Cumulative long-term safety, efficacy and patient-reported outcomes in children with juvenile idiopathic arthritis treated with intravenous abatacept: up to 7 years of treatment

The long-term efficacy and safety of intravenous abatacept in patients (pts) with juvenile idiopathic arthritis (JIA) have been reported previously from the Phase III AWAKEN trial ([1, 2]). Here, we report efficacy, safety and pt-reported outcomes from the open-label, long-term extension (LTE) of AWAKEN, with up to 7 years of follow-up. Pts entered the LTE if they were JIA ACR 30 non-responders (NR) at the end of the 4-month lead-in period (abatacept only), or if they received abatacept or placebo (pbo) in the 6-month double-blind (DB) period. The Child Health Questionnaire was used to evaluate health-related quality of life (HRQoL); physical (PhS) and psychosocial (PsS) summary and pain scores were analyzed. Pain was assessed by parent global assessment using a 100 mm visual analog scale. Efficacy and HRQoL evaluations are reported up to Day 1765 (~ Year 5.5). Safety is presented for the cumulative period (lead-in, DB and LTE), for all pts who received abatacept during the LTE. Of the 153 pts entering the LTE (58 from DB abatacept group, 59 from DB pbo group, 36 NR), 69 completed the trial (29 abatacept, 27 pbo, 13 NR). For pts treated in the LTE, mean (range) exposure to abatacept was 53.6 (5.6–85.6) months. During the LTE, incidence rates of AEs and serious AEs per 100 pt-years were 209.1 and 5.6. Thirty pts (19.6%) had serious AEs; most were unrelated and were musculoskeletal (8.5%) or infectious events (6.5%). No malignancy was reported. There was one death (accidental; unrelated). At Day 169, JIA ACR 50 and 70 response rates were 79.3% and 55.2% in the abatacept group, and 52.5% and 30.5% in the pbo group; 31.0% and 10.2% of pts in the abatacept and pbo groups, respectively, had inactive disease. By Day 1765, JIA ACR 50 and 70 response rates were 93.9% and 78.8% in the abatacept group, and 80.0% and 63.3% in the pbo group; 51.5% and 33.3% had inactive disease. In the NR group, 69.2% and 53.8% of pts achieved JIA ACR 50 and 70 responses at Day 1765, and 30.8% had inactive disease. In pts who entered the LTE, mean baseline PhS scores were below the range for healthy children (abatacept 30.2, pbo 31.0, NR 29.5). At Day 169, 38.3% of pts had reached a PhS score >50 ((1). By the end of the LTE, 43.5% of pts had reached a PhS score >50. At baseline, mean PsS scores for those who entered the LTE were slightly lower than the mean for healthy children (abatacept 43.5, pbo 44.2, NR 47.0). At Day 169, 54.9% of pts had a PsS score >50 (1). By Day 1765, 58.1% of pts had reached a PsS score >50. At baseline, the mean pain score was 42.9. By Day 169, 13.9% of pts were considered pain free (pain score = 0); this was maintained over the LTE (1).

Road-kills of the giant anteater in south-eastern Brazil: 10 years monitoring spatial and temporal determinants

Context. The giant anteater, Myrmecophaga tridactyla, is a large insectivorous mammal from Cerrado which is classified as vulnerable by the IUCN's red list. In spite of frequent giant anteater casualties, there continues to be a lack of published data on how road and landscape attributes affect road-kill rates - information that could prove useful in guiding mitigation measures.Aims. We seek to determine whether road and landscape attributes influence the incidence of road-kills of the giant anteater.Methods. From February 2002 to December 2012 (except for 2004), five roads in two regions in south-eastern Brazil were surveyed twice each month by car. We recorded temporal road-kill data for the giant anteater and related spatial road variables. These variables were also recorded at regular control sites every 2 km. We also took traffic volume data on stretches of the two roads to correlate with road-kills.Key results. Of the 45 anteater casualties recorded, there was a predominance of adult males. On roads MG-428 and SP-334, we found anteater road-kills were more common in the dry season, negatively correlated with traffic volume and related to the presence of native vegetation. Accordingly, road-kill sites tended to occur near the cerrado and grasslands and also appeared more frequently on some straight stretches of roadways. Although it was not shown to influence road-kill rates, topography data does point to regular overpass/underpass locations allowing population connectivity. Termitaria or ant nests were present at all road-kill sites, with 86% having signs of feeding.Conclusions. Native vegetation along roadways, together with straight road design, increases the probability of anteater road-kills by 40.1%.Implications. For mitigation, mowing and removing insect nests on roadsides, as well as roadside wildlife fencing in cerrado and grassland areas is suggested. Warning signs and radar to reduce vehicle speed are recommended for both human safety and anteater conservation. With regard to population connectivity, the absence of aggregated anteater road-kill data in this study meant that there were no particular crossing locations identified. However, the collected topography data do show places that could be used for roadway crossings. The measures indicated may apply to similar species and types of topography on other continents.

The increase of dairy intake is the main dietary factor associated with reduction of body weight in overweight adults after lifestyle change program

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Análise retrospectiva de 61 casos de paracoccidioidomicose diagnosticados na Faculdade de Odontologia de Araçatuba/ UNESP

Paracoccidioidomycosis is a systemic mycosis which requires prolonged treatment. It is highest prevalence in Latin America, with different endemic areas in Brazil. In this study the aim was to characterize clients suffering from mucocutaneous paracoccidioidomycosis by analysis of histopathological examinations of 61 adult patients diagnosed with mucocutaneous paracoccidioidomycosis treated at the Dental School of Araçatuba, from January 1989 to December 2004. It was observed that the disease occurred in 91.81% (56) men and 8.19% (5) women, more prevalent (78.68%) in whites, aged 40 to 59 years (62.9%) and the profession linked to agriculture in 17 patients (27.86%). All patients had oral manifestations, in multiple sites, but it was most prevalent in the oral mucosa (31.42%) and alveolar ridge (17.14%). The dentist as an integral member of the health services, must know the clinical manifestations of paracoccidioidomycosis to achieve early diagnosis and thereby to improve the quality of life of patients.

Long-Term Adult Population Fluctuations and Distribution of the Spot, <i>Leiostomus xanthurus</i>, in Mississippi

Adult specimens of the spot. Leiostomus xanthurus, were collected from bayou, Mississippi Sound, and barrier island locations along the Gulf Coast of Mississippi from November 1982 to July 1989. 7he mean total length of all spot sampled in comparable gill net sets was 219 mm (± 14 standard deviation, n=4,338). Ninety-five percent of the spot were collected in the island and sound areas, where the salinity was higher than in the bayous. Catch per unit effort was high at island and sound stations in spring and autumn, with relatively few fish caught during the winter spawning season and summer. The relatively high frequency of spot observed at the island stations in the autumn was probably influenced by spawning migrations, and the high spring values may represent a combination of two abundant year classes. The two greatest yearly collections, in 1983 and 1986, may have been influenced by sampling conditions or by environmental conditions favorable to survival either during those years or earlier when those fish were postlarvae. The smallest yearly catch occurred in 1985 and may have reflected the harsh weather conditions that year.

Titanium surface topography after brushing with fluoride and fluoride-free toothpaste simulating 10 years of use

Objectives: To conduct a controlled study contrasting titanium surface topography after procedures that simulated 10 years of brushing using toothpastes with or without fluoride. Methods: Commercially pure titanium (cp Ti) and Ti-6Al-4V disks (6 mm circle divide x 4 mm) were mirror-polished and treated according to 6 groups (n = 6) as a function of immersion (I) or brushing (B) using deionised water (W), fluoride-free toothpaste (T) and fluoride toothpaste (FT). Surface topography was evaluated at baseline (pretreatment) and post-treatment, using atomic force microscope in order to obtain three-dimensional images and mean roughness. Specimens submitted to immersion were submerged in the vehicles without brushing. For brushed specimens, procedures were conducted using a linear brushing machine with a soft-bristled toothbrush. Immersion and brushing were performed for 244 h. IFT and BFT samples were analysed under scanning electron microscope with Energy-Dispersive X-ray Spectroscopy (EDS). Pre and post-treatment values were compared using the paired Student T-test (alpha = .05). Intergroup comparisons were conducted using one-way ANOVA with Tukey post-test (alpha = .05). Results: cp Ti mean roughness (in nanometers) comparing pre and post-treatment were: IW, 2.29 +/- 0.55/2.33 +/- 0.17; IT, 2.24 +/- 0.46/2.02 +/- 0.38; IFT, 2.22 +/- 0.53/1.95 +/- 0.36; BW, 2.22 +/- 0.42/3.76 +/- 0.45; BT, 2.27 +/- 0.55/16.05 +/- 3.25; BFT, 2.27 +/- 0.51/22.39 +/- 5.07. Mean roughness (in nanometers) measured in Ti-6Al-4V disks (pre/post-treatment) were: IW, 1.79 +/- 0.25/2.01 +/- 0.25; IT, 1.61 +/- 0.13/1.74 +/- 0.19; IFT, 1.92 +/- 0.39/2.29 +/- 0.51; BW, 2.00 +/- 0.71/2.05 +/- 0.43; BT, 2.37 +/- 0.86/11.17 +/- 2.29; BFT, 1.83 +/- 0.50/15.73 +/- 1.78. No significant differences were seen after immersions (p &gt; .05). Brushing increased the roughness of cp Ti and of Ti-6Al-4V (p &lt; .01); cp Ti had topographic changes after BW, BT and BFT treatments whilst Ti-6Al-4V was significantly different only after BT and BTF. EDS has not detected fluoride or sodium ions on metal surfaces. Conclusions: Exposure to toothpastes (immersion) does not affect titanium per se; their use during brushing affects titanium topography and roughness. The associated effects of toothpaste abrasives and fluorides seem to increase roughness on titanium brushed surfaces. (C) 2012 Elsevier Ltd. All rights reserved.

Impact of FLT3 Internal Tandem Duplication on the Outcome of Related and Unrelated Hematopoietic Transplantation for Adult Acute Myeloid Leukemia in First Remission: A Retrospective Analysis

Purpose Patients with acute myeloid leukemia (AML) and FLT3/internal tandem duplication (FLT3/ITD) have poor prognosis if treated with chemotherapy only. Whether this alteration also affects outcome after allogeneic hematopoietic stem-cell transplantation (HSCT) remains uncertain. Patients and Methods We analyzed 206 patients who underwent HLA-identical sibling and matched unrelated HSCTs reported to the European Group for Blood and Marrow Transplantation with a diagnosis of AML with normal cytogenetics and data on FLT3/ITD (present: n = 120, 58%; absent: n = 86, 42%). Transplantations were performed in first complete remission (CR) after myeloablative conditioning. Results Compared with FLT3/ITD-negative patients, FLT3/ITD-positive patients had higher median leukocyte count at diagnosis (59 v 21 x 10(9)/L; P &lt; .001) and shorter interval from CR to transplantation (87 v 99 days; P = .04). Other characteristics were similar in the two groups. At 2 years, relapse incidence (RI; +/- standard deviation) was higher (30% +/- 5% v 16% +/- 5%; P = .006) and leukemia-free survival (LFS) lower (58% +/- 5% v 71% +/- 6%; P = .04) in FLT3/ITD-positive compared with FLT3/ITD-negative patients. In multivariate analyses, FLT3/ITD led to increased RI (hazard ratio [HR], 3.4; 95% CI, 1.46 to 7.94; P = .005), as did older age, female sex, shorter interval between CR and transplantation, and higher number of chemotherapy courses before achieving CR. FLT3/ITD positivity was associated with decreased LFS (HR, 0.37; 95% CI, 0.19 to 0.73; P = .002), along with older age and higher number of chemotherapy courses before achieving CR. Conclusion FLT3/ITD adversely affected the outcome of HSCT in the same direction it does after chemotherapy; despite this, more than half of the patients harboring this mutation who received transplants were alive and leukemia free at 2 years. To further improve the results, use of FLT3 inhibitors before or after HSCT deserves investigation.

Long-Term Follow-Up of Patients after Acute Kidney Injury: Patterns of Renal Functional Recovery

Background and Objectives: Patients who survive acute kidney injury (AKI), especially those with partial renal recovery, present a higher long-term mortality risk. However, there is no consensus on the best time to assess renal function after an episode of acute kidney injury or agreement on the definition of renal recovery. In addition, only limited data regarding predictors of recovery are available. Design, Setting, Participants, & Measurements: From 1984 to 2009, 84 adult survivors of acute kidney injury were followed by the same nephrologist (RCRMA) for a median time of 4.1 years. Patients were seen at least once each year after discharge until end stage renal disease (ESRD) or death. In each consultation serum creatinine was measured and glomerular filtration rate estimated. Renal recovery was defined as a glomerular filtration rate value &gt;= 60 mL/min/1.73 m2. A multiple logistic regression was performed to evaluate factors independently associated with renal recovery. Results: The median length of follow-up was 50 months (30-90 months). All patients had stabilized their glomerular filtration rates by 18 months and 83% of them stabilized earlier: up to 12 months. Renal recovery occurred in 16 patients (19%) at discharge and in 54 (64%) by 18 months. Six patients died and four patients progressed to ESRD during the follow up period. Age (OR 1.09, p &lt; 0.0001) and serum creatinine at hospital discharge (OR 2.48, p = 0.007) were independent factors associated with non renal recovery. The acute kidney injury severity, evaluated by peak serum creatinine and need for dialysis, was not associated with non renal recovery. Conclusions: Renal recovery must be evaluated no earlier than one year after an acute kidney injury episode. Nephrology referral should be considered mainly for older patients and those with elevated serum creatinine at hospital discharge.

Maternal high-sodium intake alters the responsiveness of the renin-angiotensin system in adult offspring

Aims: The goal of the current study was to evaluate the impact of maternal sodium intake during gestation on the systemic and renal renin-angiotensin-aldosterone-system (RAAS) of the adult offspring. Main methods: Female Wistar rats were fed high- (HSD-8.0% NaCl) or normal-sodium diets (NSD-1.3% NaCl) from 8 weeks of age until the delivery of their first litter. After birth, the offspring received NSD. Tail-cuff blood pressure (TcBP) was measured in the offspring between 6 and 12 weeks of age. At 12 weeks of age, the offspring were subjected to either one week of HSD or low sodium diet (LSD-0.1 6%NaCl) feeding to evaluate RAAS responsiveness or to acute saline overload to examine sodium excretory function. Plasma (PRA) and renal renin content (RRC), serum aldosterone (ALDO) levels, and renal cortical and medullary renin mRNA expression levels were evaluated at the end of the study. Key findings: TcBP was higher among dams fed HSD, but no TcBP differences were observed among the offspring. Male offspring, however, exhibited increased TcBP after one week of HSD feeding, and this effect was independent of maternal diet. Increased RAAS responsiveness to the HSD and LSD was also observed in male offspring. The baseline levels of PRA. ALDO, and cortical and medullary renin gene expression were lower but the RRC levels were higher among HSD-fed male offspring (HSDoff). Conversely, female HSDoff showed reduced sodium excretion 4 h after saline overload compared with female NSDoff. Significance: High maternal sodium intake is associated with gender-specific changes in RAAS responsiveness among adult offspring. (C) 2012 Elsevier Inc. All rights reserved.

Clinical characteristics and possible phenotypes of an adult severe asthma population

Background: Currently, there are no studies of well-characterized severe asthmatics in Brazil. We aimed to study a population of severe treated asthmatics still uncontrolled to characterize them and define possible phenotypes. Methods: Descriptive cross-sectional outpatient study of severe asthmatics, evaluating functional and inflammatory markers, health-related quality of life, anxiety and depression symptoms, clinical control status, and characteristics related to atopy, age of asthma onset, induced sputum eosinophil levels, and airflow limitation. We also grouped the subgroups characteristics to identify phenotypes. The study is registered on ClinicalTrial.gov NCT 01089322. Results: From 128 eligible patients with severe/uncontrolled asthma, 74 fulfilled the inclusion criteria. The cohort was comprised of 85% women, frequently with a body mass index higher than 31 kg m(-2), atopy (60%), early-onset disease (50%), sputum eosinophilia (80%), comorbidities, and reduced quality of life. Nonatopics had significant higher asthma onset (19 y.a.) and twice level of induced sputum eosinophil. Late-onset patients had significantly less atopy (57%) and higher levels of induced sputum eosinophils. Non-eosinophilics had lower levels of inflammatory markers. Patients with airflow limitation had more intensive care unit admissions (56%) and 1.5 times more airway resistance. Subgroups characteristics identified a priori four well-characterized phenotypes, with 55% presenting sputum eosinophilia. Conclusion: Our data emphasize the high burden of disease, the persistence of inflammation and the existence of clinical possible phenotypes population sharing common features with published cohorts. Despite the necessity of further investigation into pathogenic mechanisms, this study with clinically difficult patient group may help to improve future asthma care. (C) 2011 Elsevier Ltd. All rights reserved.

Cochlear implant in postlingual children: functional results 10 years after the surgery

The benefits of cochlear implants (CI) for communication skills are obtained over the years. There are but a few studies regarding the long-term outcomes in postlingual deaf children who grew up using the electronic device. Aim: To assess the functional results in a group of postlingual children, 10 years after using a CI. Methods: Ten postlingual deaf children, implanted before 18 years of age, participated in this study. We assessed: sentence recognition and speech intelligibility. We documented: device use and function and the patient's academic/occupational status. Study design: series. Results: The mean scores were 73% for sentence recognition in silence and 40% in noise. The average write-down intelligibility score was 92% and the average rating-scale intelligibility score was 4.15. There were no cases of device failure. Regarding educational/vocational status, three subjects graduated from the University. Five quit education after completing high school. Eight subjects had a professional activity. Conclusion: This study showed that cochlear implantation is a safe and reliable procedure. The postlingual profoundly hearing-impaired children after 10 years of CI use developed satisfactory levels regarding speech perception and intelligibility, and completed at least high school and were inserted in the labor market. Clinical Trials Registry: NCT01400178.

Epidemiology and predictors of a poor outcome in elderly patients with candidemia

Background: Candidemia affects patient populations from neonates to the elderly. Despite this, little information is available about the epidemiology of candidemia in elderly patients. Methods: We performed a retrospective analysis of 987 episodes of candidemia in adults (&gt;14 years of age) from the databases of three laboratory-based surveys of candidemia performed at 14 tertiary care hospitals. Patients aged &gt;= 60 years were considered elderly (group 1, n = 455, 46%) and were compared to younger patients (group 2, n = 532, 54%) regarding demographics, underlying diseases, comorbidities, exposure to medical procedures, species, treatment, and outcome. Results: The median APACHE II score was significantly higher in the elderly patients (19 vs. 15, p = 0.03). Variables that were observed significantly more frequently in elderly patients included admission to an intensive care unit, diabetes mellitus, renal failure, cardiac disease, lung disease, receipt of antibiotics or H2 blockers, insertion of a central venous catheter, mechanical ventilation, and candidemia due to Candida tropicalis. The 30-day mortality of elderly patients was significantly higher than that of younger patients (70% vs. 45%, p &lt; 0.001). Factors associated with higher mortality by multivariate analysis included APACHE II score and being in group 1 (elderly). Factors associated with mortality in elderly patients were lung disease and the receipt of mechanical ventilation. Conclusions: Elderly patients account for a substantial proportion of patients with candidemia and have a higher mortality compared to younger patients. (C) 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Nuts and seed: A natural yet dangerous foreign body

Rationale and aim: This paper has the object to present the impact of nuts' and seeds' injuries withdrawing data from the Susy Safe registry, highlighting that as for other foreign bodies the main item efficiently and substantially susceptible to changes to decrease the accidents' rates is the education of adults and children, that can be shared with parents both from pediatricians and general practitioners. Indeed labeling and age related warnings have also a fundamental relevance in prevention. Methods: The present study draws its data from the Susy Safe registry. Details on injuries are entered in the Susy Safe Web-registry through a standardized case report form, that includes information regarding: children age and gender, features of the object, circumstances of injury (presence of parents and activity) and hospitalization's details (lasting, complications and removal details). Cases are prospectively collected using the Susy Safe system from 06/2005; moreover, also information regarding past consecutive cases available in each centre adhering to the project have been entered in the Susy Safe registry. Results: Nuts and seeds are one of the most common food item retrieved in foreign bodies injuries in children. In Susy Safe registry they represent the 38% in food group, and almost the 10% in general cases. Trachea, bronchi and lungs were the main location of FB's retrieval, showing an incidence of 68%. Hospitalization occurred in 83% of cases, showing the major frequency for foreign bodies located in trachea. This location was also the principal site of complications, with a frequency of 68%. There were no significant associations between these outcomes and the age class of the children. The most common complications seen (22.4%) was bronchitis, followed by pneumonia (19.7%). Adult presence was recorded as positive in 71.2% of cases, showing an association (p value 0.009) between the adult supervision and the hospitalization outcome. On the contrary there was a non significant association between adult presence and the occurrence of complications. In 80.7% of cases, the incident happened while the child was eating. Among those cases, 88.6% interested trachea, lungs and bronchi. Conclusions: Food-related aspiration injuries are common events for young children, particularly under 4 years of age, and may lead to severe complication. There is a need to study in more depth specific characteristics of foreign bodies associated with increased hazard, such as size, shape, hardness or firmness, lubricity, pliability and elasticity, in order to better identify risky foods, and more precisely described the pathogenetic pathway. Parents are not adequately conscious and aware toward this risk; therefore, the number and severity of the injuries could be reduced by educating parents and children. Information about food safety should be included in all visits to pediatricians in order to make parents able to understand, select, and identify key characteristics of hazardous foods and better control the hazard level of various foods. Finally, preventive measures including warning labels on high-risk foods could be implemented. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Frequency of LCT -13910C>T single nucleotide polymorphism associated with adult-type hypolactasia/lactase persistence among Brazilians of different ethnic groups

Abstract Background Adult-type hypolactasia, the physiological decline of lactase some time after weaning, was previously associated with the LCT -13910C>T polymorphism worldwide except in Africa. Lactase non-persistence is the most common phenotype in humans, except in northwestern Europe with its long history of pastoralism and milking. We had previously shown association of LCT -13910C>T polymorphism with adult-type hypolactasia in Brazilians; thus, we assessed its frequency among different Brazilian ethnic groups. Methods We investigated the ethnicity-related frequency of this polymorphism in 567 Brazilians [mean age, 42.1 ± 16.8 years; 157 (27.7%) men]; 399 (70.4%) White, 50 (8.8%) Black, 65 (11.5%) Brown, and 53 (9.3%) Japanese-Brazilian. DNA was extracted from leukocytes; LCT -13910C>T polymorphism was analyzed by PCR-restriction fragment length polymorphism. Results Prevalence of the CC genotype associated with hypolactasia was similar (57%) among White and Brown groups; however, prevalence was higher among Blacks (80%) and those of Japanese descent (100%). Only 2 (4%) Blacks had TT genotype, and 8 (16%) had the CT genotype. Assuming an association between CC genotype and hypolactasia, and CT and TT genotypes with lactase persistence, 356 (62.8%) individuals had hypolactasia and 211 (37.2%) had lactase persistence. The White and Brown groups had the same hypolactasia prevalence (~57%); nevertheless, was 80% among Black individuals and 100% among Japanese-Brazilians (P < 0.01). Conclusion The lactase persistence allele, LCT -13910T, was found in about 43% of both White and Brown and 20% of the Black Brazilians, but was absent among all Japanese Brazilians studied.

Anti-Toxocara spp. antibodies in an adult healthy population: serosurvey and risk factors in Southeast Brazil.

Objective: To evaluate the frequency of anti-Toxocara spp. antibodies in an adult healthy population. Methods: The study was performed by interviewing 253 blood donors, from 19 to 65 years of age, in a hematological centre in Presidente Prudente, São Paulo, southeast Brazil. A survey was applied to blood donors in order to evaluate the possible factors associated to the presence of antibodies, including individual (gender and age), socioeconomic (scholarship, familial income and sanitary facilities) and habit information (contact with soil, geophagy, onycophagy and intake of raw/undercooked meat) as well as the presence of dogs or cats in the household. ELISA test was run for detection of the anti-Toxocara spp. IgG antibodies. Bivariate analysis followed by logistic regression was performed to evaluate the potential risk factors associated to seropositivity. Results: The overall prevalence observed in this study was 8.7% (22/253). Contact with soil was the unique risk factor associated with the presence of antibodies (P=0.0178 ; OR=3.52; 95% CI=1.244-9.995) Conclusions. The results of this study reinforce the necessity in promoting preventive public health measures, even for healthy adult individual, particularly those related to the deworming of pets to avoid the soil contamination, and hygiene education of the population.