Compression stockings to prevent post-thrombotic syndrome in adults, a Bayesian meta-analysis.

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, OR < 0.50) and 95% (small benefit, OR < 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.

Prevalence and antifungal susceptibility of Candida species among pregnant women attending a school maternity at Natal, Brazil.

Vulvovaginal candidiasis (VVC) is an inflammatory disease of the vulva and vagina caused by different yeasts of the genus Candida which is responsible for infection in pregnant patients who attended Maternidade Escola Januário Cicco, Rio Grande do Norte, Brazil. From 41 samples, 19 yeasts were identified phenotypically as Candida albicans and one as Candida glabrata which is reported as the non-albicans species most frequently isolated from vulvovaginitis. The susceptibility to selected antifungal agents (flucytosine, fluconazole, voriconazole, amphotericin B, caspofungin and micafungin) was determined, and the association between patient-related signs and symptoms aided the construction of an epidemiological profile. Antifungal susceptibility testing performed by automated method showed that all strains were sensitive to the drugs tested, including the C. glabrata specimen despite its known resistance or dose-dependent susceptibility to azole derivatives. Regarding patient signs and symptoms, no statistically significant association between these and the establishment of VVC was found. It can be concluded that the laboratorial diagnosis of VVC is necessary prior to the administration of treatment, since only 48·78% of the patients had VVC but for all of them antifungal therapy were prescribed. SIGNIFICANCE AND IMPACT OF THE STUDY: Vulvovaginal candidiasis (VVC) is a problem that affects a significant number of pregnant women worldwide. This type of fungal infection generates great discomfort due to the symptomatology and difficulties of diagnosis and treatment. In view of the scarcity of data in the State of Rio Grande do Norte, Brazil, regarding studies carried out on fungal populations of the genus Candida associated with VVC in pregnant women, this study considered relevant, the phenotypic and genotypic identification of the species, to estimate the prevalence, to determine their susceptibility to the antifungal and to correlate with signs and symptoms.

Incidence of infective endocarditis and its thromboembolic complications in a pediatric population over 30years.

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.

Comparing the burden of illness of haemophilia between resource-constrained and unconstrained countries: the São Paulo-Toronto Hemophilia Study.

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.

Association of interferon-induced helicase C domain (IFIH1) gene polymorphisms with systemic lupus erythematosus and a relevant updated meta-analysis.

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder presenting heterogeneous clinical manifestations. A number of genes involved in SLE susceptibility are related to the type I interferon (IFN) pathway. IFN mediates innate immune responses and its increased levels contribute to the breakdown of peripheral tolerance. Interferon-induced helicase C domain 1 (IFIH1) activates and modulates IFN responses through its caspase recruitment domain. In this study, we analyzed four IFIH1 single nucleotide polymorphisms (SNPs): rs6432714, rs10930046, rs1990760, and rs3747517, in 337 patients with SLE and 373 healthy individuals from southeast and northeast Brazil. Our results did not find an association between IFIH1 SNPs and SLE (P value >0.025 after Bonferroni's adjustment). However, meta-analysis of peer-reviewed articles from 2008 to 2015 and data from this study indicated an association between rs1990760 and SLE onset (P < 0.05). This is the first association analysis on IFIH1 polymorphisms and SLE susceptibility in Brazilian populations.

Detecting multiple DNA human profile from a mosquito blood meal.

Criminal traces commonly found at crime scenes may present mixtures from two or more individuals. The scene of the crime is important for the collection of various types of traces in order to find the perpetrator of the crime. Thus, we propose that hematophagous mosquitoes found at crime scenes can be used to perform genetic testing of human blood and aid in suspect investigation. The aim of the study was to obtain a single Aedes aegypti mosquito profile from a human DNA mixture containing genetic materials of four individuals. We also determined the effect of blood acquisition time by setting time intervals of 24, 48, and 72 h after the blood meal. STR loci and amelogenin were analyzed, and the results showed that human DNA profiles could be obtained from hematophagous mosquitos at 24 h following the blood meal. It is possible that hematophagous mosquitoes can be used as biological remains at the scene of the crime, and can be used to detect human DNA profiles of up to four individuals.

Development of CAPTSureTM - a new index for the assessment of pediatric postthrombotic syndrome.

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.

Density prediction for petroleum and derivatives by gamma-ray attenuation and artificial neural networks.

This work presents a new methodology for density prediction of petroleum and derivatives for products' monitoring application. The approach is based on pulse height distribution pattern recognition by means of an artificial neural network (ANN). The detection system uses appropriate broad beam geometry, comprised of a (137)Cs gamma-ray source and a NaI(Tl) detector diametrically positioned on the other side of the pipe in order measure the transmitted beam. Theoretical models for different materials have been developed using MCNP-X code, which was also used to provide training, test and validation data for the ANN. 88 simulations have been carried out, with density ranging from 0.55 to 1.26gcm(-3) in order to cover the most practical situations. Validation tests have included different patterns from those used in the ANN training phase. The results show that the proposed approach may be successfully applied for prediction of density for these types of materials. The density can be automatically predicted without a prior knowledge of the actual material composition.

Tumour necrosis factor-alpha (-308G/A) promoter polymorphism is associated with ulcerative colitis in Brazilian patients.

Inflammatory bowel disease consists of multifactorial diseases whose common manifestation is inflammation of the gastrointestinal tract and their pathogenesis remains unknown. This study aimed to analyse the gene polymorphisms in Brazilian patients with inflammatory bowel disease. A total of 101 patients diagnosed with inflammatory bowel disease were analysed for the tumour necrosis factor-alpha (-308 G/A; rs1800629) and interleukin-10 (-1082 G/A; rs1800896) gene polymorphisms. Genotyping was performed through polymerase chain reaction-sequence-specific primer, then fractionated on 2% agarose gel and visualized after staining by ethidium bromide. The anatomic-clinical form of Crohn's disease (CD) predominant was the inflammatory (32.75%), followed by fistulizing (29.31%) and 27.58% stricturing. As control group, a total of 136 healthy subjects, from the same geographical region, were enrolled. The statistical analyses were performed using R program. The frequency of the A allele at tumour necrosis factor-alpha was high in ulcerative colitis (UC) patients (51%) than in controls (22%; P > 0.01). No statistical difference was found with the genotypic and allelic frequencies of CD patients compared to controls (P = 0.54). The polymorphism -1082G/A of interleukin-10 was not statistical different between the diseases compared to controls. Tumour necrosis factor-alpha (TNF-α) (-308G/A) is associated with UC onset, suggesting that the presence of -308A allele could confer a relative risk of 3.62 more to develop UC in general population. Further studies, increasing the number of individuals, should be performed to ratify the role of TNF-α in the inflammatory bowel disease pathogenesis.

Pediatric post-thrombotic syndrome in children: Toward the development of a new diagnostic and evaluative measurement tool.

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.

PO-60 - Renal tumors with extensive vascular disease: management challenges in a pediatric series from the Hospital for Sick Children.

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.

Timing of low bone mineral density and predictors of bone mineral density trajectory in children on long-term warfarin: a longitudinal study.

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.

Childhood physical activity body contact risk: feasibility of a novel technique for objective measurements of impact speed, frequency, and intentionality.

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.

A rapid screening of ancestry for genetic association studies in an admixed population from Pernambuco, Brazil.

Genetic association studies determine how genes influence traits. However, non-detected population substructure may bias the analysis, resulting in spurious results. One method to detect substructure is to genotype ancestry informative markers (AIMs) besides the candidate variants, quantifying how much ancestral populations contribute to the samples' genetic background. The present study aimed to use a minimum quantity of markers, while retaining full potential to estimate ancestries. We tested the feasibility of a subset of the 12 most informative markers from a previously established study to estimate influence from three ancestral populations: European, African and Amerindian. The results showed that in a sample with a diverse ethnicity (N = 822) derived from 1000 Genomes database, the 12 AIMs had the same capacity to estimate ancestries when compared to the original set of 128 AIMs, since estimates from the two panels were closely correlated. Thus, these 12 SNPs were used to estimate ancestry in a new sample (N = 192) from an admixed population in Recife, Northeast Brazil. The ancestry estimates from Recife subjects were in accordance with previous studies, showing that Northeastern Brazilian populations show great influence from European ancestry (59.7%), followed by African (23.0%) and Amerindian (17.3%) ancestries. Ethnicity self-classification according to skin-color was confirmed to be a poor indicator of population substructure in Brazilians, since ancestry estimates overlapped between classifications. Thus, our streamlined panel of 12 markers may substitute panels with more markers, while retaining the capacity to control for population substructure and admixture, thereby reducing sample processing time.

Short Communication FYB polymorphisms in Brazilian patients with type I diabetes mellitus and autoimmune polyglandular syndrome type III.

The aim of this study was to perform an association study between seven Fyn-binding protein gene (FYB)-tag single nucleotide polymorphisms (SNPs) and type I diabetes mellitus (T1DM), as well as with disease age of onset. We also assessed the role of FYB SNPs in the insurgence of autoimmune polyglandular syndrome type III (APSIII), characterized by the simultaneous presence of autoimmune thyroid disease and celiac disease, in patients with T1DM from a Northeastern Brazilian population. One hundred and seventy-seven patients with T1DM and 190 healthy individuals were genotyped for seven tag SNPs, covering most of the FYB locus, using real-time polymerase chain reaction amplification. There was no significant difference in the distribution of allele and genotype frequencies among patients and healthy individuals. Moreover, none of the tag SNPs were associated either to T1DM age of onset or to the insurgence of APSIII. However, since the FYB protein is a key component in T cell response, its gene variants might play a role in protein function, which might be testable in a population with different genetic backgrounds or by using functional assays.

The surgical management of parotid gland tumours.

BACKGROUND: The parotid tissue can give rise to a large variety of benign and malignant neoplasms. The objective of this study was to describe the management and outcome of parotid gland tumours over a 15-year period. METHOD: The records of consecutive patients treated by parotid gland excision from January 1995 to December 2008 were reviewed retrospectively. Data recorded were age, gender, history, physical findings, surgical procedure, fine-needle aspiration biopsy (FNAB), final pathological diagnosis and complications. RESULTS: The vast majority of patients (306) had benign neoplasms, and 14 patients had malignant neoplasms. Overall, pleomorphic adenoma contributed to 76% of the lesions, and Warthin's tumour to 17%. The sensitivity and specificity of FNAB was 79% and 100%, respectively. There were 15 cases of marginal mandibular transitory paresis and 12 cases of seroma. Marginal mandibular definitive paralysis was observed in three cases with malignant tumour. CONCLUSION: Standardised parotidectomy is a safe operation, with a low complication rate.