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1.
Am J Otolaryngol ; 40(3): 404-408, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30799209

RESUMEN

OBJECTIVE: To examine global surgery involvement among general members of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) and characterize international otolaryngology surgical interventions. METHODS: Data on global surgery involvement were derived from responses provided by voluntary online survey respondent members of the AAO-HNS, obtained in October 2017. These data were compared against World Bank metrics of national health expenditure and surgical specialists per capita as benchmarks for need. RESULTS: There were 362 responses (response rate of 3.7%). A large proportion of respondents reported being involved in global surgery (61.3%). Locations where respondents worked included: South America (13.3%), Central America (17.7%), Caribbean (10.2%), Europe (4.1%), Africa (16.3%), Asia (16.6%), the Middle East (4.1%), and Oceania (3.6%). A greater proportion of respondents reported traveling to locations that have lower health care expenditure per capita and lower mean number of surgical specialists per 100,000 people, according to data from the World Bank. The primary purpose of trips was most commonly surgical mission (60.3%), followed by education (37.8%), and research (1.9%). CONCLUSION: Members of the AAO-HNS are active in global surgery efforts around the world. Collaboration among members of the AAO-HNS may serve to improve long-term sustainability of these efforts.


Asunto(s)
Salud Global , Internacionalidad , Otorrinolaringólogos/estadística & datos numéricos , Otolaringología/organización & administración , Procedimientos Quirúrgicos Otorrinolaringológicos/estadística & datos numéricos , Gastos en Salud/estadística & datos numéricos , Humanos , Área sin Atención Médica , Viaje/estadística & datos numéricos
2.
Am J Epidemiol ; 187(7): 1370-1379, 2018 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-29365014

RESUMEN

Despite established sex differences and longstanding hypotheses of sex hormone influence in the etiology of obstructive sleep apnea (OSA), we have found no studies that evaluated type of menopause and age at menopause, which affect postmenopausal hormonal milieu, in relation to OSA risk in women. We followed 50,473 postmenopausal women from the Nurses' Health Study during 2002-2012 and 53,827 postmenopausal women from the Nurses' Health Study II during 1995-2013, with 1,712 and 2,560 incident OSA diagnoses, respectively. Compared with natural menopause, the pooled hazard ratio for OSA was 1.27 (95% confidence interval (CI): 1.17, 1.38) for surgical menopause by hysterectomy/oophorectomy. The association remained the same after further accounting for age at menopause (hazard ratio = 1.26, 95% CI: 1.15, 1.38). The risk associated with surgical menopause was higher among women who were not obese as well as among women who never used hormone therapy (P for interaction < 0.05). Earlier menopause was associated with higher OSA risk prior to adjustment for type of menopause (comparing those aged <40 years versus those aged 50-54 years, hazard ratio = 1.21, 95% CI: 1.08, 1.35; P for trend = 0.008), although no association was observed after the adjustment. Surgical as compared with natural menopause was independently associated with higher OSA risk in postmenopausal women. Our results provide additional evidence for a role for sex hormones, particularly abrupt hormonal changes, in modulating OSA risk.


Asunto(s)
Factores de Edad , Menopausia , Obesidad/complicaciones , Posmenopausia , Apnea Obstructiva del Sueño/etiología , Adulto , Índice de Masa Corporal , Terapia de Reemplazo de Estrógeno/efectos adversos , Femenino , Encuestas Epidemiológicas , Humanos , Histerectomía/efectos adversos , Persona de Mediana Edad , Obesidad/fisiopatología , Ovariectomía/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/fisiopatología , Modelos de Riesgos Proporcionales , Factores de Riesgo , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/fisiopatología
3.
Eur Respir J ; 51(3)2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29449424

RESUMEN

Despite the well-known male predominance in the prevalence of obstructive sleep apnoea (OSA), sex differences in the associations between OSA and a comprehensive range of epidemiological factors remain less clear.We examined the prevalence of self-reported OSA in 143 326 females (age 48-93 years) from the Nurses' Health Study (NHS) and NHS-II and 22 896 males from the Health Professionals Follow-up Study (age 65-101 years) in 2012-2013. Multivariable logistic regression was used to estimate the sex-specific prevalence odds ratios (pOR) and 95% confidence intervals of OSA by demographic, anthropometric, lifestyle and comorbidity factors.The overall prevalence of self-reported OSA was 6.4% in females and 13.8% in males. After mutual adjustment, the associations of OSA with physical inactivity, hypertension and daytime sleepiness were stronger in females, whereas the associations with waist circumference and witnessed apnoea were stronger in males (p-heterogeneity <0.01). There were qualitative sex differences in the associations with age (pOR per 5-year increment in females 0.95, 95% CI 0.94-0.96, and males 1.04, 1.01-1.08; p-heterogeneity <0.0001) and marital status (pOR for married versus other in females 0.85, 95% CI 0.81-0.89, and males 1.11, 0.99-1.25; p-heterogeneity <0.0001).Substantial sex differences exist in the associations with various factors, suggesting sex-specific mechanisms in OSA.


Asunto(s)
Autoinforme , Factores Sexuales , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/epidemiología , Anciano , Anciano de 80 o más Años , Antropometría , Comorbilidad , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/complicaciones , Estilo de Vida , Masculino , Persona de Mediana Edad , Prevalencia , Conducta Sedentaria , Somnolencia
4.
J Am Acad Dermatol ; 78(4): 682-693, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29208416

RESUMEN

BACKGROUND: Statins are among the most commonly used medications in the United States, and statin use is associated with increased risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). However, previous studies are limited by lack of adjustment for important confounders. OBJECTIVE: Examine the relation between statins and skin cancer risk in the Nurses' Health Study and Health Professionals Follow-up Study. METHODS: Cox proportional hazards regression was used to evaluate associations. RESULTS: During follow-up (2000-2010), we documented 10,201 BCC, 1393 SCC, and 333 melanoma cases. History of high cholesterol level was not associated with risk of BCC (pooled multivariable-adjusted hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.00-1.09), SCC (HR, 0.95; 95% CI, 0.85-1.06), or melanoma (HR, 0.87; 95% CI, 0.64-1.19). Statin use was not associated with risk of BCC (HR, 1.04; 95% CI, 0.99-1.09]), SCC (HR, 1.08; 95% CI, 0.94-1.24), or melanoma (HR, 1.04; 95% CI, 0.78-1.38). There was a trend toward higher BCC risk with longer duration of statin use in men (P trend = .003) but not in women (P trend = .86). LIMITATIONS: Lack of treatment data. CONCLUSION: History of high cholesterol level was not associated with skin cancer risk. Longer duration of statin use was associated with a trend toward higher BCC risk in men.


Asunto(s)
Carcinoma Basocelular/inducido químicamente , Carcinoma Basocelular/epidemiología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/epidemiología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Medición de Riesgo
5.
Am J Epidemiol ; 186(1): 1-10, 2017 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-28525626

RESUMEN

Black individuals have a lower risk of hearing loss than do whites, possibly because of differences in cochlear melanocytes. Previous studies have suggested that darker-skinned individuals tend to have more inner ear melanin, and cochlear melanocytes are important in generating the endocochlear potential. We investigated the relationship between self-reported hearing loss and skin pigmentation by using hair color, skin tanning ability, and skin reaction to prolonged sun exposure as surrogate measures of pigmentation among 49,323 white women in the Nurses' Health Study. Cox proportional hazards regression models were used to adjust for potential confounders. During 1,190,170 person-years of follow-up (1982-2012), there was no association between risk of hearing loss and hair color (for black hair vs. red or blonde hair, multivariable-adjusted relative risk (RR) = 0.99, 95% confidence interval (CI): 0.90, 1.09), skin tanning ability (for dark tan vs. no tan, multivariable-adjusted RR = 0.98, 95% CI: 0.92, 1.05), skin reaction to prolonged sun exposure (for painful burn with blisters vs. practically no reaction, multivariable-adjusted RR = 1.01, 95% CI: 0.93, 1.08), or Fitzpatrick skin phototype (for type IV vs. type I, multivariable-adjusted RR = 0.99, 95% CI: 0.92, 1.05). In our cohort of white women, surrogates for skin pigmentation were not associated with risk of hearing loss.


Asunto(s)
Pérdida Auditiva/epidemiología , Pigmentación de la Piel , Población Blanca , Adulto , Factores de Edad , Consumo de Bebidas Alcohólicas/epidemiología , Índice de Masa Corporal , Sordera/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Dieta , Ejercicio Físico , Femenino , Color del Cabello , Humanos , Hipertensión/epidemiología , Persona de Mediana Edad , Enfermedades Mitocondriales/epidemiología , Modelos de Riesgos Proporcionales , Fumar/epidemiología , Bronceado
6.
Am J Epidemiol ; 185(1): 40-47, 2017 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-27974293

RESUMEN

Aspirin, nonsteroidal antiinflammatory drugs (NSAID), and acetaminophen are commonly used. Frequent use of analgesics has been associated with a higher risk of hearing loss. However, the association between duration of analgesic use and the risk of hearing loss is unclear. We investigated the relationship between duration of analgesic use and self-reported hearing loss among 55,850 women in the Nurses' Health Study. Cox proportional hazards regression was used to adjust for potential confounders. During 873,376 person-years of follow-up (1990-2012), longer durations of NSAID use (for >6 years of use compared with <1 year, multivariable-adjusted relative risk = 1.10, 95% confidence interval: 1.06, 1.15; P for trend < 0.001) and acetaminophen use (for >6 years of use compared with <1 year, multivariable-adjusted relative risk = 1.09, 95% confidence interval: 1.04, 1.14; P for trend < 0.001) were associated with higher risks of hearing loss. Duration of aspirin use was not associated with hearing loss (for >6 years of use compared with <1 year, multivariable-adjusted relative risk = 1.01, 95% confidence interval: 0.97, 1.05; P for trend = 0.35). In this cohort of women, longer durations of NSAID and acetaminophen use were associated with slightly higher risks of hearing loss, but duration of aspirin use was not. Considering the high prevalence of analgesic use, this may be an important modifiable contributor to hearing loss.


Asunto(s)
Acetaminofén/efectos adversos , Antiinflamatorios no Esteroideos/efectos adversos , Aspirina/efectos adversos , Relación Dosis-Respuesta a Droga , Pérdida Auditiva/inducido químicamente , Acetaminofén/administración & dosificación , Anciano , Analgésicos no Narcóticos/administración & dosificación , Analgésicos no Narcóticos/efectos adversos , Antiinflamatorios no Esteroideos/administración & dosificación , Aspirina/administración & dosificación , Femenino , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Medición de Riesgo , Autoinforme , Factores de Tiempo
7.
Ear Hear ; 38(1): 21-27, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-27556519

RESUMEN

OBJECTIVES: Gastroesophageal reflux disease (GERD) is common and often treated with proton pump inhibitors (PPIs) or H2-receptor antagonists (H2-RAs). GERD has been associated with exposure of the middle ear to gastric contents, which could cause hearing loss. Treatment of GERD with PPIs and H2-RAs may decrease exposure of the middle ear to gastric acid and decrease the risk of hearing loss. We prospectively investigated the relation between GERD, use of PPIs and H2-RAs, and the risk of hearing loss in 54,883 women in Nurses' Health Study II. DESIGN: Eligible participants, aged 41 to 58 years in 2005, provided information on medication use and GERD symptoms in 2005, answered the question on hearing loss in 2009 or in 2013, and did not report hearing loss starting before the date of onset of GERD symptoms or medication use. The primary outcome was self-reported hearing loss. Cox proportional hazards regression was used to adjust for potential confounders. RESULTS: During 361,872 person-years of follow-up, 9842 new cases of hearing loss were reported. Compared with no GERD symptoms, higher frequency of GERD symptoms was associated with higher risk of hearing loss (multivariable adjusted relative risks: <1 time/month 1.04 [0.97, 1.11], several times/week 1.17 [1.09, 1.25], daily 1.33 [1.19, 1.49]; p value for trend <0.001). After accounting for GERD symptoms, neither PPI nor H2-RA use was associated with the risk of hearing loss. CONCLUSIONS: GERD symptoms are associated with higher risk of hearing loss in women, but use of PPIs and H2-RAs are not independently associated with the risk.


Asunto(s)
Reflujo Gastroesofágico/epidemiología , Pérdida Auditiva/epidemiología , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Inhibidores de la Bomba de Protones/uso terapéutico , Adulto , Femenino , Estudios de Seguimiento , Reflujo Gastroesofágico/tratamiento farmacológico , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Factores Protectores , Factores de Riesgo , Encuestas y Cuestionarios , Estados Unidos/epidemiología
8.
World J Surg ; 41(1): 14-23, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27473131

RESUMEN

BACKGROUND: Approximately thirty percent of the global burden of disease is comprised of surgical conditions. However, five billion people lack access to surgery, with complex factors acting as barriers. We examined whether patient demographics predict barriers to care, and the relation between these factors and postoperative complications in a prospective cohort. METHODS: Participants included people presenting to a global charity in Republic of Congo with a surgical condition between August 2013 and May 2014. The outcomes were self-reported barrier to care and postoperative complications documented by medical record. Logistic regression was used to adjust for covariates. RESULTS: Of 1237 patients in our study, 1190 (96.2 %) experienced a barrier to care and 126 (10.2 %) experienced a postoperative complication. The most frequently reported barrier was cost (73 %), followed by lack of provider (8.2 %). Greater wealth was associated with decreased odds of cost as a barrier (OR 0.72 [0.57, 0.90]). Greater wealth (OR 1.52 [1.03, 2.25]) and rural home location (OR 3.35 [1.16, 9.62]) were associated with increased odds of no surgeon being available. Cost as a barrier (OR 2.82 [1.02, 7.77]), female sex (OR 3.45 [1.62, 7.33]), and lack of surgeon (OR 5.62 [1.68, 18.77]) were associated with increased odds of postoperative complication. Patient wealth was not associated with odds of postoperative complication. CONCLUSIONS: Barriers to surgery were common in Republic of Congo. Patient wealth and home location may predict barriers to surgery. Addressing gender disparities, access to providers, and patient perception of barriers in addition to removal of barriers may help maximize patient health benefits.


Asunto(s)
Accesibilidad a los Servicios de Salud , Complicaciones Posoperatorias/etiología , Servicio de Cirugía en Hospital , Adolescente , Adulto , Niño , Congo , Femenino , Humanos , Modelos Logísticos , Masculino , Estudios Prospectivos , Adulto Joven
9.
Am J Otolaryngol ; 38(6): 698-703, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28711236

RESUMEN

PURPOSE: There are no formal radiologic criteria to stratify patients for transcanal (TEES) or transmastoid endoscopic ear surgery for resection of cholesteatoma. We aim to determine 1) whether standard preoperative computed tomography (CT) findings are associated with the need for conversion to a transmastoid approach and 2) the amount of time added for conversion from TEES to transmastoid techniques. MATERIALS AND METHODS: Retrospective chart review of consecutive pediatric and adult cases of TEES for primary cholesteatoma from 2013 through 2015 (n=52). TEES cases were defined as endoscope-only procedures that did not require a transmastoid approach (n=33). Conversion cases were defined as procedures that began as TEES however, required conversion to a transmastoid approach due to the inability to complete cholesteatoma removal (n=19). Preoperative CT findings and total operating room (OR) times of TEES and conversion cases were compared. RESULTS: Preoperative CT scan characteristics that were associated with conversion included tegmen erosion (p=0.026), malleus erosion (p<0.001), incus erosion (p=0.009), mastoid opacification (p=0.009), soft tissue opacification extending into the aditus ad antrum (p=0.009) and into antrum (p=0.006). Total OR time for TEES cases was significantly shorter than conversion cases (median 143min versus 217min, p<0.001). CONCLUSIONS: Preoperative CT findings, notably extension of soft tissue in the aditus ad antrum, antrum and mastoid, are associated with need for conversion to transmastoid technique to achieve removal of cholesteatoma. Endoscope-only cases were significantly faster than cases that required conversion to a transmastoid approach.


Asunto(s)
Colesteatoma del Oído Medio/diagnóstico por imagen , Colesteatoma del Oído Medio/cirugía , Endoscopía , Hueso Temporal/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Adolescente , Adulto , Niño , Conversión a Cirugía Abierta , Estudios de Factibilidad , Femenino , Humanos , Masculino , Estudios Retrospectivos , Adulto Joven
10.
Cancer ; 119(19): 3462-71, 2013 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-23861037

RESUMEN

BACKGROUND: A subset of patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (HPV-OSCC) experience poor clinical outcomes. The authors of this report explored prognostic risk factors for overall survival (OS) and recurrence-free survival (RFS). METHODS: Patients with incident HPV-OSCC who received treatment at the Johns Hopkins Hospital between 1997 and 2008 and who had tissue available for HPV testing as well as demographic and clinicopathologic information (N = 176) were included. Tissue was tested for HPV by in situ hybridization (ISH) and/or p16 immunohistochemistry. Demographic and clinicopathologic information was extracted from medical records. RESULTS: In total, 157 of 176 patients (90%) with OSCC had HPV-associated disease (HPV-OSCC). In the patients with HPV-OSCC, the 3-year and 5-year OS rates were 93% (95% confidence interval [CI], 88%-98%) and 89% (95% CI, 81%-97%), respectively. Shorter survival was observed among older patients (hazard ratio [HR], 2.33 per 10-year increase; 95% CI, 1.05-5.16 per 10-year increase; P = .038), patients with advanced clinical T classification (HR, 5.78; 95% CI, 1.60-20.8; P = .007), and patients who were currently using tobacco (HR, 4.38; 95% CI, 1.07-18.0; P = .04). Disease recurrence was associated with advanced clinical T-classification (HR, 8.32; 95% CI, 3.06-23; P < .0001), current/former alcohol use (HR, 13; 95% CI, 1.33-120; P = .03), and unmarried status (HR, 3.28; 95% CI, 1.20-9.00; P = .02). Patients who remained recurrence free for 5 years had an 8.6% chance of recurrence by 10 years (1-sided 95% CI upper bound, 19%; P = .088). CONCLUSIONS: In this study, prognostic risk factors were identified for patients with HPV-OSCC. The observed recurrence rates between 5 years and 10 years after definitive therapy need to be validated in additional studies to determine whether extended cancer surveillance is warranted in this cancer population. Cancer 2013;119:3462-3471.. © 2013 American Cancer Society.


Asunto(s)
Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/virología , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/virología , Neoplasias Orofaríngeas/terapia , Neoplasias Orofaríngeas/virología , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Femenino , Neoplasias de Cabeza y Cuello/patología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neoplasias Orofaríngeas/patología , Infecciones por Papillomavirus/virología , Pronóstico , Factores de Riesgo , Carcinoma de Células Escamosas de Cabeza y Cuello , Análisis de Supervivencia , Resultado del Tratamiento
11.
BJU Int ; 111(1): 22-9, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22834909

RESUMEN

OBJECTIVE: To update the 2007 Partin tables in a contemporary patient population. PATIENTS AND METHODS: The study population consisted of 5,629 consecutive men who underwent RP and staging lymphadenectomy at the Johns Hopkins Hospital between January 1, 2006 and July 30, 2011 and met inclusion criteria. Polychotomous logistic regression analysis was used to predict the probability of each pathologic stage category: organ-confined disease (OC), extraprostatic extension (EPE), seminal vesicle involvement (SV+), or lymph node involvement (LN+) based on preoperative criteria. Preoperative variables included biopsy Gleason score (6, 3+4, 4+3, 8, and 9-10), serum PSA (0-2.5, 2.6-4.0, 4.1-6.0, 6.1-10.0, greater than 10.0 ng/mL), and clinical stage (T1c, T2c, and T2b/T2c). Bootstrap re-sampling with 1000 replications was performed to estimate 95% confidence intervals for predicted probabilities of each pathologic state. RESULTS: The median PSA was 4.9 ng/mL, 63% had Gleason 6 disease, and 78% of men had T1c disease. 73% of patients had OC disease, 23% had EPE, 3% had SV+ but not LN+, and 1% had LN+ disease. Compared to the previous Partin nomogram, there was no change in the distribution of pathologic state. The risk of LN+ disease was significantly higher for tumours with biopsy Gleason 9-10 than Gleason 8 (O.R. 3.2, 95% CI 1.3-7.6). The c-indexes for EPE vs. OC, SV+ vs. OC, and LN+ vs. OC were 0.702, 0.853, and 0.917, respectively. Men with biopsy Gleason 4+3 and Gleason 8 had similar predicted probabilities for all pathologic stages. Most men presenting with Gleason 6 disease or Gleason 3+4 disease have <2% risk of harboring LN+ disease and may have lymphadenectomy omitted at RP. CONCLUSIONS: The distribution of pathologic stages did not change at our institution between 2000-2005 and 2006-2011. The updated Partin nomogram takes into account the updated Gleason scoring system and may be more accurate for contemporary patients diagnosed with prostate cancer.


Asunto(s)
Estadificación de Neoplasias , Nomogramas , Neoplasias de la Próstata/patología , Adulto , Anciano , Humanos , Escisión del Ganglio Linfático/métodos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Antígeno Prostático Específico/sangre , Prostatectomía/métodos , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/cirugía , Factores de Riesgo
12.
BJU Int ; 110(8): 1122-8, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22373045

RESUMEN

UNLABELLED: What's known on the subject? and What does the study add? Men with high-risk prostate cancer experience recurrence, metastases and death at the highest rate in the prostate cancer population. Pathological stage at radical prostatectomy (RP) is the greatest predictor of recurrence and mortality in men with high-grade disease. Preoperative models predicting outcome after RP are skewed by the large proportion of men with low- and intermediate-risk features; there is a paucity of data about preoperative criteria to identify men with high-grade cancer who may benefit from RP. The present study adds comprehensive biopsy data from a large cohort of men with high-grade prostate cancer at biopsy. By adding biopsy parameters, e.g. number of high-grade cores and >50% involvement of any core, to traditional predictors of outcome (prostate-specific antigen concentration, clinical stage and Gleason sum), we can better inform men who present with high-grade prostate cancer as to their risk of favourable or unfavourable disease at RP. OBJECTIVE: To investigate preoperative characteristics that distinguish favourable and unfavourable pathological and clinical outcomes in men with high biopsy Gleason sum (8-10) prostate cancer to better select men who will most benefit from radical prostatectomy (RP). PATIENTS AND METHODS: The Institutional Review Board-approved institutional RP database (1982-2010) was analysed for men with high-Gleason prostate cancer on biopsy; 842 men were identified. The 10-year biochemical-free (BFS), metastasis-free (MFS) and prostate cancer-specific survival (CSS) were calculated using the Kaplan-Meier method to verify favourable pathology as men with Gleason <8 at RP or ≤ pT3a compared with men with unfavourable pathology with Gleason 8-10 and pT3b or N1. Preoperative characteristics were compared using appropriate comparative tests. Logistic regression determined preoperative predictors of unfavourable pathology. RESULTS: There was favourable pathology in 656 (77.9%) men. The 10-year BFS, MFS and CSS were 31.0%, 60.9% and 74.8%, respectively. In contrast, men with unfavourable pathological findings had significantly worse 10-year BFS, MFS and CSS, at 4.3%, 29.1% and 52.3%, respectively (all P < 0.001). In multivariable logistic regression, a prostate-specific antigen (PSA) concentration of >10 ng/mL (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.38-3.62, P = 0.001), advanced clinical stage (≥ cT2b; OR 2.55, 95% CI 1.55-4.21, P < 0.001), Gleason pattern 9 or 10 at biopsy (OR 2.55, 95% CI 1.59-4.09, P < 0.001), increasing number of cores positive with high-grade cancer (OR 1.16, 95% CI 1.01-1.34, P = 0.04) and >50% positive core involvement (OR 2.25, 95% CI 1.17-4.35, P = 0.015) were predictive of unfavourable pathology. CONCLUSIONS: Men with high-Gleason sum at biopsy are at high risk for biochemical recurrence, metastasis and death after RP; men with high Gleason sum and advanced pathological stage (pT3b or N1) have the worst prognosis. Among men with high-Gleason sum at biopsy, a PSA concentration of >10 ng/mL, clinical stage ≥ T2b, Gleason pattern 9 or 10, increasing number of cores with high-grade cancer and >50% core involvement are predictive of unfavourable pathology.


Asunto(s)
Prostatectomía , Neoplasias de la Próstata/cirugía , Adulto , Anciano , Biopsia con Aguja , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Pronóstico , Neoplasias de la Próstata/patología , Tasa de Supervivencia
13.
Nat Commun ; 13(1): 1359, 2022 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-35292639

RESUMEN

Inner ear gene therapy using adeno-associated viral vectors (AAV) promises to alleviate hearing and balance disorders. We previously established the benefits of Anc80L65 in targeting inner and outer hair cells in newborn mice. To accelerate translation to humans, we now report the feasibility and efficiency of the surgical approach and vector delivery in a nonhuman primate model. Five rhesus macaques were injected with AAV1 or Anc80L65 expressing eGFP using a transmastoid posterior tympanotomy approach to access the round window membrane after making a small fenestra in the oval window. The procedure was well tolerated. All but one animal showed cochlear eGFP expression 7-14 days following injection. Anc80L65 in 2 animals transduced up to 90% of apical inner hair cells; AAV1 was markedly less efficient at equal dose. Transduction for both vectors declined from apex to base. These data motivate future translational studies to evaluate gene therapy for human hearing disorders.


Asunto(s)
Dependovirus , Vectores Genéticos , Animales , Cóclea/fisiología , Dependovirus/genética , Técnicas de Transferencia de Gen , Terapia Genética/métodos , Vectores Genéticos/genética , Macaca mulatta/genética , Ratones
14.
Sleep ; 44(3)2021 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-33015707

RESUMEN

BACKGROUND AND OBJECTIVES: Chronic intermittent hypoxia resulting from obstructive sleep apnea (OSA) may activate multiple carcinogenic pathways and lead to cancer development. METHODS: We prospectively examined the association between OSA and cancer risk among 65,330 women in the Nurses' Health Study who were free of cancer in 2008 (mean age: 73.3 years). Incident cancer diagnoses were collected until 2016 and confirmed by pathology reports. Clinically diagnosed OSA was self-reported in 2008 and updated in 2012. We used time-dependent Cox regression to estimate hazard ratios (HR) for the associations of OSA with total and site-specific cancer risk. RESULTS: We documented 5,257 incident cancer diagnoses during follow-up. In the age-adjusted model, OSA was associated with a 15% (95% CI: 1.03, 1.29) increase in total cancer risk. The association became nonsignificant after adjustment for multiple cancer risk factors (HR: 1.08; 95% CI: 0.96, 1.21). When examining cancer risk by site, OSA was associated with significantly increased risk for lung (fully adjusted HR: 1.52; 95% CI: 1.07, 2.17), bladder (fully adjusted HR: 1.94; 95% CI: 1.12, 3.35), and thyroid cancer (fully adjusted HR: 2.06; 95% CI: 1.01, 4.22) and possibly increased risk for kidney cancer (fully adjusted HR: 1.59; 95% CI: 0.84, 3.01). When grouping cancer sites by risk factor profiles, OSA was positively associated with smoking-related cancers (fully adjusted HR: 1.37; 95% CI: 1.11, 1.67), and this association was stronger in never smokers than ever smokers. CONCLUSION: While OSA was not independently associated with overall cancer risk in older women, significant associations were observed for smoking-related cancers, especially in nonsmokers.


Asunto(s)
Neoplasias , Apnea Obstructiva del Sueño , Anciano , Femenino , Humanos , Neoplasias/epidemiología , Neoplasias/etiología , Estudios Prospectivos , Factores de Riesgo , Autoinforme , Apnea Obstructiva del Sueño/epidemiología
15.
J Neurosci ; 29(50): 15846-50, 2009 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-20016100

RESUMEN

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common known cause of Parkinson's disease (PD). Whether loss of LRRK2 function accounts for neurodegeneration of dopamine neurons in PD is not known, nor is it known whether LRRK2 kinase activity modulates the susceptibility of dopamine (DA) neurons to the selective dopaminergic toxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). To better understand the role of LRRK2 in DA neuronal survival and its role in the susceptibility of DA neurons to MPTP, we generated LRRK2 knock-out (KO) mice lacking the kinase domain of LRRK2. Here, we show that LRRK2 KO mice are viable and have no major abnormalities and live to adulthood. The dopaminergic system is normal in LRRK2 KO mice as assessed via HPLC for DA and its metabolites and via stereologic assessment of DA neuron number in young and aged mice. Importantly, there is no significant difference in the susceptibility of LRRK2 KO and wild-type mice to MPTP. These results suggest that LRRK2 plays little if any role in the development and survival of DA neurons under physiologic conditions. Thus, PD due to LRRK2 mutations are likely not due to a loss of function. Moreover, LRRK2 is not required for the susceptibility of DA neurons to MPTP.


Asunto(s)
Intoxicación por MPTP/genética , Intoxicación por MPTP/metabolismo , Proteínas Serina-Treonina Quinasas/deficiencia , Proteínas Serina-Treonina Quinasas/genética , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacología , Animales , Femenino , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología
16.
Laryngoscope Investig Otolaryngol ; 5(1): 117-121, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32128437

RESUMEN

OBJECTIVES: To present a histopathological case of a 91-year-old woman who was diagnosed with superior semicircular canal dehiscence postmortem. METHODS: The patient was a registered donor with the National Temporal Bone Donor Program at the NIDCD National Temporal Bone, Hearing and Balance Pathology Resource Registry. Computed tomography imaging was performed on each temporal bone. The temporal bones were decalcified with ethylenediaminetetracetate and embedded in celloidin, and tissue sections were stained with hematoxylin and eosin. Horizontal sections were taken through the left temporal bone, and vertical sections were taken through the right temporal bone. RESULTS: Histopathological sections taken through the right temporal bone demonstrated no bone between the membranous wall of the superior semicircular canal and the middle fossa dura. There was no histopathological evidence of superior semicircular canal dehiscence in the left temporal bone; however, a small dehiscence would not be identified on horizontal sections. Microcavitations were observed in the common crus of the left temporal bone. CONCLUSION: This reports describes the case of a woman who was diagnosed with superior semicircular canal dehiscence postmortem. The presence of microcavitations in the temporal bone is consistent with osteoclastic activity, which may play a role in the development of superior canal dehiscence.

17.
Am J Med ; 133(10): 1180-1186, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32387319

RESUMEN

BACKGROUND: Previous studies demonstrated higher risk of hearing loss among cigarette smokers, but longitudinal data on whether the risk is influenced by smoking cessation are limited. We prospectively investigated relations between smoking, smoking cessation, and risk of self-reported moderate or worse hearing loss among 81,505 women in the Nurses' Health Study II (1991-2013). METHODS: Information on smoking and hearing status was obtained from validated biennial questionnaires. Cox proportional hazards regression was used to estimate multivariable-adjusted relative risks (MVRR, 95% confidence interval). RESULTS: During 1,533,214 person-years of follow-up, 2760 cases of hearing loss were reported. Smoking was associated with higher risk of hearing loss and the risk tended to be higher with greater number of pack-years smoked. Compared with never smokers, the MVRR (95% confidence interval) among past smokers with 20+ pack-years of smoking was 1.30 (1.09-1.55) and 1.21 (1.02-1.43) for current smokers. The magnitude of elevated risk diminished with greater time since smoking cessation. Compared with never smokers, the MVRR among smokers who quit <5 years prior was 1.43 (1.17-1.75); 5-9 years prior was 1.27 (1.03-1.56); 10-14 years prior was 1.17 (0.96-1.41); and plateaued thereafter. Additional adjustment for pack-years smoking attenuated the results. CONCLUSIONS: The higher risk of hearing loss associated with smoking may diminish over time after quitting.


Asunto(s)
Fumar Cigarrillos/epidemiología , Pérdida Auditiva/epidemiología , Cese del Hábito de Fumar/estadística & datos numéricos , Adulto , Estudios de Cohortes , Femenino , Humanos , Estudios Longitudinales , Análisis Multivariante , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Estados Unidos/epidemiología
19.
Laryngoscope ; 128(1): 283-289, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-28144954

RESUMEN

OBJECTIVE: Intraoperative neural monitoring (IONM) of laryngeal nerves using electromyography (EMG) is routinely performed using endotracheal tube surface electrodes adjacent to the vocalis muscles. Other laryngeal muscles such as the posterior cricoarytenoid muscle (PCA) are indirectly monitored. The PCA may be directly and reliably monitored through an electrode placed in the postcricoid region. Herein, we describe the method and normative data for IONM using PCA EMG. STUDY DESIGN: Retrospective review. METHODS: Data were reviewed retrospectively for thyroid and parathyroid surgery patients with IONM of laryngeal nerves from January to August 2016. Recordings of vocalis and PCA EMG amplitudes and latencies with stimulation of laryngeal nerves were obtained using endotracheal (ET) tube-based and postcricoid surface electrodes. RESULTS: Data comprised EMG responses in vocalis and PCA recording channels with stimulation of the vagus, recurrent laryngeal nerve (RLN), and external branch of the superior laryngeal nerve from 20 subjects (11 left, 9 right), as well as PCA EMG threshold data with RLN stimulation from 17 subjects. Mean EMG amplitude was 725.69 ± 108.58 microvolts (µV) for the ipsilateral vocalis and 329.44 ± 34.12 µV for the PCA with vagal stimulation, and 1,059.75 ± 140.40 µV for the ipsilateral vocalis and 563.88 ± 116.08 µV for the PCA with RLN stimulation. There were no statistically significant differences in mean latency. For threshold cutoffs of the PCA with RLN stimulation, mean minimum and maximum threshold intensities were 0.37 milliamperes (mA) and 0.84 mA, respectively. CONCLUSION: This study shows robust and reliable PCA EMG waveforms with direct nerve stimulation. Further studies will evaluate feasibility and application of the PCA electrode as a complementary quantitative tool in IONM. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:283-289, 2018.


Asunto(s)
Electromiografía , Músculos Laríngeos/inervación , Enfermedades de las Paratiroides/cirugía , Nervio Laríngeo Recurrente/fisiología , Enfermedades de la Tiroides/cirugía , Nervio Vago/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Intraoperatorio , Disección del Cuello , Paratiroidectomía , Estudios Retrospectivos , Tiroidectomía
20.
Diabetes Care ; 41(10): 2111-2119, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30072403

RESUMEN

OBJECTIVE: Multiple lines of evidence support a complex relationship between obstructive sleep apnea (OSA) and diabetes. However, no population-based study has evaluated the potential bidirectional association between these two highly prevalent disorders. RESEARCH DESIGN AND METHODS: We followed 146,519 participants from the Nurses' Health Study (NHS; 2002-2012), Nurses' Health Study II (NHSII; 1995-2013), and Health Professionals Follow-up Study (HPFS; 1996-2012) who were free of diabetes, cardiovascular disease, and cancer at baseline. Cox proportional hazards models were used to estimate hazard ratios (HRs) for developing diabetes according to OSA status. In parallel, we used similar approaches to estimate risk of developing OSA according to diabetes status among 151,194 participants free of OSA, cardiovascular disease, and cancer at baseline. In all three cohorts, diagnoses of diabetes and OSA were identified by validated self-reports. RESULTS: Similar results were observed across the three cohorts. In the pooled analysis, 9,029 incident diabetes cases were identified during follow-up. After accounting for potential confounders, the HR (95% CI) for diabetes was 2.06 (1.86, 2.28) comparing those with versus without OSA. The association was attenuated but remained statistically significant after further adjusting for waist circumference and BMI (HR 1.37 [95% CI 1.24, 1.53]), with the highest diabetes risk observed for OSA concomitant with sleepiness (1.78 [1.13, 2.82]). In the second analysis, we documented 9,364 incident OSA cases during follow-up. Compared with those without diabetes, the multivariable HR (95% CI) for OSA was 1.53 (1.32, 1.77) in individuals with diabetes. Adjustment for BMI and waist circumference attenuated the association (1.08 [1.00, 1.16]); however, an increased risk was observed among those with diabetes who used insulin compared with those without diabetes (1.43 [1.11, 1.83]), particularly among women (1.60 [1.34, 1.89]). CONCLUSIONS: OSA is independently associated with an increased risk of diabetes, whereas insulin-treated diabetes is independently associated with a higher risk of OSA, particularly in women. Clinical awareness of this bidirectional association may improve prevention and treatment of both diseases. Future research aimed at elucidating the mechanisms that underlie each association may identify novel intervention targets.


Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/epidemiología , Adulto , Anciano , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/epidemiología , Femenino , Estudios de Seguimiento , Empleos en Salud/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Estados Unidos/epidemiología
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