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1.
J Can Assoc Gastroenterol ; 3(2): 91-95, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32328548

RESUMEN

Aims: Patient comfort during colonoscopy is an important measure of quality, which can improve patient satisfaction and compliance with future procedures. Our aim was to develop and validate a pain assessment tool based on objective behavioural cues tailored to outpatients undergoing colonoscopy: St. Paul's endoscopy comfort score (SPECS). Methods: A single-centre, prospective study was conducted in consecutive adults undergoing planned outpatient colonoscopy. Patient comfort was independently assessed by the physician, nurse and a research assistant (observer) using the SPECS and the Gloucester scale (GS). In addition, the nurse-assessed patient comfort score (NAPCOMS), nonverbal pain Assessment tool (NPAT) and Richmond agitation sedation scale (RASS) were completed by the observer. Data on subject demographics, sedation dose and duration of the procedure were collected. Following the procedure, patients completed a patient satisfaction questionnaire, including a visual analogue scale (VAS) to measure their overall perceived pain during the procedure. Results: The study enrolled 350 subjects. The SPECS showed excellent inter-rater reliability among all three raters with an intra-class coefficient (ICC) of 0.81 (95% CI, 0.78-0.84), while the GS showed good reliability with an ICC of 0.77 (95% CI, 0.73-0.80). The SPECS demonstrated moderate agreement with the patient-reported VAS ratings. Conclusions: The St. Paul's endoscopy comfort score was successfully validated, demonstrating excellent inter-rater reliability.

2.
Can J Surg ; 63(2): E174-E180, 2020 04 17.
Artículo en Inglés | MEDLINE | ID: mdl-32302084

RESUMEN

Background: Hospital readmissions after bariatric surgery can significantly increase health care costs. Rates of readmission after bariatric surgery have ranged from 0.6% to 11.3%, but the rate of complications and the factors that predict readmission have not been well characterized in Canada. The objective of this study was to characterize readmission rates and the factors that predict 30-day readmission in a Canadian centre. Methods: A retrospective study was performed on all patients who underwent bariatric surgery between 2010 and 2015 in a single Canadian centre. Procedures included laparoscopic Roux-en-Y gastric bypass (LRYGB), laparoscopic sleeve gastrectomy (LSG) and laparoscopic adjustable gastric banding (LAGB). Prospectively collected data were extracted from an administrative database. Multivariable logistic regression analysis was performed to determine which factors predict 30-day readmission. Results: A total of 1468 patients had bariatric surgery (51.0% LRYGB, 40.5% LSG, 8.6% LAGB) during the 6-year study period, with an overall 30-day readmission rate of 7.5%. LRYGB was associated with a higher readmission rate (11.4%) than LSG (3.7%) or LAGB (1.6%). Common reasons for readmission were infection (24.8%), pain (17.4%) and nausea or vomiting (10.1%). Multivariable analysis identified 3 factors that independently predicted readmission: length of stay greater than 4 days (odds ratio [OR] 2.18, 95% confidence interval [CI] 1.03-4.63, p = 0.042), LRYGB (OR 5.21, 95% CI 1.19-22.73, p = 0.028) and acute renal failure (OR 14.10, 95% CI 1.07-186.29, p = 0.045). Conclusion: Readmissions after bariatric surgery were most commonly caused by potentially preventable factors, such as pain, nausea or vomiting. Strategies to identify and address factors associated with readmission may reduce readmissions and health care costs after bariatric surgery in a publicly funded health care system.


Asunto(s)
Cirugía Bariátrica , Readmisión del Paciente/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Lesión Renal Aguda/epidemiología , Adulto , Alberta/epidemiología , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Análisis Multivariante , Estudios Retrospectivos
3.
Obes Surg ; 29(4): 1403-1409, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30706311

RESUMEN

The objective our study was to carry out a systematic review and meta-analysis to examine the impact of attention-deficit and hyperactivity disorder (ADHD) on bariatric surgery outcomes. Despite the effectiveness of bariatric surgery, about 10 to 20% of patients continue to regain weight after the procedure. New evidence supports that ADHD may be directly associated with obesity and may affect outcomes following bariatric surgery. However, certain psychiatric illnesses, such as ADHD, are rarely screened for, leading to a continued lack of data on the interaction between ADHD and bariatric surgery. A comprehensive literature search for both published and unpublished studies of ADHD and bariatric surgery from 1946 to August 2018 was performed. The search was conducted using the Medline, EMBASE, Scopus, the Cochrane Library, and Web of Science databases as well as conference abstracts. Our search strategy terms included "(ADHD OR attention deficit hyperactivity disorder) AND (bariatrics OR obesity surgery OR gastric bypass OR gastric sleeve OR Roux-en-Y OR RYGB OR sleeve gastrectomy)" and was limited to human studies in the English language. Preliminary database search of the literature yielded 104 articles after 70 duplicates were removed. A total of five studies with 492 patients were included. The overall ADHD rate was 20.9% with reported rates ranging from 7 to 38%. The weighted mean age was 44.0 ± 10.2 years, the weighted sex was 83.6% female, and the weighted mean follow-up was 22.2 months. Preoperative weighted mean BMI was 43.7 versus a postoperative weighted mean BMI of 34.7. No statistical significance was observed for mean BMI difference between non-ADHD vs. ADHD patients undergoing bariatric surgery (three studies; MD - 2.66; CI - 7.54 to 2.13; p = 0.28). Statistical significance was, however, observed for postoperative follow-up between patients with ADHD vs. non-ADHD subjects (three studies; MD - 7.28; - 13.83 to -0.73; p = 0.03). Patients with ADHD do not have a statistically significant mean BMI difference following bariatric surgery but have a statistically significant reduction in postoperative follow-up versus non-ADHD patients. Targeted strategies aimed at improving clinic attendance for this at-risk ADHD population may improve bariatric outcomes and minimize recidivism rates.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Cirugía Bariátrica/estadística & datos numéricos , Obesidad , Adulto , Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Índice de Masa Corporal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/epidemiología , Obesidad/cirugía , Resultado del Tratamiento
4.
Am J Surg ; 216(3): 604-609, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29454479

RESUMEN

BACKGROUND: Antibiotics use in acute uncomplicated diverticulitis (AUD) remains debated despite recent studies suggesting no difference in outcomes for patients treated without antibiotics. DATA SOURCES: Systematic review and meta-analysis were performed to determine the role of antibiotics in managing AUD. Literature search was conducted using Medline, EMBASE, Scopus, the Cochrane Library, and Web of Science databases from 1946 to June 2017. Eight studies with 2469 patients were included for review. Overall complication rates were not statistically significant between groups (OR 0.72; CI 0.45 to 1.16; P = 0.18), but antibiotic use was associated with a longer length of stay in hospital. Subgroup analysis revealed no difference in readmission rates, treatment failure rates, progression to complicated diverticulitis, or increased need for elective or emergent surgery between study groups. CONCLUSIONS: Antibiotic use in patients with AUD increases length of hospital stay but is not associated with a reduction in overall or individual complication rates.


Asunto(s)
Antibacterianos/uso terapéutico , Diverticulitis/tratamiento farmacológico , Intestino Grueso , Enfermedad Aguda , Progresión de la Enfermedad , Humanos , Tiempo de Internación , Resultado del Tratamiento
5.
J Biol Chem ; 291(42): 22231-22243, 2016 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-27576691

RESUMEN

Androgen receptor (AR) is a validated drug target for all stages of prostate cancer including metastatic castration-resistant prostate cancer (CRPC). All current hormone therapies for CRPC target the C-terminal ligand-binding domain of AR and ultimately all fail with resumed AR transcriptional activity. Within the AR N-terminal domain (NTD) is activation function-1 (AF-1) that is essential for AR transcriptional activity. Inhibitors of AR AF-1 would potentially block most AR mechanisms of resistance including constitutively active AR splice variants that lack the ligand-binding domain. Here we provide evidence that sintokamide A (SINT1) binds AR AF-1 region to specifically inhibit transactivation of AR NTD. Consistent with SINT1 targeting AR AF-1, it attenuated transcriptional activities of both full-length AR and constitutively active AR splice variants, which correlated with inhibition of growth of enzalutamide-resistant prostate cancer cells expressing AR splice variants. In vivo, SINT1 caused regression of CRPC xenografts and reduced expression of prostate-specific antigen, a gene transcriptionally regulated by AR. Inhibition of AR activity by SINT1 was additive to EPI-002, a known AR AF-1 inhibitor that is in clinical trials (NCT02606123). This implies that SINT1 binds to a site on AF-1 that is unique from EPI. Consistent with this suggestion, these two compounds showed differences in blocking AR interaction with STAT3. This work provides evidence that the intrinsically disordered NTD of AR is druggable and that SINT1 analogs may provide a novel scaffold for drug development for the treatment of prostate cancer or other diseases of the AR axis.


Asunto(s)
Antagonistas de Receptores Androgénicos/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Proteínas de Neoplasias , Neoplasias de la Próstata , Pirrolidinonas/farmacología , Receptores Androgénicos/biosíntesis , Activación Transcripcional/efectos de los fármacos , Animales , Línea Celular Tumoral , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismo , Dominios Proteicos , Pirrolidinonas/farmacocinética , Factor de Transcripción STAT3/metabolismo
6.
J Clin Invest ; 123(7): 2948-60, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23722902

RESUMEN

Hormone therapies for advanced prostate cancer target the androgen receptor (AR) ligand-binding domain (LBD), but these ultimately fail and the disease progresses to lethal castration-resistant prostate cancer (CRPC). The mechanisms that drive CRPC are incompletely understood, but may involve constitutively active AR splice variants that lack the LBD. The AR N-terminal domain (NTD) is essential for AR activity, but targeting this domain with small-molecule inhibitors is complicated by its intrinsic disorder. Here we investigated EPI-001, a small-molecule antagonist of AR NTD that inhibits protein-protein interactions necessary for AR transcriptional activity. We found that EPI analogs covalently bound the NTD to block transcriptional activity of AR and its splice variants and reduced the growth of CRPC xenografts. These findings suggest that the development of small-molecule inhibitors that bind covalently to intrinsically disordered proteins is a promising strategy for development of specific and effective anticancer agents.


Asunto(s)
Antagonistas de Receptores Androgénicos/farmacología , Antineoplásicos Hormonales/farmacología , Compuestos de Bencidrilo/farmacología , Clorhidrinas/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Receptores Androgénicos/metabolismo , Antagonistas de Receptores Androgénicos/química , Animales , Antineoplásicos Hormonales/química , Compuestos de Bencidrilo/química , Células COS , Proliferación Celular/efectos de los fármacos , Chlorocebus aethiops , Clorhidrinas/química , Química Clic , Expresión Génica , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Genes Reporteros , Humanos , Luciferasas/biosíntesis , Luciferasas/genética , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Orquiectomía , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Unión Proteica , Estructura Terciaria de Proteína , Receptores Androgénicos/química , Receptores Androgénicos/genética , Estereoisomerismo , Activación Transcripcional/efectos de los fármacos , Carga Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
7.
Lancet ; 375(9729): 1896-905, 2010 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-20511019

RESUMEN

BACKGROUND: We previously showed that small interfering RNAs (siRNAs) targeting the Zaire Ebola virus (ZEBOV) RNA polymerase L protein formulated in stable nucleic acid-lipid particles (SNALPs) completely protected guineapigs when administered shortly after a lethal ZEBOV challenge. Although rodent models of ZEBOV infection are useful for screening prospective countermeasures, they are frequently not useful for prediction of efficacy in the more stringent non-human primate models. We therefore assessed the efficacy of modified non-immunostimulatory siRNAs in a uniformly lethal non-human primate model of ZEBOV haemorrhagic fever. METHODS: A combination of modified siRNAs targeting the ZEBOV L polymerase (EK-1 mod), viral protein (VP) 24 (VP24-1160 mod), and VP35 (VP35-855 mod) were formulated in SNALPs. A group of macaques (n=3) was given these pooled anti-ZEBOV siRNAs (2 mg/kg per dose, bolus intravenous infusion) after 30 min, and on days 1, 3, and 5 after challenge with ZEBOV. A second group of macaques (n=4) was given the pooled anti-ZEBOV siRNAs after 30 min, and on days 1, 2, 3, 4, 5, and 6 after challenge with ZEBOV. FINDINGS: Two (66%) of three rhesus monkeys given four postexposure treatments of the pooled anti-ZEBOV siRNAs were protected from lethal ZEBOV infection, whereas all macaques given seven postexposure treatments were protected. The treatment regimen in the second study was well tolerated with minor changes in liver enzymes that might have been related to viral infection. INTERPRETATION: This complete postexposure protection against ZEBOV in non-human primates provides a model for the treatment of ZEBOV-induced haemorrhagic fever. These data show the potential of RNA interference as an effective postexposure treatment strategy for people infected with Ebola virus, and suggest that this strategy might also be useful for treatment of other emerging viral infections. FUNDING: Defense Threat Reduction Agency.


Asunto(s)
Ebolavirus/genética , Fiebre Hemorrágica Ebola/prevención & control , Interferencia de ARN , ARN Interferente Pequeño/uso terapéutico , Animales , Chlorocebus aethiops , Ebolavirus/aislamiento & purificación , Ebolavirus/fisiología , Femenino , Fiebre Hemorrágica Ebola/virología , Infusiones Intravenosas , Interferón-alfa/biosíntesis , Interleucina-6/biosíntesis , Macaca mulatta , Masculino , Ratones , Ratones Endogámicos ICR , ARN Interferente Pequeño/efectos adversos , ARN Interferente Pequeño/farmacología , Células Vero/virología , Proteínas Virales/genética , Viremia , Replicación Viral
8.
J Clin Invest ; 119(3): 661-73, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19229107

RESUMEN

siRNAs that specifically silence the expression of cancer-related genes offer a therapeutic approach in oncology. However, it remains critical to determine the true mechanism of their therapeutic effects. Here, we describe the preclinical development of chemically modified siRNA targeting the essential cell-cycle proteins polo-like kinase 1 (PLK1) and kinesin spindle protein (KSP) in mice. siRNA formulated in stable nucleic acid lipid particles (SNALP) displayed potent antitumor efficacy in both hepatic and subcutaneous tumor models. This was correlated with target gene silencing following a single intravenous administration that was sufficient to cause extensive mitotic disruption and tumor cell apoptosis. Our siRNA formulations induced no measurable immune response, minimizing the potential for nonspecific effects. Additionally, RNAi-specific mRNA cleavage products were found in tumor cells, and their presence correlated with the duration of target mRNA silencing. Histological biomarkers confirmed that RNAi-mediated gene silencing effectively inhibited the target's biological activity. This report supports an RNAi-mediated mechanism of action for siRNA antitumor effects, suggesting a new methodology for targeting other key genes in cancer development with siRNA-based therapeutics.


Asunto(s)
Terapia Genética , Neoplasias/genética , Neoplasias/terapia , Interferencia de ARN , ARN Interferente Pequeño/genética , Animales , Proteínas de Ciclo Celular/genética , Modelos Animales de Enfermedad , Duplicación de Gen , Ratones , Neoplasias Experimentales/genética , Neoplasias Experimentales/patología , Reacción en Cadena de la Polimerasa , Proteínas Serina-Treonina Quinasas/deficiencia , Proteínas Serina-Treonina Quinasas/genética , Proteínas Proto-Oncogénicas/deficiencia , Proteínas Proto-Oncogénicas/genética , ARN Mensajero/genética , ARN Neoplásico/genética
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