Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 76
Filtrar
1.
J Intensive Care Med ; 38(1): 86-94, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35731642

RESUMO

BACKGROUND: Spontaneous awakening trials (SATs), spontaneous breathing trials (SBTs), delirium assessment/management, early mobility have been termed the ABCDE bundle. The ABCDE bundle has been proven to improve patient outcomes. However, there is often a long gap in dissemination and implementation of evidence-based medicine. OBJECTIVES: To determine the prevalent implementation of and determinants for ABCDE protocol adoption in Pennsylvania. METHODS: We developed a survey of ABCDE bundle protocols. We surveyed factors around implementation including written protocol presence, standardized assessments to guide protocols, timing of creation of protocols, and estimated adherence to protocols. We also collected data on factors that might be determinants for protocol adoption including ICU staffing models, hospital and ICU level factors. We validated the survey tool using the Michigan Health and Hospital Association Keystone ICU collaborative. We then administered the validated survey to a leader of the medical ICU or mixed medical-surgical ICU of all Pennsylvania Hospitals. Multivariable logistic and ordinal regression were used to determine associations between ICU staffing models and hospital and ICU level factors with the presence of ABCDE bundle protocols. RESULTS: In the study cohort of Pennsylvania ICUs (n = 144), we had 100 respondents (69% response). The median number of hospital beds among the respondents was 185 (IQR 111-355) with a median of 14 ICU beds (IQR 10-20). 86% reported spontaneous awakening trial protocols, 60% reported spontaneous breathing trial protocols, 43% reported delirium assessment/management protocols, and 27% reported early mobility protocols. Being a medical ICU compared to a mixed medical-surgical ICU (OR 3.48, 95% CI 1.19-10.21, P = .02) and presence of multidisciplinary rounds (OR 4.97, 95% CI 2.07-11.94, P < .001) were associated with increasing number of ABCDE bundle protocol components. CONCLUSIONS: Variable implementation of ABCDE bundle protocols was present across Pennsylvania. Team communication is important to implementation of these protocols.


Assuntos
Delírio , Deambulação Precoce , Humanos , Deambulação Precoce/métodos , Cuidados Críticos/métodos , Delírio/diagnóstico , Delírio/terapia , Unidades de Terapia Intensiva , Inquéritos e Questionários
2.
Nat Med ; 25(10): 1505-1511, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31591596

RESUMO

The essential product of the Duchenne muscular dystrophy (DMD) gene is dystrophin1, a rod-like protein2 that protects striated myocytes from contraction-induced injury3,4. Dystrophin-related protein (or utrophin) retains most of the structural and protein binding elements of dystrophin5. Importantly, normal thymic expression in DMD patients6 should protect utrophin by central immunologic tolerance. We designed a codon-optimized, synthetic transgene encoding a miniaturized utrophin (µUtro), deliverable by adeno-associated virus (AAV) vectors. Here, we show that µUtro is a highly functional, non-immunogenic substitute for dystrophin, preventing the most deleterious histological and physiological aspects of muscular dystrophy in small and large animal models. Following systemic administration of an AAV-µUtro to neonatal dystrophin-deficient mdx mice, histological and biochemical markers of myonecrosis and regeneration are completely suppressed throughout growth to adult weight. In the dystrophin-deficient golden retriever model, µUtro non-toxically prevented myonecrosis, even in the most powerful muscles. In a stringent test of immunogenicity, focal expression of µUtro in the deletional-null German shorthaired pointer model produced no evidence of cell-mediated immunity, in contrast to the robust T cell response against similarly constructed µDystrophin (µDystro). These findings support a model in which utrophin-derived therapies might be used to treat clinical dystrophin deficiency, with a favorable immunologic profile and preserved function in the face of extreme miniaturization.


Assuntos
Terapia Genética , Distrofias Musculares/terapia , Distrofia Muscular Animal/terapia , Distrofia Muscular de Duchenne/terapia , Utrofina/genética , Animais , Dependovirus/genética , Modelos Animais de Doenças , Cães , Distrofina/genética , Humanos , Camundongos , Camundongos Endogâmicos mdx , Contração Muscular/genética , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Distrofias Musculares/genética , Distrofias Musculares/patologia , Distrofia Muscular Animal/genética , Distrofia Muscular Animal/patologia , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/patologia , Transgenes/genética , Utrofina/uso terapêutico
3.
AIDS Res Hum Retroviruses ; 35(10): 934-940, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31347379

RESUMO

HIV-positive people are at increased risk for malignancies associated with human papillomavirus (HPV) infection, including oropharyngeal squamous cell carcinoma (OPSCC). The purpose of this study was to determine whether cancer treatment disparities exist between HIV-positive and HIV-negative people with OPSCC. We conducted a retrospective cohort study comparing OPSCC treatment adequacy and treatment outcomes in HIV-positive and HIV-negative people in the post-antiretroviral therapy era. Treatment adequacy was determined by measuring two primary endpoints associated with OPSCC survival: time to therapy and total radiation dose. Treatment outcomes were assessed by measuring disease-free and overall survival. We identified a total of 37 HIV-positive and 149 HIV-negative people with OPSCC. HIV-positive people experienced a median delay of 10 days from time of OPSCC diagnosis to start of therapy compared with HIV-negative people [hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.38-0.98]. Total post-radiation dose in HIV-positive people was lower than that in HIV-negative people [58.5 Gray (Gy) versus 64.4 Gy, p = .04]. HIV-positive people also experienced greater hazards for disease recurrence (HR 3.43, 95% CI 1.39-8.46) and death (HR 4.21, 95% CI 1.29-13.80) compared with HIV-negative people. In conclusion, we detected a clinically important delay in time to therapy as well as worse disease-free and overall survival in HIV-positive people with OPSCC compared with their HIV-negative counterparts. These findings are relevant to understanding how HIV-positive people are diagnosed and undergo therapy for HPV-associated malignancies and highlight the need to address cancer treatment disparities in this group.


Assuntos
Carcinoma de Células Escamosas/complicações , Infecções por HIV/complicações , Neoplasias Orofaríngeas/complicações , Adulto , Idoso , Fármacos Anti-HIV/uso terapêutico , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/terapia , Terapia Combinada , Comorbidade , Fatores de Confusão Epidemiológicos , Intervalo Livre de Doença , Feminino , Infecções por HIV/tratamento farmacológico , Soronegatividade para HIV , Soropositividade para HIV , Papillomavirus Humano 16/isolamento & purificação , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Razão de Chances , Neoplasias Orofaríngeas/epidemiologia , Neoplasias Orofaríngeas/terapia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Tempo para o Tratamento , Fumar Tabaco/epidemiologia , Resultado do Tratamento , Estados Unidos/epidemiologia , Carga Viral
4.
Am J Emerg Med ; 37(7): 1219-1223, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30197233

RESUMO

BACKGROUND: Concussion guidelines recommend a vestibular and oculomotor (VOM) examination be performed for all patients with concern for concussion, however the feasibility of performing testing is unknown. We aimed to measure rates of exam performance after implementation of training and support tools in a pediatric emergency department. METHODS: We conducted a retrospective study of patients age 6 to 18 years old presenting over a 12-month period. Charts were obtained via natural language processing, where concussion was suggested as a diagnosis in the electronic health record, and then manually reviewed to record patient and provider factors. A multivariable logistic regression was performed to determine factors associated with exam performance, and a classification and regression tree (CART) analysis was performed to determine if a specific patient type was at risk for not having testing performed. RESULTS: Four hundred patients were included in the analysis. Sixty-four percent received a VOM examination (including 73% of those diagnosed with concussion). Provider type, concussion history, symptom burden, injury mechanism, and final diagnosis were all significantly associated with exam performance. CART analysis determined patients with a non-concussion diagnosis, a non-sports injury mechanism, no prior history of concussion, and two or fewer symptoms had the lowest likelihood (46%) of receiving the exam. CONCLUSION: Performing a VOM examination for concussion is feasible in the acute setting following provider education and using clinical support tools. The exam is more likely to be performed on those children with history or exam findings associated with perceived risk for ongoing symptoms.


Assuntos
Concussão Encefálica/diagnóstico , Movimentos Oculares , Testes de Função Vestibular , Adolescente , Criança , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Estudos Retrospectivos
5.
J Palliat Med ; 21(6): 820-824, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29676957

RESUMO

BACKGROUND: When attempting to share information about comfort-oriented care, many use "palliative," "supportive," and "hospice" care terminology interchangeably, but we lack evidence about the effects of using these different terms. OBJECTIVES: This study was designed to test whether the use of "palliative," "supportive," or "hospice" terminology can improve the dissemination of information among breast cancer patients-a large and growing oncology population. Design, Setting, and Measurement: This experimental study was conducted at a major U.S. hospital serving a diverse population. Patients visiting a cancer clinic encountered opportunities to learn more about cancer care. They were offered health materials that were described as reporting on "palliative," "supportive," or "hospice" care and the primary outcome was whether a patient decided to select or reject each. As a secondary outcome, the study measured the patient's level of interest in receiving each. RESULTS: Compared with alternatives, materials labeled as "supportive" care were most likely to be selected and considered valuable (p value <0.01). CONCLUSIONS: In this study, the terminology used had a large effect and, compared with alternatives, the information labeled as being about "supportive" care was significantly more likely to be selected. If these effects are supported by additional research, there may be low-cost, highly feasible changes in language choice that increase the dissemination of relevant health information.


Assuntos
Comunicação , Cuidados Paliativos na Terminalidade da Vida/classificação , Disseminação de Informação/métodos , Neoplasias/enfermagem , Cuidados Paliativos/classificação , Conforto do Paciente/classificação , Terminologia como Assunto , Feminino , Cuidados Paliativos na Terminalidade da Vida/normas , Humanos , Pessoa de Meia-Idade , Cuidados Paliativos/normas , Conforto do Paciente/normas , Estados Unidos
6.
Am J Health Promot ; 32(4): 932-938, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29050506

RESUMO

PURPOSE: To test the effects of different messengers on the dissemination of health information. DESIGN: An experimental study exposed participants to 12 news articles pertaining to 1 of 3 health topics framed from the perspective of 4 generic messengers: religious figures, doctors, celebrity patients, or ordinary patients. Participants select as many of the 12 articles as desired. SETTING: A cancer clinic within a large, urban hospital serving a sociodemographically diverse patient population. PARTICIPANTS: Eighty-nine patients with a history of cancer. MEASURES: The primary outcome was the frequency with which each news story was selected. ANALYSIS: Summary statistics and a general estimating equation model. RESULTS: For each health topic, news articles using celebrity messengers were the least likely to be selected; almost half of the participants (36 [41.4%] of 87) rejected all such articles. Articles linked to religious figures were equally unpopular ( P = .59). Articles that used doctors or ordinary patients as the messenger were very likely to be selected: Nearly all women (84 [96.6%] of 87) selected at least one of these. Furthermore, the odds of choosing articles linked to celebrities or religious leaders were statistically significantly lower than the odds of choosing those linked to ordinary patients or doctors ( P < .01). CONCLUSION: Commonly used generic messengers had large effects on the dissemination of information. Health materials linked to celebrities or religious figures were consistently less likely to be selected than those linked to ordinary patients, or doctors.


Assuntos
Promoção da Saúde/métodos , Disseminação de Informação/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/psicologia , Clero , Pessoas Famosas , Feminino , Humanos , Pessoa de Meia-Idade , Grupo Associado , Médicos
7.
Am J Respir Crit Care Med ; 195(3): 360-368, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-27602993

RESUMO

RATIONALE: The aromatase inhibitor anastrozole blocks the conversion of androgens to estrogen and blunts pulmonary hypertension in animals, but its efficacy in treating patients with pulmonary arterial hypertension (PAH) is unknown. OBJECTIVES: We aimed to determine the safety and efficacy of anastrozole in PAH. METHODS: We performed a randomized, double-blind, placebo-controlled trial of anastrozole in patients with PAH who received background therapy at two centers. MEASUREMENTS AND MAIN RESULTS: A total of 18 patients with PAH were randomized to anastrozole 1 mg or matching placebo in a 2:1 ratio. The two co-primary outcomes were percent change from baseline in 17ß-estradiol levels (E2) and tricuspid annular plane systolic excursion (TAPSE) at 3 months. Anastrozole significantly reduced E2 levels compared with placebo (percent change: -40%; interquartile range [IQR], -61 to -26% vs. -4%; IQR, -14 to +4%; P = 0.003), but there was no difference in TAPSE. Anastrozole significantly increased the 6-minute-walk distance (median change = +26 m) compared with placebo (median change = -12 m) (median percent change: anastrozole group, 8%; IQR, 2 to 17% vs. placebo -2%; IQR, -7 to +1%; P = 0.042). Anastrozole had no effect on circulating biomarkers, functional class, or health-related quality of life. There was no difference in adverse events. CONCLUSIONS: Anastrozole significantly reduced E2 levels in patients with PAH but had no effect on TAPSE. Anastrozole was safe, well tolerated, and improved 6-minute-walk distance in this small "proof-of-principle" study. Larger and longer phase II clinical trials of anastrozole may be warranted in patients with PAH. Clinical trial registered with www.clinicaltrials.gov (NCT 1545336).


Assuntos
Inibidores da Aromatase/uso terapêutico , Hormônios Esteroides Gonadais/sangue , Hipertensão Pulmonar/tratamento farmacológico , Nitrilas/uso terapêutico , Esteroides/sangue , Triazóis/uso terapêutico , Anastrozol , Inibidores da Aromatase/administração & dosagem , Inibidores da Aromatase/efeitos adversos , Biomarcadores/sangue , Método Duplo-Cego , Estradiol/sangue , Estrona/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas/administração & dosagem , Nitrilas/efeitos adversos , Progesterona/sangue , Triazóis/administração & dosagem , Triazóis/efeitos adversos
8.
J Pediatr ; 182: 375-377.e2, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27939107

RESUMO

To compare pulse oximetry measurement bias between infants with hypoxemia with either dark skin or light skin with Masimo Radical 7 and Nellcor Oximax. There was no significant difference in systematic bias based on skin pigment for either oximeter.


Assuntos
Cardiopatias Congênitas/diagnóstico , Hipóxia/diagnóstico , Recém-Nascido Prematuro , Oximetria/métodos , Pigmentação da Pele/fisiologia , Estado Terminal , Estudos Transversais , Feminino , Hospitais Pediátricos , Humanos , Hipóxia/sangue , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Masculino , Estudos Prospectivos , Sensibilidade e Especificidade , Estatísticas não Paramétricas
9.
AIDS Behav ; 21(6): 1676-1683, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27878639

RESUMO

Identifying a relationship between depression and sexual risk behavior in HIV-infected patients could establish a mechanism to enhance prevention efforts. We conducted a cross-sectional analysis using data from the University of Pennsylvania Center for AIDS Research and used ordinal logistic regression to measure the association between depression and non-condom use. 716 men who have sex with men (MSM), 262 heterosexual men and 277 heterosexual women were included. The association between depression and non-condom use was strongest in heterosexual men with and without HIV-infected regular partners (OR 8.53, 95% CI 1.18-61.89 and OR 2.30, 95% CI 0.99-5.36 respectively), but absent in heterosexual women regardless of partner. Although the OR was low in MSM overall, an association was detected in MSM without HIV-infected regular partners (OR 2.44, 95% CI 1.39-4.31). In conclusion, we demonstrated an association between depression and non-condom use driven by heterosexual men and MSM without HIV-infected regular partners. Sexual risk should be addressed when intervening on depressive symptoms in these subgroups.


Assuntos
Preservativos/estatística & dados numéricos , Depressão/epidemiologia , Infecções por HIV/diagnóstico , Infecções por HIV/psicologia , Heterossexualidade/psicologia , Homossexualidade Masculina/psicologia , Sexo Seguro/estatística & dados numéricos , Comportamento Sexual/estatística & dados numéricos , Adulto , Estudos Transversais , Depressão/psicologia , Feminino , Infecções por HIV/epidemiologia , Heterossexualidade/estatística & dados numéricos , Homossexualidade Masculina/estatística & dados numéricos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Assunção de Riscos , Comportamento Sexual/psicologia , Parceiros Sexuais , Inquéritos e Questionários , Estados Unidos/epidemiologia
10.
J Dermatol Sci ; 82(2): 123-8, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26874971

RESUMO

BACKGROUND: Patients with pruritus have been shown to have an increased incidence of certain subtypes of malignancy. OBJECTIVE: To assess predictors of malignancy in patients with chronic pruritus without prior dermatologic diagnoses. METHODS: Case-control study of 398 patients with chronic pruritus who developed a malignancy were compared with 8346 patients with chronic pruritus who did not develop a malignancy. Primary outcomes were odds of developing incident malignancy. RESULTS: Age greater than 60 years (OR 4.04, 95% CI 3.08, 5.31), male sex (OR 1.39, 95% CI 1.13, 1.71) and liver disease (OR 2.37, 95% CI 1.00, 5.65) were predictors of malignancy development in patients with chronic pruritus and non-diseased skin. In an exploratory analysis with multiple imputation via chained equations, age greater than 60 years (OR 4.13, 95% CI 3.15, 5.42), male sex (OR 1.26, 95% CI 1.02, 1.55), and current or prior smoking (OR 2.02, 95% CI 1.42, 2.88) were predictors of malignancy development in patients with chronic pruritus and non-diseased skin. LIMITATIONS: Potential for misclassification and detection biases. Missing data. CONCLUSIONS AND RELEVANCE: In patients with chronic pruritus without concomitant dermatologic diagnoses, older age, male sex, liver disease and tobacco abuse increase the odds of an underlying malignancy.


Assuntos
Neoplasias/epidemiologia , Prurido/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Doença Crônica , Estudos de Coortes , Detecção Precoce de Câncer , Feminino , Humanos , Incidência , Hepatopatias/complicações , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Neoplasias/etiologia , Medição de Risco , Fatores Sexuais , Fumar/efeitos adversos , Reino Unido/epidemiologia
11.
J Neurotrauma ; 33(8): 734-40, 2016 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-26414329

RESUMO

We have developed and implemented a noninvasive, objective neurofunctional assessment for evaluating the sustained effects of traumatic brain injury (TBI) in piglets with both diffuse and focal injury types. Derived from commercial actigraphy methods in humans, this assessment continuously monitors the day/night activity of piglets using close-fitting jackets equipped with tri-axial accelerometers to monitor movements of the thorax. Acceleration metrics were correlated (N = 7 naïve piglets) with video images to define values associated with a range of activities, from recumbancy (rest) to running. Both focal (N = 8) and diffuse brain injury (N = 9) produced alterations in activity that were significant 4 days post-TBI. Compared to shams (N = 6) who acclimated to the animal facility 4 days after an anesthesia experience by blurring the distinction between day and night activity, post-TBI time-matched animals had larger fractions of inactive periods during the daytime than nighttime, and larger fractions of active time in the night were spent in high activity (e.g., constant walking, intermittent running) than during the day. These persistent disturbances in rest and activity are similar to those observed in human adults and children post-TBI, establishing actigraphy as a translational metric, used in both humans and large animals, for assessment of injury severity, progressions, and intervention.


Assuntos
Actigrafia/métodos , Lesões Encefálicas Difusas/fisiopatologia , Ritmo Circadiano/fisiologia , Atividade Motora/fisiologia , Animais , Animais Recém-Nascidos , Lesões Encefálicas/fisiopatologia , Feminino , Humanos , Suínos
12.
Neurourol Urodyn ; 35(6): 738-42, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-25995132

RESUMO

AIM: To determine the association between self-reported adherence to anticholinergic medication and clinical outcomes in women with overactive bladder (OAB). METHODS: A prospective study of women with OAB treated with fesoterodine for 8 weeks. Adherence to medication was measured using the Medication Adherence Self-report Inventory (MASRI). A self reported adherence rate of ≥80% was considered adherent. The association between self-reported adherence and clinical outcomes (Global Index of Improvement, Global impression of Severity, urinary symptom and quality of life scores) was examined. We hypothesized that adherent women would have greater improvement in urinary symptoms and quality of life than non-adherent women. RESULTS: Based on the MASRI, 115 (62.5%) women were adherent and 69 (37.5%) were non-adherent to anticholinergic medication at 8weeks. Adherent women were more likely to report overall improvement in their symptoms compared to non-adherent women (84% vs. 24%, P < 0.001). Significantly more non-adherent women described their bladder symptoms as "moderate" or "severe" at 8 weeks compared to adherent women (74% vs. 44%, P = 0.03). At 8 weeks, adherent women reported significantly greater improvement (change) in urinary symptoms from baseline to 8 weeks than non-adherent women (-13.3 ± 25.8 vs. 2.5 ± 14.4, P = 0.04). Similarly, adherent women reported greater improvement in quality of life scores than non-adherent women (- 7.9 ± 24.0 vs. -1.8 ± 11.9, P = 0.003). CONCLUSION: Self-reported non-adherence, as measured by the MASRI, is associated with clinically meaningful outcomes in women with OAB. This further validates the MASRI as a clinically useful tool for measuring adherence to anticholinergic medications in women with OAB. Neurourol. Urodynam. 35:738-742, 2016. © 2015 Wiley Periodicals, Inc.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Adesão à Medicação , Antagonistas Muscarínicos/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico , Agentes Urológicos/uso terapêutico , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Autorrelato , Resultado do Tratamento
14.
PLoS One ; 10(7): e0131093, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26176544

RESUMO

Over the past ten years, unconventional gas and oil drilling (UGOD) has markedly expanded in the United States. Despite substantial increases in well drilling, the health consequences of UGOD toxicant exposure remain unclear. This study examines an association between wells and healthcare use by zip code from 2007 to 2011 in Pennsylvania. Inpatient discharge databases from the Pennsylvania Healthcare Cost Containment Council were correlated with active wells by zip code in three counties in Pennsylvania. For overall inpatient prevalence rates and 25 specific medical categories, the association of inpatient prevalence rates with number of wells per zip code and, separately, with wells per km2 (separated into quantiles and defined as well density) were estimated using fixed-effects Poisson models. To account for multiple comparisons, a Bonferroni correction with associations of p<0.00096 was considered statistically significant. Cardiology inpatient prevalence rates were significantly associated with number of wells per zip code (p<0.00096) and wells per km2 (p<0.00096) while neurology inpatient prevalence rates were significantly associated with wells per km2 (p<0.00096). Furthermore, evidence also supported an association between well density and inpatient prevalence rates for the medical categories of dermatology, neurology, oncology, and urology. These data suggest that UGOD wells, which dramatically increased in the past decade, were associated with increased inpatient prevalence rates within specific medical categories in Pennsylvania. Further studies are necessary to address healthcare costs of UGOD and determine whether specific toxicants or combinations are associated with organ-specific responses.


Assuntos
Exposição Ambiental , Hospitalização/estatística & dados numéricos , Fraturamento Hidráulico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pennsylvania/epidemiologia , Medição de Risco
15.
Brain Pathol ; 25(3): 289-303, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25904045

RESUMO

We have developed the first immature large animal translational treatment trial of a pharmacologic intervention for traumatic brain injury (TBI) in children. The preclinical trial design includes multiple doses of the intervention in two different injury types (focal and diffuse) to bracket the range seen in clinical injury and uses two post-TBI delays to drug administration. Cyclosporin A (CsA) was used as a case study in our first implementation of the platform because of its success in multiple preclinical adult rodent TBI models and its current use in children for other indications. Tier 1 of the therapy development platform assessed the short-term treatment efficacy after 24 h of agent administration. Positive responses to treatment were compared with injured controls using an objective effect threshold established prior to the study. Effective CsA doses were identified to study in Tier 2. In the Tier 2 paradigm, agent is administered in a porcine intensive care unit utilizing neurological monitoring and clinically relevant management strategies, and intervention efficacy is defined as improvement in longer term behavioral endpoints above untreated injured animals. In summary, this innovative large animal preclinical study design can be applied to future evaluations of other agents that promote recovery or repair after TBI.


Assuntos
Lesões Encefálicas/tratamento farmacológico , Ciclosporina/uso terapêutico , Modelos Animais de Doenças , Fármacos Neuroprotetores/uso terapêutico , Pesquisa Translacional Biomédica , Animais , Relação Dose-Resposta a Droga , Feminino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Exame Neurológico , Suínos , Fatores de Tempo , Resultado do Tratamento
16.
Mech Ageing Dev ; 146-148: 23-7, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25804384

RESUMO

Genes which confer a relative longevity advantage may be regulated at the level of transcription or translation. Alternatively, pro-longevity genes may mediate their effects at the level of protein structure-functional relationships that are beneficially optimized in long-lived species. Longevity associated genes (LAGs) may be operationally defined as genes that confer beneficial effects and are relatively more conserved among long-lived species. Global and local protein sequence alignments of over 10,000 genes across at least 30 mammalian species were examined to identify LAGs. Known LAGs, including growth hormone receptor (GHR), and breast cancer 1, early onset (BRCA1), have strong associations with maximum lifespan by our analysis. Several common categories of protein function were observed among genes ranked with the strongest associations with MLS identified by all regression models. These genes included those that function in the immune system, cell cycle regulation, and DNA damage response. We provide a ranking of genes with the strongest associations with species maximum lifespan (MLS) by several phylogenetic generalized least squares regression models, including adjustment for confounding variables such as body weight and gestation length.


Assuntos
Bases de Dados Genéticas , Longevidade/genética , Modelos Genéticos , Animais , Humanos
17.
Neurourol Urodyn ; 34(5): 424-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24719232

RESUMO

AIM: To validate a self-administered instrument, the Medication Adherence Self-Report Inventory (MASRI) for measuring adherence to anti-cholinergic medication for overactive bladder (OAB). METHODS: Prospective study in 131 women with OAB treated with fesoterodine. Adherence was measured at 8 and 12 weeks using an interviewer administered brief medication questionnaire (BMQ) that assesses barriers to adherence (criterion standard), the MASRI, and pill count. Construct, concurrent and discriminant validity of the MASRI was assessed. We hypothesized that women who were non-adherent as measured by the MASRI would be more likely to have a belief barrier than women who were adherent to medication. RESULTS: Women diagnosed as non-adherent by the MASRI were more likely to report a belief barrier to taking medication as compared to adherent women at 8 weeks (80% vs. 38%, P < 0.001) and at 12 weeks (70% vs. 40%, P = 0.003). Significant correlations were noted between adherence rates measured by the MASRI and the BMQ at 8 weeks (r = 0.87, P < 0.001) and 12 weeks (r = 0.90, P < 0.001). Moderate correlation was noted between the adherence rate as measured by the MASRI and pill count at 8 weeks (r = 0.49, P = 0.02) but not at 12 weeks (r = 0.05, P = 0.87). The MASRI correctly identified 93% and 96% of non-adherent women at 8 and 12 weeks, respectively. Sensitivity, specificity, and positive likelihood ratio of the MASRI for predicting non-adherence was 91%, 82%, and 5.1 at 8 weeks and 90%, 85% and 6.1 at 12 weeks. CONCLUSIONS: The MASRI is a valid self-administered tool for measuring adherence to anti-cholinergic medication in women with OAB.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Adesão à Medicação , Antagonistas Muscarínicos/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico , Idoso , Atitude Frente a Saúde , Antagonistas Colinérgicos/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Inquéritos e Questionários
18.
Neurourol Urodyn ; 34(6): 539-43, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24752925

RESUMO

AIMS: Disability, an individual's reduced capacity to perform physical tasks encountered in daily routine, is associated with urinary incontinence in the elderly. Our objective was to determine if urinary incontinence is associated with disability in community-dwelling women 40 years and older. METHODS: Cross-sectional study among US women ≥40 years (n = 4,458) from National Health and Nutrition Examination Surveys 2005-2010. We estimated the age-stratified weighted prevalence and factors independently associated with disability (Activities of Daily Living (ADLs), Instrumental Activities of Daily Living (IADLs), mobility, and functional limitations) in women with and without urinary incontinence while controlling for confounders of the association between disability and urinary incontinence. RESULTS: The weighted prevalence of all disabilities was higher in women with urinary incontinence than women without urinary incontinence across most decades of life with the greatest difference in the prevalence of mobility disabilities: 40-49 years (12.1% vs. 7.0%), 50-59 years (17.0% vs. 9.2%), 60-69 years (28.3% vs. 19.8%), and 70+ years (43.8% vs. 33.0%, all P < 0.05). On multivariable analysis, after controlling for the confounding effect of age, co-morbidities, and income-poverty ratio, urinary incontinence was weakly associated with disabilities. The adjusted odds ratio (95% confidence interval) of disabilities for urinary incontinence was ADL 1.96 (1.07, 3.58), IADL 1.18 (0.78, 1.78), mobility 1.26 (1.01, 1.56), and functional limitations 1.36 (1.07, 1.73). CONCLUSIONS: Urinary incontinence is weakly associated with disabilities and cannot be implicated as a cause of disability in community dwelling women.


Assuntos
Incontinência Urinária/epidemiologia , Atividades Cotidianas , Adulto , Fatores Etários , Idoso , Estudos Transversais , Avaliação da Deficiência , Feminino , Inquéritos Epidemiológicos , Humanos , Renda , Pessoa de Meia-Idade , Limitação da Mobilidade , Inquéritos Nutricionais , Pobreza , Prevalência , Fatores Socioeconômicos , Estados Unidos/epidemiologia , Incontinência Urinária/etiologia , Adulto Jovem
19.
Proc Natl Acad Sci U S A ; 111(47): 16830-5, 2014 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-25385584

RESUMO

The cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs) may be influenced by interactions with antiplatelet doses of aspirin. We sought to quantitate precisely the propensity of commonly consumed NSAIDs­ibuprofen, naproxen, and celecoxib­to cause a drug-drug interaction with aspirin in vivo by measuring the target engagement of aspirin directly by MS. We developed a novel assay of cyclooxygenase-1 (COX-1) acetylation in platelets isolated from volunteers who were administered aspirin and used conventional and microfluidic assays to evaluate platelet function. Although ibuprofen, naproxen, and celecoxib all had the potential to compete with the access of aspirin to the substrate binding channel of COX-1 in vitro, exposure of volunteers to a single therapeutic dose of each NSAID followed by 325 mg aspirin revealed a potent drug-drug interaction between ibuprofen and aspirin and between naproxen and aspirin but not between celecoxib and aspirin. The imprecision of estimates of aspirin consumption and the differential impact on the ability of aspirin to inactivate platelet COX-1 will confound head-to-head comparisons of distinct NSAIDs in ongoing clinical studies designed to measure their cardiovascular risk.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Aspirina/farmacologia , Plaquetas/efeitos dos fármacos , Ciclo-Oxigenase 1/metabolismo , Acetilação , Plaquetas/enzimologia , Humanos , Microfluídica
20.
Int J Environ Res Public Health ; 11(6): 6517-27, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25003172

RESUMO

Pennsylvania Marcellus Shale region residents have reported medical symptoms they believe are related to nearby Unconventional Natural Gas Development (UNGD). Associations between medical symptoms and UNGD have been minimally explored. The objective of this descriptive study is to explore whether shale region Pennsylvania residents perceive UNGD as a health concern and whether they attribute health symptoms to UNGD exposures. A questionnaire was administered to adult volunteers with medical complaints in a primary-care medical office in a county where UNGD was present. Participants were asked whether they were concerned about health effects from UNGD, and whether they attributed current symptoms to UNGD or to some other environmental exposure. There were 72 respondents; 22% perceived UNGD as a health concern and 13% attributed medical symptoms to UNGD exposures. Overall, 42% attributed one or more of their medical symptoms to environmental causes, of which UNGD was the most frequent. A medical record review conducted on six participants who attributed their medical symptoms to UNGD revealed that only one of these records documented both the symptoms in question and the attribution to UNGD. The results of this pilot study suggest that there is substantial concern about adverse health effects of UNGD among Pennsylvania Marcellus Shale residents, and that these concerns may not be adequately represented in medical records. Further efforts to determine the relationship between UNGD and health are recommended in order to address community concerns.


Assuntos
Atitude Frente a Saúde , Exposição Ambiental/efeitos adversos , Indústrias Extrativas e de Processamento , Indicadores Básicos de Saúde , Campos de Petróleo e Gás , Indústrias Extrativas e de Processamento/métodos , Feminino , Humanos , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Gás Natural , Pennsylvania/epidemiologia , Projetos Piloto , Inquéritos e Questionários
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA