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1.
J Neurooncol ; 162(2): 337-342, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36988747

RESUMEN

PURPOSE: This study seeks to expound upon risk factor etiologies for surgical site infection (SSI) and investigate their combinatorial effects on infection rate following craniotomy for neuro-oncologic pathology. METHODS: Patients who underwent neuro-oncologic craniotomy between 2006 and 2020 were included. Medical records were reviewed to identify the occurrence of wound infection at ≤ 3 months postoperatively. Potential risk factors for infection included tumor pathology, location, anesthesia type, indication, ventricular entry, foreign body, brachytherapy, lumbar drain, prior operation, prior cranial radiation, prior infection, bevacizumab, and medical comorbidities (hypertension, obesity, diabetes, hyperlipidemia, other cancer, cirrhosis). Logistic regression was implemented to determine risk factors for SSI. Chi-square tests were used to assess whether the number of risk factors (e.g., 0, ≥ 1, ≥2, ≥ 3, ≥4) increases the risk of SSI compared to patients with fewer risk factors. The relative increase with each additional risk factor was also evaluated. RESULTS: A total of 1209 patients were included. SSI occurred in 42 patients (3.5%) by 90 days after surgery. Significant risk factors on multivariate logistic regression were bevacizumab (OR 40.84; p < 0.001), cirrhosis (OR 14.20, p = 0.03), foreign body placement (OR 4.06; P < 0.0001), prior radiation (OR 2.20; p = 0.03), and prior operation (OR 1.92; p = 0.04). Infection rates in the combinatorial analysis were as follows: ≥1 risk factor = 5.9% (OR 2.74; p = 0.001), ≥ 2 = 6.7% (OR 2.28; p = 0.01), ≥ 3 = 19.0% (OR 6.5; p < 0.0001), ≥ 4 = 100% (OR 30.2; p < 0.0001). CONCLUSIONS: Risk factors in aggregate incrementally increase the risk of postoperative SSI after craniotomy for tumor.


Asunto(s)
Neoplasias , Infección de la Herida Quirúrgica , Humanos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Bevacizumab , Factores de Riesgo , Craneotomía/efectos adversos , Neoplasias/complicaciones , Estudios Retrospectivos
2.
J Biol Chem ; 297(3): 101003, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34303705

RESUMEN

Autophagy is an evolutionarily conserved pathway mediating the breakdown of cellular proteins and organelles. Emphasizing its pivotal nature, autophagy dysfunction contributes to many diseases; nevertheless, development of effective autophagy modulating drugs is hampered by fundamental deficiencies in available methods for measuring autophagic activity or flux. To overcome these limitations, we introduced the photoconvertible protein Dendra2 into the MAP1LC3B locus of human cells via CRISPR/Cas9 genome editing, enabling accurate and sensitive assessments of autophagy in living cells by optical pulse labeling. We used this assay to perform high-throughput drug screens of four chemical libraries comprising over 30,000 diverse compounds, identifying several clinically relevant drugs and novel autophagy modulators. A select series of candidate compounds also modulated autophagy flux in human motor neurons modified by CRISPR/Cas9 to express GFP-labeled LC3. Using automated microscopy, we tested the therapeutic potential of autophagy induction in several distinct neuronal models of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In doing so, we found that autophagy induction exhibited discordant effects, improving survival in disease models involving the RNA binding protein TDP-43, while exacerbating toxicity in neurons expressing mutant forms of UBQLN2 and C9ORF72 associated with familial ALS/FTD. These studies confirm the utility of the Dendra2-LC3 assay, while illustrating the contradictory effects of autophagy induction in different ALS/FTD subtypes.


Asunto(s)
Autofagia , Proteínas Adaptadoras Transductoras de Señales/genética , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/terapia , Autofagia/efectos de los fármacos , Proteínas Relacionadas con la Autofagia/genética , Proteína C9orf72/genética , Sistemas CRISPR-Cas , Proteínas de Unión al ADN/genética , Ensayos de Selección de Medicamentos Antitumorales , Demencia Frontotemporal/genética , Demencia Frontotemporal/terapia , Células HEK293 , Ensayos Analíticos de Alto Rendimiento , Humanos , Proteínas Luminiscentes/genética , Proteínas Asociadas a Microtúbulos/genética , Modelos Biológicos , Neuronas Motoras/metabolismo , Mutación
3.
Value Health ; 25(2): 268-275, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35094800

RESUMEN

OBJECTIVES: To investigate the extent to which stated preferences for treatment criteria elicited using multicriteria decision analysis (MCDA) methods are consistent with the trade-offs (implicitly) applied in cost-effectiveness analysis (CEA), and the impact of any differences on the prioritization of treatments. METHODS: We used existing MCDA and CEA models developed to evaluate interventions for knee osteoarthritis in the New Zealand population. We established equivalent input parameters for each model, for the criteria "treatment effectiveness," "cost," "risk of serious harms," and "risk of mild-to-moderate harms" across a comprehensive range of (hypothetical) interventions to produce a complete ranking of interventions from each model. We evaluated the consistency of these rankings between the 2 models and investigated any systematic differences between the (implied) weight placed on each criterion in determining rankings. RESULTS: There was an overall moderate-to-strong correlation in intervention rankings between the MCDA and CEA models (Spearman correlation coefficient = 0.51). Nevertheless, there were systematic differences in the evaluation of trade-offs between intervention attributes and the resulting weights placed on each criterion. The CEA model placed lower weights on risks of harm and much greater weight on cost (at all accepted levels of willingness-to-pay per quality-adjusted life-year than did respondents to the MCDA survey. CONCLUSIONS: MCDA and CEA approaches to inform intervention prioritization may give systematically different results, even when considering the same criteria and input data. These differences should be considered when designing and interpreting such studies to inform treatment prioritization decisions.


Asunto(s)
Técnicas de Apoyo para la Decisión , Atención a la Salud/economía , Osteoartritis de la Rodilla/terapia , Adulto , Anciano , Anciano de 80 o más Años , Análisis Costo-Beneficio , Toma de Decisiones , Humanos , Persona de Mediana Edad , Modelos Teóricos , Nueva Zelanda , Años de Vida Ajustados por Calidad de Vida , Factores de Riesgo , Encuestas y Cuestionarios , Resultado del Tratamiento
4.
Acta Neurochir (Wien) ; 164(3): 867-874, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35028744

RESUMEN

PURPOSE: Postoperative surgical site infections (SSIs) constitute a significant source of morbidity for neurosurgical patients. Protocols that minimize postoperative wound infections are integral to improving outcomes and curtailing expenditures. The present study seeks to identify risk factors for infection and assess the efficacy of prophylactic betadine irrigation and vancomycin powder in addition to standard antibiotic irrigation. METHODS: We reviewed craniotomies performed by THS at Weill Cornell/New York Presbyterian Hospital to treat neuro-oncologic pathology. Patients were divided into three groups: group 1 - antibiotic irrigation, group 2 - antibiotic irrigation and betadine irrigation, group 3 - antibiotic irrigation, betadine irrigation, and vancomycin powder. SSI was confirmed with bacterial culture. Risk factor identification and assessment of treatment paradigms was performed using chi-square tests and univariate logistic regression. RESULTS: Among 1209 total patients, the 30- and 90-day SSI rates were 1.7% and 3.5%, respectively. Significant predictors of SSI included preoperative use of bevacizumab (OR 40.84; p < 0.0001), foreign body (OR 4.06; p < 0.0001), prior radiation (OR 2.20; p = 0.03), and prior operation/biopsy (OR 1.92; p = 0.04). Risk of infection was 2.1% in low-risk cases and 6.9% in high-risk cases. A significant, incremental decrement in SSIs was identified between the prophylaxis groups, although only among low-risk cases: group 1: 4.53%, group 2: 1.39%, group 3: 0.42% (p = 0.02). Neither vancomycin powder nor betadine significantly reduced the risk of SSI in patients with one or more risk factors. CONCLUSION: Vancomycin powder with betadine irrigation decreased SSI rates following neuro-oncologic cranial procedures in patients at low risk of infection (i.e., no preoperative risk factors).


Asunto(s)
Povidona Yodada , Vancomicina , Antibacterianos/uso terapéutico , Profilaxis Antibiótica/métodos , Estudios de Cohortes , Humanos , Incidencia , Povidona Yodada/uso terapéutico , Polvos , Estudios Retrospectivos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/prevención & control , Vancomicina/uso terapéutico
5.
Brain Inj ; 36(2): 258-270, 2022 01 28.
Artículo en Inglés | MEDLINE | ID: mdl-35143350

RESUMEN

PRIMARY OBJECTIVE: To describe the collaborative development of a New Zealand Rugby Concussion Assessment (NZRCA) for primary care and to provide normative baseline data from a representative group of high school rugby players. METHODS: This study, conducted over the 2018 and 2019 community rugby season where players were baseline tested during the pre- or start of season period. RESULTS: Data were collected from 1428 players (males n = 1121, females n = 307) with a mean age of 15.9 ± 1.4 years. The mean ± SD symptom severity score was 11.3 ± 8.6, the mean number of endorsed symptoms was 8.5 ± 5.3 and the percentage feeling "normal" was 80.2 ± 15.3%. Only 5.3% of players reported no symptoms at baseline. The most common reported were: 'distracted easily' (72.5%), 'forgetful' (68.5%), and 'often tired' (62.6%). None of the participants achieved a perfect score for the SAC50. The majority of participants (89.7%) passed the tandem gait test with a time of 12.2 ± 1.7 seconds. Age, gender, and ethnicity were associated with NZRCA performance; albeit weakly. CONCLUSION: This study provides normative reference values for high-school rugby players. These data will aid healthcare providers in their identification of suspected concussion in the absence of individualized baselines.


Asunto(s)
Traumatismos en Atletas , Conmoción Encefálica , Fútbol Americano , Adolescente , Traumatismos en Atletas/diagnóstico , Conmoción Encefálica/diagnóstico , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Nueva Zelanda/epidemiología , Atención Primaria de Salud , Rugby , Instituciones Académicas
6.
Brain Inj ; 35(11): 1433-1442, 2021 09 19.
Artículo en Inglés | MEDLINE | ID: mdl-34658272

RESUMEN

OBJECTIVE: To report pre-season baseline concussion assessment performance among senior rugby players and explore associations between assessment performance and player demographics. DESIGN: A cross-sectional study using the New Zealand Rugby Concussion Assessments (NZRCA), comprising symptom, cognitive and dynamic coordination assessments was conducted in the 2018-2019 season. METHODS: Players' baseline assessments were characterised using descriptive statistics; effect sizes (ES) and t-tests were used to explore associations between player demographic characteristics and NZRCA performance. RESULTS: A total of 733 players (11.4% female) aged between 16 and 52 years completed the NZRCA. The median (range) value for symptom severity, endorsed symptoms and "percentage normal" was respectively, 5 (0-40), 5 (0-21) and 90% (30-100%). A perfect standardised assessment of concussion score was achieved by one participant; seven achieved ≥27/30 for immediate recall, and 22 achieved a perfect delayed recall score. Most participants (n = 674, 92%) passed the tandem gait test. Associations between NZRCA performance and gender, concussion history, and Pasifika ethnicity were observed with effect sizes ranging from small (0.18) to large (0.70). Six hundred and twenty-three (85%) participants reported at least one symptom. CONCLUSIONS: The results from this study could help support decision-making by clinicians, improving the management of concussions in the community setting.


Asunto(s)
Traumatismos en Atletas , Conmoción Encefálica , Fútbol Americano , Adolescente , Adulto , Traumatismos en Atletas/diagnóstico , Conmoción Encefálica/diagnóstico , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Rugby , Adulto Joven
7.
J Med Internet Res ; 22(6): e18315, 2020 06 05.
Artículo en Inglés | MEDLINE | ID: mdl-32442143

RESUMEN

BACKGROUND: Digital technologies connect young people with health services and resources that support their self-care. The lack of accessible, reliable digital resources tailored to young people with persistent musculoskeletal pain is a significant gap in the health services in Australia. Recognizing the intense resourcing required to develop and implement effective electronic health (eHealth) interventions, the adaptation of extant, proven digital technologies may improve access to pain care with cost and time efficiencies. OBJECTIVE: This study aimed to test the acceptability and need for adaptation of extant digital technologies, the painHEALTH website and the iCanCope with Pain app, for use by young Australians with musculoskeletal pain. METHODS: A 3-phased, mixed methods evaluation was undertaken from May 2019 to August 2019 in Australia. Young people aged 15 to 25 years with musculoskeletal pain for >3 months were recruited. Phases were sequential: (1) phase 1, participant testing (3 groups, each of n=5) of co-designed website prototypes compared with a control website (painHEALTH), with user tasks mapped to eHealth quality and engagement criteria; (2) phase 2, participants' week-long use of the iCanCope with Pain app with engagement data captured using a real-time analytic platform (daily check-ins for pain, interference, sleep, mood, physical activity, and energy levels; goal setting; and accessing resources); and (3) phase 3, semistructured interviews were conducted to gain insights into participants' experiences of using these digital technologies. RESULTS: Fifteen young people (12/15, 80% female; mean age 20.5 [SD 3.3] years; range 15-25 years) participated in all 3 phases. The phase 1 aggregated group data informed the recommendations used to guide 3 rapid cycles of prototype iteration. Adaptations included optimizing navigation, improving usability (functionality), and enhancing content to promote user engagement and acceptability. In phase 2, all participants checked in, with the highest frequency of full check-ins attributed to pain intensity (183/183, 100.0%), pain interference (175/183, 95.6%), and mood (152/183, 83.1%), respectively. Individual variability was evident for monitoring progress with the highest frequency of history views for pain intensity (51/183, 32.3%), followed by pain interference (24/183, 15.2%). For the goals set feature, 87% (13/15) of participants set a total of 42 goals covering 5 areas, most frequently for activity (35/42, 83%). For phase 3, metasynthesis of qualitative data highlighted that these digital tools were perceived as youth-focused and acceptable. A total of 4 metathemes emerged: (1) importance of user-centered design to leverage user engagement; (2) website design (features) promoting user acceptability and engagement; (3) app functionality supporting self-management; and (4) the role of wider promotion, health professional digital prescriptions, and strategies to ensure longer-term engagement. CONCLUSIONS: Leveraging extant digital tools, with appropriate user-informed adaptations, can help to build capacity tailored to support young people's self-management of musculoskeletal pain.


Asunto(s)
Dolor Musculoesquelético/terapia , Automanejo/métodos , Telemedicina/métodos , Adolescente , Adulto , Femenino , Humanos , Masculino , Adulto Joven
8.
Curr Oncol Rep ; 21(4): 30, 2019 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-30835007

RESUMEN

PURPOSE OF REVIEW: Temozolomide is a first-line treatment for newly diagnosed glioblastoma. In this review, we will examine the use of temozolomide in other contexts for treating gliomas, including recurrent glioblastoma, glioblastoma in the elderly, diffuse low- and high-grade gliomas, non-diffuse gliomas, diffuse intrinsic pontine glioma (DIPG), ependymoma, pilocytic astrocytoma, and pleomorphic xanthoastrocytoma. RECENT FINDINGS: Temozolomide improved survival in older patients with glioblastoma, anaplastic gliomas regardless of 1p/19q deletion status, and progressive ependymomas. Temozolomide afforded less toxicity and comparable efficacy to radiation in high-risk low-grade gliomas and to platinum-based chemotherapy in pediatric high-grade gliomas. The success of temozolomide in promoting survival has expanded beyond glioblastoma to benefit patients with non-glioblastoma tumors. Identifying practical biomarkers for predicting temozolomide susceptibility, and establishing complementary agents for chemosensitizing tumors to temozolomide, will be key next steps for future success.


Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Práctica Clínica Basada en la Evidencia , Glioblastoma/tratamiento farmacológico , Temozolomida/uso terapéutico , Neoplasias Encefálicas/patología , Glioblastoma/patología , Humanos
9.
Hum Mol Genet ; 23(5): 1376-86, 2014 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-24150846

RESUMEN

Spinobulbar muscular atrophy (SBMA) is an inherited neuromuscular disorder caused by the expansion of a CAG repeat encoding a polyglutamine tract in exon 1 of the androgen receptor (AR) gene. SBMA demonstrates androgen-dependent toxicity due to unfolding and aggregation of the mutant protein. There are currently no disease-modifying therapies, but of increasing interest for therapeutic targeting is autophagy, a highly conserved cellular process mediating protein quality control. We have previously shown that genetic manipulations inhibiting autophagy diminish skeletal muscle atrophy and extend the lifespan of AR113Q knock-in mice. In contrast, manipulations inducing autophagy worsen muscle atrophy, suggesting that chronic, aberrant upregulation of autophagy contributes to pathogenesis. Since the degree to which autophagy is altered in SBMA and the mechanisms responsible for such alterations are incompletely defined, we sought to delineate autophagic status in SBMA using both cellular and mouse models. Here, we confirm that autophagy is induced in cellular and knock-in mouse models of SBMA and show that the transcription factors transcription factor EB (TFEB) and ZKSCAN3 operate in opposing roles to underlie these changes. We demonstrate upregulation of TFEB target genes in skeletal muscle from AR113Q male mice and SBMA patients. Furthermore, we observe a greater response in AR113Q mice to physiological stimulation of autophagy by both nutrient starvation and exercise. Taken together, our results indicate that transcriptional signaling contributes to autophagic dysregulation and provides a mechanistic framework for the pathologic increase of autophagic responsiveness in SBMA.


Asunto(s)
Autofagia/genética , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Regulación de la Expresión Génica , Trastornos Musculares Atróficos/genética , Factores de Transcripción/metabolismo , Activación Transcripcional , Animales , Modelos Animales de Enfermedad , Humanos , Masculino , Ratones , Ratones Transgénicos , Trastornos Musculares Atróficos/metabolismo , Péptidos/genética , Condicionamiento Físico Animal , Receptores Androgénicos/genética
10.
BMC Med Educ ; 16: 62, 2016 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-26879982

RESUMEN

BACKGROUND: To qualitatively explore physiotherapy students' perceptions of online e-learning for chronic disease management using a previously developed, innovative and interactive, evidence-based, e-learning package: Rheumatoid Arthritis for Physiotherapists e-Learning (RAP-eL). METHODS: Physiotherapy students participated in three focus groups in Perth, Western Australia. Purposive sampling was employed to ensure maximum heterogeneity across age, gender and educational background. To explore students' perspectives on the advantages and disadvantages of online e-learning, ways to enhance e-learning, and information/learning gaps in relation to interdisciplinary management of chronic health conditions, a semi-structured interview schedule was developed. Verbatim transcripts were analysed using inductive methods within a grounded theory approach to derive key themes. RESULTS: Twenty-three students (78 % female; 39 % with previous tertiary qualification) of mean (SD) age 23 (3.6) years participated. Students expressed a preference for a combination of both online e-learning and lecture-style learning formats for chronic disease management, citing flexibility to work at one's own pace and time, and access to comprehensive information as advantages of e-learning learning. Personal interaction and ability to clarify information immediately were considered advantages of lecture-style formats. Perceived knowledge gaps included practical application of interdisciplinary approaches to chronic disease management and developing and implementing physiotherapy management plans for people with chronic health conditions. CONCLUSIONS: Physiotherapy students preferred multi-modal and blended formats for learning about chronic disease management. This study highlights the need for further development of practically-oriented knowledge and skills related to interdisciplinary care for people with chronic conditions among physiotherapy students. While RAP-eL focuses on rheumatoid arthritis, the principles of learning apply to the broader context of chronic disease management.


Asunto(s)
Artritis Reumatoide/rehabilitación , Enfermedad Crónica/rehabilitación , Instrucción por Computador/normas , Educación a Distancia/normas , Estudios Interdisciplinarios/normas , Especialidad de Fisioterapia/educación , Estudiantes del Área de la Salud/psicología , Adulto , Instrucción por Computador/métodos , Comportamiento del Consumidor , Educación a Distancia/métodos , Femenino , Grupos Focales , Humanos , Internet , Masculino , Evaluación de Programas y Proyectos de Salud , Investigación Cualitativa , Australia Occidental , Adulto Joven
11.
Nat Chem Biol ; 9(2): 112-8, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23222885

RESUMEN

We sought new strategies to reduce amounts of the polyglutamine androgen receptor (polyQ AR) and achieve benefits in models of spinobulbar muscular atrophy, a protein aggregation neurodegenerative disorder. Proteostasis of the polyQ AR is controlled by the heat shock protein 90 (Hsp90)- and Hsp70-based chaperone machinery, but mechanisms regulating the protein's turnover are incompletely understood. We demonstrate that overexpression of Hsp70 interacting protein (Hip), a co-chaperone that enhances binding of Hsp70 to its substrates, promotes client protein ubiquitination and polyQ AR clearance. Furthermore, we identify a small molecule that acts similarly to Hip by allosterically promoting Hsp70 binding to unfolded substrates. Like Hip, this synthetic co-chaperone enhances client protein ubiquitination and polyQ AR degradation. Both genetic and pharmacologic approaches targeting Hsp70 alleviate toxicity in a Drosophila model of spinobulbar muscular atrophy. These findings highlight the therapeutic potential of allosteric regulators of Hsp70 and provide new insights into the role of the chaperone machinery in protein quality control.


Asunto(s)
Proteínas HSP70 de Choque Térmico/metabolismo , Péptidos/química , Animales , Relación Dosis-Respuesta a Droga , Doxorrubicina/análogos & derivados , Doxorrubicina/farmacología , Drosophila , Femenino , Células HEK293 , Células HeLa , Humanos , Concentración 50 Inhibidora , Modelos Químicos , Chaperonas Moleculares/química , Trastornos Musculares Atróficos/metabolismo , Neurotoxinas/química , Células PC12 , Estructura Terciaria de Proteína , Proteínas/química , Piridinas/farmacología , Ratas , Receptores Androgénicos/química , Receptores Androgénicos/metabolismo , Tiazoles/farmacología , Ubiquitinación
12.
Nitric Oxide ; 46: 165-71, 2015 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-25446250

RESUMEN

OBJECTIVE: The present study was designed to investigate whether H2S can protect testicular germ cells against heat exposure induced injury and the underlying mechanisms. RESULTS: It was found that all three H2S generating enzymes, cystathionine ß-synthase (CBS), cystathionine γ-lysase (CSE), and 3-mercaptopyruvate sulfurtransferase (3 MST), were expressed in mouse testicular tissue. Three episodes of heat exposure (42 °C, 30 min/day, 3 days) significantly decreased endogenous H2S production and down-regulated the expression of CBS and CSE in testes. In primary cultured testicular germ cells, exogenous application of NaHS (an H2S donor) attenuated heat stress (42 °C, 30 min) induced cell death and apoptosis. This was mediated by the inhibitory effects of H2S on cytochrome C release and the ratio of the Bax/Bcl-2. NaHS also improved mitochondrial function by decreasing oxygen consumption and increasing ATP production. NaHS treatment also stimulated SOD activity and reduced ROS production. CONCLUSIONS: Our results revealed both physiological and pharmacological roles of H2S in testicular germ cells. Exogenous application of H2S may protect germ cells by preservation of mitochondrial function and stimulation of anti-oxidant activity.


Asunto(s)
Antioxidantes/farmacología , Células Germinativas/efectos de los fármacos , Respuesta al Choque Térmico/efectos de los fármacos , Sulfuro de Hidrógeno/farmacología , Testículo/efectos de los fármacos , Testículo/lesiones , Animales , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Germinativas/metabolismo , Sulfuro de Hidrógeno/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Especies Reactivas de Oxígeno/metabolismo , Testículo/citología
13.
Am J Ther ; 22(1): 73-9, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-23344107

RESUMEN

The number of patients with heart failure presenting for surgery continues to rise, and anesthesiologists are increasingly being called upon to provide quality, safe care in the operating room for patients with low ejection fraction (EF). Perioperative goals in the management of these patients include maintaining forward flow, promoting inotropy without inducing or exacerbating ischemia, and returning patients to their preoperative level of function after surgery. Oftentimes, these goals can be met with pharmacologic support, including the use of calcium channel blockers, phosphodiesterase inhibitors, and novel agents, such as nesiritide and levosimendan. Many patients with diminished EF have implantable cardioverter-defibrillators (ICDs) in place. These devices can be complex to manage, and concern often arises regarding electromagnetic interference from monopolar cautery. Although simply placing a magnet on the device will often disable the antitachycardia interventions of an ICD, this is not always the case. The safest way to manage an ICD in the perioperative period is to interrogate and reprogram the device before and after surgery. Another helpful device in dealing with patients with low EF, particularly those in acute cardiogenic shock, is the intra-aortic balloon pump. These devices can serve a critical role in managing patients who have inadequate responses to pharmacologic therapy or in whom vasopressor and inotropic support are suboptimal because of concerns for increasing myocardial work. With full understanding of available pharmacologic agents, and an appreciation of the capabilities of ICDs and intra-aortic balloon pumps, anesthesiologists will be better equipped to meet the perioperative needs of the patient with low EF.


Asunto(s)
Anestesia/métodos , Anestésicos/administración & dosificación , Insuficiencia Cardíaca/fisiopatología , Anestesia/efectos adversos , Anestesiología/métodos , Anestésicos/efectos adversos , Desfibriladores Implantables , Insuficiencia Cardíaca/cirugía , Humanos , Contrapulsador Intraaórtico , Atención Perioperativa/métodos
14.
J Cardiothorac Vasc Anesth ; 29(5): 1148-54, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25824449

RESUMEN

OBJECTIVE: The purpose of this study was to examine the acute effects of pacing at different ventricular sites on hemodynamics and left ventricular (LV) rotational mechanics using speckle-tracking echocardiography (STE) in a porcine model. DESIGN: A prospective laboratory investigation. SETTING: University research laboratory. PARTICIPANTS: Yorkshire pigs. INTERVENTIONS: In 9 pigs, after midline sternotomy, epicardial pacing was performed from the right ventricular outflow tract (RVOT), right ventricular apex (RVA), and LV free wall. MEASUREMENTS AND MAIN RESULTS: Two-dimensional STE and conductance catheter-derived LV pressure-volume measurements were made to determine the impact of pacing from various sites on LV rotational parameters (twist/untwist) and hemodynamics. RVOT pacing caused the least decrease in end-systolic pressure from baseline (-9.5%), when compared with RVA (-19.1%) and LV (-23.4%). Systolic and diastolic parameters (Emax, Tau) also were different among RVOT (4.7±0.8 mmHg/mL, 32±4 ms), RVA (3.9±0.7 mmHg/mL, 37±6 ms), and LV sites (3.6±0.8 mmHg/mL, 42±7 ms). Similar to the effects of pacing on hemodynamics, RVOT pacing better preserved LV twist (11.1±1.8 v 8.6±1.7, 5.9±0.7 °) and untwisting rate (64.6±8.5 v 56.2±5.3, 48.2±8.5 °/s) when compared with RV apical pacing and LV pacing. Furthermore, prolongation of conduction from LV lateral to anteroseptal at LV base (26.5±3.8 v 13.8±3.3 ms, p<0.05) and LV midpapillary muscle level (35.6±5.6 v 14.1±2.4 ms, p<0.05) was observed with LV pacing compared with RVOT pacing. CONCLUSIONS: The present data showed that the LV twist/untwist and cardiac systolic and diastolic function were least affected by RVOT pacing. This finding may be explained by the proximity of this location to the native ventricular conduction system.


Asunto(s)
Estimulación Cardíaca Artificial/métodos , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/fisiopatología , Función Ventricular Izquierda/fisiología , Animales , Ventrículos Cardíacos/diagnóstico por imagen , Hemodinámica/fisiología , Estudios Prospectivos , Porcinos , Ultrasonografía
15.
BMC Health Serv Res ; 15: 509, 2015 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-26573487

RESUMEN

BACKGROUND: The prevalence and impact of musculoskeletal conditions are predicted to rapidly escalate in the coming decades. Effective strategies are required to minimise 'evidence-practice', 'burden-policy' and 'burden-service' gaps and optimise health system responsiveness for sustainable, best-practice healthcare. One mechanism by which evidence can be translated into practice and policy is through Models of Care (MoCs), which provide a blueprint for health services planning and delivery. While evidence supports the effectiveness of musculoskeletal MoCs for improving health outcomes and system efficiencies, no standardised national approach to evaluation in terms of their 'readiness' for implementation and 'success' after implementation, is yet available. Further, the value assigned to MoCs by end users is uncertain. This qualitative study aimed to explore end users' views on the relevance of musculoskeletal MoCs to their work and value of a standardised evaluation approach. METHODS: A cross-sectional qualitative study was undertaken. Subject matter experts (SMEs) with health, policy and administration and consumer backgrounds were drawn from three Australian states. A semi-structured interview schedule was developed and piloted to explore perceptions about musculoskeletal MoCs including: i) aspects important to their work (or life, for consumers) ii) usefulness of standardised evaluation frameworks to judge 'readiness' and 'success' and iii) challenges associated with standardised evaluation. Verbatim transcripts were analysed by two researchers using a grounded theory approach to derive key themes. RESULTS: Twenty-seven SMEs (n = 19; 70.4 % female) including five (18.5 %) consumers participated in the study. MoCs were perceived as critical for influencing and initiating changes to best-practice healthcare planning and delivery and providing practical guidance on how to implement and evaluate services. A 'readiness' evaluation framework assessing whether critical components across the health system had been considered prior to implementation was strongly supported, while 'success' was perceived as an already familiar evaluation concept. Perceived challenges associated with standardised evaluation included identifying, defining and measuring key 'readiness' and 'success' indicators; impacts of systems and context changes; cost; meaningful stakeholder consultation and developing a widely applicable framework. CONCLUSIONS: A standardised evaluation framework that includes a strong focus on 'readiness' is important to ensure successful and sustainable implementation of musculoskeletal MoCs.


Asunto(s)
Actitud Frente a la Salud , Enfermedades Musculoesqueléticas/terapia , Adulto , Actitud del Personal de Salud , Enfermedad Crónica , Estudios Transversales , Atención a la Salud/organización & administración , Femenino , Programas de Gobierno , Política de Salud , Humanos , Modelos Organizacionales , Enfermedades Musculoesqueléticas/psicología , Nueva Gales del Sur , Victoria , Australia Occidental
16.
J Cardiothorac Vasc Anesth ; 28(1): 69-75, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24290748

RESUMEN

OBJECTIVE: The aim of this study was to determine the pertinent anesthetic considerations for patients undergoing surgical sympathectomy for electrical storm (incessant ventricular tachycardia (VT) refractory to traditional therapies). DESIGN: This is a retrospective review of a prospective database. SETTING: This single-center study took place in a university hospital setting. PARTICIPANTS: Twenty-six patients were enrolled. INTERVENTIONS: Fifteen patients underwent left-sided sympathectomy, whereas 11 patients underwent bilateral sympathectomy. MEASUREMENTS AND MAIN RESULTS: Anesthetic management of these patients was quite complex, requiring invasive monitoring, transesophageal echocardiography, one-lung ventilation, programming of cardiac rhythm management devices, and titration of vasoactive medications. Paired t test of hemodynamic data before, during, and after surgery showed no significant difference between preoperative and postoperative blood pressure values, regardless of whether the patient underwent unilateral or bilateral sympathectomy. Eight patients remained free of VT, three patients responded well to titration of oral medications, and one patient required 2 radiofrequency ablations after sympathectomy to control his VT. Three patients continued to have VT episodes, although reduced in frequency compared with before the procedure. Four patients were lost to followup. Overall, five patients within the cohort died within 30 days of the procedure. No patients developed any anesthetic complications or Horner's syndrome. The overall perioperative mortality (within the first 7 days of the procedure) was 2 of 26, or 7.7%. CONCLUSIONS: The anesthetic management of patients undergoing surgical sympathectomy for electrical storm can be quite complex, because these patients often present in a moribund and emergent state and cannot be optimized using current ACC/AHA guidelines. Expertise in invasive monitoring, transesophageal echocardiography, one-lung ventilation, cardiac rhythm device management, and pressor management is crucial for optimal anesthetic care.


Asunto(s)
Anestesia/métodos , Ganglios Simpáticos/cirugía , Ganglionectomía/métodos , Taquicardia Ventricular/cirugía , Toracoscopía/métodos , Anciano , Ecocardiografía Transesofágica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
17.
Healthcare (Basel) ; 12(6)2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38540605

RESUMEN

In recent years, the surge in sport and exercise participation, particularly in running, has coincided with the widespread adoption of running-related technology, such as fitness trackers. This study investigates the correlation between the use of running-related technology and running-related injuries among recreational and elite long-distance runners. We conducted a quantitative, cross-sectional online survey of 282 adult runners. Data were analyzed using descriptive statistics and a multivariable logistic regression analysis. Participants, with an average age of 37.4 years, reported varied running experience, with 90.07% utilizing running-related technology during their runs to some degree, primarily smartwatches like Garmin and Apple Watch. Running-related technology users showed a higher likelihood of experiencing running-related injuries compared to non-users (OR = 0.31, p < 0.001). However, those who utilized the metrics obtained from running-related technology to guide their training decisions did not exhibit a higher risk of injury. This nuanced relationship highlights the importance of considering individual training behaviors and the potential psychological impacts of technology on running practices. The study underscores the need for future research integrating biomechanical and psychosocial factors into running-related technology to enhance injury prevention strategies.

18.
J Vitreoretin Dis ; 8(1): 34-44, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38223768

RESUMEN

Purpose: To examine the implementation of a teleophthalmology program for diabetic retinopathy (DR) screening at a metropolitan hospital system and identify the challenges that the clinical teams encountered using the program. Methods: The study was conducted in 2 parts. The first was a pilot retrospective chart review of 300 consecutive patients screened for DR by the teleophthalmology screening program. The baseline variables, DR capture rate and staging, and continuity of care for those diagnosed with DR were analyzed. The second was a web-based survey identifying the barriers encountered by 36 physicians and clinical staff as they participated in the teleophthalmology screening program. Results: Part 1: Of the patients evaluated, 57 (19.0%) were diagnosed with DR; 42 (73.7%) had mild nonproliferative DR (NPDR), 7 (12.3%) had moderate NPDR, none had severe NPDR, and 8 (14.0%) had PDR. Thirty-one patients (54.4%) with retinopathy diagnoses were referred for an in-person follow-up at the clinic while the rest continued monitoring via the program. Of this subset, 22 (71.0%) completed the follow-up visit. Part 2: The survey respondents comprised 28 physicians (77.8%), 6 licensed nurse practitioners (16.7%), and 2 medical assistants (5.6%). Twenty-two providers (71.0%) preferred initiating referrals for in-person annual examinations over teleophthalmology screening referrals. The most common barriers described were related to workflow interruption, time constraints, and staff shortages. Conclusions: The teleophthalmology DR screening program allowed identification of early or absent DR at clinics in an urban setting (New York City). The findings suggest areas for targeted improvement in the screening program to better complement internal referral practices' workflows.

19.
Ann Coloproctol ; 40(1): 3-12, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37004990

RESUMEN

Sarcopenia, which is characterized by progressive and generalized loss of skeletal muscle mass and strength, has been well described to be associated with numerous poor postoperative outcomes, such as increased perioperative mortality, postoperative sepsis, prolonged length of stay, increased cost of care, decreased functional outcome, and poorer oncological outcomes in cancer surgery. Multimodal prehabilitation, as a concept that involves boosting and optimizing the preoperative condition of a patient prior to the upcoming stressors of a surgical procedure, has the purported benefits of reversing the effects of sarcopenia, shortening hospitalization, improving the rate of return to bowel activity, reducing the costs of hospitalization, and improving quality of life. This review aims to present the current literature surrounding the concept of sarcopenia, its implications pertaining to colorectal cancer and surgery, a summary of studied multimodal prehabilitation interventions, and potential future advances in the management of sarcopenia.

20.
Arthritis Care Res (Hoboken) ; 75(5): 1147-1157, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-34806338

RESUMEN

OBJECTIVE: The Osteoarthritis Research Society International (OARSI) recommends assessment of physical function using a performance-based test of stair negotiation but was unable to recommend any specific test. We assessed the reliability, validity, responsiveness, measurement error, and minimum important change (MIC) of the 6-step timed Stair Climb Test (SCT). METHODS: We used pooled data from 397 participants with hip or knee osteoarthritis (54% women) from 4 clinical trials (86% retained at 12-week follow-up). Construct validity was assessed by testing 6 a priori hypotheses against other OARSI-recommended physical function measures. A self-reported Global Rating of Change scale was used to classify participants as worsened, improved, and stable. Participants who worsened in physical function were excluded from all analyses. Responsiveness and MIC were assessed using multiple anchor-based and distribution-based approaches. Test-retest reliability, standard error of measurement (SEM), and smallest detectable change (SDC) were assessed on stable participants. RESULTS: Five of 6 hypotheses (83%) for construct validity were met. Test-retest reliability was excellent (intraclass correlation coefficient2,1 0.83; 95% confidence interval 0.71-0.90). The SEM and SDC values were 0.44 and 1.21 seconds, respectively. We did not find adequate support for responsiveness. The MIC values ranged from 0.78 to 1.95 seconds using different approaches (median 1.37 seconds). CONCLUSION: The 6-step timed SCT adequately assesses the construct of physical function in individuals with hip or knee osteoarthritis with excellent 12-week test-retest reliability. However, support for its responsiveness was inadequate to recommend its use as an outcome measure in people with osteoarthritis for research and clinical practice.


Asunto(s)
Osteoartritis de la Cadera , Osteoartritis de la Rodilla , Humanos , Adulto , Femenino , Masculino , Reproducibilidad de los Resultados , Prueba de Esfuerzo , Evaluación de Resultado en la Atención de Salud , Encuestas y Cuestionarios
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