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BACKGROUND: Prescription of compression stockings to prevent post-thrombotic syndrome (PTS) in adults is controversial. We sought to estimate the efficacy of compression stockings vs. placebo/no intervention (control) in preventing PTS, and to estimate the probability of observing a benefit when prescribing compression stockings to prevent PTS. METHODS: We conducted a systematic review of the literature in MEDLINE, EMBASE, and the Cochrane Central Register of Randomized Trials, searching for randomized controlled trials that compared compression stockings, applied in the acute setting of deep vein thrombosis, vs. control to prevent PTS. We used a Bayesian approach for data analysis. RESULTS: Four studies met our inclusion criteria. When comparing intervention vs. control, the estimated odds ratio (OR) was 0.57 (95% Credible Interval (CrI): 0.21 to 1.20) for PTS vs. no PTS and 0.79 (95% CrI 0.31 to 1.67) for severe vs. no/mild/moderate PTS. The probabilities of observing treatment benefits in the population if prescribing compression stockings ranged between 47% (large benefit, ORâ¯<â¯0.50) and 95% (small benefit, ORâ¯<â¯1.00) for any PTS and between 16% and 82% (from large to small benefit) for severe PTS. The probabilities of observing benefit of compression stockings in a future study ranged 44%-76% and 25%-72% (from large to small benefit) for any PTS and severe PTS, respectively. CONCLUSION: Despite heterogeneity, data show that it is still probable to observe some degree of treatment benefit when prescribing compression stockings and to observe some degree of treatment benefit in a future study.
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Síndrome Postrombótico/prevención & control , Medias de Compresión , Teorema de Bayes , Humanos , Oportunidad Relativa , Síndrome Postrombótico/etiología , Probabilidad , Ensayos Clínicos Controlados Aleatorios como Asunto , Trombosis de la Vena/complicaciones , Trombosis de la Vena/terapiaRESUMEN
BACKGROUND: Pediatric infective endocarditis (IE) has been associated with high morbidity and mortality, mostly related to thromboembolic complications (TEC). The objective of our study was to describe the experience in children with IE and to review the changes over a thirty-year period, regarding origin of IE, incidence of vegetations, TEC and their respective morbidity and mortality rates. METHODS: A retrospective chart review of children aged 0-18years with IE defined by the Duke Criteria and admitted to The Hospital for Sick Children, was conducted. Data were divided into three periods (P); P1 (1979-1988); P2 (1989-1998); and P3 (1999-2008). RESULTS: The study included 113 patients, median age 7yrs.; females: 46 (41%), congenital heart defects 95 (84%), comparable in all periods. Overall, cardiac vegetations were found in 68/113 patients (60%); large vegetations (≥1cm) in 32 patients (28%). Fourty-five (45/133 [40%]) TEC were documented, 22 patients (20%) developed cerebrovascular events (CVE) and 23 patients (20%) had non-CVE. Patients diagnosed during P3 were older, had more vegetations (p<0.05), and a higher incidence of community acquired-IE (p<0.05). Overall, mortality was 15%, comparable in all periods. Significant risk factors for mortality were vegetations (HR 6.44; 95% CI: 2.07-20.01, p=0.002) and heart failure (HR 28.39; 95% CI: 10.49-76.85, p<0.001). CONCLUSIONS: Over the study period, we report a growing incidence of community acquired pediatric IE in older children accompanied by an increasing rate of TEC. Heart failure and vegetations were associated with an increased mortality. These preliminary data need to be confirmed by prospective data.
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Infección Hospitalaria/diagnóstico , Infección Hospitalaria/epidemiología , Endocarditis/diagnóstico , Endocarditis/epidemiología , Tromboembolia/diagnóstico , Tromboembolia/epidemiología , Adolescente , Niño , Preescolar , Estudios de Cohortes , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estudios Retrospectivos , Factores de RiesgoRESUMEN
INTRODUCTION: Although the regular replacement of clotting factor concentrates (prophylaxis) has been well established as the standard of care for severe haemophilia, the high cost of factor concentrates has limited access to prophylaxis in countries with under-developed or developing economies. AIMS: We studied the health gap that could be addressed by providing unlimited access to clotting factor concentrates with implementation of long-term prophylaxis initiated from an early age in life. METHODS: We performed a cross-sectional study of a random, representative sample of boys with moderate and severe haemophilia at three haemophilia treatment centres in Sao Paulo, Brazil, and one centre in Toronto, Canada. RESULTS: Canadian subjects were more often treated with prophylaxis, and began treatment at an earlier age. Fewer Canadian subjects had bleeds within the preceding 6 months (19 vs. 34, P = 0.003). Canadian subjects had lower (better) Pettersson radiographic scores (1.5 vs. 6.0, P = 0.0016), lower (better) Hemophilia Joint Health Scores (5.5 vs. 10.5, P = 0.0038), higher (better) Activity Scale for Kids scores (96.6 vs. 92.0, P = 0.033), more time spent in vigorous activity, and higher (better) social participation scores. CONCLUSIONS: Our findings suggest that increasing access to clotting factor concentrates for young boys with severe haemophilia is a global imperative.
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Costo de Enfermedad , Países en Desarrollo , Recursos en Salud , Hemofilia A/epidemiología , Adolescente , Brasil/epidemiología , Canadá/epidemiología , Niño , Estudios Transversales , Indicadores de Salud , Hemofilia A/diagnóstico , Hemofilia A/terapia , Humanos , Masculino , Calidad de Vida , Índice de Severidad de la EnfermedadRESUMEN
Essentials We developed a discriminative and evaluative index for pediatric postthrombotic syndrome (PTS). A Delphi-survey was used for item reduction and multi-criteria decision analysis for item weighting. The new index assesses limb PTS based on the relative severity of each sign and symptom. Higher scores related to higher odds of parental dissatisfaction with their child's condition. SUMMARY: Background Postthrombotic syndrome (PTS) is a complication of deep vein thrombosis defined by the presence of characteristic signs and symptoms. We developed a discriminative and evaluative index for the assessment of upper extremity (UE) and lower extremity (LE) pediatric PTS. Methods The items to be included in the index were voted for by 26 pediatric thrombosis experts invited to participate in a Delphi survey. Subsequent item weighting was based on item importance elicited by the use of multicriteria decision analysis (MCDA); 122 healthcare providers and patients/parents were invited to participate in item weighting. The implications of the overall scores were explored by comparison with PTS diagnosis (independently assessed by two clinical experts) and parental satisfaction/dissatisfaction with their child's current condition. Results Items voted for inclusion by at least 70% of the Delphi survey respondents (81% response rate) were pain, paresthesia, swelling, heaviness, endurance, collateral circulation and arm circumference difference for the UE, and pain, paresthesia, swelling, heaviness, tightness, tired limb, redness/purple or blotchy skin, endurance, ulcers and thigh/calf circumference difference for the LE. Items were then weighted by the use of MCDA (82% response rate). The index had excellent discrimination for patients with/without PTS. For every 10-point increase in index scores (with higher scores being indicative of worse PTS), the odds of parental dissatisfaction increased by 75% and 92% in the UE and LE, respectively. Conclusion We report the development of the CAPTSure™ (index for the Clinical Assessment of Postthrombotic Syndrome in children), which reflects collective judgement of the severity of pediatric PTS. We also provide information on the meaning of the scores.
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Pediatría/métodos , Síndrome Postrombótico/diagnóstico , Índice de Severidad de la Enfermedad , Trombosis de la Vena/complicaciones , Trombosis de la Vena/diagnóstico , Niño , Preescolar , Toma de Decisiones , Técnica Delphi , Femenino , Humanos , Extremidad Inferior , Masculino , Curva ROC , Sensibilidad y Especificidad , Evaluación de Síntomas , Resultado del Tratamiento , Extremidad SuperiorRESUMEN
OBJECTIVE: Our goal was to conduct the item generation and piloting phases of a new discriminative and evaluative tool for pediatric post-thrombotic syndrome. METHODS: We followed a formative model for the development of the tool, focusing on the signs/symptoms (items) that define post-thrombotic syndrome. For item generation, pediatric thrombosis experts and subjects diagnosed with extremity post-thrombotic syndrome during childhood nominated items. In the piloting phase, items were cross-sectionally measured in children with limb deep vein thrombosis to examine item performance. RESULT: Twenty-three experts and 16 subjects listed 34 items, which were then measured in 140 subjects with previous diagnosis of limb deep vein thrombosis (70 upper extremity and 70 lower extremity). The items with strongest correlation with post-thrombotic syndrome severity and largest area under the curve were pain (in older children), paresthesia, and swollen limb for the upper extremity group, and pain (in older children), tired limb, heaviness, tightness and paresthesia for the lower extremity group. CONCLUSION: The diagnostic properties of the items and their correlations with post-thrombotic syndrome severity varied according to the assessed venous territory. The information gathered in this study will help experts decide which item should be considered for inclusion in the new tool.
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Extremidad Inferior/irrigación sanguínea , Síndrome Postrombótico/diagnóstico , Extremidad Superior/irrigación sanguínea , Niño , Preescolar , Femenino , Humanos , Extremidad Inferior/patología , Masculino , Síndrome Postrombótico/etiología , Extremidad Superior/patología , Trombosis de la Vena/complicacionesAsunto(s)
Circulación Colateral , Extremidad Inferior/irrigación sanguínea , Síndrome Postrombótico/sangre , Extremidad Superior/irrigación sanguínea , Niño , Preescolar , Estudios de Cohortes , Humanos , Síndrome Postrombótico/diagnóstico , Síndrome Postrombótico/etiología , Trombosis de la Vena/complicacionesRESUMEN
INTRODUCTION: Venous thrombotic events (VTE) are becoming more and more common in children, particularly in the hospital setting. To date, 1 in 200 children admitted to tertiary pediatric hospitals are now being recognized to develop VTE. Amongst those patients with an identified thrombotic occlusion, pediatric patients diagnosed with renal tumors have long been recognized, but their ideal management in the instances of vascular invasion remains controversial. AIM: We describe the clinical behavior of patients diagnosed with renal tumors and extra renal vascular involvement at The Hospital for Sick Children in Toronto, Canada. MATERIALS AND METHODS: A retrospective analysis was conducted in patients diagnosed from 1990 to 2012. Data collected included: age, gender, symptoms at presentation, staging, pathology report, radiological evidence of intravascular thrombus [i.e. renal veins (RV), inferior vena cava (IVC) and right atrium (RA)], intraoperative findings, therapeutic protocol implemented and anticoagulation; for outcomes, tumor and/or thrombus recurrence, thromboembolic phenomena [i.e. pulmonary embolism (PE)] and survival. RESULTS: Of 299 patients with renal tumors identified, 292 were included: Wilms (219), Renal Cell Carcinoma (RCC, 29), Clear Cell Sarcoma of the Kidney (CCSK, 12), others (32). The median age of the group was 4.53years (4days - 18 years). Extra renal vascular disease was identified in 29 patients, with a median age 7.05years (0.6-16 years; p=0.03), including Wilms tumors (22/219, 10%), RCC (2/29, 7%), CCSK (1/12, 8.3%) and others (4/32, 12.5%; p=0.01). Vascular involvement comprised exclusive evidence of RV disease (7), IVC disease (19; 15 infra-hepatic), RA disease (3) and PE (5).Treatment escalation because of vascular disease included neo-adjuvant chemotherapy (12; Wilms [11], RCC [1]), intraoperative cavectomy/ thrombectomy (1; Wilms), and cavotomies (11 Wilms [7], RCC [1], CCSK [1], PNET [1], sarcoma [1]). Four patients were placed under cardiopulmonary bypass. Anticoagulation was administered in 9/29 patients for their tumor-related thrombus, and one had a minor bleeding complications (oozing from the central venous line insertion site). CONCLUSIONS: Renal tumors with vascular invasion are a rare and challenging entity. Treatment included mostly cancer-related therapies and the role of vascular surgical approaches and/or systemic anticoagulation remains to be clarified.
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UNLABELLED: We studied bone mineral density (BMD) of children exposed to long-term warfarin. BMD Z-scores ≤ -2.0 were estimated to occur in less than one fifth of the patients after 10 years of warfarin exposure, and BMI and growth hormone deficiency predicted BMD changes over time. These predictors can help identify high-risk patients. INTRODUCTION: Children with chronic diseases are at increased risk of developing thrombosis, which may require long-term warfarin therapy. Warfarin could further jeopardize the bone health of a population already at risk for bone fragility. Our objective was to investigate the occurrence and timing of low bone mineral density (BMD) and the predictors that influence BMD trajectory in children receiving warfarin for >1 year. METHODS: We analyzed the results of an institutional protocol that includes dual-energy X-ray absorptiometry, with or without spinal X-rays and laboratory biomarkers, as required. RESULTS: Low BMD (age, sex, race, and height-for-age-Z-score adjusted BMD Z-score ≤ -2.0) was detected in 13 % (9/70) of the patients at some point during their follow-up; these patients were more likely to have complex underlying medical conditions and low body mass index (BMI) percentile. BMD Z-scores remained within normal range in 87 % of children. Survival analysis showed that the estimated 10-year abnormal BMD-free rate for the entire group was 81 % (95 % confidence interval [CI] 69 to 93 %). Trajectory analysis revealed that BMI percentiles at baseline and growth hormone deficiency (GHD) were associated with lower BMD Z-scores at the first assessment, whereas baseline BMI percentile was the only predictor of BMD Z-score over time. CONCLUSIONS: Our findings identified BMI and GHD as risk factors influencing BMD in children exposed to long-term warfarin, creating an opportunity for early detection and intervention in these patients.
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Anticoagulantes/efectos adversos , Osteoporosis/inducido químicamente , Warfarina/efectos adversos , Absorciometría de Fotón/métodos , Anticoagulantes/administración & dosificación , Índice de Masa Corporal , Densidad Ósea/efectos de los fármacos , Niño , Preescolar , Progresión de la Enfermedad , Esquema de Medicación , Femenino , Hormona de Crecimiento Humana/deficiencia , Humanos , Lactante , Estudios Longitudinales , Masculino , Osteoporosis/fisiopatología , Fracturas Osteoporóticas/inducido químicamente , Fracturas Osteoporóticas/fisiopatología , Estudios Retrospectivos , Factores de Riesgo , Warfarina/administración & dosificaciónRESUMEN
INTRODUCTION: Children at risk for bleeding injuries are restricted from body contact during physical activity but current recommendations are based on expert opinion. AIM: Evaluate high-speed digital video recording as an objective measure of body contact risk during physical activity. METHODS: Observational study of physical activities among healthy children, grouped according to participation in teams (vs. individual) and on their perceived risk of injury (high/low). High speed digital video recordings documented the collision target (floor/ground/ice, people, wall, equipment), estimated speed, and impact rates for team and individual activities, with and without expected body contact. RESULTS: Among 348 participating children (3-16 years, 51% female), 32% to 78% experienced at least one contact. Impact type varied significantly (chi-square, p < 0.001) by activity category. Unstructured and Team high risk activity impacts were primarily with the floor/ground, whereas Individual low risk activities were characterized by equipment impacts. Impact speeds were typically 1.0 to 2.1 m s(-1) . Higher impact speeds occurred during instructional classes (2.1 m s(-1) ), unstructured free swim (1.9 m s(-1) ) and ball hockey (1.7 m s(-1) ). Impact rates were higher during Team high risk and Team low risk sports (3.0 and 1.8 impacts per minute, respectively) compared to Individual (high or low risk) or Unstructured activities (0.2-0.3 impacts per minute). CONCLUSIONS: High speed video recordings of childhood physical activity are a feasible method for characterizing the frequency, type, direction and speed of impacts. Quantifying the impacts that occur during childhood physical activity could inform the guidelines for physical activity participation among children with identified bleeding risks.
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Ejercicio Físico , Intención , Grabación en Video , Adolescente , Traumatismos en Atletas/etiología , Niño , Preescolar , Estudios de Factibilidad , Femenino , Humanos , Masculino , RiesgoRESUMEN
Health-related quality of life (HRQoL) is an important outcome from the perspective of boys with haemophilia and their parents. Few studies have captured the HRQoL of boys with haemophilia in developing countries. This article reports on the cross-cultural adaptation of the Canadian Haemophilia Outcomes - Kids Life Assessment Tool (CHO-KLAT) for use in São Paulo, Brazil. The CHO-KLAT(2.0) was translated into Portuguese, and then translated back into English. The original English and back-translation versions were compared by a group of three clinicians, whose first language was Portuguese. The resulting Portuguese version was assessed through a series of cognitive debriefing interviews with children and their parents. This process identified concepts that were not clear and revised items to ensure appropriate understanding through an iterative process. The initial back-translation was not discrepant from the original English version. We made changes to 66% of the CHO-KLAT(2.0) items based on clinical expert review and 26% of the items based on cognitive debriefings. In addition, two new items were added to the final Portuguese version to reflect the local cultural context. The final result had good face validity. This process was found to be extremely valuable in ensuring the items were accurately interpreted by the boys/parents in São Paulo Brazil. The results suggest that professional translators, clinical experts and cognitive debriefing are all required to achieve a culturally appropriate instrument. The Portuguese CHO-KLAT(2.0) is well understood by Sao Paulo boys/parents. The next step will be to test its validity and reliability locally.
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Hemofilia A/psicología , Hemofilia B/psicología , Calidad de Vida , Adolescente , Brasil , Niño , Humanos , Entrevistas como Asunto , Masculino , Apoyo Social , Encuestas y Cuestionarios , TraducciónRESUMEN
Psychosocial outcomes are important in the perspective of boys with haemophilia. However, health-related quality of life (HRQoL) is based on self-report, and assumes adequate literacy. Yet, literacy is rarely assessed prior to data collection. This study sought to identify criteria that might indicate the level of literacy of children being recruited for clinical trials and to develop a simple method to prescreen those whose literacy was uncertain. We developed a brief screening tool in the form of two stories, at a grade 3 reading level, followed by comprehension questions. We applied the screening test to a sample of haemophilic boys between the ages of 7 and 13 years to assess their literacy. The data were analysed to determine the best criteria to use in identifying the ability to independently self-report for HRQoL studies. Twenty-four Brazilian boys (7.9-12.8) completed the testing. The results showed that 17 (70.8%) were literate (were able to both read and comprehend), and could complete a questionnaire without assistance. All boys over 11.0 years of age were sufficiently literate. Grade level was not found to be a helpful criterion. We recommend that all children under the age of 11.0 years be prescreened before providing self-reported HRQoL data. Those with limited literacy should be provided assistance to ensure comprehension of the questions. This is important to ensure high-quality data on HRQoL for future clinical trials.
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Hemofilia A/psicología , Hemofilia B/psicología , Calidad de Vida , Adolescente , Brasil , Niño , Escolaridad , Estado de Salud , Humanos , Masculino , Encuestas y CuestionariosRESUMEN
BACKGROUND: Heparin-induced thrombocytopenia (HIT) has increasingly been reported in children as an indication for use of new alternative anticoagulant drugs (NAADs). OBJECTIVES: To systematically review the literature regarding: (i) the incidence and prevalence of seroconversion and HIT and (ii) the clinical/laboratory findings and management of HIT in children. DESIGN/METHODS: MEDLINE and EMBASE databases were searched for studies that reported pediatric cases of HIT. Methodological reliability assessment of studies was performed with the Loney scale. RESULTS: The incidence of seroconversion in neonates ranged between 0% and 1.7%. There were no cases of neonatal HIT in the included cohorts. The incidence range of seroconversion in the non-neonatal population was 1.3-52%. The incidence of HIT in non-neonates after cardiopulmonary bypass was 0.33% (95%CI, < 0.01-2.04). Whereas more than half of pediatric cases labeled as HIT (30/52) did not include pivotal features of this syndrome, 80% of them received NAADs. CONCLUSION: The incidence of HIT is likely to have been overestimated in children, leading to potential misuse of NAADs in many cases. Clinical findings and laboratory assessment of pediatric cases are poorly described in the literature at present. Thorough laboratory investigation, proper reporting of cases and adequate design of studies are mandatory to elucidate the clinical/laboratory picture of pediatric HIT.
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Anticoagulantes/efectos adversos , Heparina/efectos adversos , Trombocitopenia/inducido químicamente , Niño , Humanos , Incidencia , Trombocitopenia/epidemiologíaAsunto(s)
Anticoagulantes/farmacocinética , Hidrocarburo de Aril Hidroxilasas/genética , Coagulación Sanguínea/efectos de los fármacos , Oxigenasas de Función Mixta/genética , Warfarina/farmacocinética , Adolescente , Factores de Edad , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Anticoagulantes/sangre , Hidrocarburo de Aril Hidroxilasas/metabolismo , Biotransformación , Niño , Preescolar , Estudios Transversales , Citocromo P-450 CYP2C9 , Monitoreo de Drogas/métodos , Inglaterra , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Hemorragia/inducido químicamente , Hemorragia/genética , Humanos , Lactante , Relación Normalizada Internacional , Masculino , Oxigenasas de Función Mixta/metabolismo , Ontario , Farmacogenética , Fenotipo , Estudios Retrospectivos , Factores de Riesgo , Vitamina K Epóxido Reductasas , Warfarina/administración & dosificación , Warfarina/efectos adversos , Warfarina/sangreAsunto(s)
Cateterismo Venoso Central/efectos adversos , Catéteres Venosos Centrales/efectos adversos , Pruebas Diagnósticas de Rutina/normas , Síndrome Postrombótico/diagnóstico , Trombosis Venosa Profunda de la Extremidad Superior/diagnóstico , Actividades Cotidianas , Adulto , Factores de Edad , Cateterismo Venoso Central/instrumentación , Niño , Técnicas de Diagnóstico Cardiovascular/normas , Evaluación de la Discapacidad , Humanos , Dimensión del Dolor/normas , Examen Físico/normas , Síndrome Postrombótico/etiología , Síndrome Postrombótico/prevención & control , Valor Predictivo de las Pruebas , Pronóstico , Calidad de Vida , Encuestas y Cuestionarios/normas , Terminología como Asunto , Trombosis Venosa Profunda de la Extremidad Superior/etiología , Trombosis Venosa Profunda de la Extremidad Superior/terapiaAsunto(s)
Extremidad Inferior/irrigación sanguínea , Síndrome Postrombótico/clasificación , Terminología como Asunto , Trombosis de la Vena/complicaciones , Factores de Edad , Niño , Humanos , Síndrome Postrombótico/sangre , Síndrome Postrombótico/diagnóstico , Síndrome Postrombótico/etiología , Síndrome Postrombótico/fisiopatología , Valor Predictivo de las Pruebas , Pronóstico , Reproducibilidad de los Resultados , Trombosis de la Vena/sangre , Trombosis de la Vena/fisiopatologíaRESUMEN
BACKGROUND: Unfractionated heparin (UFH) is a widely used anticoagulant. Current American College of Chest Physicians guidelines for infants extrapolated from adults recommend 28 U kg(-1) h(1) of UFH to achieve an anti-factor Xa level of 0.35-0.7 IU mL(-1). OBJECTIVE: To assess the profile of anti-FXa-based UFH dosing guidelines in infants. PATIENTS/METHODS: We included all infants aged < 6 months treated with per-protocol intravenous UFH at the Hospital for Sick Children, Toronto, over a 3.5-year period. RESULTS: Of 100 infants, 11% achieved sustained therapeutic anti-FXa levels with current dose recommendations. Only 15% achieved target anti-FXa levels within 24 h with per-protocol dose escalations. Seventeen per cent of patients never achieved therapeutic anti-FXa levels, despite up to 60 days of therapy and triple the recommended dose. The median dose needed to achieve therapeutic anti-FXa levels in the remaining 83 infants was 33 U kg(-1) h(-1) (interquartile range, 30-36). Two in three infants had decreased thrombus size at completion of therapy and no thrombus progression/recurrence, and 11/100 infants suffered major bleeding. Without exclusion of extracorporeal membrane oxygenation patients, an activated partial thromboplastin time (APTT) of > 180 s was detected as a risk factor for major bleeding. CONCLUSIONS: UFH monitoring is challenging in infants. Despite their delay in reaching therapeutic anti-FXa levels, infants monitored with the adult-based anti-FXa range have a high thrombus resolution rate, no thrombus progression, but a relatively high bleeding rate. Extreme APTT elevation may contribute to this bleeding risk, particularly in critically ill patients. Current UFH guidelines for young infants may still be inadequate, and laboratory methods with age-appropriate ranges may be required to further improve clinical outcomes within this population.
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Anticoagulantes/administración & dosificación , Pruebas de Coagulación Sanguínea , Coagulación Sanguínea/efectos de los fármacos , Monitoreo de Drogas/métodos , Inhibidores del Factor Xa , Fibrinolíticos/administración & dosificación , Heparina/administración & dosificación , Trombosis/tratamiento farmacológico , Trombosis/prevención & control , Factores de Edad , Anticoagulantes/efectos adversos , Distribución de Chi-Cuadrado , Cálculo de Dosificación de Drogas , Femenino , Fibrinolíticos/efectos adversos , Hemorragia/inducido químicamente , Heparina/efectos adversos , Hospitales Pediátricos , Humanos , Lactante , Recién Nacido , Modelos Logísticos , Masculino , Oportunidad Relativa , Ontario , Tiempo de Tromboplastina Parcial , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Trombosis/sangre , Trombosis/diagnóstico , Resultado del TratamientoRESUMEN
The population dynamics of Staphylococcus spp. was studied during the ripening of Canastra Minas cheese at three farms located in the State of Minas Gerais, Brazil. The presence of coagulase (coa), thermonuclease (nuc), and enterotoxin (sea, seb, sec, and sed) genes was investigated in Staphylococcus strains isolated during the 60-day cheese-ripening period. The presence of the staphylococcal enterotoxins A, C, and D was also investigated in the cheese samples. Cheese samples that were matured for 0, 7, 15, 30, and 45 days presented staphylococci counts from 10³ to 10(8)cfu/g. All isolates considered coagulase-positive by physiological tests had the coa gene. However, no association was observed between the results obtained with biochemical tests and those obtained by PCR using gene-specific primers for coagulase-negative strains. Coagulase and thermonuclease genes occurred simultaneously in 41.3 percent of Staphylococcus spp. tested. None of the investigated Staphylococcus strains expressed enterotoxins SEA, SEB, SEC, and SED. Enterotoxins A, C, and D were not detected in any of the cheese samples.
Estudou-se a dinâmica das populações de Staphylococcus spp. durante a maturação do queijo Canastra, em três fazendas localizadas no estado de Minas Gerais. A presença dos genes que codificam para a produção das enzimas coagulase (coa), termonuclease (nuc) e produção de enterotoxinas (sea, seb, sec e sed), em linhagens de Staphylococcus isoladas durante os 60 dias de maturação do queijo foi analisada. Também foi investigada a presença de enterotoxina estafilocócica A, C e D nas amostras de queijo. As amostras de queijo com 0, 7, 15, 30 e 45 dias de maturação apresentaram contagens de Staphylococcus spp. entre 10³ e 10(8)ufc / g. Todos os isolados coagulase positivo nos testes fisiológicos apresentaram o gene coa. Não foi observada associação entre os resultados obtidos com os testes bioquímicos e aqueles obtidos com a PCR usando iniciadores gene-específicos para linhagens coagulase negativa. Os genes da coagulase e termonuclease ocorreram simultaneamente em 41,3 por cento dos Staphylococcus spp. testados. Nenhum dos isolados de Staphylococcus apresentou os genes que codificam para a produção das enterotoxinas SEA, SEB, SEC ou SED. As enterotoxinas A, C ou D não foram detectadas em nenhuma das amostras de queijo analisadas.
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Humanos , Queso/clasificación , Staphylococcus , Coagulasa/metabolismo , Enterotoxinas/toxicidad , Fisiología/métodosRESUMEN
BACKGROUND: Different rates of inhibitor development after either plasma-derived (pdFVIII) or recombinant (rFVIII) FVIII have been suggested. However, conflicting results are reported in the literature. OBJECTIVES: To systematically review the incidence rates of inhibitor development in previously untreated patients (PUPs) with hemophilia A treated with either pdFVIII or rFVIII and to explore the influence of both study and patient characteristics. METHODS: Summary incidence rates (95% confidence interval) from all included studies for both pdFVIII and rFVIII results were recalculated and pooled. Sensitivity analysis was used to investigate the effect of study design, severity of disease and inhibitor characteristics. Meta-regression and analysis-of-variance were used to investigate the effect of covariates (testing frequency, follow-up duration and intensity of treatment). RESULTS: Two thousand and ninety-four patients (1965 treated with pdFVIII, 887 with rFVIII; median age, 9.6 months) from 24 studies were investigated and 420 patients were observed to develop inhibitors. Pooled incidence rate was 14.3% (10.4-19.4) for pdFVIII and 27.4% (23.6-31.5) for rFVIII; high responding inhibitor incidence rate was 9.3% (6.2-13.7) for pdFVIII and 17.4% (14.2-21.2) for rFVIII. In the multi-way anova study design, study period, testing frequency and median follow-up explained most of the variability, while the source of concentrate lost statistical significance. It was not possible to analyse the effect of intensity of treatment or trigger events such as surgery, and to completely exclude multiple reports of the same patient or changes of concentrate. CONCLUSIONS: These findings underscore the need for randomized controlled trials to address whether or not the risk of inhibitor in PUPs with hemophilia A differs between rFVIII and pdFVIII.
Asunto(s)
Factor VIII/uso terapéutico , Hemofilia A/tratamiento farmacológico , Humanos , Estudios Prospectivos , Análisis de RegresiónRESUMEN
BACKGROUND: Childhood pulmonary embolism (PE) causes significant mortality and evidence suggests that it is under-diagnosed. Clinical probability scores and D-dimer estimation to assess pre-test probability have not been studied in children with suspected PE. PATIENTS/METHODS: This retrospective cohort study evaluated Wells simplified probability score for PE in 50 children with PE and 25 PE negative control patients, and D-dimer values in 27 PE positive and 12 PE negative children. RESULTS: PE positive and PE negative groups had similar rates of risk factors for venous thromboembolism (VTE). Wells simplified probability score showed a small difference between PE positive and PE negative children (median score: PE positive, 4.5; PE negative, 4; P = 0.009), children with PE are more likely to obtain a 'PE likely' score (score > 4), P = 0.012. The difference was of slightly greater significance when the Wells score was adjusted to account for pediatric normal ranges for heart rate, P = 0.007, and signs/symptoms of upper limb DVT, P = 0.006. Children with PE were as likely as PE negative patients to have a D-dimer value within the normal range (PE positive, 15%; PE negative, 25%; P = 0.654). A combination of a 'PE unlikely' score and normal D-dimer value occurred in 1/12 (8%) of PE negative children. CONCLUSIONS: The Wells clinical probability score and D-dimer estimation may lack utility in the determination of pre-test probability of PE in children. Validation of a pediatric clinical probability score, incorporating D-dimer estimation, by prospective study, would be difficult as a result of the rarity of childhood PE.