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Irradiation of the vertebrae in prepubertal patients, if non-homogenous, can result in future growth deformities including kyphoscoliosis. Vertebral delineation and dosimetry were assessed for 101 paediatric cases reviewed within QUARTET-affiliated trials. Despite the availability of published consensus guidelines, a high variability in vertebral delineation was observed, with impact on dosimetry.
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Oncología por Radiación , Columna Vertebral , Niño , Humanos , Predicción , Ensayos Clínicos como AsuntoRESUMEN
Background: Equine coronavirus (ECoV) leads to outbreaks with variable morbidity and mortality. Few previous reports of risk factors for infection are available in the literature. Objectives: To describe unique clinical findings and risk factors for infection and development of clinical disease. Animals: 135 horses on a farm affected by ECoV outbreak. Methods: Retrospective cohort study. Data obtained included age, breed, gender, activity level, housing, and feed at the onset of the outbreak. Factors were evaluated for assessment of risk of infection using simple logistic regression or Fisher's exact test. Significance was set at p ≤ 0.05. Results and findings: Forty-three of 54 (79.6%) horses tested on the farm were positive on fecal PCR for ECoV, and 17 horses (12.6%) developed clinical signs consistent with ECoV. Out of 17 horses in which the presence or absence of signs of colic was noted, 6 of 17 (35.3%) showed signs of colic. Three of these horses had small colon impactions, 2 of which required surgical intervention. Significant risk factors for having positive PCR results included being primarily stalled (OR 167.1, 95% CI 26.4-1719), housing next to a positive horse (OR 7.5, 95% CI 3.1-19.0), being in work (OR 26.9, 95% CI 4.6-281.9), being fed rationed hay vs. ad libitum (OR 1,558, 95% CI 130.8-15,593), and being fed alfalfa hay (OR 1,558, 95% CI 130.8-15,593). Conclusions and clinical importance: This report describes risk factors for ECoV infection many of which were associated with intensive management of show horses. Clinicians should be aware that clinical signs vary and can include severe colic.
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OBJECTIVES: To measure the magnitude of intra-fraction prostate motion (IFPM) during stereotactic radiotherapy (SBRT) delivered without intra-fraction tracking.To assess if current margins adequately cover IFPM.To derive margins using new guidelines. METHODS: IFPM was determined in 20 patients receiving 36.25 Gy in 5 fractions using 97 pairs of pre- and post-treatment cone beam CT (CBCT) scans. Correlation of time between CBCT acquisitions and motion was determined. The magnitude of IFPM was compared to current margins (6 mm isotropic, 3 mm posterior). Margins were calculated using IFPM alone and updated guidelines. RESULTS: The averaged 3D root mean square IFPM was 2.5 mm (4.2 mm). Independent prostate motion was predominantly posterior (70%) and inferior (63%). There was weak correlation between posterior (ρ = 0.38) and inferior (ρ = 0.36) IFPM and time. IFPM greater than current margins occurred in 8 of 97 fractions, six in the posterior direction. Margins were ≤3.5 mm using IFPM alone and ≤3.3 mm Left 3.5 mm Right, 7.0 mm inferior, 3.7 mm superior, 4.4 mm anterior and 3.3 mm posterior using new guidelines, compensating for motion in 92% of fractions. CONCLUSIONS: Our current SBRT margins account for 92% of IFPM, predominantly posterior and inferior. Although updated guidelines suggest an increase in margins inferiorly, any increase must be balanced against the possibility of increased toxicity, particularly if biochemical control and side-effects are favourable with current practice. ADVANCES IN KNOWLEDGE: The difference between current clinical margins and those determined using updated guidance is demonstrated. The implications must be considered against clinical outcomes.
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Neoplasias de la Próstata , Radiocirugia , Radioterapia Guiada por Imagen , Masculino , Humanos , Próstata/diagnóstico por imagen , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Incertidumbre , Movimiento (Física) , Tomografía Computarizada de Haz Cónico , Planificación de la Radioterapia Asistida por ComputadorRESUMEN
PURPOSE: Our purpose was to report 5-year efficacy and toxicity of intraprostatic lesion boosting using standard and hypofractionated radiation therapy. METHODS AND MATERIALS: DELINEATE (ISRCTN 04483921) is a single center phase 2 multicohort study including standardly fractionated (cohort A: 74 Gy/37F to prostate and seminal vesicles [PSV]; cohort C 74 Gy/37F to PSV plus 60 Gy/37F to pelvic lymph nodes) and moderately hypofractionated (cohort B: 60 Gy/20F to PSV) prostate intensity-modulated radiation therapy patients with National Comprehensive Cancer Network intermediate/high-risk disease. Patients received an integrated boost of 82 Gy (cohorts A and C) or 67 Gy (cohort B) to multiparametric magnetic resonance imaging identified lesion(s). Primary endpoint was late Radiation Therapy Oncology Group (RTOG) gastrointestinal (GI) toxicity at 1 year. Secondary endpoints were acute and late toxicity (clinician and patient reported) and freedom from biochemical/clinical failure at 5 years. RESULTS: Two hundred and sixty-five men were recruited and 256 were treated (55 cohort A, 153 cohort B, and 48 cohort C). Median follow-up for each cohort was >5 years. Cumulative late RTOG grade 2+ GI toxicity at 1 year was 3.6% (95% confidence interval [CI], 0.9%-13.8%) (cohort A), 7.2% (95% CI, 4%-12.6%) (cohort B), and 8.4% (95% CI, 3.2%-20.8%) (cohort C). Cumulative late RTOG grade 2+ GI toxicity to 5 years was 12.8% (95% CI, 6.3%-25.1%) (cohort A), 14.6% (95% CI, 9.9%-21.4%) (cohort B), and 20.7% (95% CI, 11.2%-36.2%) (cohort C). Cumulative RTOG grade 2+ genitourinary toxicity to 5 years was 12.9% (95% CI, 6.4%-25.2%) (cohort A), 18.2% (95% CI, 12.8%-25.4%) (cohort B), and 18.2% (95% CI, 9.5%-33.2%) (cohort C). Five-year freedom from biochemical/clinical failure was 98.2% (95% CI, 87.8%-99.7%) (cohort A), 96.7% (95% CI, 91.3%- 98.8%) (cohort B), and 95.1% (95% CI, 81.6-98.7%) (cohort C). CONCLUSIONS: The DELINEATE trial has shown safety, tolerability, and feasibility of focal boosting in 20 or 37 fractions. Efficacy results indicate a low chance of prostate cancer recurrence 5 years after radiation therapy. Evidence from ongoing phase 3 randomized trials is awaited.
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Enfermedades Gastrointestinales , Neoplasias de la Próstata , Radioterapia de Intensidad Modulada , Humanos , Masculino , Enfermedades Gastrointestinales/etiología , Recurrencia Local de Neoplasia/etiología , Próstata/patología , Neoplasias de la Próstata/patología , Hipofraccionamiento de la Dosis de Radiación , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodosRESUMEN
With a unique and large size of testing results of 1,842 samples collected from 12 wastewater treatment plants (WWTP) for 14 months through from low to high prevalence of COVID-19, the sensitivity of RT-qPCR detection of SARS-CoV-2 RNA in wastewater that correspond to the communities was computed by using Probit analysis. This study determined the number of new COVID-19 cases per 100,000 population required to detect SARS-CoV-2 RNA in wastewater at defined probabilities and provided an evidence-based framework of wastewater-based epidemiology surveillance (WBE). Input data were positive and negative test results of SARS-CoV-2 RNA in wastewater samples and the corresponding new COVID-19 case rates per 100,000 population served by each WWTP. The analyses determined that RT-qPCR-based SARS-CoV-2 RNA detection threshold at 50%, 80% and 99% probability required a median of 8 (range: 4-19), 18 (9-43), and 38 (17-97) of new COVID-19 cases /100,000, respectively. Namely, the positive detection rate at 50%, 80% and 99% probability were 0.01%, 0.02%, and 0.04% averagely for new cases in the population. This study improves understanding of the performance of WBE SARS-CoV-2 RNA detection using the large datasets and prolonged study period. Estimated COVID-19 burden at a community level that would result in a positive detection of SARS-CoV-2 in wastewater is critical to support WBE application as a supplementary warning/monitoring system for COVID-19 prevention and control.
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COVID-19 , Humanos , COVID-19/epidemiología , SARS-CoV-2/genética , Aguas Residuales/análisis , ARN Viral/genética , ARN Viral/análisis , Alberta/epidemiologíaRESUMEN
The correlations between SARS-CoV-2 RNA levels in wastewater from 12 wastewater treatment plants and new COVID-19 cases in the corresponding sewersheds of 10 communities were studied over 17 months. The analysis from the longest continuous surveillance reported to date revealed that SARS-CoV-2 RNA levels correlated well with temporal changes of COVID-19 cases in each community. The strongest correlation was found during the third wave (r = 0.97) based on the population-weighted SARS-CoV-2 RNA levels in wastewater. Different correlations were observed (r from 0.51 to 0.86) in various sizes of communities. The population in the sewershed had no observed effects on the strength of the correlation. Fluctuation of SARS-CoV-2 RNA levels in wastewater mirrored increases and decreases of COVID-19 cases in the corresponding community. Since the viral shedding to sewers from all infected individuals is included, wastewater-based surveillance provides an unbiased and no-discriminate estimation of the prevalence of COVID-19 compared with clinical testing that was subject to testing-seeking behaviors and policy changes. Wastewater-based surveillance on SARS-CoV-2 represents a temporal trend of COVID-19 disease burden and is an effective and supplementary monitoring when the number of COVID-19 cases reaches detectable thresholds of SARS-CoV-2 RNA in wastewater of treatment facilities serving various sizes of populations.
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PURPOSE/OBJECTIVE: Total body irradiation (TBI) remains a key component of conditioning for allogeneic haemopoietic stem cell transplant (HSCT), with interstitial pneumonitis (IP) and chronic kidney disease (CKD) important late sequelae. We undertook a retrospective service evaluation of TBI patients treated with a forward-planned intensity modulated radiotherapy technique (FP IMRT). MATERIAL/METHODS: 74 adult patients were identified; all received step and shoot FP IMRT TBI, 14.4 Gy in 8 fractions over 4 days. Mean doses to the lungs and kidneys were 12-12.5 Gy. Toxicities were defined as per CTCAE v4.0: IP as multilobar infiltrates on CT with symptoms of dyspnoea, and renal dysfunction as an Estimated Glomerular Filtration rate (eGFR) < 60 ml/min/1.73 m2 for > 3 months. Secondary endpoints were overall survival (OS), progression free survival (PFS), cumulative incidence of non-relapse mortality (NRM), relapse risk and of acute and chronic GvHD. RESULTS: Patients received treatment for the following diagnosis: ALL/LBL (n = 37); AML (n = 33), CML-BC (n = 2) and High grade NHL (n = 2). The rate of IP due to any cause was 30%; positive microbiological evidence in 73% (16 /22). Idiopathic IP was seen in 8%, with only 4% (n = 3) having IP Grade ≥ 3. Two (4%) of 52 long term survivors developed CKD, one with thrombotic microangiopathy. 4 year NRM was 16% (CI 11-32%); no treatment related deaths in matched sibling or umbilical cord blood HSCT. CONCLUSION: FP IMRT TBI, reducing dose to the lungs and kidneys, has lower rates of idiopathic IP and CKD compared to the literature. This technique is safe and effective conditioning for full intensity HSCT.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Enfermedades Pulmonares Intersticiales , Radioterapia de Intensidad Modulada , Insuficiencia Renal Crónica , Adulto , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Incidencia , Enfermedades Pulmonares Intersticiales/epidemiología , Enfermedades Pulmonares Intersticiales/etiología , Radioterapia de Intensidad Modulada/efectos adversos , Estudios Retrospectivos , Acondicionamiento Pretrasplante/efectos adversos , Trasplante Homólogo , Irradiación Corporal Total/efectos adversosRESUMEN
One of the most prevalent causes of bridge failure around the world is "scour"-the gradual erosion of soil around a bridge foundation due to fast-flowing water. A reliable technique for monitoring scour would help bridge engineers take timely countermeasures to safeguard against failure. Although vibration-based techniques for monitoring structural damage have had limited success, primarily due to insufficient sensitivity, these have tended to focus on the detection of local damage. High natural frequency sensitivity has recently been reported for scour damage. Previous experiments to investigate this have been limited as a result of the cost of full-scale testing and the fact that scaled-down soil-structure models tested outside a centrifuge do not adequately simulate full-scale behaviour. This paper describes the development of what is believed to be the first-ever centrifuge-testing programme to establish the sensitivity of bridge natural frequency to scour. A 1/60 scale model of a two-span integral bridge with 15 m spans was tested at varying levels of scour. For the fundamental mode of vibration, these tests found up to a 40% variation in natural frequency for 30% loss of embedment. Models of three other types of foundation, which represent a shallow pad foundation, a deep pile bent and a deep monopile, were also tested in the centrifuge at different scour levels. The shallow foundation model showed lower frequency sensitivity to scour than the deep foundation models. Another important finding is that the frequency sensitivity to "global scour" is slightly higher than the sensitivity to "local scour", for all foundation types. The level of frequency sensitivity (3.1-44% per scour depth equivalent to 30% of embedment of scour) detected in this experiment demonstrates the potential for using natural frequency as an indicator of both local and global scour of bridges, particularly those with deep foundations.
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Hemocyanin is a multi-functional protein located in the hemolymph (blood) of certain arthropods and molluscs. In addition to its well-defined role in oxygen transport, hemocyanin can be converted into a phenoloxidase-like enzyme. Herein, we tested the antimicrobial properties of horseshoe crab (Limulus polyphemus) hemocyanin-derived phenoloxidase reaction products using broad ranges of phenolic substrates (e.g. l-DOPA) and microbial targets (Gram-positive/negative bacteria, yeast). The enzyme-catalysed turnover of several substrates generated (by)products that reduced significantly the number of colony forming units. Microbicidal effects of hemocyanin-derived phenoloxidase were thwarted by the inhibitor phenylthiourea. Data presented here further support a role for hemocyanin in invertebrate innate immunity.
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Antiinfecciosos/farmacología , Hemocianinas/farmacología , Cangrejos Herradura/metabolismo , Monofenol Monooxigenasa/metabolismo , Animales , Hemolinfa/inmunologíaRESUMEN
BACKGROUND: Emergency department (ED) visit volumes can be especially high during the Christmas-New Year holidays, a period occurring during the influenza season in Canada. METHODS: Using daily data, we examined the relationship between ED visits for the chief complaint "cough" (for Edmonton, Alberta residents) and laboratory detections for influenza A and respiratory syncytial virus (RSV) (for Edmonton and surrounding areas), lagged 0-5 days ahead, for non-pandemic years (2004-2008 and 2010-2014) using multivariable linear regression adjusting for temporal variables. We defined these cough-related visits as influenza-like illness (ILI)-related ED visits and, for 2004-2014, compared Christmas-New Year holiday (December 24-January 3) and non-holiday volumes during the influenza season (October-April). RESULTS: Adjusting for temporal variables, ILI-related ED visits were significantly associated with laboratory detections for influenza A and RSV. During non-pandemic years, the highest peak in ILI-related visit volumes always occurred during the holidays. The median number of holiday ILI-related visits/day (42.5) was almost twice the non-holiday median (24) and was even higher in 2012-2013 (80) and 2013-2014 (86). Holiday ILI-related ED visit volumes/100 000 population ranged from 56.0 (2010-2011) to 117.4 (2012-2013). In contrast, lower visit volumes occurred during the holidays of pandemic-affected years (2008-2010). CONCLUSIONS: During non-pandemic years, ILI-related ED visit volumes were associated with variations in detections for influenza A and RSV and always peaked during the Christmas-New Year holidays. This predictability should be used to prepare for, and possibly prevent, this increase in healthcare use; however, interventions beyond disease prevention strategies are likely needed.
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Técnicas de Laboratorio Clínico/estadística & datos numéricos , Servicio de Urgencia en Hospital , Gripe Humana/diagnóstico , Vigilancia de la Población , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/diagnóstico , Adolescente , Adulto , Alberta/epidemiología , Canadá/epidemiología , Niño , Preescolar , Brotes de Enfermedades/prevención & control , Brotes de Enfermedades/estadística & datos numéricos , Femenino , Humanos , Lactante , Recién Nacido , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/epidemiología , Gripe Humana/virología , Masculino , Persona de Mediana Edad , Pandemias/prevención & control , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Estaciones del Año , Adulto JovenRESUMEN
OBJECTIVE: In June of 2013, southern Alberta underwent flooding that affected approximately 100,000 people. We describe the process put in place for public health surveillance and assessment of the impacts on health. METHODS: Public health surveillance was implemented for the six-week period after the flood to detect anticipated health events, including injuries, mental health problems and infectious diseases. Data sources were emergency departments (EDs) for presenting complaints, public health data on the post-exposure administration of tetanus vaccine/immunoglobulin, administrative data on prescription drugs, and reportable diseases. RESULTS: An increase in injuries was detected through ED visits among Calgary residents (rate ratio [RR] 1.28, 95% confidence interval [CI]: 1.14-1.43) and was supported by a 75% increase in the average weekly administration of post-exposure prophylaxis against tetanus. Mental health impacts in High River residents were observed among females through a 1.64-fold (95% CI: 1.11-2.43) and 2.32-fold (95% CI: 1.45-3.70) increase in new prescriptions for anti-anxiety medication and sleep aids respectively. An increase in sexual assaults presenting to EDs (RR 3.18, 95% CI: 1.29-7.84) was observed among Calgary residents. No increases in infectious gastrointestinal disease or respiratory illness were identified. Timely identification and communication of surveillance alerts allowed for messaging around the use of personal protective equipment and precautions for personal safety. CONCLUSION: Existing data sources were used for surveillance following an emergency situation. The information produced, though limited, was sufficiently timely to inform public health decision-making.
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Inundaciones , Práctica de Salud Pública , Vigilancia en Salud Pública , Alberta/epidemiología , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Humanos , Masculino , Trastornos Mentales/epidemiología , Profilaxis Posexposición/estadística & datos numéricos , Medicamentos bajo Prescripción/uso terapéutico , Delitos Sexuales/estadística & datos numéricos , Tétanos/prevención & control , Heridas y Lesiones/epidemiologíaRESUMEN
BACKGROUND: Antibiotic administration to individuals with Shiga toxin-producing Escherichia coli (STEC) infection remains controversial. We assessed if antibiotic administration to individuals with STEC infection is associated with development of hemolytic uremic syndrome (HUS). METHODS: The analysis included studies published up to 29 April 2015, that provided data from patients (1) with STEC infection, (2) who received antibiotics, (3) who developed HUS, and (4) for whom data reported timing of antibiotic administration in relation to HUS. Risk of bias was assessed; strength of evidence was adjudicated. HUS was the primary outcome. Secondary outcomes restricted the analysis to low-risk-of-bias studies employing commonly used HUS criteria. Pooled estimates of the odds ratio (OR) were obtained using random-effects models. RESULTS: Seventeen reports and 1896 patients met eligibility; 8 (47%) studies were retrospective, 5 (29%) were prospective cohort, 3 (18%) were case-control, and 1 was a trial. The pooled OR, including all studies, associating antibiotic administration and development of HUS was 1.33 (95% confidence interval [CI], .89-1.99; I(2) = 42%). The repeat analysis including only studies with a low risk of bias and those employing an appropriate definition of HUS yielded an OR of 2.24 (95% CI, 1.45-3.46; I(2) = 0%). CONCLUSIONS: Overall, use of antibiotics was not associated with an increased risk of developing HUS; however, after excluding studies at high risk of bias and those that did not employ an acceptable definition of HUS, there was a significant association. Consequently, the use of antibiotics in individuals with STEC infections is not recommended.
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Antibacterianos , Infecciones por Escherichia coli , Síndrome Hemolítico-Urémico , Escherichia coli Shiga-Toxigénica , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/microbiología , Síndrome Hemolítico-Urémico/tratamiento farmacológico , Síndrome Hemolítico-Urémico/epidemiología , Síndrome Hemolítico-Urémico/microbiología , Humanos , Estudios Prospectivos , Estudios Retrospectivos , Escherichia coli Shiga-Toxigénica/efectos de los fármacos , Escherichia coli Shiga-Toxigénica/patogenicidadRESUMEN
BACKGROUND: Meeting the challenge of tuberculosis (TB) elimination will require adopting new models of delivering patient-centered care customized to diverse settings and contexts. In areas of low incidence with cases spread out across jurisdictions and large geographic areas, a "virtual" model is attractive. However, whether "virtual" clinics and telemedicine deliver the same outcomes as face-to-face encounters in general and within the sphere of public health in particular, is unknown. This evidence is generated here by analyzing outcomes between the "virtual" and "outpatient" public health TB clinics in Alberta, a province of Western Canada with a large geographic area and relatively small population. METHODS: In response to the challenge of delivering equitable TB services over long distances and to hard to reach communities, Alberta established three public health clinics for the delivery of its program: two outpatient serving major metropolitan areas, and one virtual serving mainly rural areas. The virtual clinic receives paper-based or electronic referrals and generates directives which are acted upon by local providers. Clinics are staffed by dedicated public health nurses and university-based TB physicians. Performance of the two types of clinics is compared between the years 2008 and 2012 using 16 case management and treatment outcome indicators and 12 contact management indicators. FINDINGS: In the outpatient and virtual clinics, respectively, 691 and 150 cases and their contacts were managed. Individually and together both types of clinics met most performance targets. Compared to outpatient clinics, virtual clinic performance was comparable, superior and inferior in 22, 3, and 3 indicators, respectively. CONCLUSIONS: Outpatient and virtual public health TB clinics perform equally well. In low incidence settings a combination of the two clinic types has the potential to address issues around equitable service delivery and declining expertise.
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Instituciones de Atención Ambulatoria , Atención Dirigida al Paciente , Evaluación de Programas y Proyectos de Salud , Consulta Remota/métodos , Tuberculosis/terapia , Adolescente , Adulto , Alberta/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Salud Pública , Tuberculosis/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Each year in Canada there are 5 million episodes of acute gastroenteritis (AGE) with up to 70% attributed to an unidentified pathogen. Moreover, 90% of individuals with AGE do not seek care when ill, thus, burden of disease estimates are limited by under-diagnosing and under-reporting. Further, little is known about the pathogens causing AGE as the majority of episodes are attributed to an "unidentified" etiology. Our team has two main objectives: 1) to improve health through enhanced enteric pathogen identification; 2) to develop economic models incorporating pathogen burden and societal preferences to inform enteric vaccine decision making. METHODS/DESIGN: This project involves multiple stages: 1) Molecular microbiology experts will participate in a modified Delphi process designed to define criteria to aid in interpreting positive molecular enteric pathogen test results. 2) Clinical data and specimens will be collected from children aged 0-18 years, with vomiting and/or diarrhea who seek medical care in emergency departments, primary care clinics and from those who contact a provincial medical advice line but who do not seek care. Samples to be collected will include stool, rectal swabs (N = 2), and an oral swab. Specimens will be tested employing 1) stool culture; 2) in-house multiplex (N = 5) viral polymerase chain reaction (PCR) panel; and 3) multi-target (N = 15) PCR commercially available array. All participants will have follow-up data collected 14 days later to enable calculation of a Modified Vesikari Scale score and a Burden of Disease Index. Specimens will also be collected from asymptomatic children during their well child vaccination visits to a provincial public health clinic. Following the completion of the initial phases, discrete choice experiments will be conducted to enable a better understanding of societal preferences for diagnostic testing and vaccine policy. All of the results obtained will be integrated into economic models. DISCUSSION: This study is collecting novel samples (e.g., oral swabs) from previously untested groups of children (e.g., those not seeking medical care) which are then undergoing extensive molecular testing to shed a new perspective on the epidemiology of AGE. The knowledge gained will provide the broadest understanding of the epidemiology of vomiting and diarrhea of children to date.
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Gastroenteritis/epidemiología , Enfermedad Aguda , Adolescente , Alberta/epidemiología , Niño , Preescolar , Costo de Enfermedad , Análisis Costo-Beneficio , Diarrea/microbiología , Heces/microbiología , Gastroenteritis/economía , Gastroenteritis/microbiología , Humanos , Lactante , Recién Nacido , Técnicas Microbiológicas , Modelos Económicos , Índice de Severidad de la Enfermedad , Manejo de Especímenes , Vómitos/microbiologíaAsunto(s)
Infecciones por Enterovirus/epidemiología , Infecciones por Enterovirus/virología , Enterovirus/clasificación , Enterovirus/aislamiento & purificación , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Adolescente , Alberta/epidemiología , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , MasculinoRESUMEN
BACKGROUND: Antimicrobial resistance testing and behavioral data combined with Neisseria gonorrhoeae multiantigen sequence typing (NG-MAST) can help to define gonococcal populations and identify, characterize, and compare clusters of infection. METHODS: Antimicrobial resistance testing, using E test, was reviewed for gonococcal isolates in Alberta, Canada, from 2007 to 2011. Antimicrobial resistance testing was conducted on isolates demonstrating antimicrobial resistance and those with cefixime minimum inhibitory concentrations (MICs) of 0.06 µg/mL or greater. Demographic and behavioral information was obtained from provincial surveillance data. NG-MAST typing was conducted on a proportion of isolates. RESULTS: Gonococcal isolates were available for 2250 (26.4%) of 8535 cases of gonorrhea in Alberta from 2007 to 2011. The proportion of cases with decreased susceptibility to cefixime (≥0.06 µg/mL) increased from 0.7% to 2.4% between 2007 and 2009 to a high of 10.1% in 2010 and 8.9% in 2011. Six isolates with cefixime MIC of 0.25 µg/mL were noted: 5 were from men who have sex with men (MSM) and 1 was a pharyngeal isolate from a heterosexual female. Twenty-four (1.1%) isolates were azithromycin resistant (MIC ≥2.0 µg/mL); there were no significant differences between cases resistant or susceptible to azithromycin. NG-MAST of gonococcal isolates in Alberta suggests the entry of multiple strains into the province. Three clusters were identified: Cluster A predominantly in MSM, including sequence type 1407, a ST previously associated with decreased susceptibility to expanded spectrum cephalosporins; Cluster B, a predominantly heterosexual cluster with most cases in Edmonton; and Cluster C among MSM. CONCLUSIONS: Our data highlight the use of NG-MAST in further defining gonococcal populations.
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Antibacterianos/farmacología , Antígenos Bacterianos/genética , Farmacorresistencia Bacteriana , Gonorrea/epidemiología , Neisseria gonorrhoeae/aislamiento & purificación , Alberta/epidemiología , Azitromicina/farmacología , Técnicas de Tipificación Bacteriana , Cefixima/farmacología , Ceftriaxona/farmacología , Cefalosporinas/farmacología , ADN Bacteriano/química , ADN Bacteriano/genética , Femenino , Gonorrea/tratamiento farmacológico , Heterosexualidad , Homosexualidad Femenina , Homosexualidad Masculina , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Neisseria gonorrhoeae/clasificación , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/genética , Filogenia , Estudios RetrospectivosRESUMEN
The synthesis and inhibitory potencies of a novel series of 3,5-diaryl-1H-pyrazoles as specific inhibitors of prokaryotic arylamine N-acetyltransferase enzymes is described. The series is based on hit compound 1 3,5-diaryl-1H-pyrazole identified from a high-throughout screen that has been carried out previously and found to inhibit the growth of Mycobacterium tuberculosis.
Asunto(s)
Antituberculosos/síntesis química , Arilamina N-Acetiltransferasa/antagonistas & inhibidores , Diseño de Fármacos , Inhibidores Enzimáticos/síntesis química , Pirazoles/química , Antituberculosos/química , Antituberculosos/farmacología , Arilamina N-Acetiltransferasa/metabolismo , Sitios de Unión , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Simulación del Acoplamiento Molecular , Mycobacterium tuberculosis/efectos de los fármacos , Estructura Terciaria de Proteína , Pirazoles/síntesis química , Pirazoles/farmacología , Relación Estructura-ActividadRESUMEN
BACKGROUND: In March 2009, global surveillance started detecting cases of influenza-like illness in Mexico. By mid-April 2009, two pediatric patients were identified in the United States who were confirmed to be infected by a novel influenza A (H1N1) strain. The present article describes the first identified severe respiratory infection and the first death associated with pandemic H1N1 (pH1N1) in Canada. METHODS: Enhanced public health and laboratory surveillance for pH1N1 was implemented throughout Alberta on April 24, 2009. Respiratory specimens from all patients with a respiratory illness and travel history or those presenting with a severe respiratory infection requiring hospitalization underwent screening for respiratory viruses using molecular methods. For the first severe case identified and the first death due to pH1N1, histocompatibility leukocyte antigens were compared by molecular methods. RESULTS: The first death (a 39-year-old woman) occurred on April 28, 2009, and on May 1, 2009, a 10-year-old child presented with severe respiratory distress due to pH1N1. Both patients had no travel or contact with anyone who had travelled to Mexico; the cases were not linked. Histocompatibility antigen comparison of both patients did not identify any notable similarity. pH1N1 strains identified in Alberta did not differ from the Mexican strain. CONCLUSION: Rapid transmission of pH1N1 continued to occur in Alberta following the first death and the first severe respiratory infection in Canada, which were identified without any apparent connection to Mexico or the United States. Contact tracing follow-up suggested that oseltamivir may have prevented ongoing transmission of pH1N1.