Predicted residual activity of rilpivirine in HIV-1 infected patients failing therapy including NNRTIs efavirenz or nevirapine

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Efficacy and Safety of Using Amplatzer Ductal Occluder for Transcatheter Closure of Perimembranous Ventricular Septal Defect in Pediatrics

Background: Perimembranous Ventricular Septal Defect (PMVSD) is the most common subtype of ventricular septal defects. Transcatheter closure of PMVSD is a challenging procedure in management of moderate or large defects. Objectives: The purpose of this study was to show that transcatheter closure of perimembranous ventricular septal defect with Amplatzer Ductal Occluder (ADO) is an effective and safe method. Patients and Methods: Between April 2012 and April 2013, 28 patients underwent percutaneous closure of PMVSD using ADO. After obtaining the size of VSD from the ventriculogram a device at least 2 mm larger than the narrowest diameter of VSD at right ventricular side was chosen. The device deployed after confirmation of its good position by echocardiography and left ventriculography. Follow up evaluations were done 1 month, 6 months, 12 months and yearly after discharge with transthoracic echocardiography and 12 lead electrocardiography. Results: The mean age of patients at procedure was 4.7 ± 6.3 (range 2 to 14) years, mean weight 14.7 ± 10.5 (range 10 to 40) kg. The mean defect size of the right ventricular side was 4.5 ± 1.6 mm. The average device size used was 7.3 ± 3.2mm (range 4 to 12 mm). The ADOs were successfully implanted in all patients. The VSD occlusion rate was 65.7% at completion of the procedure, rising up to 79.5% at discharge and 96.4% during follow-up. Small residual shunts were seen at completion of the procedure, but they disappeared during follow-up in all but one patient. The mean follow-up period was 8.3 ± 3.6 months (range 1 to 18 months). Complete atrioventricular block (CAVB), major complication or death was not observed in our study. Conclusions: Transcatheter closure of PMVSD with ADO in children is a safe and effective treatment associated with excellent success and closure rates, but long-term follow-up in a large number of patients would be warranted.

Anxiety in children with attention-deficit/hyperactivity disorder

OBJECTIVES: Although anxiety is common in children with attention-deficit/hyperactivity disorder (ADHD), it is unclear how anxiety influences the lives of these children. This study examined the association between anxiety comorbidities and functioning by comparing children with ADHD and no, 1, or ≥2 anxiety comorbidities. Differential associations were examined by current ADHD presentation (subtype). METHODS: Children with diagnostically confirmed ADHD (N = 392; 5-13 years) were recruited via 21 pediatrician practices across Victoria, Australia. Anxiety was assessed by using the Anxiety Disorders Interview Schedule for Children-IV. Functional measures included parent-reported: quality of life (QoL; Pediatric Quality of Life Inventory 4.0), behavior and peer problems (Strengths and Difficulties Questionnaire), daily functioning (Daily Parent Rating of Evening and Morning Behavior), and school attendance. Teacher-reported behavior and peer problems (Strengths and Difficulties Questionnaire) were also examined. Linear and logistic regression controlled for ADHD severity, medication use, comorbidities, and demographic factors. RESULTS: Children with ≥2 anxiety comorbidities (n = 143; 39%) had poorer QoL (effect size: -0.8) and more difficulties with behavior (effect size: 0.4) and daily functioning (effect size: 0.3) than children without anxiety (n = 132; 36%). Poorer functioning was not observed for children with 1 anxiety comorbidity (n = 95; 26%). Two or more anxiety comorbidities were associated with poorer functioning for children with both ADHD-Inattentive and ADHD-Combined presentation. CONCLUSIONS: Children with ADHD demonstrate poorer QoL, daily functioning and behavior when ≥2 anxiety comorbidities are present. Future research should examine whether treating anxiety in children with ADHD improves functional outcomes.

Swine influenza virus PA and neuraminidase gene reassortment into human H1N1iInfluenza Virus is associated with an altered pathogenic phenotype linked to increased MIP-2 expression

Swine are susceptible to infection by both avian and human influenza viruses, and this feature is thought to contribute to novel reassortant influenza viruses. In this study, the influenza virus reassortment rate in swine and human cells was determined. Coinfection of swine cells with 2009 pandemic H1N1 virus (huH1N1) and an endemic swine H1N2 (A/swine/Illinois/02860/09) virus (swH1N2) resulted in a 23% reassortment rate that was independent of α2,3- or α2,6-sialic acid distribution on the cells. The reassortants had altered pathogenic phenotypes linked to introduction of the swine virus PA and neuraminidase (NA) into huH1N1. In mice, the huH1N1 PA and NA mediated increased MIP-2 expression early postinfection, resulting in substantial pulmonary neutrophilia with enhanced lung pathology and disease. The findings support the notion that swine are a mixing vessel for influenza virus reassortants independent of sialic acid distribution. These results show the potential for continued reassortment of the 2009 pandemic H1N1 virus with endemic swine viruses and for reassortants to have increased pathogenicity linked to the swine virus NA and PA genes which are associated with increased pulmonary neutrophil trafficking that is related to MIP-2 expression. IMPORTANCE: Influenza A viruses can change rapidly via reassortment to create a novel virus, and reassortment can result in possible pandemics. Reassortments among subtypes from avian and human viruses led to the 1957 (H2N2 subtype) and 1968 (H3N2 subtype) human influenza pandemics. Recent analyses of circulating isolates have shown that multiple genes can be recombined from human, avian, and swine influenza viruses, leading to triple reassortants. Understanding the factors that can affect influenza A virus reassortment is needed for the establishment of disease intervention strategies that may reduce or preclude pandemics. The findings from this study show that swine cells provide a mixing vessel for influenza virus reassortment independent of differential sialic acid distribution. The findings also establish that circulating neuraminidase (NA) and PA genes could alter the pathogenic phenotype of the pandemic H1N1 virus, resulting in enhanced disease. The identification of such factors provides a framework for pandemic modeling and surveillance.

Service use in children aged 6-8 years with attention deficit hyperactivity disorder

OBJECTIVE: This study investigated prevalence, types and predictors of professional service use in families of children identified with attention deficit hyperactivity disorder (ADHD) in the community.

DESIGN: SETTING: children with ADHD were identified through 43 schools using parent and teacher screening questionnaires (Conners 3 ADHD Index) followed by case confirmation using the Diagnostic Interview Schedule for Children Version IV. Parents completed a survey about professional service use in the last 12 months.

MAIN OUTCOME MEASURES: data on variables potentially associated with service use were collected from parents (interview and questionnaires), teachers (questionnaires) and children (direct assessment). Logistic regression was used to examine predictors of service use in univariate and multivariable analyses.

RESULTS: The sample comprised 179 children aged 6-8 years with ADHD. Over one-third (37%) had not received professional services in the last 12 months. The strongest predictors of service use were older child age (adjusted OR=3.0, 95% CI 1.0 to 8.9, p=0.05), and the degree to which the child's behaviour impacted on the family (adjusted OR=2.0, 95% CI 1.3 to 3.3, p=0.007), after controlling for ADHD subtype and severity, externalising comorbidities, academic achievement and parent-reported impairment.

CONCLUSIONS: A substantial proportion of children with ADHD are not accessing professional services. Our findings suggest that the child's age and the impact of the child's behaviour on the family are the strongest predictors of service use. Given the demonstrated benefits from various interventions in ADHD, there is a need to improve case identification and referral for services.

El fenotipo "basal-her2" en el cáncer de mama: caracterización clínico-molecular e implicaciones terapéuticas

Clinically HER2+ (cHER2+) breast cancer (BC), as exclusively determined by immunohistochemistry of HER2 protein overexpression and/or fluorescence in situ hybridization of HER2 gene amplification, has been largely considered a single disease entity in terms of clinical outcome and in the susceptibility to the anti-HER2 monoclonal antibody trastuzumab (Herceptin). However, although the adjuvant/neoadjuvant use of the trastuzumab has been shown to significantly reduce recurrence risk when added to standard chemotherapy in women with early-stage cHER2+ BC, not all cases derive similar benefit from trastuzumab because a significant number of cHER2+ BC patients develop disease recurrence. Unfortunately, the identification of a robust clinical predictor of trastuzumab benefit, including HER2 itself, has proven challenging in the adjuvant/neoadjuvant setting. Thus, we suggest that a new generation of research needs to refine the prognostic taxonomy of cHER2+ BC and develop easy-to-use, clinicbased prediction algorithms to distinguish between good- and poor- responders to trastuzumab-based therapy ab initio. This study offered two hypotheses: 1.) HER2 overexpression can unexpectedly take place in a molecular background owned by basal-like BC (a commonly HER2-negative BC subtype which possesses many epithelial-mesenchymal transition (EMT) characteristics and exhibits robust cancer stem cell [CSC]-like features), thus generating a so-called basal/cHER2+ BC subtype; 2.) the basal/cHER2+ phenotype confers poor prognosis and delineates a subgroup of intrinsically aggressive cHER2+ BC with primary resistance to trastuzumab...

Genetic Polymorphisms in Replication-related Genes and Risk of Breast Cancer Among European and East Asian Women

Background: The role of common, low to intermediate risk alleles in breast cancer need to be examined due to their relatively high prevalence. Among many cellular pathways, replication has a pivotal role in cell division and frequently targeted during carcinogenesis. Replication is governed by a host of genes involved in a number of different pathways. This study investigates the effects of replication-gene variants in relation to breast cancer and how this relationship is affected by ethnicity, menopausal status and breast tumour subtype. Methods: Data from a case-control study with 997 incident breast cancer cases and 1,050 age frequency matched controls in Vancouver, British Columbia and Kingston, Ontario were used. Unconditional logistic regression was used to calculate odds ratios between 45 replication gene variants and breast cancer risk, assuming an additive genetic model adjusted for age and centre, presented for Europeans and East Asians separately. Polytomous logistic regression was used to assess odds ratios between each SNP and four breast cancer subtypes defined by hormone receptor status among Europeans. All analyses were stratified by menopausal status. The Benjamini–Hochberg false discovery rate (FDR) was used to address multiple comparisons. Results: Among Europeans, the SNPs in FGFR2, TOX3 and 11q13 loci were associated with breast cancer after controlling for multiple comparisons. Test of heterogeneity showed the SNPs rs1045185, rs4973768, rs672888, rs1219648, rs2420946 among Europeans and rs889312 among East Asians conferred differential risk across the tumour subtypes. Conclusions: Specific SNPs in replication genes were associated with breast cancer, and the risk level differed by tumour subtype defined by ER/PR/Her2 status and ethnicity.

Prevalence and genetic diversity of Blastocystis in family units living in the United States

The human gut is host to a diversity of microorganisms including the single-celled microbial eukaryote Blastocystis. Although Blastocystis has a global distribution, there is dearth of information relating to its prevalence and diversity in many human populations. The mode of Blastocystis transmission to humans is also insufficiently characterised, however, it is speculated to vary between different populations. Here we investigated the incidence and genetic diversity of Blastocystis in a US population and also the possibility of Blastocystis human-human transmission between healthy individuals using family units (N = 50) living in Boulder, Colorado as our sample-set. Ten of the 139 (~ 7%) individuals in our dataset were positive for Blastocystis, nine of whom were adults and one individual belonging to the children/adolescents group. All positive cases were present in different family units. A number of different Blastocystis subtypes (species) were detected with no evidence of mixed infections. The prevalence of Blastocystis in this subset of the US population is comparatively low relative to other industrialised populations investigated to date; however, subtype diversity was largely consistent with that previously reported in studies of European populations. The distribution of Blastocystis within family units indicates that human-human transmission is unlikely to have occurred within families that participated in this study. It is not unexpected that given the world-wide variation in human living conditions and lifestyles between different populations, both the prevalence of Blastocystis and its mode of transmission to humans may vary considerably.

The relationship between divorce and children with AD/HD of different subtypes and comorbidity: results from a clinically referred sample

This study investigated the relationship between divorce and thesymptom profile of children with attention deficit/hyperactivity disorder(AD/HD). The files of 1,201 children from a pediatric practicein Sydney, Australia were used in this study. Children wereaged 6 to 18 years, and were diagnosed with either the inattentiveor combined type of AD/HD. Results show that 213 children hadparents who were divorced. Children with the combined type, andespecially boys with comorbid conduct disorder/oppositional defiantdisorder (CD/ODD) were more common in the divorced group,and children of the inattentive type with comorbid learning disabilitieswere overrepresented in nondivorced families. Results suggestthat divorce is associated with disruptive behavior patterns inchildren with AD/HD. The importance of including marital status asan important correlate in AD/HD treatment outcomes is discussed.

Child AD/HD severity and psychological functioning in relation to divorce, remarriage, multiple transitions and the quality of family relationships

Both Attention-Deficit/Hyperactivity Disorder (AD/HD) and divorce are very prevalent in western societies, and they may occur together. AD/HD is generally viewed as a neurobiological disorder, which has led to a commonly held belief that social-environmental factors play little role in the symptom profile of children diagnosed with the disorder. This study investigated the association between parental divorce, remarriage, multiple transitions, the quality of relationships with family members and the psychological well-being of children and adolescents with AD/HD. First, differences in children’s AD/HD symptom profiles in relation to parents’ divorce status (single/multiple divorce) and family composition (single parent/stepfamily) were examined. Second, the association between the quality of children’s relationships with each family member and parents’ marital status (divorced/non-divorced) and family composition was investigated. In addition, age, gender and AD/HD subtype differences were assessed. Third, the association between the quality of children’s interactions with family members and children’s AD/HD symptom profile was explored. No significant differences in children’s behavioural profiles were found in terms of parents’ divorce status. Living in stepfamilies was associated with greater AD/HD severity and social malfunctioning. Disruptive parent–child and sibling relationships were found to be related to children’s age, gender, AD/HD subtype and parents’ marital status. Further, poor interactions with family members correlated with children’s AD/HD severity and psychological well-being. In summary, divorce, remarriage and the quality of relationships with family members are important correlates of the symptom profile of children with AD/HD, and this emphasises the need for special treatment modules for these families.

Estado de las enfermedades raras que cursan con discapacidad intelectual en Colombia

Las enfermedades raras o huérfano son una problemática que ha tomado mucha importancia en el contexto mundial del presente siglo, estas se han definido como crónicas, de difícil tratamiento de sus síntomas y con baja prevalencia en la población; muchas de estas enfermedades cursan con varios tipos de discapacidad, siendo el objetivo del presente trabajo el enfocarse en aquellas enfermedades raras que cursan con discapacidad intelectual. Para poder profundizar en estas enfermedades se realizó una revisión teórica sobre las enfermedades raras, así como de la discapacidad psíquica y su importancia a nivel mundial y nacional. A partir de estas definiciones, se revisaron en profundidad 3 enfermedades raras que cursan con discapacidad intelectual en el contexto colombiano, como son: el síndrome de Rett, el síndrome de Prader-Willi y el síndrome de X frágil. En cada una de estas enfermedades además se explicaron los tipos de diagnóstico, intervención, prevención, grupos de apoyo y tipos de evaluación que más se usan en el contexto nacional

Ideación suicida y desesperanza en pacientes con cáncer

El objetivo de la presente investigación fue identificar la relación entre ideación suicida y desesperanza en 160 pacientes con cáncer. La ideación suicida se midió a través de dos ítems de una entrevista semiestructurada, la escala de ideación suicida (ISS), el ítem 9 del inventario de depresión de Beck (BDI-IA). La desesperanza se midió con la escala de desesperanza de Beck (BHS). Los resultados obtenidos indicaron una relación significativa (p=.000) entre ideación suicida y desesperanza; una prevalencia de ideación suicida en los pacientes con cáncer entre 4.4% y 13.8% y de riesgo de suicidio entre 5.6% y 30.6%; y algún grado de desesperanza en 31.9 % de los participantes. De acuerdo con lo anterior, se confirma que existe relación entre la desesperanza y la ideación suicida en pacientes oncológicos adultos. Adicionalmente, que estas variables están presentes en los pacientes y que ameritan atención en la intervención interdisciplinaria.