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1.
J Nucl Cardiol ; 30(1): 46-58, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36536088

RESUMEN

BACKGROUND: With the increase in cardiac PET/CT availability and utilization, the development of a PET/CT-based major adverse cardiovascular events, including death, myocardial infarction (MI), and revascularization (MACE-Revasc) risk assessment score is needed. Here we develop a highly predictive PET/CT-based risk score for 90-day and one-year MACE-Revasc. METHODS AND RESULTS: 11,552 patients had a PET/CT from 2015 to 2017 and were studied for the training and development set. PET/CT from 2018 was used to validate the derived scores (n = 5049). Patients were on average 65 years old, half were male, and a quarter had a prior MI or revascularization. Baseline characteristics and PET/CT results were used to derive the MACE-Revasc risk models, resulting in models with 5 and 8 weighted factors. The PET/CT 90-day MACE-Revasc risk score trended toward outperforming ischemic burden alone [P = .07 with an area under the curve (AUC) 0.85 vs 0.83]. The PET/CT one-year MACE-Revasc score was better than the use of ischemic burden alone (P < .0001, AUC 0.80 vs 0.76). Both PET/CT MACE-Revasc risk scores outperformed risk prediction by cardiologists. CONCLUSION: The derived PET/CT 90-day and one-year MACE-Revasc risk scores were highly predictive and outperformed ischemic burden and cardiologist assessment. These scores are easy to calculate, lending to straightforward clinical implementation and should be further tested for clinical usefulness.


Asunto(s)
Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Humanos , Masculino , Anciano , Femenino , Tomografía Computarizada por Tomografía de Emisión de Positrones , Factores de Riesgo , Tomografía de Emisión de Positrones , Medición de Riesgo/métodos , Valor Predictivo de las Pruebas , Pronóstico , Angiografía Coronaria
2.
J Nucl Cardiol ; 29(3): 1034-1046, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-33090340

RESUMEN

BACKGROUND: Takotsubo (stress) cardiomyopathy (TCM) is characterized by transient apical left ventricular dysfunction precipitated by emotional or physical stress. Its presentation makes it difficult to differentiate from an acute coronary syndrome. A suggestive echocardiogram plus normal coronary angiography most often are used for diagnosis. Radionuclide perfusion study (RPS) findings in TCM, including by positron emission tomography (PET), have been poorly characterized. METHODS AND RESULTS: Intermountain Healthcare electronic medical records were searched from 2009 to 2019 for patients with a discharge diagnosis of TCM, stress CM, or takotsubo syndrome. 16 TCM patients with an RPS, including by PET in 8, were identified: 13 (81%) were women; age averaged 72 years (50-89 years); 14 had an identified stressor. TCM diagnosis was definite in 11 and probable/possible in 5. RPS was abnormal in 11, with 9 showing an apical perfusion deficit, whereas angiography in 14 showed normal coronaries in 12 and non-obstructive disease in 2. Echo ejection fraction averaged 41% (29%-60%); an apical wall motion abnormality was present in 14 (88%). Troponin elevations were noted in 14/15. The presenting ECG was abnormal is 14, frequently showing ST-T-wave abnormalities. 13 patients were discharged on a beta-blocker. Follow-up echo (in 12) showed recovered ejection fraction in 9 and recovered apical wall motion in 11. CONCLUSIONS: Despite having normal or non-obstructive epicardial coronary arteries on angiography, TCM patients frequently present with apical wall motion abnormalities and matching RPS perfusion defects. These findings suggest microvascular abnormalities, whose pathophysiology, temporal course, and clinical implications should be the subject of further investigation.


Asunto(s)
Cardiomiopatía de Takotsubo , Anciano , Ecocardiografía , Electrocardiografía , Femenino , Humanos , Masculino , Perfusión , Cardiomiopatía de Takotsubo/diagnóstico por imagen , Función Ventricular Izquierda
3.
J Dairy Sci ; 105(4): 3234-3247, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35151481

RESUMEN

Johne's disease, or paratuberculosis, is an infectious disorder of the intestines that can affect domestic and wild ruminants that is caused by an infection with Mycobacterium avium ssp. paratuberculosis (MAP). Although the economic losses due to Johne's disease in dairy cattle herds and the benefits and costs of various potential control practices have been estimated before, little is known about the economic value of purchasing MAP-negative dairy replacements in major dairy-producing regions. This study used Markov Chain Monte Carlo simulation techniques to compare 2 sets of MAP-negative and MAP-positive herds across a comprehensive selection of regions: herds purchasing MAP-negative replacement animals and herds purchasing replacement animals with unknown MAP infection status. The economic benefits per MAP-negative replacement purchased were then estimated over a 10-yr horizon, and the additional value of MAP-negative replacements when compared with unknown status replacements were calculated as a percentage premium of the average aggregated dairy replacement price in each region. An average benefit of US$76 per MAP-negative replacement purchase was estimated in major dairy-producing regions, equivalent to a premium of 13%, with higher premiums in regions characterized by below-average replacement prices and on-average farm-gate prices. It was also estimated that the greatest benefits from MAP-negative replacement purchases are associated with MAP-negative herds that successfully remain uninfected.


Asunto(s)
Enfermedades de los Bovinos , Mycobacterium avium subsp. paratuberculosis , Paratuberculosis , Animales , Bovinos , Enfermedades de los Bovinos/microbiología , Costos y Análisis de Costo , Industria Lechera/métodos , Paratuberculosis/microbiología
4.
Am Heart J ; 239: 129-134, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34051172

RESUMEN

BACKGROUND: Several recent trials have evaluated invasive versus medical therapy for stable ischemic heart disease. Importantly, patients with significant left main coronary stenosis (LMCS) were excluded from these trials. In the ISCHEMIA trial, these patients were identified by a coronary CT angiogram (CCTA), which adds time, expense, and contrast exposure. We tested whether a coronary artery calcium scan (CACS), a simpler, less expensive test, could replace CCTA to exclude significant LMCS. METHODS: We hypothesized that patients with ≥50% LMCS would have a LM CACS score > 0. As a corollary, we postulated that a LM CACS = 0 would exclude patients with LMCS. To test this, we searched Intermountain Healthcare's electronic medical records database for all adult patients who had undergone non-contrast cardiac CT for quantitative CACS scoring prior to invasive coronary angiography (ICA). Patients aged <50 and those with a heart transplant were excluded. Cases with incomplete (qualitative) angiographic reports for LMCS and those with incomplete or discrepant LM CACS results were reviewed and reassessed blinded to CACS or ICA findings, respectively. RESULTS: Among 669 candidate patients with CACS followed by ICA, 36 qualifying patients were identified who had a quantitative CACS score and LMCS ≥ 50%. Their age averaged 71.8 years, and 81% were men. Angiographic LMCS averaged 72% (range 50%-99%). Median time between CACS and ICA was 6 days. Total CACS score averaged 2,383 Agatston Units (AU), range 571-6,636. LM CACS score averaged 197 AU, range 31-610. Importantly, no LMCS patient had a LM CACS score of 0 vs 57% (362/633) of non-LMCS controls (P < .00001). CONCLUSIONS: Our results support the hypothesis that an easily administered, inexpensive, low radiation CACS can identify a large subset of patients with a very low risk of LMCS who would not have the need for routine CCTA. Using CACS to exclude LMCS may efficiently allow for safe implementation of an initial medical therapy strategy of patients with stable ischemic heart disease in clinical practice. These promising results deserve validation in larger data sets.


Asunto(s)
Angiografía Coronaria/métodos , Vasos Coronarios , Tomografía Computarizada por Rayos X/métodos , Calcificación Vascular/diagnóstico por imagen , Anciano , Algoritmos , Investigación sobre la Eficacia Comparativa , Enfermedad de la Arteria Coronaria/diagnóstico , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología , Análisis Costo-Beneficio , Registros Electrónicos de Salud/estadística & datos numéricos , Femenino , Humanos , Masculino , Estudios Observacionales como Asunto , Evaluación de Procesos y Resultados en Atención de Salud , Medición de Riesgo/economía , Medición de Riesgo/métodos
5.
J Dairy Sci ; 104(3): 3123-3143, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33455766

RESUMEN

Johne's disease (JD), or paratuberculosis, is an infectious inflammatory disorder of the intestines primarily associated with domestic and wild ruminants including dairy cattle. The disease, caused by an infection with Mycobacterium avium subspecies paratuberculosis (MAP) bacteria, burdens both animals and producers through reduced milk production, premature culling, and reduced salvage values among MAP-infected animals. The economic losses associated with these burdens have been measured before, but not across a comprehensive selection of major dairy-producing regions within a single methodological framework. This study uses a Markov chain Monte Carlo approach to estimate the annual losses per cow within MAP-infected herds and the total regional losses due to JD by simulating the spread and economic impact of the disease with region-specific economic variables. It was estimated that approximately 1% of gross milk revenue, equivalent to US$33 per cow, is lost annually in MAP-infected dairy herds, with those losses primarily driven by reduced production and being higher in regions characterized by above-average farm-gate milk prices and production per cow. An estimated US$198 million is lost due to JD in dairy cattle in the United States annually, US$75 million in Germany, US$56 million in France, US$54 million in New Zealand, and between US$17 million and US$28 million in Canada, one of the smallest dairy-producing regions modeled.


Asunto(s)
Enfermedades de los Bovinos , Paratuberculosis , Animales , Canadá , Bovinos , Enfermedades de los Bovinos/epidemiología , Industria Lechera , Femenino , Francia , Alemania , Nueva Zelanda , Estados Unidos
6.
J Dairy Sci ; 104(4): 4549-4560, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33663863

RESUMEN

We developed a custom bovine leukemia virus (BLV) control program for the Alberta dairy industry, consisting of a risk assessment and a comprehensive list of best management practices (BMP) aimed at prevention of BLV transmission between cattle. This control program was implemented on 11 farms for approximately 1 yr. Blood samples were collected from all cattle ≥12 mo old, and serum was tested with a commercial ELISA. Risk assessments were performed on each farm, risk-connected on-farm management was identified, and management changes expected to prevent transmission of BLV between cattle were suggested by the first author and agreed upon with each farmer. Throughout the following year, all participating farmers were visited multiple times to identify and overcome barriers to implementation and to monitor progress. After approximately 1 yr of implementing BLV control, all cattle ≥12 mo old on farm with a negative or no previous test result were sampled, and the within-herd prevalence was determined. The median number of cattle on farm that were ≥12 mo was 195 (range 110-524). The initial prevalence averaged 39% (13-66%). On average, 5 BMP (3-7) were suggested to each farmer. On average, 4 BMP (1-7) were implemented. At the second sampling, the average within-herd prevalence of all animals that tested positive (including the previous sampling) was 36% (12-62%). Eight farms reduced their within-herd BLV prevalence, within-herd prevalence stayed constant on 1 farm, and it increased on 1 farm. The remaining farm terminated their participation before the second sampling. The number of seroconversions per farm ranged from 3 to 109, highlighting the success of some producers to minimize new infections. The risk assessment was proven to be a valuable tool to identify flaws in on-farm management, although risk assessment score was unrelated to the within-herd BLV prevalence. Finally, it appeared that implementation of BMP aimed at prevention of BLV transmission between cattle could reduce within-herd BLV prevalence when farmers committed to their implementation.


Asunto(s)
Enfermedades de los Bovinos , Leucosis Bovina Enzoótica , Virus de la Leucemia Bovina , Alberta/epidemiología , Animales , Bovinos , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/prevención & control , Industria Lechera , Leucosis Bovina Enzoótica/epidemiología , Leucosis Bovina Enzoótica/prevención & control , Granjas
7.
J Dairy Sci ; 104(6): 6358-6375, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33741150

RESUMEN

Bovine leukemia virus (BLV) infection, endemic in North American dairy herds, has production-limiting effects. A literature review of available papers published since 1995 concerning BLV transmission and its control was conducted. Although confirmed transmission routes were reviewed (blood, natural breeding, in utero, colostrum, and milk), there is still a lack of detailed information on other specific risks for transmission (e.g., contact transmission and hoof-trimming knives). Eradication of BLV has been achieved by combined management, segregation, and culling approaches. In contrast, although sole implementation of best management practices aimed at prevention of BLV transmission has decreased within-herd BLV prevalence, it has not eradicated BLV from a herd. Therefore, control and eradication of BLV by best management practices only should be further investigated. Additionally, the role of proviral load in infected cattle was investigated. Cattle with a high proviral load seem to be more likely to infect others, whereas those with a very low proviral load seem to have low risks of transmitting BLV. Information on proviral load could be taken into account when controlling BLV in high-prevalence herds. In conclusion, there is a need for detailed, large-scale studies investigating roles of specific transmission routes, knowing proviral load of infected individuals.


Asunto(s)
Enfermedades de los Bovinos , Leucosis Bovina Enzoótica , Virus de la Leucemia Bovina , Animales , Anticuerpos Antivirales , Bovinos , Calostro , Leucosis Bovina Enzoótica/epidemiología , Leucosis Bovina Enzoótica/prevención & control , Femenino , Leche , Embarazo , Provirus
8.
J Dairy Sci ; 103(12): 11750-11761, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32981721

RESUMEN

Lameness is a detrimental health and welfare concern of dairy cattle with high prevalence in North American herds. As a practical and farm-specific approach toward its mitigation in Alberta, Canada, a score-based lameness risk assessment questionnaire (RAQ) was developed for veterinarians to conduct with their clients; however, its accuracy in identifying risk for lameness and hoof lesions has not been evaluated. Our objectives were to (1) provide an update on prevalence of lameness and hoof lesions in Alberta freestall herds, (2) validate the RAQ by determining the association between RAQ scores and the prevalence of herd lameness and herd lesions, and (3) determine the association between presence of common hoof lesions and lameness. For the first 2 objectives, 65 Alberta dairy farms were visited between March and October 2018 to collect a completed RAQ, hoof trimming records from their hoof trimmer, and video footage of the entire lactating herd. For the third objective, 10 participant herds were visited twice between November 2013 and June 2014 to take video footage of the entire lactating herd and collect hoof trimming records from their hoof trimmer within 48 h after video footage collection. Median herd-level lameness prevalence was 20% (range = 2-56%), infectious lesion prevalence was 10% (range = 0-49%), and noninfectious lesion prevalence was 15% (range = 2-39%). Of cows that were lame, 93% had a lesion, whereas 21% of cows with a lesion were lame. Cows with an infectious and noninfectious lesion were, respectively, 1.5 and 3.1 times more likely to be lame than cows with no lesion. Total RAQ score and herd lameness prevalence were correlated (r = 0.26) and noninfectious RAQ score and noninfectious lesion prevalence were correlated (r = 0.45), whereas infectious RAQ score and infectious lesion prevalence were not. Cow-level mixed logistic regression models indicated no associations between any of the RAQ scores and presence of lameness or a hoof lesion. Lameness prevalence in Alberta remains high, indicative of a low adoption rate of mitigation strategies by producers. Improvement of the RAQ could allow for better reflection of lameness and lesions on farm and can be achieved through further risk factor analysis within the RAQ, which may result in removal or addition of questions as well as the adjustment of scores based on risk factors' strength of association with lameness and lesions.


Asunto(s)
Enfermedades de los Bovinos/epidemiología , Industria Lechera , Enfermedades del Pie/veterinaria , Cojera Animal/epidemiología , Alberta/epidemiología , Animales , Bovinos , Enfermedades de los Bovinos/patología , Femenino , Pie/patología , Enfermedades del Pie/epidemiología , Enfermedades del Pie/patología , Marcha , Pezuñas y Garras , Lactancia , Cojera Animal/complicaciones , Cojera Animal/patología , Modelos Logísticos , Prevalencia , Medición de Riesgo
9.
BMC Public Health ; 18(1): 195, 2018 01 30.
Artículo en Inglés | MEDLINE | ID: mdl-29378563

RESUMEN

BACKGROUND: This study examined associations between students' physical fitness and physical activity (PA), as well as what specific physical fitness components were more significant correlates to being physically active in different settings for boys and girls. METHODS: A total of 265 fifth-grade students with an average age of 11 voluntarily participated in this study. The students' physical fitness was assessed using four FitnessGram tests, including Progressive Aerobic Cardiovascular Endurance Run (PACER), curl-up, push-up, and trunk lift tests. The students' daily PA was assessed in various settings using a daily PA log for 7 days. Data was analyzed with descriptive statistics, univariate analyses, and multiple R-squared liner regression methods. RESULTS: Performance on the four physical fitness tests was significantly associated with the PA minutes spent in physical education (PE) class and recess for the total sample and for girls, but not for boys. Performance on the four fitness tests was significantly linked to participation in sports/dances outside school and the total weekly PA minutes for the total sample, boys, and girls. Further, boys and girls who were the most physically fit spent significantly more time engaging in sports/dances and had greater total weekly PA than boys and girls who were not physically fit. In addition, the physically fit girls were more physically active in recess than girls who were not physically fit. CONCLUSIONS: Overall, students' performance on the four physical fitness tests was significantly associated with them being physically active during PE and in recess and engaging in sports/dances, as well as with their total weekly PA minutes, but not with their participation in non-organized physical play outside school. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03015337 , registered date: 1/09/2017, as "retrospectively registered".


Asunto(s)
Ejercicio Físico/psicología , Educación y Entrenamiento Físico , Aptitud Física/fisiología , Estudiantes/psicología , Niño , Femenino , Humanos , Actividades Recreativas/psicología , Masculino , Instituciones Académicas , Estudiantes/estadística & datos numéricos , Factores de Tiempo
10.
J Cardiovasc Electrophysiol ; 28(12): 1468-1474, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28960745

RESUMEN

INTRODUCTION: The recent MagnaSafe Registry demonstrated safety of nonthoracic magnetic resonance imaging (MRI) with nonconditional cardiac implantable electronic devices (CIEDs). However, independent validation and extension to thoracic MRIs are needed. METHODS AND RESULTS: We prospectively examined 178 consecutive patients with CIEDs who underwent 212 MRI scans (62 with implantable cardioverter/defibrillators) for clinical reasons between February 2014 and August 2016. Scans were done in standard modes with a limit of 2 W/kg. Pacing modes were ODO or OVO for intrinsic rates > 40 and DOO or VOO for rates ≤ 40. Patients were cleared prescan by both radiology and cardiology, and pre- and postscan CIED interrogations were performed. Primary outcome events were death and generator or lead failure. Secondary events included battery voltage loss > 0.04 V, decrease in P wave voltage > 50% or R wave voltage > 25%, threshold increase of > 0.5 V, and impedance change > 50 Ω. Scan sites were 87 (41%) C-spine/head/neck, 28 (13%) T-spine/cardiac/shoulder (thoracic), 69 (33%) L-spine/abdomen/pelvis, and 28 (13%) lower extremity. No primary or secondary outcome events occurred, and no periscan disruption of pacing was noted. CONCLUSION: In a real-world MRI experience in patients with CIEDs representing a broad range of models, types, and scan sites (including thoracic scans), no adverse safety signals were noted. This experience validates and extends that of the large but inclusion-restricted MagnaSafe Registry, profiles MRI scanning in CIED patients in general clinical practice, and argues against replacing nonconditional with conditional devices when MRI is performed in a carefully controlled environment.


Asunto(s)
Arritmias Cardíacas/diagnóstico por imagen , Desfibriladores Implantables/tendencias , Diseño de Equipo/tendencias , Imagen por Resonancia Magnética/tendencias , Sistema de Registros , Adulto , Anciano , Anciano de 80 o más Años , Arritmias Cardíacas/fisiopatología , Arritmias Cardíacas/cirugía , Desfibriladores Implantables/normas , Diseño de Equipo/métodos , Diseño de Equipo/normas , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/normas , Masculino , Persona de Mediana Edad , Marcapaso Artificial/normas , Marcapaso Artificial/tendencias , Estudios Prospectivos , Sistema de Registros/normas
11.
J Sports Sci Med ; 15(1): 102-10, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26957932

RESUMEN

This study was to examine how well fourth- and fifth-grade students demonstrated motor skill competency assessed with selected PE Metrics assessment rubrics (2009). Fourth- and fifth-grade students (n = 1,346-1,926) were assessed on their performance of three manipulative skills using the PE Metrics Assessment Rubrics during the pre-intervention year, the post-intervention year 1, and the post-intervention year 3. Descriptive statistics, independent t-test, ANOVA, and follow-up comparisons were conducted for data analysis. The results indicated that the post-intervention year 2 cohort performed significantly more competent than the pre-intervention cohort and the post-intervention year 1 cohort on the three manipulative skill assessments. The post-intervention year 1 cohort significantly outperformed the pre-intervention cohort on the soccer dribbling, passing, and receiving and the striking skill assessments, but not on the throwing skill assessment. Although the boys in the three cohorts performed significantly better than the girls on all three skills, the girls showed substantial improvement on the overhand throwing and the soccer skills from baseline to the post-intervention year 1 and the post-intervention year 2. However, the girls, in particular, need to improve striking skill. The CTACH PE was conducive to improving fourth- and fifth-grade students' motor skill competency in the three manipulative skills. This study suggest that PE Metrics assessment rubrics are feasible tools for PE teachers to assess levels of students' demonstration of motor skill competency during a regular PE lesson. Key pointsCATCH PE is an empirically-evidenced quality PE curricular that is conducive to improving students' manipulative skill competency.Boys significantly outperformed than girls in all three manipulative skills.Girls need to improve motor skill competency in striking skill. PE Metrics are feasible assessment rubrics that can be easily used by trained physical education teachers to assess students' manipulative skill competency.

12.
J Sports Sci Med ; 15(2): 335-43, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27274673

RESUMEN

This study examined the extent to which four essential dimensions of quality physical education teaching (QPET) were associated with healthy levels of physical fitness in elementary school students. Participants were nine elementary PE teachers and 1, 201 fourth- and fifth-grade students who were enrolled in nine elementary schools. The students' physical fitness were assessed using four FITNESSGRAM tests. The PE teachers' levels of QPET were assessed using the Assessing Quality Teaching Rubrics (AQTR). The AQTR consisted of four essential dimensions including Task Design, Task Presentation, Class Management, and Instructional Guidance. Codes were confirmed through inter-rater reliability (82.4% and 84.5%). Data were analyzed through descriptive statistics, multiple R-squared regression models, and independent sample t-tests. The four essential teaching dimensions of QPET were significantly associated with the students' cardiovascular endurance, muscular strength and endurance, and flexibility. However, they accounted for relatively low percentage of the total variance in PACER test, followed by Curl-up test, while explaining very low portions of the total variance in Push-up and Trunk Lift tests. This study indicated that the students who had experienced high level of QPET were more physically fit than their peers who did not have this experience in PACER and Curl-up tests, but not in Push-up and Trunk lift tests. In addition, the significant contribution of the four essential teaching dimensions to physical fitness components was gender-specific. It was concluded that the four teaching dimensions of QPET were significantly associated with students' health-enhancing physical fitness. Key pointsAlthough Task Design, Task Presentation, Class Management, and Instructional Guidance has its unique and critical teaching components, each essential teaching dimensions is intertwined and immersed in teaching practices.Four essential teaching dimensions all significantly contributed to students' health-enhancing physical fitness.Implementation of QPET in a lesson plays more significant role in contributing to improving girls' cardiovascular endurance.Implementation of QPET in a lesson contributed significantly to improving boy's abdominal, upper-body, and back extensor muscular strength and endurance as well as flexibility.

13.
Antimicrob Agents Chemother ; 58(6): 3233-44, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24663024

RESUMEN

BI 224436 is an HIV-1 integrase inhibitor with effective antiviral activity that acts through a mechanism that is distinct from that of integrase strand transfer inhibitors (INSTIs). This 3-quinolineacetic acid derivative series was identified using an enzymatic integrase long terminal repeat (LTR) DNA 3'-processing assay. A combination of medicinal chemistry, parallel synthesis, and structure-guided drug design led to the identification of BI 224436 as a candidate for preclinical profiling. It has antiviral 50% effective concentrations (EC50s) of <15 nM against different HIV-1 laboratory strains and cellular cytotoxicity of >90 µM. BI 224436 also has a low, ∼2.1-fold decrease in antiviral potency in the presence of 50% human serum and, by virtue of a steep dose-response curve slope, exhibits serum-shifted EC95 values ranging between 22 and 75 nM. Passage of virus in the presence of inhibitor selected for either A128T, A128N, or L102F primary resistance substitutions, all mapping to a conserved allosteric pocket on the catalytic core of integrase. BI 224436 also retains full antiviral activity against recombinant viruses encoding INSTI resistance substitutions N155S, Q148H, and E92Q. In drug combination studies performed in cellular antiviral assays, BI 224436 displays an additive effect in combination with most approved antiretrovirals, including INSTIs. BI 224436 has drug-like in vitro absorption, distribution, metabolism, and excretion (ADME) properties, including Caco-2 cell permeability, solubility, and low cytochrome P450 inhibition. It exhibited excellent pharmacokinetic profiles in rat (clearance as a percentage of hepatic flow [CL], 0.7%; bioavailability [F], 54%), monkey (CL, 23%; F, 82%), and dog (CL, 8%; F, 81%). Based on the excellent biological and pharmacokinetic profile, BI 224436 was advanced into phase 1 clinical trials.


Asunto(s)
Inhibidores de Integrasa VIH/farmacología , VIH-1/efectos de los fármacos , VIH-1/enzimología , Sustitución de Aminoácidos/genética , Sustitución de Aminoácidos/fisiología , Animales , Fármacos Anti-VIH/farmacología , Células CACO-2 , Clonación Molecular , Inhibidores Enzimáticos del Citocromo P-450/farmacología , ADN Viral/efectos de los fármacos , Farmacorresistencia Viral , Integrasa de VIH/biosíntesis , Integrasa de VIH/genética , Integrasa de VIH/metabolismo , Inhibidores de Integrasa VIH/metabolismo , Inhibidores de Integrasa VIH/farmacocinética , Hepatocitos/metabolismo , Humanos , Ratones , Ratas , Suero/virología , Replicación Viral/efectos de los fármacos
14.
Int Dent J ; 73(4): 566-573, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36925392

RESUMEN

BACKGROUND: The Oral Health Observatory (OHO), launched in 2014 by FDI World Dental Federation, aims to provide a coordinated approach to international oral health data collection. A feasibility project involving 12 countries tested the implementation of the methodology and data collection tools and assessed data quality from 6 countries. METHODS: National dental associations (NDAs) recruited dentists following a standardised sampling method. Dentists and patients completed paired questionnaires (N = 7907) about patients' demographics, dental attendance, oral health-related behaviours, oral impacts, and clinical measures using a mobile app. In addition, participating dentists (n = 93) completed an evaluation survey, and NDAs completed a survey and participated in workshops to assess implementation feasibility. RESULTS: Feasibility data are presented from the 12 participating countries. In addition, the 6 countries most advanced with data collection as of July 2020 (China, Colombia, India, Italy, Japan, and Lebanon) were included in the assessment of data quality and qualitative evaluation of implementation feasibility. All NDAs in these 6 countries reported interest in collecting standardised, international data for policy and communication activities and to understand service use and needs. Eighty-two percent of dentists (n = 76) reported a patient response rate of between 80% and 100%. More than 70% (n = 71) of dentists were either satisfied or very satisfied with the patient recruitment and data collection methods. There were variations in patient oral health and behaviours across countries, such as self-reporting twice-daily brushing which ranged from 45% in India to 83% in Colombia. CONCLUSIONS: OHO provides a feasible model for collecting international standardised data in dental practices. Reducing time implications, ensuring mobile app reliability, and allowing practitioners to access patient-reported outcomes to inform practice may enhance implementation.


Asunto(s)
Odontólogos , Salud Bucal , Humanos , Proyectos Piloto , Reproducibilidad de los Resultados , Encuestas y Cuestionarios
15.
Prev Vet Med ; 189: 105297, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33677407

RESUMEN

Johne's disease (JD), or paratuberculosis, is an infectious disorder primarily associated with cattle and sheep and resulting in significant economic losses for dairy producers. The dairy cattle herd-level prevalence in Canada has recently been estimated to be greater than 40%, but the willingness to pay for JD control practices such as testing-and-culling and vaccination among Canadian dairy producers is unknown. This study used confidential cost-of-production data from the Canadian Dairy Commission to develop a Canadian dairy production model incorporating feed, land, labor, and machinery. A second dataset from a nationally distributed questionnaire (closed in March 2020) was used to estimate individual dairy producer valuations of the reduced per-cow cost of milk production that would result from JD control. This is a novel application of compensating variation and equivalent variation (CV and EV), with dairy producers framed as consumers of production inputs and milk output as a proxy for utility. Assuming a within-herd prevalence of 12.5% and a 50% reduction of that prevalence over 10 years, it was estimated JD control has an annual value of CA$28 per cow for the average Canadian dairy producer. Within-herd prevalence, the effectiveness of control at reducing within-herd prevalence, and the time required to achieve that reduction were identified as important factors. With the same assumption of 12.5% within-herd prevalence but with 100% reductions in that prevalence, estimated values ranged from over CA$55 to over CA$90 per cow per year depending on the timeframe of the control program. When assuming a 10-year period required to achieve control, the estimated values exceeded CA$90 per cow per year in various scenarios for herds with higher within-herd prevalence (greater than 20%).


Asunto(s)
Enfermedades de los Bovinos , Industria Lechera/economía , Paratuberculosis , Animales , Canadá/epidemiología , Bovinos , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/prevención & control , Femenino , Leche , Paratuberculosis/epidemiología , Paratuberculosis/prevención & control
16.
J Cardiovasc Pharmacol Ther ; 26(6): 648-655, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34546822

RESUMEN

BACKGROUND: Flecainide is a useful antiarrhythmic for atrial fibrillation (AF). However, because of ventricular proarrhythmia risk, a history of myocardial infarction (MI) or coronary artery disease (CAD) is a flecainide exclusion, and stress testing is used to exclude ischemia. We assessed whether absent/mild coronary artery calcium (CAC) can supplement or avoid the need for stress testing. METHODS: We assessed ischemic burden using regadenoson Rb-82 PET/CT in 1372 AF patients ≥50 years old without symptoms or signs of clinical CAD. CAC was determined qualitatively by low dose attenuation computed tomography (CT) (n = 816) or by quantitative CT (n = 556). Ischemic burden and clinical outcomes were compared by CAC burden. RESULTS: Patients with CAC absent or mild (n = 766, 57.2%) were younger, more frequently female, and had higher BMI but lower rates of diabetes, hypertension, and dyslipidemia. Average ischemic burden was lower in CAC-absent/mild patients, and CAC-absent/mild patients showed greater coronary flow reserve, had fewer referrals for coronary angiography, and less often had obstructive CAD. Revascularization at 90 days was lower, and the rate of longer-term major adverse cardiovascular events was favorable. CONCLUSIONS: An easily administered, inexpensive, low radiation CAC scan can identify a subset of flecainide candidates with a low ischemic burden on PET stress testing that rarely needs coronary angiography/intervention and has favorable outcomes. Absent or mild CAC-burden combined with other clinical information may avoid or complement routine stress testing. However, additional, ideally randomized and multicenter trials are indicated to confirm these findings before replacing stress testing with CAC screening in selecting patients for flecainide therapy in clinical practice.


Asunto(s)
Calcio/análisis , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Prueba de Esfuerzo/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Anciano , Antiarrítmicos/uso terapéutico , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Femenino , Flecainida/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Radioisótopos de Rubidio , Utah
17.
Am J Cardiol ; 125(3): 341-348, 2020 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-31806210

RESUMEN

Atherosclerotic cardiovascular disease (ASCVD) is the most important cause of morbidity and mortality nationally and internationally. Improving ASCVD risk prediction is a high clinical priority. We sought to determine which of 3 ASCVD risk scores best predicts the need for revascularization and incident major adverse coronary events (MACE) in symptomatic patients at low-to-intermediate primary ASCVD risk referred for regadenoson-stress positron emission tomography (PET). Risk scores included the standard ASCVD pooled cohort equation (PCE), the multiethnic study of atherosclerosis (MESA) risk equation, and the coronary artery calcium score (CACS), obtained by PET. All qualifying patients in our institution at primary ASCVD risk referred for PET-stress tests in whom PCE, MESA, and CAC scores could be calculated were studied. CACS categories were: 0, 1 to 10, 11 to 299, 300 to 999, and 1000+. MESA and PCE scores were divided into quartiles. Logistic regression modeling was used to predict clinical/PET-driven early revascularization (within 90 days) and 1-year MACE (death, myocardial infarction, or any-time revascularization). A total of 981 patients (54% men, age 67 ± 10 years) qualified and were studied. Scores including CAC (MESA, CACS) performed better than PCE for predicting overall 1-year MACE (MESA p <0.001, CACS p = 0.012 vs PCE), which was driven by early revascularization. In conclusion, in a large population of patients at primary ASCVD risk referred for PET-stress testing, risk scores including CAC (CACS, MESA), which better predicted early revascularization and 1-year MACE, may be particularly useful in primary coronary risk assessment when considering whom to refer for PET-stress testing.


Asunto(s)
Aterosclerosis/epidemiología , Calcio/metabolismo , Enfermedad de la Arteria Coronaria/epidemiología , Vasos Coronarios/diagnóstico por imagen , Revascularización Miocárdica , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Calcificación Vascular/epidemiología , Anciano , Aterosclerosis/diagnóstico , Aterosclerosis/cirugía , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/cirugía , Vasos Coronarios/metabolismo , Prueba de Esfuerzo/métodos , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Medición de Riesgo/métodos , Factores de Riesgo , Factores de Tiempo , Calcificación Vascular/diagnóstico , Calcificación Vascular/cirugía
18.
Dev Med Child Neurol ; 51(8): 642-6, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19416324

RESUMEN

Auditory neuropathy, or dyssynchrony, is defined by an abnormal or absent auditory brainstem response but intact otoacoustic emissions or cochlear microphonics. It is associated with impaired hearing on behavioural pure-tone audiometry, absent acoustic reflexes, and poor speech perception, particularly in noisy environments. These results suggest a disorder of inner hair-cell and or eighth-nerve function. We describe a case-note survey of patients with and without auditory neuropathy, using data from the local newborn hearing screening programme collected prospectively from 2002 to 2007. During this period, 45 050 infants were screened with otoacoustic emissions, 30 patients were diagnosed with suspected severe to profound hearing loss (16 males, 14 females), and 12 of those 30 had auditory neuropathy (six males, six females). Mean gestational age was 33 weeks 1 day in the auditory neuropathy group and 35 weeks in the non-auditory neuropathy group. The most significant risk factors for auditory neuropathy were hyperbilirubinaemia (p=0.018), sepsis (p=0.024), and gentamicin exposure (p=0.024). Children with auditory neuropathy comprise a subgroup of patients with hearing impairment involving different pathologies most commonly associated with the risk factors related to admission to neonatal intensive care units. Improvement is possible with maturity, at least in a minority.


Asunto(s)
Nervio Coclear , Pérdida Auditiva/diagnóstico , Tamizaje Neonatal , Enfermedades del Nervio Vestibulococlear/diagnóstico , Enfermedades del Nervio Vestibulococlear/epidemiología , Audiometría de Tonos Puros , Estudios de Cohortes , Potenciales Evocados Auditivos del Tronco Encefálico , Femenino , Pérdida Auditiva/etiología , Pérdida Auditiva/fisiopatología , Humanos , Lactante , Recién Nacido , Masculino , Emisiones Otoacústicas Espontáneas , Reflejo Acústico , Estudios Retrospectivos , Factores de Riesgo , Enfermedades del Nervio Vestibulococlear/rehabilitación
19.
IEEE Trans Neural Syst Rehabil Eng ; 15(1): 59-66, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17436877

RESUMEN

Direct brain interface (BI) systems provide an alternative communication and control solution for individuals with severe motor disabilities, bypassing impaired interface pathways. Most BI systems are aimed to be operated by individuals with severe disabilities. With these individuals, there is no observable indicator of their intent to control or communicate with the BI system. In contrast, able-bodied subjects can perform the desired physical movements such as finger flexion and one can observe the movement as the indicator of intent. Since no external knowledge of intention is available for individuals with severe motor disabilities, generating the data for system training is problematic. This paper introduces three methods for generating training-data for self-paced BI systems and compares their performances with four alternative methods of training-data generation. Results of the offline analysis on the electroencephalogram data of eight subjects during self-paced BI experiments show that two of the proposed methods increase true positive rates (at fixed false positive rate of 2%) over that of the four alternative methods from 50.8%-58.4% to about 62% which corresponds to 3.6%-11.2% improvement.


Asunto(s)
Inteligencia Artificial , Encéfalo/fisiopatología , Electroencefalografía/métodos , Imaginación , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/rehabilitación , Interfaz Usuario-Computador , Adulto , Cognición , Simulación por Computador , Potenciales Evocados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Neurológicos , Reconocimiento de Normas Patrones Automatizadas/métodos , Análisis y Desempeño de Tareas
20.
J Neural Eng ; 3(2): 87-94, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16705264

RESUMEN

The low-frequency asynchronous switch design (LF-ASD) has been introduced as a direct brain interface (BI) for asynchronous control applications. Asynchronous interfaces, as opposed to synchronous interfaces, have the advantage of being operational at all times and not only at specific system-defined periods. This paper modifies the LF-ASD design by incorporating into the system more knowledge about the attempted movements. Specifically, the history of feature values extracted from the EEG signal is used to detect a right index finger movement attempt. Using data collected from individuals with high-level spinal cord injuries and able-bodied subjects, it is shown that the error characteristics of the modified design are significantly better than the previous LF-ASD design. The true positive rate percentage increased by up to 15 which corresponds to 50% improvement when the system is operating with false positive rates in the 1-2% range.


Asunto(s)
Encéfalo/fisiopatología , Equipos de Comunicación para Personas con Discapacidad , Electroencefalografía/instrumentación , Procesamiento de Señales Asistido por Computador/instrumentación , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/rehabilitación , Interfaz Usuario-Computador , Adulto , Inteligencia Artificial , Electroencefalografía/métodos , Diseño de Equipo , Análisis de Falla de Equipo , Potenciales Evocados Motores , Femenino , Humanos , Imaginación , Masculino , Persona de Mediana Edad , Reconocimiento de Normas Patrones Automatizadas/métodos
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