinoma (ACC) most frequently arises in the parotid gland. Treatment consists of surgical resection and sometimes adjuvant therapy. ACC is most often a low-grade malignancy with good prognosis. Higher-grade tumors are often treated aggressively with total parotidectomy, neck dissection, and adjuvant therapy; however, the effect of parotid gland resection extent on oncologic outcomes has not been studied. Herein, we examine predictors of oncologic outcomes, including the effect of extent of resection. METHODS: Patients with diagnosis of parotid ACC treated at our institution were included in this retrospective study. Patient factors were examined, and patients were grouped by extent of resection and tumor grade. RESULTS: 58 patients, including 32 low-grade, 7 intermediate-grade, and 14 high-grade were included. Patients with low-grade tumors were more likely to undergo lesser extent of parotidectomy and less likely to undergo neck dissection. Two patients with low grade tumors developed recurrence, one local and one regional. Recurrence rate did not differ with resection extent in low-grade tumors. High tumor grade was found to be associated with disease progression. There was no association with adjuvant treatment and outcomes. Across all tumor grades advanced AJCC stage was found to be associated with disease progression. CONCLUSIONS: In ACC patients with low-grade tumors and lower disease stage who undergo lesser extent of surgical resection oncologic outcomes were favorable. Patients with high-grade tumors carry a high risk of recurrence, despite aggressive treatment. AJCC stage and histopathologic grade may predict outcomes and guide treatment.
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PURPOSE: Despite the introduction of Relative Energy Deficiency in Sport (RED-s) in 2014, there is evidence to suggest that male endurance athletes still present with a high prevalence of low energy availability (LEA). Previous findings suggest that energy availability (EA) status is strongly correlated with impairments in endocrine function such as reduced leptin, triiodothyronine (T3), and insulin, and elevated bone loss. This study aimed to report the current EA status, endocrine function and bone health of highly trained Irish male endurance athletes. METHODS: In this cross-sectional study, participants (n = 3 triathletes; n = 10 runners) completed a 7-day testing period during the competition season using lab-based measures, to ascertain EA status, hormone level and rates of bone metabolism. Serum blood samples were obtained to assess hormone levels and markers of bone metabolism. RESULTS: Mean EA was < 30 kcal/kg lean body mass (LBM)/day in 76.9% of athletes. There was a strong association between LEA and low carbohydrate intake, and lower LBM. Mean levels of insulin, IGF-1 and leptin were significantly lower than their reference ranges. Elevated mean concentrations of ß-CTX and a mean P1NP: ß-CTX ratio < 100, indicated a state of bone resorption. CONCLUSION: The EA level, carbohydrate intake, hormone status and bone metabolism status of highly trained male endurance athletes are a concern. Based on the findings of this study, more frequent assessment of EA across a season is recommended to monitor the status of male endurance athletes, in conjunction with nutritional education specific to EA and the associated risks.
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OBJECTIVE: Analyze the duration of symptom-free intervals following laser wedge excision (LWE) for recurrent idiopathic subglottic stenosis (iSGS). Secondary aim includes evaluating the influence of patient-related or disease factors. STUDY DESIGN: Retrospective review. SETTING: Tertiary center. METHODS: Review of iSGS patients who underwent LWE between 2002 and 2021. LWE patients without prior airway surgery were labeled LWE primary (LWEP) and those with prior history of dilation were labeled LWE secondary (LWES). A conditional frailty repeated events model was used to analyze the median time to recurrence (MTR) for each nth recurrence. Secondary analysis included stratification by use of medical therapy and initial preoperative characteristics of scar (Myer-Cotton grade, distance between the glottis and superior-most aspect of scar, DGS; length of scar, DL). RESULTS: Two hundred and ten iSGS patients underwent LWE (131 LWEP, 79 LWES). The proportion of patients experiencing at least 1, 3, 6, and 12 recurrences, respectively, was 68.0% (n = 143), 40.7% (n = 85), 20.0% (n = 42), and 5.2% (n = 11). There was exponential time-shortening from the 1st to 12th recurrence (P < .0001). While MTR was 4.1 years after the first LWE, this fell to 2.8, 1.7, 1.0, and 0.7 years for the 2nd, 3rd, 6th, and 12th recurrences. Furthermore, LWEP patients experienced longer MTR than LWES counterparts within the first 6 recurrences (P < .01). There was no significant relationship between intersurgical interval and medication adherence, DL, DGS, or grade for recurrences beyond the first (P = .207, P = .20, P = .43, P = .16). CONCLUSION: Symptom-free intervals in iSGS shorten with each subsequent recurrence and LWE. The difference in MTR between LWEP and LWES groups was significant within the first 6 recurrences with LWEP having longer MTR.
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The Department of Veterans Affairs provides a shallow subsidy (i.e., subsidizing 50% of an individual's rent for two years) to Veterans experiencing housing instability. We sought to describe the characteristics of Veterans who received these subsidies. Methods. We conducted a retrospective cohort study of Veterans between 10/2019-9/2021. We identified Veteran-level characteristics associated with receiving a shallow subsidy using a multivariable two-part regression model. We also conducted qualitative interviews to identify how shallow subsidies are allocated. Results Black race, higher income, more education, and older age were positively associated with receiving a shallow subsidy; previous homelessness, prior VA outpatient cost, and participating in permanent supportive housing were negatively associated with receiving a shallow subsidy. Interviews revealed that income was the most influential determinant of whether to give shallow subsidies. Discussion Our mixed methods findings were consistent, indicating that socioeconomic stability is an important driver of shallow subsidy allocation decisions.
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United States Department of Veterans Affairs , Veteranos , Humanos , Veteranos/estatística & dados numéricos , Veteranos/psicologia , Estados Unidos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Feminino , Idoso , Habitação/economia , Adulto , Fatores Socioeconômicos , Pessoas Mal AlojadasRESUMO
As homelessness remains an urgent public health crisis in the United States, specific programs in the US Department of Veterans Affairs (VA) system may serve as a roadmap for addressing it. We examine lessons learned from the first decade (2012-2022) of the Supportive Services for Veteran Families (SSVF) program, a cornerstone in the VA continuum of homeless services aimed at both preventing homelessness among those at risk and providing rapid rehousing for veterans and their families who are currently experiencing homelessness. Drawing on information from annual reports and other relevant literature, we have identified 3 themes of SSVF that emerged as features to comprehensively deliver support for homeless veterans and their families: (1) responsiveness and flexibility, (2) coordination and integration, and (3) social resource engagement. Using these strategies, SSVF reached nearly three quarters of a million veterans and their families in its first decade, thereby becoming one of the VA's most substantial programmatic efforts designed to address homelessness. We discuss how each feature might apply to addressing homelessness in the general population as well as future research directions. (Am J Public Health. 2024;114(6):610-618. https://doi.org/10.2105/AJPH.2024.307625).
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Pessoas Mal Alojadas , United States Department of Veterans Affairs , Veteranos , Humanos , Estados Unidos , United States Department of Veterans Affairs/organização & administração , Família , Apoio SocialRESUMO
BACKGROUND: 1.8 million Veterans are estimated to need legal services, such as for housing eviction prevention, discharge upgrades, and state and federal Veterans benefits. While having one's legal needs met is known to improve one's health and its social determinants, many Veterans' legal needs remain unmet. Public Law 116-315 enacted in 2021 authorizes VA to fund legal services for Veterans (LSV) by awarding grants to legal service providers including nonprofit organizations and law schools' legal assistance programs. This congressionally mandated LSV initiative will award grants to about 75 competitively selected entities providing legal services. This paper describes the protocol for evaluating the initiative. The evaluation will fulfill congressional reporting requirements, and inform continued implementation and sustainment of LSV over time. METHODS: Our protocol calls for a prospective, mixed-methods observational study with a repeated measures design, aligning to the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) and Integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) frameworks. In 2023, competitively selected legal services-providing organizations will be awarded grants to implement LSV. The primary outcome will be the number of Veterans served by LSV in the 12 months after the awarding of the grant. The evaluation has three Aims. Aim 1 will focus on measuring primary and secondary LSV implementation outcomes aligned to RE-AIM. Aim 2 will apply the mixed quantitative-qualitative Matrixed Multiple Case Study method to identify patterns in implementation barriers, enablers, and other i-PARIHS-aligned factors that relate to observed outcomes. Aim 3 involves a mixed-methods economic evaluation to understand the costs and benefits of LSV implementation. DISCUSSION: The LSV initiative is a new program that VA is implementing to help Veterans who need legal assistance. To optimize ongoing and future implementation of this program, it is important to rigorously evaluate LSV's outcomes, barriers and enablers, and costs and benefits. We have outlined the protocol for such an evaluation, which will lead to recommending strategies and resource allocation for VA's LSV implementation.
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Veteranos , Estados Unidos , Humanos , Serviços Jurídicos , United States Department of Veterans Affairs , Estudos Prospectivos , Impulso (Psicologia) , Estudos Observacionais como AssuntoRESUMO
BACKGROUND: US military veterans who have experienced homelessness often have high rates of housing transition. Disruptions caused by these transitions likely exacerbate this population's health problems and interfere with access to care and treatment engagement. Individuals experiencing homelessness increasingly use smartphones, contributing to improved access to medical and social services. Few studies have used smartphones as a data collection tool to systematically collect information about the daily life events that precede and contribute to housing transitions, in-the-moment emotions, behaviors, geographic movements, and perceived social support. OBJECTIVE: The study aims to develop and test a smartphone app to collect longitudinal data from veterans experiencing homelessness (VEH) and to evaluate the feasibility and acceptability of using the app in a population that is unstably housed or homeless. METHODS: This study's design had 3 phases. Phase 1 used ethnographic methods to capture detailed data on day-to-day lived experiences of up to 30 VEH on topics such as housing stability, health, and health behaviors. Phase 2 involved focus groups and usability testing to develop and refine mobile phone data collection methods. Phase 3 piloted the smartphone mobile data collection with 30 VEH. We included mobile ethnography, real-time surveys through an app, and the collection of GPS data in phase 3. RESULTS: The project was launched in June 2020, and at this point, some data collection and analysis for phases 1 and 2 are complete. This project is currently in progress. CONCLUSIONS: This multiphase study will provide rich data on the context and immediate events leading to housing transitions among VEH. This study will ensure the development of a smartphone app that will match the actual needs of VEH by involving them in the design process from the beginning. Finally, this study will offer important insights into how best to develop a smartphone app that can help intervene among VEH to reduce housing transitions. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53022.
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Antropologia Cultural , Pessoas Mal Alojadas , Aplicativos Móveis , Smartphone , Humanos , Pessoas Mal Alojadas/psicologia , Antropologia Cultural/métodos , Veteranos/psicologia , Masculino , Feminino , Adulto , Grupos Focais , Estados UnidosRESUMO
OBJECTIVE: To compare clinical outcomes in patients with and without history of tobacco use who underwent Zenker's diverticulotomy (ZD). STUDY DESIGN: Single institution retrospective review. SETTING: Tertiary care academic hospital. METHODS: A retrospective review of patients who underwent ZD via an open stapler, rigid endoscopic CO2 laser, stapler or harmonic scalpel, and flexible endoscopic technique from January 2006 to December 2020 was performed. Data were abstracted for patient demographics, diverticular features, and rates of adverse events and symptomatic recurrence. RESULTS: Out of 424 patients, 146 (34.4 %) had a history of tobacco use: 126 (29.7 %) were former smokers, and 20 (4.7 %) were active smokers. In univariable cross-sectional analyses, the likelihood of postoperative bleeding, perforation, emergency department visits, unplanned readmission, or recurrence did not demonstrate an association with tobacco use history even after adjustment for age, sex, and surgical approach. Similarly, in Cox Proportional Hazards regression, tobacco use was not associated with an increased risk of recurrence, even after correcting for age, sex, and type of surgery. The median time to recurrence observed in our cohort was 11.5 years amongst non-smokers, 8.7 years amongst former smokers, and 1.2 years amongst active smokers (p = 0.94). CONCLUSIONS: There were no significant differences in post-operative adverse events or frequency of recurrence of ZD between active, former, and non-smokers. Although underpowered and not statistically significant, median time to recurrence appears to be shorter in smokers when compared with former and non-smokers following surgery.
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Recidiva , Divertículo de Zenker , Humanos , Divertículo de Zenker/cirurgia , Masculino , Feminino , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Uso de Tabaco/efeitos adversos , Estudos TransversaisRESUMO
Background: Migrants in the United Kingdom (UK) may be at higher risk of SARS-CoV-2 exposure; however, little is known about their risk of COVID-19-related hospitalisation during waves 1-3 of the pandemic. Methods: We analysed secondary care data linked to Virus Watch study data for adults and estimated COVID-19-related hospitalisation incidence rates by migration status. To estimate the total effect of migration status on COVID-19 hospitalisation rates, we ran mixed-effect Poisson regression for wave 1 (01/03/2020-31/08/2020; wildtype), and mixed-effect negative binomial regressions for waves 2 (01/09/2020-31/05/2021; Alpha) and 3 (01/06/2020-31/11/2021; Delta). Results of all models were then meta-analysed. Results: Of 30,276 adults in the analyses, 26,492 (87.5 %) were UK-born and 3,784 (12.5 %) were migrants. COVID-19-related hospitalisation incidence rates for UK-born and migrant individuals across waves 1-3 were 2.7 [95 % CI 2.2-3.2], and 4.6 [3.1-6.7] per 1,000 person-years, respectively. Pooled incidence rate ratios across waves suggested increased rate of COVID-19-related hospitalisation in migrants compared to UK-born individuals in unadjusted 1.68 [1.08-2.60] and adjusted analyses 1.35 [0.71-2.60]. Conclusion: Our findings suggest migration populations in the UK have excess risk of COVID-19-related hospitalisations and underscore the need for more equitable interventions particularly aimed at COVID-19 vaccination uptake among migrants.
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OBJECTIVE: To report on a series of patients with cANCA/PR3-positive, granulomatosis with polyangiitis (GPA)-associated subglottic stenosis (SGS) and evaluate response to medical maintenance therapy with rituximab versus other immunosuppressants following initial endoscopic laser excision. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary academic center. METHODS: A retrospective chart review of patients with SGS and cANCA/PR3-positive GPA who received immunosuppressive maintenance therapy following endoscopic laser excision at our institution from June 1989 to March 2020 was performed. Data pertaining to patient demographics, clinical features, medications, and endoscopic laser procedures were collected. RESULTS: A total of 27 patients (15 women) with mean age (range) of 40 (19-59) years and mean (range) follow-up of 12.6 years (1.5-28.6) were identified. Sixteen patients (60%) had limited GPA. Six patients (24%) had previously received local intervention with open surgery (n = 1, 4%) or endoscopic techniques (n = 5, 20%). All patients experienced symptom improvement following initial CO2 laser excision at our institution without any procedural complications or adverse events. Following initial laser excision, 15 patients (60%) were treated with rituximab and 10 patients (40%) were treated with nonrituximab immunosuppressive agents. Patients treated with rituximab were less likely to recur (P = 0.040). Limited GPA was associated with an increased incidence of recurrence (P = 0.031). Median time (years) to recurrence (range) was 3.2 (0.3-19.3) and was not significantly associated with treatment or GPA subtype. CONCLUSION: Endoscopic CO2 laser excision is a safe and effective local intervention for GPA-associated SGS. Medical maintenance therapy with rituximab reduces risk of recurrence following initial laser excision relative to treatment with non-rituximab agents.
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Granulomatose com Poliangiite , Imunossupressores , Laringoestenose , Terapia a Laser , Rituximab , Humanos , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/tratamento farmacológico , Feminino , Masculino , Laringoestenose/cirurgia , Laringoestenose/etiologia , Adulto , Estudos Retrospectivos , Pessoa de Meia-Idade , Rituximab/uso terapêutico , Terapia a Laser/métodos , Imunossupressores/uso terapêutico , Resultado do Tratamento , Adulto Jovem , Laringoscopia , Quimioterapia de ManutençãoRESUMO
PURPOSE: Liver transplantation is curative for hepatocellular carcinoma (HCC). Checkpoint inhibitor therapy (CPIT) has been used in unresectable HCC, but recent advances have demonstrated CPIT as an innovative method of downstaging advanced HCC with the caveat that CPIT prior to transplantation has risks including irreversible graft rejection. We report the outcomes of Mayo Clinic Arizona patients who underwent downstaging with CPIT. METHODS: This retrospective chart review was conducted for Mayo Clinic Arizona patients who were diagnosed with HCC who underwent downstaging with CPIT with the goal of meeting criteria for transplantation. RESULTS: We present nine cases with HCC outside Milan who underwent CPIT. Four received a transplant; one was delisted due to his exceptional therapeutic response. All received liver-directed therapy. Peak alpha-fetoprotein pre-CPIT ranged from 8-29,523 ng/mL, which decreased to 2.2-19.6 ng/mL on CPIT. CPIT included atezolizumab/bevacizumab, ipilimumab/nivolumab, nivolumab, and pembrolizumab; one patient received two regimens. CPIT was held prior to transplant at a median of 3 months. Three patients received methylprednisolone for immunosuppression induction; one received thymoglobulin. One patient developed acute cellular rejection at 5 weeks, 9 weeks, and 5 months post-transplant; given the late onset, these were not attributed to CPIT and were successfully treated. During an average follow-up of 16.5 months, no tumor recurrence has occurred. CONCLUSION: We describe nine patients with HCC outside Milan with inadequate response with liver-directed therapy, who achieved marked responses with CPIT, allowing for consideration of successful liver transplantation. Our case series supports the consideration of locoregional therapies and CPIT for downstaging to within transplant criteria.
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Carcinoma Hepatocelular , Inibidores de Checkpoint Imunológico , Neoplasias Hepáticas , Transplante de Fígado , Estadiamento de Neoplasias , Humanos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Feminino , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Nivolumabe/uso terapêutico , Resultado do TratamentoRESUMO
The Department of Veterans Affairs (VA) aims to reduce homelessness among veterans through programs such as Supportive Services for Veteran Families (SSVF). An important component of SSVF is temporary financial assistance. Previous research has demonstrated the effectiveness of temporary financial assistance in reducing short-term housing instability, but studies have not examined its long-term effect on housing outcomes. Using data from the VA's electronic health record system, we analyzed the effect of temporary financial assistance on veterans' housing instability for three years after entry into SSVF. We extracted housing outcomes from clinical notes, using natural language processing, and compared the probability of unstable housing among veterans who did and did not receive temporary financial assistance. We found that temporary financial assistance rapidly reduced the probability of unstable housing, but the effect attenuated after forty-five days. Our findings suggest that to maintain long-term housing stability for veterans who have exited SSVF, additional interventions may be needed.
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Pessoas Mal Alojadas , Veteranos , Estados Unidos , Humanos , Habitação , United States Department of Veterans Affairs , ProbabilidadeRESUMO
OBJECTIVES: Social determinants of health (SDOH) can influence access to cancer care, clinical trials, and oncologic outcomes. We investigated the association between SDOH, distance from treatment center, and treatment type with outcomes in human papillomavirus associated oropharyngeal squamous cell carcinoma [HPV(+)OPSCC] patients treated at a tertiary care center. STUDY DESIGN: Retrospective review. METHODS: HPV(+)OPSCC patients treated surgically from 2006 to 2021 were selected from our departmental Oropharyngeal Cancer RedCap database. Demographic data, treatment, and oncologic outcomes were extracted. Distance was calculated in miles between the centroid of each patient zip code and our hospital zip code (zipdistance). RESULTS: 874 patients (89 % male; mean age: 58 years) were identified. Most patients (96 %) reported Non-Hispanic White as their primary race. 204 patients (23 %) had a high-school degree or less, 217 patients (25 %) reported some college education or a 2-year degree, 153 patients (18 %) completed a four-year college degree, and 155 patients (18 %) had post-graduate degrees. Relative to those with a high-school degree, patients with higher levels of education were more likely to live further away from our institution (p < 0.0001). Patients who received adjuvant radiation therapy elsewhere lived, on average, 104 miles further away than patients receiving radiation at our institution (Estimate 104.3, 95 % CI 14.2-194.4, p-value = 0.02). In univariable Cox PH models, oncologic outcomes did not significantly differ by zipdistance. CONCLUSIONS: Education level-and access to resources-varied proportionally to a patient's distance from our center. Patients travelling further distances for surgical management of OPSCC were more likely to pursue adjuvant radiation therapy at an outside institution. Distance traveled was not associated with oncologic outcomes. Breaking down barriers to currently excluded populations may improve access to clinical trials and improve oncologic outcomes for diverse patient populations.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Papillomavirus Humano , Carcinoma de Células Escamosas/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/patologia , Determinantes Sociais da Saúde , Neoplasias Orofaríngeas/patologia , Estudos Retrospectivos , Neoplasias de Cabeça e Pescoço/complicaçõesRESUMO
Cells respond to DNA double-strand breaks by initiating DSB repair and ensuring a cell cycle checkpoint. The primary responder to DSB repair is non-homologous end joining, which is an error-prone repair pathway. However, when DSBs are generated after DNA replication in the G2 phase of the cell cycle, a second DSB repair pathway, homologous recombination, can come into action. Both ATM and ATR are important for DSB-induced DSB repair and checkpoint responses. One method of ATM and ATR working together is through the DNA end resection of DSBs. As a readout and marker of DNA end resection, RPA is phosphorylated at Ser4/Ser8 of the N-terminus of RPA32 in response to DSBs. Here, the significance of RPA32 Ser4/Ser8 phosphorylation in response to DNA damage, specifically in the S phase to G2 phase of the cell cycle, is examined. RPA32 Ser4/Ser8 phosphorylation in G2 synchronized cells is necessary for increases in TopBP1 and Rad9 accumulation on chromatin and full activation of the ATR-dependent G2 checkpoint. In addition, our data suggest that RPA Ser4/Ser8 phosphorylation modulates ATM-dependent KAP-1 phosphorylation and Rad51 chromatin loading in G2 cells. Through the phosphorylation of RPA Ser4/Ser8, ATM acts as a partner with ATR in the G2 phase checkpoint response, regulating key downstream events including Rad9, TopBP1 phosphorylation and KAP-1 phosphorylation/activation via the targeting of RPA32 Ser4/Ser8.
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Proteínas de Ligação a DNA , DNA , Fosforilação , Pontos de Checagem da Fase G2 do Ciclo Celular/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , DNA/metabolismo , CromatinaRESUMO
Background: Despite growing scientific knowledge of Zika virus (ZIKV) infection, questions remain regarding ZIKV infection in pregnancy and congenital ZIKV syndrome (CZS). Methods: The ZIKAction Paediatric Registry is an international registry of children with documented ZIKV exposure in utero and/or with confirmed or suspected CZS. Its aim is to characterize these children (i.e., clinical, radiological, neurodevelopmental features) and describe outcomes, longer-term sequelae and management through retrospective case note review. This analysis described the maternal and perinatal characteristics of children in the Registry's Bahia arm, assessed their neuroimaging, ophthalmic, hearing and electroencephalography abnormalities by microcephaly classification and reported on hospitalisations. Children born in 2015-2018 and enrolled 2020-2021 in three public health facilities in Salvador were included. Results: Of 129 (57% female) children, 15 (11·6%) had laboratory-confirmed congenital ZIKV infection and 114 (88·4%) suspected CZS. At delivery, 15 (11·6%) were normocephalic, 30 (23·3%) moderately microcephalic, and 84 (65·1%) severely microcephalic. Median birth head circumference z-score was -3·51 [IQR, -4·69,-2·73]. During follow-up, all children had abnormal neuroimaging, 80·3% (94/117) abnormal electroencephalogram, 62·2% (77/120) ophthalmic abnormalities, and 27·4% (34/124) hearing impairment. Microcephaly classification was significantly associated with gestational age, and ophthalmological and electroencephalography abnormalities. Of 125 children with hospitalisation data, 52 (41·6%) had been hospitalised by most recent follow-up, at median age of 15·8 [4·0, 34·4] months; infections were the leading cause. Conclusion: Congenital ZIKV infection is an emerging disease with a varied and incompletely understood spectrum. Continued long-term follow-up is essential to understand longer-term prognosis and to inform future health and educational needs.
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The Electronic Health Record (EHR) contains information about social determinants of health (SDoH) such as homelessness. Much of this information is contained in clinical notes and can be extracted using natural language processing (NLP). This data can provide valuable information for researchers and policymakers studying long-term housing outcomes for individuals with a history of homelessness. However, studying homelessness longitudinally in the EHR is challenging due to irregular observation times. In this work, we applied an NLP system to extract housing status for a cohort of patients in the US Department of Veterans Affairs (VA) over a three-year period. We then applied inverse intensity weighting to adjust for the irregularity of observations, which was used generalized estimating equations to estimate the probability of unstable housing each day after entering a VA housing assistance program. Our methods generate unique insights into the long-term outcomes of individuals with a history of homelessness and demonstrate the potential for using EHR data for research and policymaking.
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Registros Eletrônicos de Saúde , Pessoas Mal Alojadas , Humanos , Processamento de Linguagem Natural , Habitação , Determinantes Sociais da SaúdeRESUMO
Background: Household overcrowding is associated with increased risk of infectious diseases across contexts and countries. Limited data exist linking household overcrowding and risk of COVID-19. We used data collected from the Virus Watch cohort to examine the association between overcrowded households and SARS-CoV-2. Methods: The Virus Watch study is a household community cohort of acute respiratory infections in England and Wales. We calculated overcrowding using the measure of persons per room for each household. We considered two primary outcomes: PCR-confirmed positive SARS-CoV-2 antigen tests and laboratory-confirmed SARS-CoV-2 antibodies. We used mixed-effects logistic regression models that accounted for household structure to estimate the association between household overcrowding and SARS-CoV-2 infection. Results:26,367 participants were included in our analyses. The proportion of participants with a positive SARS-CoV-2 PCR result was highest in the overcrowded group (9.0%; 99/1,100) and lowest in the under-occupied group (4.2%; 980/23,196). In a mixed-effects logistic regression model, we found strong evidence of an increased odds of a positive PCR SARS-CoV-2 antigen result (odds ratio 2.45; 95% CI:1.43-4.19; p-value=0.001) and increased odds of a positive SARS-CoV-2 antibody result in individuals living in overcrowded houses (3.32; 95% CI:1.54-7.15; p-value<0.001) compared with people living in under-occupied houses. Conclusion:Public health interventions to prevent and stop the spread of SARS-CoV-2 should consider the risk of infection for people living in overcrowded households and pay greater attention to reducing household transmission.