A follow-up study on the quality of alcohol dependence-related information on the web.

ABSTRACT: In order to evaluate the one-year evolution of web-based information on alcohol dependence, we re-assessed alcohol-related sites in July 2007 with the same evaluating tool that had been used to assess these sites in June 2006. Websites were assessed with a standardized form designed to rate sites on the basis of accountability, presentation, interactivity, readability, and content quality. The DISCERN scale was also used, which aimed to assist persons without content expertise in assessing the quality of written health publications. Scores were highly stable for all components of the form one year later (r = .77 to .95, p < .01). Analysis of variance for repeated measures showed no time effect, no interaction between time and scale, no interaction between time and group (affiliation categories), and no interaction between time, group, and scale. The study highlights lack of change of alcohol-dependence-related web pages across one year.

Life partnerships in childhood cancer survivors, their siblings, and the general population.

BACKGROUND: Life partnerships other than marriage are rarely studied in childhood cancer survivors (CCS). We aimed (1) to describe life partnership and marriage in CCS and compare them to life partnerships in siblings and the general population; and (2) to identify socio-demographic and cancer-related factors associated with life partnership and marriage. METHODS: As part of the Swiss Childhood Cancer Survivor Study (SCCSS), a questionnaire was sent to all CCS (aged 20-40 years) registered in the Swiss Childhood Cancer Registry (SCCR), aged <16 years at diagnosis, who had survived ≥ 5 years. The proportion with life partner or married was compared between CSS and siblings and participants in the Swiss Health Survey (SHS). Multivariable logistic regression was used to identify factors associated with life partnership or marriage. RESULTS: We included 1,096 CCS of the SCCSS, 500 siblings and 5,593 participants of the SHS. Fewer CCS (47%) than siblings (61%, P < 0.001) had life partners, and fewer CCS were married (16%) than among the SHS population (26%, P > 0.001). Older (OR = 1.14, P < 0.001) and female CCS (OR = 1.85, <0.001) were more likely to have life partners. CCS who had undergone radiotherapy, bone marrow transplants (global P Treatment = 0.018) or who had a CNS diagnosis (global P Diagnosis < 0.001) were less likely to have life partners. CONCLUSION: CCS are less likely to have life partners than their peers. Most CCS with a life partner were not married. Future research should focus on the effect of these disparities on the quality of life of CCS.

Evaluation of prenatal ultrasound diagnosis of fetal abdominal wall defects by 19 European registries.

OBJECTIVES: To evaluate the current effectiveness of routine prenatal ultrasound screening in detecting gastroschisis and omphalocele in Europe. DESIGN: Data were collected by 19 congenital malformation registries from 11 European countries. The registries used the same epidemiological methodology and registration system. The study period was 30 months (July 1st 1996-December 31st 1998) and the total number of monitored pregnancies was 690,123. RESULTS: The sensitivity of antenatal ultrasound examination in detecting omphalocele was 75% (103/137). The mean gestational age at the first detection of an anomaly was 18 +/- 6.0 gestational weeks. The overall prenatal detection rate for gastroschisis was 83% (88/106) and the mean gestational age at diagnosis was 20 +/- 7.0 gestational weeks. Detection rates varied between registries from 25 to 100% for omphalocele and from 18 to 100% for gastroschisis. Of the 137 cases of omphalocele less than half of the cases were live births (n = 56; 41%). A high number of cases resulted in fetal deaths (n = 30; 22%) and termination of pregnancy (n = 51; 37%). Of the 106 cases of gastroschisis there were 62 (59%) live births, 13 (12%) ended with intrauterine fetal death and 31 (29%) had the pregnancies terminated. CONCLUSIONS: There is significant regional variation in detection rates in Europe reflecting different policies, equipment and the operators' experience. A high proportion of abdominal wall defects is associated with concurrent malformations, syndromes or chromosomal abnormalities, stressing the need for the introduction of repeated detailed ultrasound examination as a standard procedure. There is still a relatively high rate of elective termination of pregnancies for both defects, even in isolated cases which generally have a good prognosis after surgical repair.

My Group Beats Your Group: Evaluating Non-Income Inequalities

This paper proposes a new methodology, the Domination Index, to evaluate non-income inequalities between social groups such as inequalities of educational attainment, occupational status, health or subjective well-being. The Domination Index does not require specific cardinalisation assumptions, but only uses the ordinal structure of these non-income variables. We approach from an axiomatic perspective and show that a set of desirable properties for a group inequality measure when the variable of interest is ordinal, characterizes the Domination Index up to a positive scalar transformation. Moreover we make use of the Domination Index to explore the relation between inequality and segregation and show how these two concepts are related theoretically.

β-Glucan antigenemia assay for the diagnosis of invasive fungal infections in patients with hematological malignancies: a systematic review and meta-analysis of cohort studies from the Third European Conference on Infections in Leukemia (ECIL-3).

BACKGROUND: Invasive fungal infections (IFIs) are life-threatening complications in patients with hemato-oncological malignancies, and early diagnosis is crucial for outcome. The compound 1,3-β-D-glucan (BG), a cell wall component of most fungal species, can be detected in blood during IFI. Four commercial BG antigenemia assays are available (Fungitell, Fungitec-G, Wako, and Maruha). This meta-analysis from the Third European Conference on Infections in Leukemia (ECIL-3) assessed the performance of BG assays for the diagnosis of IFI in hemato-oncological patients. METHODS: Studies reporting the performance of BG antigenemia assays for the diagnosis of IFI (European Organization for Research and Treatment of Cancer and Mycoses Study Group criteria) in hemato-oncological patients were identified. The analysis was focused on high-quality cohort studies with exclusion of case-control studies. Meta-analysis was performed by conventional meta-analytical pooling and bivariate analysis. RESULTS: Six cohort studies were included (1771 adult patients with 414 IFIs of which 215 were proven or probable). Similar performance was observed among the different BG assays. For the cutoff recommended by the manufacturer, the diagnostic performance of the BG assay in proven or probable IFI was better with 2 consecutive positive test results (diagnostic odds ratio for 2 consecutive vs one single positive results, 111.8 [95% confidence interval {CI}, 38.6-324.1] vs 16.3 [95% CI, 6.5-40.8], respectively; heterogeneity index for 2 consecutive vs one single positive results, 0% vs 72.6%, respectively). For 2 consecutive tests, sensitivity and specificity were 49.6% (95% CI, 34.0%-65.3%) and 98.9% (95% CI, 97.4%-99.5%), respectively. Estimated positive and negative predictive values for an IFI prevalence of 10% were 83.5% and 94.6%, respectively. CONCLUSIONS: Different BG assays have similar accuracy for the diagnosis of IFI in hemato-oncological patients. Two consecutive positive antigenemia assays have very high specificity, positive predictive value, and negative predictive value. Because sensitivity is low, the test needs to be combined with clinical, radiological, and microbiological findings.

Valproic acid related idiosyncratic drug induced hepatotoxicity in a glioblastoma patient treated with temozolomide.

Glioblastoma patients undergoing treatment with surgery followed by radiation and temozolomide chemotherapy often develop a state of immunosuppression and are at risk for opportunistic infections and reactivation of hepatitis and herpes viruses. We report the case of a 48-year-old glioblastoma patient who developed acute cholestatic hepatitis with hepatic failure during adjuvant treatment with temozolomide and the integrin inhibitor cilengitide. A viral hepatitis was excluded and valproic acid treatment was stopped. Upon normalisation of the liver tests, temozolomide treatment was resumed without perturbation of the liver tests. Valproic acid related idiosyncratic drug induced hepatotoxicity should be considered as a differential diagnosis in glioblastoma patients undergoing adjuvant therapy.

CYP3A activity measured by the midazolam test is not related to 3435 C >T polymorphism in the multiple drug resistance transporter gene.

A recent study with 69 Japanese liver transplants treated with tacrolimus found that the MDR13435 C >T polymorphism, but not the MDR12677 G >T polymorphism, was associated with differences in the intestinal expression level of CYP3A4 mRNA. In the present study, over 6 h, we measured the kinetics of a 75 microg oral dose of midazolam, a CYP3A substrate, in 21 healthy subjects genotyped for the MDR13435 C >T and 2677 G >T polymorphism. No statistically significant differences were found in the calculated pharmacokinetic parameters between the three 3435 C >T genotypes (TT, CT and CC group, respectively: Cmax (mean +/- SD: 0.30 +/- 0.08 ng/ml, 0.31 +/- 0.09 ng/ml and 0.31 +/- 0.11 ng/ml; Apparent clearance: 122 +/- 29 l/h, 156 +/- 92 l/h and 111 +/- 35 l/h; t1/2: 1.9 +/- 1.1 h, 1.6 +/- 0.90 h and 1.7 +/- 0.7 h). In addition, the 30-min 1'OH midazolam to midazolam ratio, a marker of CYP3A activity, determined in 74 HIV-positive patients before the introduction of antiretroviral treatment, was not significantly different between the three 3435 C >T genotypes (mean ratio +/- SD: 3.65 +/- 2.24, 4.22 +/- 3.49 and 4.24 +/- 2.03, in the TT, CT and CC groups, respectively). Similarly, no association was found between the MDR12677 G >T polymorphism and CYP3A activity in the healthy subjects or in the HIV-positive patients. The existence of a strong association between the activity of CYP3A and MDR13435 C >T and 2677 G >T polymorphisms appears unlikely, at least in Caucasian populations and/or in the absence of specific environmental factors.

Prevalence and clinical importance of mesenteric venous thrombosis in the Swiss Inflammatory Bowel Disease Cohort

OBJECTIVE: The purpose of this study was to evaluate the prevalence of mesenteric venous thrombosis (MVT) in the Swiss Inflammatory Bowel Disease Cohort Study and to correlate MVT with clinical outcome. MATERIALS AND METHODS: Abdominal portal phase CT was used to examine patients with inflammatory bowel disease (IBD). Two experienced abdominal radiologists retrospectively analyzed the images, focusing on the superior and inferior mesenteric vein branches and looking for signs of acute or chronic thrombosis. The location of abnormalities was registered. The presence of MVT was correlated with IBD-related radiologic signs and complications. RESULTS: The cases of 160 patients with IBD (89 women, 71 men; Crohn disease [CD], 121 patients; ulcerative colitis [UC], 39 patients; median age at diagnosis, 27 years for patients with CD, 32 years for patients with UC) were analyzed. MVT was detected in 43 patients with IBD (26.8%). One of these patients had acute MVT; 38, chronic MVT; and four, both. The prevalence of MVT did not differ between CD (35/121 [28.9%]) and UC (8/39 [20.5%]) (p = 0.303). The location of thrombosis was different between CD and UC (CD, jejunal or ileal veins only [p = 0.005]; UC, rectocolic veins only [p = 0.001]). Almost all (41/43) cases of thrombosis were peripheral. MVT in CD patients was more frequently associated with bowel wall thickening (p = 0.013), mesenteric fat hypertrophy (p = 0.005), ascites (p = 0.002), and mesenteric lymph node enlargement (p = 0.036) and was associated with higher rate of bowel stenosis (p < 0.001) and more intestinal IBD-related surgery (p = 0.016) in the outcome. Statistical analyses for patients with UC were not relevant because of the limited population (n = 8). CONCLUSION: MVT is frequently found in patients with IBD. Among patients with CD, MVT is associated with bowel stenosis and CD-related intestinal surgery.

ESCMID* guideline for the diagnosis and management of Candida diseases 2012: prevention and management of invasive infections in neonates and children caused by Candida spp.

Invasive candidiasis (IC) is a relatively common syndrome in neonates and children and is associated with significant morbidity and mortality. These guidelines provide recommendations for the prevention and treatment of IC in neonates and children. Appropriate agents for the prevention of IC in neonates at high risk include fluconazole (A-I), nystatin (B-II) or lactoferrin ± Lactobacillus (B-II). The treatment of IC in neonates is complicated by the high likelihood of disseminated disease, including the possibility of infection within the central nervous system. Amphotericin B deoxycholate (B-II), liposomal amphotericin B (B-II), amphotericin B lipid complex (ABLC) (C-II), fluconazole (B-II), micafungin (B-II) and caspofungin (C-II) can all be potentially used. Recommendations for the prevention of IC in children are largely extrapolated from studies performed in adults with concomitant pharmacokinetic data and models in children. For allogeneic HSCT recipients, fluconazole (A-I), voriconazole (A-I), micafungin (A-I), itraconazole (B-II) and posaconazole (B-II) can all be used. Similar recommendations are made for the prevention of IC in children in other risk groups. With several exceptions, recommendations for the treatment of IC in children are extrapolated from adult studies, with concomitant pharmacokinetic studies. Amphotericin B deoxycholate (C-I), liposomal amphotericin B (A-I), ABLC (B-II), micafungin (A-I), caspofungin (A-I), anidulafungin (B-II), fluconazole (B-I) and voriconazole (B-I) can all be used.

Influence of the host related factors in the development of the hepatosplenic form of schistosomiasis mansoni

The frequency of hepatosplenomegaly in endemic areas is not proportional to the fecal ova count. This may be explained by epidemiological genetic. The occurrence of two or more cases of schistosomal hepatosplenomegaly in nuclear family is much higher than expected. The concentration is higher among siblings than it is among mothers and children of further and children. It is not significant between father and mother. If the mother, instead of the father has hepatosplenic schistosomiasis the relative risk for the child to acquire hepatosplenomegaly is at least five times (the maternal affect). The inbreeding is highler in the hepatosplenic than in the hepatointestinal patients. In some areas in Brazil the hepatosplenic form of the schistosomiasis mansoni occurs with much higher frequency in whites than in blacks. After treatment, reversion of hepatosplenic schistosomiasis occurs more frequently in non-whithers. It seems that the resistance of blacks to the hepatosplenic form of schistosomiasis may be related to the glyoxalase system , perhaps associated to another genetic marker. The hepatosplenic schistosomiasis is less frequent in longilineal individuals. In some areas the hepatosplenic form of schistosomiasis is more frequent in A blood group of ABO sistem. The family heredograms do not suggest a single mendelian inheritance, but probably a multifactorial and possibility poligenic one.

Clinical significance of the CCR5delta32 allele in hepatitis C.

BACKGROUND: The CCR5 receptor, expressed on Th1 cells, may influence clinical outcomes of HCV infection. We explored a possible link between a CCR5 32-base deletion (CCR5delta32), resulting in the expression of a non-functioning receptor, and clinical outcomes of HCV infection. METHODS: CCR5 and HCV-related phenotypes were analysed in 1,290 chronically infected patients and 160 patients with spontaneous clearance. RESULTS: Carriage of the CCR5delta32 allele was observed in 11% of spontaneous clearers compared to 17% of chronically infected patients (OR = 0.59, 95% CI interval 0.35-0.99, P = 0.047). Carriage of this allele also tended to be observed more frequently among patients with liver inflammation (19%) compared to those without inflammation (15%, OR = 1.38, 95% CI interval 0.99-1.95, P = 0.06). The CCR5delta32 was not associated with sustained virological response (P = 0.6), fibrosis stage (P = 0.8), or fibrosis progression rate (P = 0.4). CONCLUSIONS: The CCR5delta32 allele appears to be associated with a decreased rate of spontaneous HCV eradication, but not with hepatitis progression or response to antiviral therapy.

Molecular detection and identification of zygomycetes species from paraffin-embedded tissues in a murine model of disseminated zygomycosis: a collaborative European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Fungal Infection Study Group (EFISG) evaluation.

The present study was performed to assess the interlaboratory reproducibility of the molecular detection and identification of species of Zygomycetes from formalin-fixed paraffin-embedded kidney and brain tissues obtained from experimentally infected mice. Animals were infected with one of five species (Rhizopus oryzae, Rhizopus microsporus, Lichtheimia corymbifera, Rhizomucor pusillus, and Mucor circinelloides). Samples with 1, 10, or 30 slide cuts of the tissues were prepared from each paraffin block, the sample identities were blinded for analysis, and the samples were mailed to each of seven laboratories for the assessment of sensitivity. A protocol describing the extraction method and the PCR amplification procedure was provided. The internal transcribed spacer 1 (ITS1) region was amplified by PCR with the fungal universal primers ITS1 and ITS2 and sequenced. As negative results were obtained for 93% of the tissue specimens infected by M. circinelloides, the data for this species were excluded from the analysis. Positive PCR results were obtained for 93% (52/56), 89% (50/56), and 27% (15/56) of the samples with 30, 10, and 1 slide cuts, respectively. There were minor differences, depending on the organ tissue, fungal species, and laboratory. Correct species identification was possible for 100% (30 cuts), 98% (10 cuts), and 93% (1 cut) of the cases. With the protocol used in the present study, the interlaboratory reproducibility of ITS sequencing for the identification of major Zygomycetes species from formalin-fixed paraffin-embedded tissues can reach 100%, when enough material is available.

A novel tool for the assessment of pain: validation in low back pain.

BACKGROUND: Adequate pain assessment is critical for evaluating the efficacy of analgesic treatment in clinical practice and during the development of new therapies. Yet the currently used scores of global pain intensity fail to reflect the diversity of pain manifestations and the complexity of underlying biological mechanisms. We have developed a tool for a standardized assessment of pain-related symptoms and signs that differentiates pain phenotypes independent of etiology. METHODS AND FINDINGS: Using a structured interview (16 questions) and a standardized bedside examination (23 tests), we prospectively assessed symptoms and signs in 130 patients with peripheral neuropathic pain caused by diabetic polyneuropathy, postherpetic neuralgia, or radicular low back pain (LBP), and in 57 patients with non-neuropathic (axial) LBP. A hierarchical cluster analysis revealed distinct association patterns of symptoms and signs (pain subtypes) that characterized six subgroups of patients with neuropathic pain and two subgroups of patients with non-neuropathic pain. Using a classification tree analysis, we identified the most discriminatory assessment items for the identification of pain subtypes. We combined these six interview questions and ten physical tests in a pain assessment tool that we named Standardized Evaluation of Pain (StEP). We validated StEP for the distinction between radicular and axial LBP in an independent group of 137 patients. StEP identified patients with radicular pain with high sensitivity (92%; 95% confidence interval [CI] 83%-97%) and specificity (97%; 95% CI 89%-100%). The diagnostic accuracy of StEP exceeded that of a dedicated screening tool for neuropathic pain and spinal magnetic resonance imaging. In addition, we were able to reproduce subtypes of radicular and axial LBP, underscoring the utility of StEP for discerning distinct constellations of symptoms and signs. CONCLUSIONS: We present a novel method of identifying pain subtypes that we believe reflect underlying pain mechanisms. We demonstrate that this new approach to pain assessment helps separate radicular from axial back pain. Beyond diagnostic utility, a standardized differentiation of pain subtypes that is independent of disease etiology may offer a unique opportunity to improve targeted analgesic treatment.