Utility of serum biomarker indices for staging of hepatic fibrosis before and after venesection in patients with hemochromatosis caused by variants in HFE

Background & Aims Hemochromatosis that is associated with variants in the homeostatic iron regulator gene (HFE) is characterized by intestinal absorption of iron and excessive body and hepatic iron stores; it can lead to hepatic fibrosis and cirrhosis. Fibrosis has been staged by analysis of liver biopsies, but non-invasive staging methods are available. We evaluated the ability of aspartate aminotransferase:platelet ratio index (APRI), the fibrosis-4 (FIB-4) index, and gamma-glutamyl transferase:platelet ratio (GPR) to assess hepatic fibrosis staging in subjects with HFE-associated hemochromatosis, using liver biopsy-staged fibrosis as the reference standard. Methods We performed a retrospective, cross-sectional analysis of 181 subjects with HFE-associated hemochromatosis and hepatic fibrosis staged by biopsy analysis and available serum samples. We calculated APRI, FIB-4, and GPR at diagnosis for all 181 subjects and following venesection therapy in 64 of these subjects (7 subjects had follow-up biopsy analysis). We used area under the receiver operating characteristic curve (AUROC) analysis to assess the relationships between APRI score, FIB-4 score, and GPR and advanced (F3–F4) fibrosis and to select cut-off values. Results Hepatic fibrosis stage correlated with APRI score (r = 0.54; P \u3c .0001), FIB-4 score (r = 0.35; P \u3c .0001), and GPR (r = 0.36, P \u3c .0001). An APRI score above 0.44 identified patients with advanced fibrosis with an AUROC of 0.88, 79.4% sensitivity, 79.4% specificity, and 81% accuracy. A FIB-4 score above 1.1 identified patients with advanced fibrosis with an AUROC of 0.86, 80% sensitivity, 80.3% specificity, and 81% accuracy. A GPR above 0.27 identified patients with advanced fibrosis with an AUROC of 0.76, 67.7% sensitivity, 70.3% specificity, and 69% accuracy. APRI score was significantly more accurate than GPR (P = .05) in detecting advanced fibrosis; there was no difference between APRI and FIB-4. Venesection treatment was associated with significant reductions in APRI (P \u3c .0001) and GPR (P\u3c .001), paralleling fibrosis regression observed in available liver biopsies. Post-venesection APRI identified 87% of subjects with advanced fibrosis that decreased to levels that indicate stage F1–F2 fibrosis. Conclusions In a retrospective study of 181 subjects with HFE-associated hemochromatosis, we found that APRI and FIB-4 scores identified patients with advanced hepatic fibrosis with 81% accuracy. APRI scores might also be used to monitor fibrosis regression following venesection

Long-term morbidity and mortality following bloodstream infection: a systematic literature review

Bloodstream infection results in significant short-term morbidity and mortality. No literature review has studied the long-term outcome following a bloodstream infection. This PROSPERO registered systematic review evaluated studies, which measured the association of a bloodstream infection with long-term morbidity and mortality.Databases were systematically searched for studies of adult patients reporting morbidity and/or mortality one year or more following a bloodstream infection in comparison to a matched cohort without a bloodstream infection.Ten observational studies were included in the final analysis. Five studies assessed only mortality, two assessed morbidity and mortality and three studies assessed morbidity only. The one year mortality ranged from between 8 and 48% for patients with bloodstream infection. The pooled risk ratio of death at one year was significantly higher for patients with bloodstream infection when compared to the matched cohort (RR 4.04 [95% CI 1.84-8.87]).Bloodstream infection was associated with poor long-term outcome measured at one year when compared to matched controls. More evidence is needed to determine if this association is causative

Efficacy of a trivalent influenza vaccine against seasonal strains and against 2009 pandemic H1N1: a randomized, placebo-controlled trial

Background: Before pandemic H1N1 vaccines were available, the potential benefit of existing seasonal trivalent inactivated influenza vaccines (IIV3s) against influenza due to the 2009 pandemic H1N1 influenza strain was investigated, with conflicting results. This study assessed the efficacy of seasonal IIV3s against influenza due to 2008 and 2009 seasonal influenza strains and against the 2009 pandemic H1N1 strain. Methods: This observer-blind, randomized, placebo-controlled study enrolled adults aged 18–64 years during 2008 and 2009 in Australia and New Zealand. Participants were randomized 2:1 to receive IIV3 or placebo. The primary objective was to demonstrate the efficacy of IIV3 against laboratory-confirmed influenza. Participants reporting an influenza-like illness during the period from 14 days after vaccination until 30 November of each study year were tested for influenza by real-time reverse transcription polymerase chain reaction. Results: Over a study period of 2 years, 15,044 participants were enrolled (mean age ± standard deviation: 35.5 ± 14.7 years; 54.4% female). Vaccine efficacy of the 2008 and 2009 IIV3s against influenza due to any strain was 42% (95% confidence interval [CI]: 30%, 52%), whereas vaccine efficacy against influenza due to the vaccine-matched strains was 60% (95% CI: 44%, 72%). Vaccine efficacy of the 2009 IIV3 against influenza due to the 2009 pandemic H1N1 strain was 38% (95% CI: 19%, 53%). No vaccine-related deaths or serious adverse events were reported. Solicited local and systemic adverse events were more frequent in IIV3 recipients than placebo recipients (local: IIV3 74.6% vs placebo 20.4%, p < 0.001; systemic: IIV3 46.6% vs placebo 39.1%, p < 0.001). Conclusions: The 2008 and 2009 IIV3s were efficacious against influenza due to seasonal influenza strains and the 2009 IIV3 demonstrated moderate efficacy against influenza due to the 2009 pandemic H1N1 strain

Health service utilization patterns of primary care patients with osteoarthritis

Contains fulltext : 53455.pdf ( ) (Open Access)BACKGROUND: To assess factors associated with visits to GPs, orthopaedists, and non-physician practitioners of complementary medicine (alternative practitioners) by primary care patients with osteoarthritis (OA). METHODS: Cross-sectional survey among 1250 consecutively addressed patients from 75 primary care practices in Germany. All patients suffered from OA of the knee or hip according to ACR criteria. They received questionnaires collecting sociodemographic data, data about health service utilisation, prescriptions, comorbidities. They also included established instruments as the Arthritis Impact Measurement Scale (AIMS2-SF) to assess disease-specific quality of life and the Patient Health Questionnaire (PHQ-9) to assess depression. Hierarchical stepwise multiple linear regression models were used to reveal significant factors influencing health service utilization. RESULTS: 1021 of 1250 (81.6%) questionnaires were returned. Nonrespondents did not differ from participants. Factors associated with health service use (HSU) varied between providers of care. Not being in a partnership, achieving a high score on the PHQ-9, increased pain severity reflected in the "symptom" scale of the AIMS2-SF, and an increased number of drug prescriptions predicted a high frequency of GP visits. The PHQ-9 score was also a predictor for visits to orthopaedists, as were previous GP contacts, a high score in the "symptom" scale as well as a high score in the "lower limb scale" of the AIMS2-SF. Regarding visits to alternative practitioners, a high score in the AIMS -"social" scale was a positive predictor as older people were less likely to visit them. CONCLUSION: Our results emphasize the need for awareness of psychological factors contributing to the use of health care providers. Addressing the revealed factors associated with HSU appropriately may lead to decreased health care utilization. But further research is needed to assess how this can be done successfully

Work-group emotional climate, emotion management skills, and service attitudes and performance

At the same time that the emotional demands of service work are receiving increasing attention in the literature, academic and popular authors are proposing that person characteristics, namely emotional intelligence or emotional competencies, determine one's effectiveness in dealing with these emotional demands. In this article, we argue for a multi-level perspective of emotions, where the emotional characteristics of organisations and groups affect and are affected by the emotional characteristics of the individuals comprising them. In particular, we develop a theoretical model depicting the dynamic interplay between a workgroups' emotional climate, employee emotion management skills and customer and provider satisfaction in a service setting. © 2008 Australian Human Resources Institute

CpG island methylation in sessile serrated adenomas increases with age, indicating lower risk of malignancy in young patients

Among sessile serrated adenomas (SSAs) with identical histologic features, some never progress whereas others become dysplastic and develop into invasive cancers. Development of the CpG island methylator phenotype (CIMP) is a feature of SSA progression; we examined the CIMP status of 448 SSAs and examined the association with patient outcomes. Overall 190 SSAs were CIMP positive. CIMP positivity was associated with older patient age (

A Decrease in Maternal Iron Levels Is the Predominant Factor Suppressing Hepcidin during Pregnancy in Mice

In order to supply adequate iron during pregnancy, the levels of the iron regulatory hormone hepcidin in the maternal circulation are suppressed, thereby increasing dietary iron absorption and storage iron release. Whether this decrease in maternal hepcidin is caused by changes in factors known to regulate hepcidin expression, or by other unidentified pregnancy factors, is not known. To investigate this, we examined iron parameters during pregnancy in mice. We observed that hepatic iron stores and transferrin saturation, both established regulators of hepcidin production, were decreased in mid and late pregnancy in normal and iron loaded dams, indicating an increase in iron utilization. This can be explained by a significant increase in maternal erythropoiesis, a known suppressor of hepcidin production, by mid-pregnancy, as indicated by an elevation in circulating erythropoietin and an increase in spleen size and splenic iron uptake. Iron utilization increased further in late pregnancy due to elevated fetal iron demand. By increasing maternal iron levels in late gestation, we were able to stimulate the expression of the gene encoding hepcidin, suggesting that the iron status of the mother is the predominant factor influencing hepcidin levels during pregnancy. Our data indicate that pregnancy-induced hepcidin suppression likely occurs because of reductions in maternal iron reserves due to increased iron requirements, which predominantly reflect stimulated erythropoiesis in mid-gestation and increased fetal iron requirements in late gestation, and that there is no need to invoke other factors, including novel pregnancy factor(s), to explain these changes

Measuring exposure to S. japonicum in China. I. Activity diaries to assess water contact and comparison to other measures

We introduce a new method, activity diaries, in order to evaluate human water contact among fishing communities in an area moderately endemic for Schistosoma japonicum in the Dongting Lake region of Southern China. Two hundred and forty-nine subjects (76% male) were followed prospectively over a 9-month-period in order to verify exposure and reinfection. Exposure was determined crudely with questionnaires, direct 12-h water observations, and more precisely with activity diaries and an adjusted exposure model which took into account the time of day, the duration of contact and the percent body surface area in contact with water. Cohort subjects filled in activity diaries for an average of 85 days as compared with 2 days for the direct water observations. The typical unadjusted mean daily water contact (duration) based on the activity diaries was 53 min with 62% of this time spent in fishing. In contrast, the direct water observations revealed an average daily duration of 149 min with 53% of the time spent in fishing. Human water contact patterns (min/day) by site, activity and body part exposed were examined with the activity diaries. Individuals in the 36-49-year-old age range had the highest degree of water contact. Most of this daily contact occurred by males on the hands (mean±S.D.; 83.53±67.80 min/day) while fishing (mean±S.D.; 87.84±68.88 min/day) on the lake (mean±S.D.; 85.98±69.90 min/day). There was a strong positive log correlation (r=0.95) between the crude and adjusted (based on our derived exposure model) diary outcomes for the entire study sample, however, at higher exposure levels this relationship was differentially weaker (r=0.70). Results from this study suggest that current methods used in evaluating schistosomiasis exposure in China may overestimate and bias measures of the risk of infection. Activity diaries adjusted for the time of day, duration and the percent body surface area exposed are cost-effective and practical instruments to accurately quantify human exposure in the vast lake regions of Southern China where most of the endemic schistosomiasis japonica occurs. Copyright (C) 1998 Elsevier Science B.V

The presence of knockdown resistance mutations reduces male mating competitiveness in the major arbovirus vector, Aedes aegypti.

BackgroundThe development of insecticide resistance in mosquitoes can have pleiotropic effects on key behaviours such as mating competition and host-location. Documenting these effects is crucial for understanding the dynamics and costs of insecticide resistance and may give researchers an evidence base for promoting vector control programs that aim to restore or conserve insecticide susceptibility.Methods and findingsWe evaluated changes in behaviour in a backcrossed strain of Aedes aegypti, homozygous for two knockdown resistance (kdr) mutations (V1016G and S989P) isolated in an otherwise fully susceptible genetic background. We compared biting activity, host location behaviours, wing beat frequency (WBF) and mating competition between the backcrossed strain, and the fully susceptible and resistant parental strains from which it was derived. The presence of the homozygous kdr mutations did not have significant effects on blood avidity, the time to locate a host, or WBF in females. There was, however, a significant reduction in mean WBF in males and a significant reduction in estimated male mating success (17.3%), associated with the isolated kdr genotype.ConclusionsOur results demonstrate a cost of insecticide resistance associated with an isolated kdr genotype and manifest as a reduction in male mating success. While there was no recorded difference in WBF between the females of our strains, the significant reduction in male WBF recorded in our backcrossed strain might contribute to mate-recognition and mating disruption. These consequences of resistance evolution, especially when combined with other pleiotropic fitness costs that have been previously described, may encourage reversion to susceptibility in the absence of insecticide selection pressures. This offers justification for the implementation of insecticide resistance management strategies based on the rotation or alternation of different insecticide classes in space and time

Measuring exposure to S. japonicum in China. II. Activity diaries, pathways to infection and immunological correlates

In this study we examine the pathways to schistosomiasis exposure and infection among residents residing on two islands (large, Qingshan; small, Niangashan) in the Dongting Lake region (Hunan province) of China. An exposure model, based on activity diaries, was used to quantify an individual's square-metre-minute (sq.m.min) daily water contact. Subjects living on the small island had a significantly higher (P=0.0002) degree of exposure (mean±S.D., 13.2±11.0 sq.m.min) than individuals dwelling on the large island (mean±S.D., 5.5±7.1 sq.m.min). Participants identified as stool egg positive (mean±S.D., 8.3±10.4 sq.m.min) had higher exposures than for those never treated (mean±S.D., 2.2±3.4 sq.m.min) for schistosomiasis, and these high exposures rose steadily to peak at 35-49 years of age and decline after age 50. This exposure pattern differs markedly from those reported for African or South American schistosomiasis. The majority of human water contact occurs on the lake. Egg-positive subjects reported significantly higher (