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1.
Curr Otorhinolaryngol Rep ; : 1-14, 2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37362031

RESUMO

Purpose of Review: The purpose of this review is to summarize some of the recent research studies on healthcare disparities across various subspecialties within otolaryngology. This review also highlights the impact of COVID-19 pandemic on disparities and proposes potential interventions to mitigate disparities. Recent Findings: Significant healthcare disparities in care and treatment outcomes have been reported across all areas of otolaryngology. Notable differences in survival, disease recurrence, and overall mortality have been noted based on race, ethnicity, socioeconomic status (SES), insurance status, etc. This is most well-researched in head and neck cancer (HNC) within otolaryngology. Summary: Healthcare disparities have been identified by numerous research studies within otolaryngology for many vulnerable groups that include racial and ethnic minority groups, low-income populations, and individuals from rural areas among many others. These populations continue to experience suboptimal access to timely, quality otolaryngologic care that exacerbate disparities in health outcomes.

4.
Aesthetic Plast Surg ; 47(2): 631-639, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35999465

RESUMO

BACKGROUND: Hair loss causes significant psychosocial distress to patients. Health utility measurements offer an objective, quantitative assessment of health-related quality of life (QOL). METHODS: We performed a prospective cohort study on patients with hair loss between January 1, 2018 and December 31, 2020. Patient metrics were compared with layperson perception of alopecia, prospectively collected between August 1 and December 31, 2017. Health utility measures were quantified using the visual analog scale (VAS), standard gamble (SG), and time trade-off (TTO) in quality-adjusted life-years (QALYs) and relative to the minimal clinically important difference (MCID). Bonferroni correction to the significance threshold was performed. RESULTS: Thirty-one patients with alopecia were compared with 237 laypeople. Patient metrics for female hair loss were all significantly lower than laypeople measures (VAS QALYs 0.65 ± 0.21 vs. 0.83 ± 0.18, p = 0.0001). Mean SG QALYs were lower for patients in the male alopecia state (0.86 ± 0.23 vs. 0.96 ± 0.12, p = 0.0278). Post-hair transplant improvement in TTO was significantly greater for patients (+ 0.08 ± 0.12 vs. + 0.02 ± 0.09, p = 0.0070) and significantly more often exceeded the MCID (45.2% vs. 16.9%, p = 0.0006). CONCLUSIONS: Alopecia negatively impacts QOL, and the true patient experience is more taxing than what is perceived by laypeople. Hair transplantation improves QOL more for male patients than common perception. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Assuntos
Alopecia , Qualidade de Vida , Humanos , Masculino , Feminino , Estudos Prospectivos , Alopecia/diagnóstico , Alopecia/cirurgia , Cabelo , Anos de Vida Ajustados por Qualidade de Vida
5.
Otolaryngol Head Neck Surg ; 166(6): 1182-1191, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35439084

RESUMO

OBJECTIVE: To evaluate strategies to increase racial and ethnic diversity in the surgical workforce among trainees and faculty across surgical specialties. DATA SOURCES: Embase, OVID/Medline, and Web of Science Core Collection. REVIEW METHODS: A review of US-based, peer-reviewed articles examining the effect of targeted strategies on racial and ethnic diversity in the surgical workforce was conducted from 2000 to 2020 with the PRISMA checklist and STROBE tool. Studies without an outlined strategy and associated outcomes were excluded. Eleven studies met inclusion criteria and were completed in general surgery, orthopaedic surgery, and otolaryngology-head and neck surgery. CONCLUSIONS: Efforts to increase exposure to surgery through internship programs and required clerkships with efforts to improve mentorship were common (6 of 11 [54.5%] and 3 of 11 [27.3%] studies, respectively). Three (27.3%) studies aimed to diversify the recruitment and selection process for the residency match and faculty hiring, and 2 (18.2%) aimed to increase representation among trainees, faculty, and leadership through holistic review processes paired with departmental commitment. Outcome metrics included surgical residency applications for individuals underrepresented in medicine, interview and match rates, faculty hiring, measures of a successful academic surgical career, and leadership representation. All strategies were successful in increasing diversity in the surgical workforce. IMPLICATIONS FOR PRACTICE: A convincing yet limited body of literature exists to describe strategies and outcomes that address racial and ethnic diversity in the surgical workforce. While future inquiry is needed to move this field of interest forward, the evidence presented provides a framework for surgical residency programs/departments to develop approaches to increase racial and ethnic diversity.


Assuntos
Internato e Residência , Especialidades Cirúrgicas , Diversidade Cultural , Etnicidade , Humanos , Grupos Raciais , Recursos Humanos
6.
Laryngoscope ; 132(11): 2157-2161, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35188669

RESUMO

OBJECTIVE: This study aimed to evaluate functional and aesthetic patient-reported outcomes using validated metrics after component dorsal hump reduction (DHR) with spreader graft placement, which have not been previously reported. STUDY DESIGN: Prospective cohort study. METHODS: This prospective cohort study was conducted in a tertiary care medical center. Participants underwent septorhinoplasty (SRP) with spreader graft placement with cosmetic, component DHR (cosmetic DHR), or SRP with spreader graft placement without dorsal hump reduction (noncosmetic, non-DHR). The Nasal Obstruction Symptom Evaluation (NOSE) scale and the FACE-Q Satisfaction with Nose, Nostrils, and Social Functioning scales were administered to patients preoperatively and postoperatively (at 2, 4, 6, and/or 12 months). Pre- and postoperative NOSE and FACE-Q scores were compared. RESULTS: A total of 226 patients underwent SRP with spreader graft placement; 113 (50.0%) with cosmetic DHR and 113 (50.0%) noncosmetic, non-DHR (control). Patients who completed the NOSE and FACE-Q surveys preoperatively and at least at one postoperative time point were included. Both cohorts had a statistically and clinically significant improvement in NOSE and FACE-Q scores. There were similar improvements in NOSE scores in both cohorts. Postoperative FACE-Q scores were higher in the cosmetic DHR cohort despite lower preoperative FACE-Q scores when compared to the control cohort. CONCLUSIONS: Although there are multiple techniques for DHR, component DHR with spreader graft placement has long been considered the standard. Therefore, it is important to note the significant postoperative cosmetic and functional improvements reported by patients who have undergone this procedure to compare to newer techniques as they evolve. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:2157-2161, 2022.


Assuntos
Obstrução Nasal , Rinoplastia , Estética , Humanos , Obstrução Nasal/cirurgia , Septo Nasal/cirurgia , Estudos Prospectivos , Rinoplastia/métodos
8.
Facial Plast Surg Aesthet Med ; 24(3): 240-246, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34494891

RESUMO

Objective: To compare the patient-reported outcomes among patients with nasal obstruction undergoing two rhinoplasty techniques to a control group. Methods: Prospective longitudinal study in a university-based tertiary care medical center. All patients undergoing functional septorhinoplasty for correction of lateral wall insufficiency between October 2015 and March 2019 were included; n = 704, mean age (standard deviation) 39.0 (15.4) years, 52.7% females. Patients completed the Nasal Obstruction Symptom Evaluation (NOSE) and FACE-Q subscales pre- and postoperatively. Patients were divided into three cohorts: spreader and lateral crural strut (LCS) grafts (n = 141), spreader and alar rim (AR) grafts (n = 104), and the control spreader grafts alone (n = 218). Results: The median NOSE scores at last postoperative visit were improved from baseline (p < 0.001) for all cohorts. The FACE-Q nasal satisfaction median scores also improved postoperatively in all cohorts, AR, LCS, and spreader, respectively (p = 0.001, p < 0.001, and p < 0.0001). Conclusions: There was no detectable difference in the improved subjective nasal function, nor adverse aesthetic outcomes in the patients with lateral wall insufficiency treated with functional rhinoplasty techniques in this study.


Assuntos
Obstrução Nasal , Rinoplastia , Adulto , Cartilagem/cirurgia , Cartilagem/transplante , Feminino , Humanos , Estudos Longitudinais , Masculino , Obstrução Nasal/cirurgia , Estudos Prospectivos , Rinoplastia/métodos
9.
Otolaryngol Head Neck Surg ; 166(6): 1172-1173, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-33687293

RESUMO

This commentary emphasizes health disparities related to systemic racism, highlighted by the COVID-19 pandemic, and provides recommendations to mitigate these disparities, including increasing racial and ethnic diversity in the surgical workforce.


Assuntos
COVID-19 , Racismo , COVID-19/epidemiologia , Disparidades em Assistência à Saúde , Humanos , Pandemias , Racismo Sistêmico
10.
Laryngoscope Investig Otolaryngol ; 6(6): 1358-1366, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34938875

RESUMO

OBJECTIVES: The majority of patients with head and neck squamous cell carcinoma (HNSCC) do not commence postoperative radiation treatment (PORT) within the recommended 6 weeks. We explore how delayed PORT affects survival outcomes, what factors are associated with delayed PORT initiation, and what interventions exist to reduce delays in PORT initiation. METHODS: We conducted a PubMed search to identify articles discussing timely PORT for HNSCC. We performed a narrative review to assess survival outcomes of delayed PORT as well as social determinants of health (SDOH) and clinical factors associated with delayed PORT, using the PROGRESS-Plus health equity framework to guide our analysis. We reviewed interventions designed to reduce delays in PORT. RESULTS: Delayed PORT is associated with reduced overall survival. Delays in PORT disproportionately burden patients of racial/ethnic minority backgrounds, Medicaid or no insurance, low socioeconomic status, limited access to care, more comorbidities, presentation at advanced stages, and those who experience postoperative complications. Delays in PORT initiation tend to occur during transitions in head and neck cancer care. Delays in PORT may be reduced by interventions that identify patients who are most likely to experience delayed PORT, support patients according to their specific needs and barriers to care, and streamline care and referral processes. CONCLUSIONS: Both SDOH and clinical factors are associated with delays in timely PORT. Structural change is needed to reduce health disparities and promote equitable access to care for all. When planning care, providers must consider not only biological factors but also SDOH to maximize care outcomes.

11.
Hum Mol Genet ; 30(17): 1607-1617, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34075397

RESUMO

Neurofibromatosis Type II (NF2) is an autosomal dominant cancer predisposition syndrome in which germline haploinsufficiency at the NF2 gene confers a greatly increased propensity for tumor development arising from tissues of neural crest derived origin. NF2 encodes the tumor suppressor, Merlin, and its biochemical function is incompletely understood. One well-established function of Merlin is as a negative regulator of group A serine/threonine p21-activated kinases (PAKs). In these studies we explore the role of PAK1 and its closely related paralog, PAK2, both pharmacologically and genetically, in Merlin-deficient Schwann cells and in a genetically engineered mouse model (GEMM) that develops spontaneous vestibular and spinal schwannomas. We demonstrate that PAK1 and PAK2 are both hyper activated in Merlin-deficient murine schwannomas. In preclinical trials, a pan Group A PAK inhibitor, FRAX-1036, transiently reduced PAK1 and PAK2 phosphorylation in vitro, but had insignificant efficacy in vivo. NVS-PAK1-1, a PAK1 selective inhibitor, had a greater but still minimal effect on our GEMM phenotype. However, genetic ablation of Pak1 but not Pak2 reduced tumor formation in our NF2 GEMM. Moreover, germline genetic deletion of Pak1 was well tolerated, while conditional deletion of Pak2 in Schwann cells resulted in significant morbidity and mortality. These data support the further development of PAK1-specific small molecule inhibitors and the therapeutic targeting of PAK1 in vestibular schwannomas and argue against PAK1 and PAK2 existing as functionally redundant protein isoforms in Schwann cells.


Assuntos
Neurofibromatose 2/genética , Quinases Ativadas por p21/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Genes Supressores de Tumor/efeitos dos fármacos , Indóis , Longevidade , Camundongos , Neurilemoma/genética , Neurofibromatose 2/metabolismo , Neurofibromina 2/genética , Fosforilação , Piperidinas , Pirimidinas , Células de Schwann/metabolismo , Quinases Ativadas por p21/genética
12.
Ann Otol Rhinol Laryngol ; 130(7): 840-842, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33094651

RESUMO

OBJECTIVE: To describe the retrograde removal of a tracheoesophageal (TE) prosthesis embedded in the common wall between the trachea and esophagus with preservation of the original tracheoesophageal puncture (TEP) tract with subsequent placement of new tracheoesophageal prosthesis for voice restoration. METHODS: The Blom-Singer TEP Set (InHealth Technologies, Carpinteria, CA) was used to facilitate this procedure. The coated wire leader cable was threaded through the small opening in the posterior tracheal wall and into the lumen of the old TE prosthesis. The wire was pulled through the mouth in retrograde fashion - bringing the old TE prosthesis out with it and dilating the existing TEP tract. A new prosthesis was then placed over the end of the wire and returned through the stoma, delivering the prosthesis through the TE tract and into the stoma. RESULTS: Safe, voice restoration with avoidance of need for multiple procedures. CONCLUSION: Removal of an embedded prosthesis and simultaneous replacement of a new prosthesis was safely and efficiently achieved using a retrograde technique which maintained the patency of the prior TE tract and restored voice.


Assuntos
Remoção de Dispositivo/métodos , Esôfago/cirurgia , Próteses e Implantes , Falha de Prótese , Traqueia/cirurgia , Idoso de 80 Anos ou mais , Humanos , Masculino
13.
Laryngoscope ; 131(2): E631-E634, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32330306

RESUMO

OBJECTIVE/HYPOTHESIS: To assess the long-term decannulation outcomes of bioresorbable microplates as an external stent for pediatric tracheostomy patients with suprastomal collapse. STUDY DESIGN: Retrospective cohort study. METHODS: Hospital records of all patients who underwent a bioresorbable microplate for suprastomal collapse from 2016 to 2019 were reviewed at a single institution. The primary outcome measure was tracheostomy decannulation. RESULTS: A total of nine patients underwent placement of bioabsorbable microplates to treat suprastomal collapse. After initial tracheostomy, four patients received a laryngotracheal reconstruction prior to their external stent placement, and one patient received a mandibular distraction. The average age at the time of external stent placement was 32 (±21) months, excluding one patient who received a stent at the age of 29 years. Eight patients (88.9%) were successfully decannulated following the procedure. Decannulated patients were followed for an average of 21 (±12.5) months postoperatively, and all these patients have remained decannulated since their initial procedure. This is a total of 173 months (14.4 years) of observation postprocedure in which these patients have remained decannulated. One patient experienced postoperative crepitus requiring washout but still maintained decannulation. CONCLUSION: Bioabsorbable microplates have a reasonable chance of long-term successful decannulation when an appropriate patient is selected. Decannulation is maintained beyond the 6-month time frame in which the 85:15 poly(L-lactide-co-glycolide) polymer that comprises the external stent takes to bioabsorb. This procedure should be considered for the often difficult problem of pediatric tracheostomy with isolated suprastomal collapse. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E631-E634, 2021.


Assuntos
Implantes Absorvíveis/efeitos adversos , Stents/efeitos adversos , Traqueostomia/efeitos adversos , Pré-Escolar , Humanos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Tempo , Traqueia/patologia , Traqueostomia/métodos
14.
Head Neck ; 43(2): 438-448, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33015935

RESUMO

BACKGROUND: Identifying and linking barriers to access to head and neck cancer care, specifically provider density, to stage of diagnosis and survival outcomes is important to serve as a foundation for policy interventions. METHODS: Retrospective cohort study using patients with head and neck squamous cell (HNSCC) in the Surveillance, Epidemiology, and End Results (SEER) database from 2007 to 2016 and Area Resource File. Primary outcomes included stage of presentation and cancer-specific 5-year survival and relation to provider density. RESULTS: The initial cohort consisted of 18 342 patients with oral cavity, 21 809 oropharyngeal, 15 860 laryngeal, and 2887 patients with hypopharyngeal malignancy. Non-Hispanic Black race and being uninsured increased the odds of presenting with advanced stage HNSCC and increased hazard of death. There was no significant and consistent association identified between Health Service Areas provider density and advanced stage at diagnosis or cancer-specific 5-year mortality. CONCLUSIONS: Provider density of otolaryngologists and primary care physicians and dentists was not significantly associated with stage of presentation or cancer-specific survival for HNSCC while race and insurance status remained independent predictors for worse outcomes.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Médicos , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Estadiamento de Neoplasias , Estudos Retrospectivos , Programa de SEER , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia
15.
Head Neck ; 43(2): 733-738, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33205536

RESUMO

This article provides best practice guidelines regarding nasopharyngolaryngoscopy and OHNS clinic reopening during the COVID-19 pandemic. The aim is to provide evidence-based recommendations defining the risks of COVID-19 in clinic, the importance of pre-visit screening in addition to testing, along with ways to adhere to CDC guidelines for environmental, source, and engineering controls.


Assuntos
COVID-19/prevenção & controle , Transmissão de Doença Infecciosa/prevenção & controle , Otolaringologia/normas , COVID-19/diagnóstico , COVID-19/transmissão , Teste para COVID-19/normas , Endocrinologia/normas , Humanos , Programas de Rastreamento/normas , Procedimentos Cirúrgicos Nasais/normas , Equipamento de Proteção Individual , Risco , SARS-CoV-2
17.
JAMA Otolaryngol Head Neck Surg ; 146(9): 1-10, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32745204

RESUMO

Importance: Women comprise an increasing proportion of the otolaryngology workforce. Prior studies have demonstrated gender-based disparity in physician practice and income in other clinical specialties; however, research has not comprehensively examined whether gender-based income disparities exist within the field of otolaryngology. Objective: To determine whether diversity of practice, clinical productivity, and Medicare payment differ between male and female otolaryngologists and whether any identified variation is associated with practice setting. Design, Setting, and Participants: Retrospective cross-sectional analysis of publicly available Medicare data summarizing payments to otolaryngologists from January 1 through December 31, 2017. Male and female otolaryngologists participating in Medicare in facility-based (FB; hospital-based) and non-facility-based settings (NFB; eg, physician office) for outpatient otolaryngologic care were included. Main Outcomes and Measures: Number of unique billing codes (diversity of practice) per physician, number of services provided per physician (physician productivity), and Medicare payment per physician. Outcomes were stratified by practice setting (FB vs NFB). Results: A total of 8456 otolaryngologists (1289 [15.2%] women; 7167 [84.8%] men) received Medicare payments in 2017. Per physician, women billed fewer unique codes (mean difference, -2.10; 95% CI, -2.46 to -1.75; P < .001), provided fewer services (mean difference, -640; 95% CI, -784 to -496; P < .001), and received less Medicare payment than men (mean difference, -$30 246 (95% CI, -$35 738 to -$24 756; P < .001). When stratified by practice setting, women in NFB settings billed 1.65 fewer unique codes (95% CI, -2.01 to -1.29; P < .001) and provided 633 fewer services (95% CI, -791 to -475; P < .001). In contrast, there was no significant gender-based difference in number of unique codes billed (mean difference, 0.04; 95% CI, -0.217 to 0.347; P = .81) or number of services provided (mean difference, 5.1; 95% CI, -55.8 to 45.6; P = .85) in the FB setting. Women received less Medicare payment in both settings compared with men (NFB: mean difference, -$27 746; 95% CI, -$33 502 to -$21 989; P < .001; vs FB: mean difference, -$4002; 95% CI, -$7393 to -$612; P = .02), although the absolute difference was lower in the FB setting. Conclusions and Relevance: Female sex is associated with decreased diversity of practice, lower clinical productivity, and decreased Medicare payment among otolaryngologists. Gender-based inequity is more pronounced in NFB settings compared with FB settings. Further efforts are necessary to better evaluate and address gender disparities within otolaryngology.


Assuntos
Eficiência , Renda , Reembolso de Seguro de Saúde/economia , Medicare/economia , Otolaringologia/economia , Padrões de Prática Médica/economia , Estudos Transversais , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores Sexuais , Estados Unidos
18.
World J Surg ; 44(11): 3616-3619, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32642795

RESUMO

BACKGROUND: Congenital anomalies are one component of the overwhelming surgical disease burden in low- and middle-income countries (LMICs). Lymphatic malformations (LMs) are a common congenital deformity of the head and neck in which the utilization of sclerotherapy may avoid surgery and yield superior outcomes. To be useful in LMICs, sclerosing agents must be widely available, inexpensive, and effective. METHODS: A retrospective review of 10 pediatric patients with macrocystic or mixed LMs who were treated with self-compounded doxycycline sclerotherapy at Rwanda's Central University Teaching Hospital of Kigali was performed. Doxycycline oral tablets were crushed by hand, mixed with normal saline at a concentration of doxycycline 10 mg/mL, and injected directly into LMs of the head and neck. RESULTS: Ten pediatric patients underwent 21 sclerotherapy sessions with a mean of 2.1 sessions per patient (SD 1.3, range 1-5). Of the 8 patients that were seen in follow-up, all achieved at least 80% resolution, 6 of 8 achieved 100% resolution, and none required surgery. One patient developed an infection at the injection site which resolved with antibiotics. CONCLUSIONS: Self-compounded doxycycline sclerotherapy is a safe, effective, and widely available treatment option for sclerotherapy of LMs in LMICs.


Assuntos
Anormalidades Congênitas/terapia , Doxiciclina , Escleroterapia , Criança , Doxiciclina/uso terapêutico , Cabeça/anormalidades , Humanos , Pescoço/anormalidades , Estudos Retrospectivos , Ruanda , Resultado do Tratamento
19.
Otolaryngol Head Neck Surg ; 162(4): 566-571, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32122241

RESUMO

OBJECTIVE: To analyze the prevalence of pediatric allergic airway disease (PAA) and recognize its impact on cognitive function, childhood activities, use of early intervention, and missed school days. STUDY DESIGN: Cross-sectional analysis of National Health Interview Survey (NHIS), 2014 to 2017. SETTING: US households. SUBJECTS AND METHODS: An NHIS survey of US children and responding caregivers was analyzed to determine the prevalence of PAA, including allergic rhinitis and allergic asthma. Associations were determined between the presence of PAA and activities limited by difficulty remembering, limitation in the amount of childhood play, use of special education/early intervention, and number of missed school days in the past 12 months. Multivariate analysis was used to adjust for age, sex, race, ethnicity, and income level. RESULTS: An estimated 11.1 million (10.6-11.6 million, 95% confidence interval) children (mean age, 9.9 years; 56.9% male) reported a diagnosis of PAA (15.1% [14.6-15.6%]). Children with PAA missed 4.0 (3.7-4.4) school days per year vs 2.2 (2.1-2.4) days for those without PAA (P < .001, adjusted). PAA was associated with limited daily activities due to difficulty with memory (odds ratio, 1.8 [1.2-2.9]), limitations in childhood play (3.2 [2.2-4.7]), and need for special education/early intervention services (1.6 [1.4-1.8]) after adjusting for age, sex, race, ethnicity, and income level. CONCLUSION: PAA is a common condition and is associated with declines in cognitive function and school attendance as well as increased use of special education/early intervention. Given the significant prevalence and burden of illness of PAA, further attention is needed to ensure timely diagnosis and treatment.


Assuntos
Asma/epidemiologia , Asma/psicologia , Cognição , Qualidade de Vida , Rinite Alérgica/epidemiologia , Rinite Alérgica/psicologia , Criança , Efeitos Psicossociais da Doença , Estudos Transversais , Feminino , Humanos , Masculino , Prevalência
20.
Mol Cancer Ther ; 18(12): 2321-2330, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31527226

RESUMO

Neurofibromatosis Type 1 (NF1) is one of the most common genetic tumor predisposition syndromes in humans. Mutant NF1 results in dysregulated RAS allowing neoplasms throughout the neuroaxis. Plexiform neurofibromas (pNF) afflict up to 50% of patients with NF1. They are complex tumors of the peripheral nerve that cause major morbidity via nerve dysregulation and mortality via conversion to malignant sarcoma. Genetically engineered mouse models (GEMM) of NF1 provide valuable insights for the identification of therapies that have utility in people with pNF. Preclinical studies in GEMMs implicate mast cells and the c-Kit/Kit ligand pathway in pNF tumorigenesis. Kit ligand is a potent chemokine secreted by tumorigenic, Nf1-deficient Schwann cells. Ketotifen is an FDA-approved drug for the treatment of allergic conjunctivitis and asthma that promotes mast cell stabilization and has been used in prior case studies to treat or prevent pNFs. This study investigated the effect of ketotifen on mast cell infiltration and degranulation in the presence and absence of Kit ligand provocation and the effect of ketotifen on shrinking or preventing pNF formation in the Nf1flox/flox ;PostnCre + GEMM. Ketotifen decreased mast cell infiltration in response to exogenous Kit ligand administration, but did not affect mast cell degranulation. Importantly, ketotifen did not reduce mast cells numbers or activity in pNF and did not prevent pNF formation or decrease the volume of established pNF despite administration of pharmacologically active doses. These findings suggest that ketotifen has limited use as monotherapy to prevent or reduce pNF burden in the setting of Nf1 mutations.


Assuntos
Quimiotaxia/fisiologia , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Cetotifeno/uso terapêutico , Mastócitos/efeitos dos fármacos , Neurofibroma/genética , Neurofibromina 1/deficiência , Animais , Antagonistas dos Receptores Histamínicos H1/farmacologia , Cetotifeno/farmacologia , Camundongos , Fator de Células-Tronco
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