Patients with Mutations in Nphs2 (Podocin) Do not Respond To Standard Steroid Treatment of Nephrotic Syndrome

Nephrotic syndrome (NS) represents the association of proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Steroid-resistant NS (SRNS) is defined by primary resistance to standard steroid therapy. It remains one of the most intractable causes of ESRD in the first two decades of life. Mutations in the NPHS2 gene represent a frequent cause of SRNS, occurring in approximately 20 to 30% of sporadic cases of SRNS. On the basis of a very si nail number of patients, it was suspected that children with homozygous or compound heterozygous mutations in NPHS2 might exhibit primary steroid resistance and a decreased risk of FSGS recurrence after kidney transplantation. To test this hypothesis, NPHS2 mutational analysis was performed with direct sequencing for 190 patients with SRNS from 165 different families and, as a control sample, 124 patients with steroid-sensitive NS from 120 families. Homozygous or compound heterozygous mutations in NPHS2 were detected for 43 of 165 SRNS families (26%). Conversely, no homozygous or compound heterozygous mutations in NPHS2 were observed for the 120 steroid-sensitive NS families. Recurrence of FSGS in a renal transplant was noted for seven of 20 patients with SRNS (35%) without NPHS2 mutations, whereas it occurred for only two of 24 patients with SRNS (8%) with homozygous or compound heterozygous mutations in NPHS2. None of 29 patients with homozygous or compound heterozygous mutations in NPHS2 who were treated with cyclosporine A or cyclophosphamide demonstrated complete remission of NS. It was concluded that patients with SRNS with homozygous or compound heterozygous mutations in NPHS2 do not respond to standard steroid treatment and have a reduced risk for recurrence of FSGS in a renal transplant. Because these findings might affect the treatment plan for childhood SRNS, it might be advisable to perform mutational analysis of NPHS2, if the patient consents, in parallel with the start of the first course of standard steroid therapy.WoSScopu

Clinical and epidemiological factors associated with spontaneous preterm birth: a multicentre cohort of low risk nulliparous women

The objective of this study was to determine incidence and risk factors associated with spontaneous preterm birth (sPTB). It was a prospective multicentre cohort study performed in five Brazilian referral maternity hospitals and enrolling nulliparous women at 19–21 weeks. Comprehensive maternal data collected during three study visits were addressed as potentially associated factors for sPTB. Bivariate and multivariate analysis estimated risk ratios. The main outcomes measures were birth before 37 weeks due to spontaneous preterm labour or premature rupture of membranes (sPTB). The comparison group was comprised of women with term births (≥37weeks). Outcome data was available for 1,165 women, 6.7% of whom had sPTB, 16% had consumed alcohol and 5% had used other illicit drugs during the first half of pregnancy. Current drinking at 19–21 weeks (RR 3.96 95% CI [1.04–15.05]) and a short cervix from 18–24 weeks (RR 4.52 95% CI [1.08–19.01]) correlated with sPTB on bivariate analysis. Increased incidence of sPTB occurred in underweight women gaining weight below quartile 1 (14.8%), obese women gaining weight above quartile 3 (14.3%), women with a short cervix (<25 mm) at 18–24 weeks (31.2%) and those with a short cervix and vaginal bleeding in the first half of pregnancy (40%). Cervical length (RRadj 4.52 95% CI [1.08–19.01]) was independently associated with sPTB. In conclusion, the incidence of sPTB increased in some maternal phenotypes, representing potential groups of interest, the focus of preventive strategies. Similarly, nulliparous women with a short cervix in the second trimester require further exploration

Home screening for bacteriuria in children with spina bifida and clean intermittent catheterization

<p>Abstract</p> <p>Background</p> <p>Significant bacteriuria (SBU) and urinary tract infections (UTIs) are common in patients with spina bifida and neuropathic detrusor sphincter dysfunction. Laboratory agar plated culture is the gold standard to establish SBU. It has the disadvantage of diagnostic and subsequent therapeutic delay. Leukocyte esterase tests (LETs) and dip slides proved to be useful in the general populations to exclude SBU and UTI. The aim of this study was to evaluate the reliability of LET and dip slide in children with spina bifida without symptoms of UTI. The reliability in children with asymptomatic SBU was not studied before.</p> <p>Methods</p> <p>In one hundred and twelve children with spina bifida on clean intermittent catheterization LETs and dip slides were compared with laboratory cultures. Both tests and agar plated cultures were performed on catheterized urine samples. The hypothesis was that the home tests are as accurate as laboratory cultures.</p> <p>Results</p> <p>A SBU was found in 45 (40%) of the 112 laboratory cultures. A negative LET excluded SBU (negative predictive value 96%), while a positive LET had a positive predictive value of 72%. The false positive rate was 28%. Dip slide determination of bacterial growth had no added value, other than serving as transport medium.</p> <p>Conclusions</p> <p>In spina bifida children, leukocyte esterase testing can be used to exclude significant bacteriuria at home, while dip slide tests have no added value to diagnose or exclude significant bacteriuria.</p

Terminologia de incidentes com medicamentos no contexto hospitalar Terminology for drug incidents in the hospital context

Incidentes com medicamentos geram problemas aos pacientes e custos adicionais ao sistema de saúde. A variedade de termos utilizada para comunicá-los propicia divergências nos resultados de pesquisas e confundem notificadores. Objetivou-se revisar os termos utilizados para descrever estes incidentes confrontando-os com as conceituações/definições oficiais disponíveis. Pesquisaram-se as bases PubMed, MEDLINE, IPA e LILACS para selecionar estudos publicados entre janeiro de 1990 e dezembro de 2005. Selecionaram-se 33 publicações. Verificou-se que a terminologia supranacional recomendada para descrever incidentes com medicamentos é insuficiente, mas que há consenso de uso das expressões em função do gênero do incidente. O termo Reação Adversa a Medicamento é mais utilizado quando não se verifica intencionalidade. A expressão Evento Adverso a Medicamento foi mais usada quando se descreviam incidentes durante a hospitalização; e Problema Relacionado a Medicamento foi mais utilizada em estudos que avaliaram atenção/cuidados farmacêuticos (uso/falta do medicamento). Ainda assim, a linha divisória entre essas três categorias não é clara e simples. Futuros estudos das relações entre as categorias e investigações multidisciplinares sobre erro humano podem subsidiar a proposição de novas conceituações.<br>In-hospital drug incidents cause problems for patients and additional costs for the health system. The variety of terms used to report them leads to disparities in research results and confuses the professionals that report them. This study aimed to review the terms used to describe drug incidents by collating them with the official concepts and definitions. PubMed, MEDLINE, IPA, and LILACS were searched to select studies published from January 1990 to December 2005. Thirty-three publications were selected. The supranational terminology recommended for describing drug incidents proved insufficient, but there was consensus that the expressions are used as a function of the type of incident. Adverse drug reaction is used when no intent is identified. Adverse drug event mainly describes incidents during hospitalization, and drug-related problem is used in studies on pharmaceutical care (use or lack of the drug). Still, the division between these categories is neither clear nor simple. Future studies on the relations between categories and multidisciplinary research on human error could support proposals for new concepts