Impact of common risk factors of fibrosis progression in chronic hepatitis C.

OBJECTIVE The natural course of chronic hepatitis C varies widely. To improve the profiling of patients at risk of developing advanced liver disease, we assessed the relative contribution of factors for liver fibrosis progression in hepatitis C. DESIGN We analysed 1461 patients with chronic hepatitis C with an estimated date of infection and at least one liver biopsy. Risk factors for accelerated fibrosis progression rate (FPR), defined as ≥0.13 Metavir fibrosis units per year, were identified by logistic regression. Examined factors included age at infection, sex, route of infection, HCV genotype, body mass index (BMI), significant alcohol drinking (≥20 g/day for ≥5 years), HIV coinfection and diabetes. In a subgroup of 575 patients, we assessed the impact of single nucleotide polymorphisms previously associated with fibrosis progression in genome-wide association studies. Results were expressed as attributable fraction (AF) of risk for accelerated FPR. RESULTS Age at infection (AF 28.7%), sex (AF 8.2%), route of infection (AF 16.5%) and HCV genotype (AF 7.9%) contributed to accelerated FPR in the Swiss Hepatitis C Cohort Study, whereas significant alcohol drinking, anti-HIV, diabetes and BMI did not. In genotyped patients, variants at rs9380516 (TULP1), rs738409 (PNPLA3), rs4374383 (MERTK) (AF 19.2%) and rs910049 (major histocompatibility complex region) significantly added to the risk of accelerated FPR. Results were replicated in three additional independent cohorts, and a meta-analysis confirmed the role of age at infection, sex, route of infection, HCV genotype, rs738409, rs4374383 and rs910049 in accelerating FPR. CONCLUSIONS Most factors accelerating liver fibrosis progression in chronic hepatitis C are unmodifiable.

Molecular epidemiology of hepatitis B virus infection in Switzerland: a retrospective cohort study.

BACKGROUND Chronic hepatitis B virus (HBV) infection affects up to 7 % of the European population. Specific HBV genotypes are associated with rapid progression to end-stage liver disease and sub-optimal interferon treatment responses. Although the geographic distribution of HBV genotypes differs between regions, it has not been studied in Switzerland, which lies at the crossroads of Europe. METHODS In a retrospective analysis of 465 HBV samples collected between 2002 and 2013, we evaluated the HBV genotype distribution and phylogenetic determinants, as well as the prevalence of serological evidence of hepatitis delta, hepatitis C and HIV infections in Switzerland. Baseline characteristics of patients were compared across their region of origin using Fisher's exact test and ANOVA, and risk factors for HBeAg positivity were assessed using logistic regression. RESULTS The Swiss native population represented 15.7 % of HBV-infected patients living in Switzerland. In the overall population, genotype D was most prevalent (58.3 %), whereas genotype A (58.9 %) was the predominant genotype among the Swiss native population. The prevalence of patients with anti-HDV antibodies was 4.4 %. Patients of Swiss origin were most likely to be HBeAg-positive (38.1 %). HBV genotypes of patients living in Switzerland but sharing the same original region of origin were consistent with their place of birth. CONCLUSIONS The molecular epidemiology of HBV infection in Switzerland is driven by migration patterns and not by the genotype distribution of the native population. The prevalence of positive anti-HDV antibodies in our cohort was very low.

Accumulation rates and predominant atmospheric sources of natural and anthropogenic Hg and Pb on the Faroe Islands

A monolith representing 5420 14C yr of peat accumulation was collected from a blanket bog at Myrarnar, Faroe Islands. The maximum Hg concentration (498 ng/g at a depth of 4.5 cm) coincides with the maximum concentration of anthropogenic Pb (111 μg/g). Age dating of recent peat accumulation using 210Pb (CRS model) shows that the maxima in Hg and Pb concentrations occur at AD 1954 ± 2. These results, combined with the isotopic composition of Pb in that sample (206Pb/207Pb = 1.1720 ± 0.0017), suggest that coal burning was the dominant source of both elements. From the onset of peat accumulation (ca. 4286 BC) until AD 1385, the ratios Hg/Br and Hg/Se were constant (2.2 ± 0.5 × 10-4 and 8.5 ± 1.8 × 10-3, respectively). Since then, Hg/Br and Hg/Se values have increased, also reaching their maxima in AD 1954. The age date of the maximum concentrations of anthropogenic Hg and Pb in the Faroe Islands is consistent with a previous study of peat cores from Greenland and Denmark (dated using the atmospheric bomb pulse curve of 14C), which showed maximum concentrations in AD 1953. The average rate of atmospheric Hg accumulation from 1520 BC to AD 1385 was 1.27 ± 0.38 μg/m2/yr. The Br and Se concentrations and the background Hg/Br and Hg/Se ratios were used to calculate the average rate of natural Hg accumulation for the same period, 1.32 ± 0.36 μg/m2/yr and 1.34 ± 0.29 μg/m2/yr, respectively. These fluxes are similar to the preanthropogenic rates obtained using peat cores from Switzerland, southern Greenland, southern Ontario, Canada, and the northeastern United States. Episodic volcanic emissions and the continual supply of marine aerosols to the Faroe Islands, therefore, have not contributed significantly to the Hg inventory or the Hg accumulation rates, relative to these other areas. The maximum rate of Hg accumulation was 34 μg/m2/yr. The greatest fluxes of anthropogenic Hg accumulation calculated using Br and Se, respectively, were 26 and 31 μg/m2/yr. The rate of atmospheric Hg accumulation in 1998 (16 μg/m2/yr) is comparable to the values recently obtained by atmospheric transport modeling for Denmark, the Faroe Islands, and Greenland.

Small Cell Carcinoma of the Urinary Bladder: A Retrospective, Multicenter Rare Cancer Network Study of 107 Patients

PURPOSE Small cell carcinomas of the bladder (SCCB) account for fewer than 1% of all urinary bladder tumors. There is no consensus regarding the optimal treatment for SCCB. METHODS AND MATERIALS Fifteen academic Rare Cancer Network medical centers contributed SCCB cases. The eligibility criteria were as follows: pure or mixed SCC; local, locoregional, and metastatic stages; and age ≥18 years. The overall survival (OS) and disease-free survival (DFS) were calculated from the date of diagnosis according to the Kaplan-Meier method. The log-rank and Wilcoxon tests were used to analyze survival as functions of clinical and therapeutic factors. RESULTS The study included 107 patients (mean [±standard deviation, SD] age, 69.6 [±10.6] years; mean follow-up time, 4.4 years) with primary bladder SCC, with 66% of these patients having pure SCC. Seventy-two percent and 12% of the patients presented with T2-4N0M0 and T2-4N1-3M0 stages, respectively, and 16% presented with synchronous metastases. The most frequent curative treatments were radical surgery and chemotherapy, sequential chemotherapy and radiation therapy, and radical surgery alone. The median (interquartile range, IQR) OS and DFS times were 12.9 months (IQR, 7-32 months) and 9 months (IQR, 5-23 months), respectively. The metastatic, T2-4N0M0, and T2-4N1-3M0 groups differed significantly (P=.001) in terms of median OS and DFS. In a multivariate analysis, impaired creatinine clearance (OS and DFS), clinical stage (OS and DFS), a Karnofsky performance status <80 (OS), and pure SCC histology (OS) were independent and significant adverse prognostic factors. In the patients with nonmetastatic disease, the type of treatment (ie radical surgery with or without adjuvant chemotherapy vs conservative treatment) did not significantly influence OS or DFS (P=.7). CONCLUSIONS The prognosis for SCCB remains poor. The finding that radical cystectomy did not influence DFS or OS in the patients with nonmetastatic disease suggests that conservative treatment is appropriate in this situation.

The palaeoecological history of the Praz-Rodet bog (Swiss Jura) based on pollen, plant macrofossils and testate amoebae (Protozoa)

Stratigraphy, radiocarbon dating and analyses of pollen, plant macrofossils and testate amoebae were used to reconstruct the development and ecology of a small raised bog in a karst-dominated landscape in the Swiss Jura Mountains. Special focus was on past vegetation and on the history of Pinus rotundata in relation to anthropogenic and climatic influences. Testate amoebae were used to reconstruc-t past local soil pH and water-table depth. The inferred development of the Praz-Rodet bog typifies a classic hydroseral tefrestrialization of a small basin. Two features are specific for this site. First, the bog was much wetter than today for a long period; according to our hypothesis, this only changed as a consequence of human activities. Second, two hiatuses are present at the coring location (Younger Dryas--early Preboreal, and 4700-2800 cal. yr BP), the former probably caused by low lake productivity due to cold temperatures and the latter by the erosional activity of the adjacent small river. The date of 2800 cal. yr BP for renewed peat accumulation may be related to climatic change (Subboreal-Subatlantic transition). Pollen indicators failed to show one hiatus: an apparently complete pollen sequence is therefore no guarantee of an uninterrupted sediment accumulation. Evidence of early minor human impact on the vegetation in the Joux Valley dates back to c. 6850 calendar years, congruous with the early Neolithic in the Jura Mountains. The history of Pinuis rotindata appears to be more complex than previously believed. Human activity is clearly responsible for the present abundance of this species, but the tree was naturally present on the bog long before the first evidence of important human disturbance of the site (1500 cal. yr BP). It is suggested that, in karst-dominated landscapes, dense forests growing on mineral soils around raised bogs may significantly reduce summer evapotranspiration by acting as windbreaks. Forest clearance results in increased evapotranspiration, causing a lowering of the water table on the bog and a modification of the vegetation cover. This hypothesis has implications for the management of similar small raised bogs in karst-dominated landscape.

Impact of the early use of immunomodulators or TNF antagonists on bowel damage and surgery in Crohn's disease.

BACKGROUND The impact of early treatment with immunomodulators (IM) and/or TNF antagonists on bowel damage in Crohn's disease (CD) patients is unknown. AIM To assess whether 'early treatment' with IM and/or TNF antagonists, defined as treatment within a 2-year period from the date of CD diagnosis, was associated with development of lesser number of disease complications when compared to 'late treatment', which was defined as treatment initiation after >2 years from the time of CD diagnosis. METHODS Data from the Swiss IBD Cohort Study were analysed. The following outcomes were assessed using Cox proportional hazard modelling: bowel strictures, perianal fistulas, internal fistulas, intestinal surgery, perianal surgery and any of the aforementioned complications. RESULTS The 'early treatment' group of 292 CD patients was compared to the 'late treatment' group of 248 CD patients. We found that 'early treatment' with IM or TNF antagonists alone was associated with reduced risk of bowel strictures [hazard ratio (HR) 0.496, P = 0.004 for IM; HR 0.276, P = 0.018 for TNF antagonists]. Furthermore, 'early treatment' with IM was associated with reduced risk of undergoing intestinal surgery (HR 0.322, P = 0.005), and perianal surgery (HR 0.361, P = 0.042), as well as developing any complication (HR 0.567, P = 0.006). CONCLUSIONS Treatment with immunomodulators or TNF antagonists within the first 2 years of CD diagnosis was associated with reduced risk of developing bowel strictures, when compared to initiating these drugs >2 years after diagnosis. Furthermore, early immunomodulators treatment was associated with reduced risk of intestinal surgery, perianal surgery and any complication.

Single crowns versus conventional fillings for the restoration of root-filled teeth.

BACKGROUND Endodontic treatment involves removal of the dental pulp and its replacement by a root canal filling. Restoration of root filled teeth can be challenging due to structural differences between vital and non-vital root-filled teeth. Direct restoration involves placement of a restorative material e.g. amalgam or composite, directly into the tooth. Indirect restorations consist of cast metal or ceramic (porcelain) crowns. The choice of restoration depends on the amount of remaining tooth, and may influence durability and cost. The decision to use a post and core in addition to the crown is clinician driven. The comparative clinical performance of crowns or conventional fillings used to restore root-filled teeth is unknown. This review updates the original, which was published in 2012. OBJECTIVES To assess the effects of restoration of endodontically treated teeth (with or without post and core) by crowns versus conventional filling materials. SEARCH METHODS We searched the following databases: the Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE via OVID, EMBASE via OVID, CINAHL via EBSCO, LILACS via BIREME. We also searched the reference lists of articles and ongoing trials registries.There were no restrictions regarding language or date of publication. The search is up-to-date as of 26 March 2015. SELECTION CRITERIA Randomised controlled trials (RCTs) or quasi-randomised controlled trials in participants with permanent teeth that have undergone endodontic treatment. Single full coverage crowns compared with any type of filling materials for direct restoration or indirect partial restorations (e.g. inlays and onlays). Comparisons considered the type of post and core used (cast or prefabricated post), if any. DATA COLLECTION AND ANALYSIS Two review authors independently extracted data from the included trial and assessed its risk of bias. We carried out data analysis using the 'treatment as allocated' patient population, expressing estimates of intervention effect for dichotomous data as risk ratios, with 95% confidence intervals (CI). MAIN RESULTS We included one trial, which was judged to be at high risk of performance, detection and attrition bias. The 117 participants with a root-filled, premolar tooth restored with a carbon fibre post, were randomised to either a full coverage metal-ceramic crown or direct adhesive composite restoration. None experienced a catastrophic failure (i.e. when the restoration cannot be repaired), although only 104 teeth were included in the final, three-year assessment. There was no clear difference between the crown and composite group and the composite only group for non-catastrophic failures of the restoration (1/54 versus 3/53; RR 0.33; 95% CI 0.04 to 3.05) or failures of the post (2/54 versus 1/53; RR 1.96; 95% CI 0.18 to 21.01) at three years. The quality of the evidence for these outcomes is very low. There was no evidence available for any of our secondary outcomes: patient satisfaction and quality of life, incidence or recurrence of caries, periodontal health status, and costs. AUTHORS' CONCLUSIONS There is insufficient evidence to assess the effects of crowns compared to conventional fillings for the restoration of root-filled teeth. Until more evidence becomes available, clinicians should continue to base decisions about how to restore root-filled teeth on their own clinical experience, whilst taking into consideration the individual circumstances and preferences of their patients.

Breastfeeding-Associated Hypernatremia: A Systematic Review of the Literature.

There are increasing reports on hypernatremia, a potentially devastating condition, in exclusively breastfed newborn infants. Our purposes were to describe the clinical features of the condition and identify the risk factors for it. We performed a review of the existing literature in the National Library of Medicine database and in the search engine Google Scholar. A total of 115 reports were included in the final analysis. Breastfeeding-associated neonatal hypernatremia was recognized in infants who were ≤ 21 days of age and had ≥ 10% weight loss of birth weight. Cesarean delivery, primiparity, breast anomalies or breastfeeding problems, excessive prepregnancy maternal weight, delayed first breastfeeding, lack of previous breastfeeding experience, and low maternal education level were significantly associated with breastfeeding-associated hypernatremia. In addition to excessive weight loss (≥ 10%), the following clinical findings were observed: poor feeding, poor hydration state, jaundice, excessive body temperature, irritability or lethargy, decreased urine output, and epileptic seizures. In conclusion, the present survey of the literature identifies the following risk factors for breastfeeding-associated neonatal hypernatremia: cesarean delivery, primiparity, breastfeeding problems, excessive maternal body weight, delayed breastfeeding, lack of previous breastfeeding experience, and low maternal education level.

Quality of Life in Swiss Paediatric Inflammatory Bowel Disease Patients: Do Patients and Their Parents Experience Disease in the Same Way?

BACKGROUND AND AIMS Inflammatory bowel diseases (IBDs) may impair quality of life (QoL) in paediatric patients. We aimed to evaluate in a nationwide cohort whether patients experience QoL in a different way when compared with their parents. METHODS Sociodemographic and psychosocial characteristics were prospectively acquired from paediatric patients and their parents included in the Swiss IBD Cohort Study. Disease activity was evaluated by the Paediatric Crohn's Disease Activity Index (PCDAI) and the Paediatric Ulcerative Colitis Activity Index (PUCAI). We assessed QoL using the KIDSCREEN questionnaire. The QoL domains were analysed and compared between children and parents according to type of disease, parents' age, origin, education and marital status. RESULTS We included 110 children and parents (59 Crohn's disease [CD], 45 ulcerative colitis [UC], 6 IBD unclassified [IBDU]). There was no significant difference in QoL between CD and UC/IBDU, whether the disease was active or in remission. Parents perceived overall QoL, as well as 'mood', 'family' and 'friends' domains, lower than the children themselves, independently of their place of birth and education. However, better concordance was found on 'school performance' and 'physical activity' domains. Marital status and age of parents significantly influenced the evaluation of QoL. Mothers and fathers being married or cohabiting perceived significantly lower mood, family and friends domains than their children, whereas mothers living alone had a lower perception of the friends domain; fathers living alone had a lower perception of family and mood subscores. CONCLUSION Parents of Swiss paediatric IBD patients significantly underestimate overall QoL and domains of QoL of their children independently of origin and education.