Blood donor screening: how to decrease the risk of transfusion-transmitted hepatitis B virus?

QUESTIONS UNDER STUDY: The risk of transfusion-transmitted HBV remains significant in Switzerland, where routine screening for hepatitis B virus (HBV) in blood donations relies solely on serological hepatitis B surface antigen (HBsAg) testing. This study was designed to determine the prevalence of anti-hepatitis B core (anti-HBc) and HBV nucleic acid testing (NAT) positive donations in two different Swiss donor populations, to help in deciding whether supplemental testing may bring additional safety to blood products. METHODS: In a first population of donors, 18143 consecutive donations were screened initially for HBsAg, anti-HBc (with one EIA assay) and with HBV NAT in minipools of 24 donations. The screening repeatedly reactive anti-HBc donations were then "confirmed" with two supplemental anti-HBc assays, an anti-hepatitis B surface assay (anti-HBs) and with single donation HBV NAT. In a second population of donors, 4186 consecutive donations were screened initially with two different anti-HBc assays in addition to the mandatory HBsAg screening test. The screening repeatedly reactive donations with at least one anti-HBc assay were tested for anti-HBs. RESULTS: In the first subset of 18143 donations, 17593 (97.0%) were negative for HBsAg, anti-HBc and HBV NAT in minipools. 549 (3.0%) were HBsAg and HBV NAT negative, but repeatedly reactive for anti-HBc. Of these 549 donations, 287 could not be "confirmed" with two additional anti-HBc assays and were negative with an anti-HBs assay, as well as with single donation HBV NAT. Only 211 (1.2% of the total screened donations) were "confirmed" positive with at least one of two supplemental anti-HBc assays. One repeatedly reactive HBsAg donation, from a first-time donor, was confirmed positive for HBsAg and anti-HBc, as well as with single donation HBV NAT. In the second subset of 4186 donations, 4014 (95.9%) were screened negative for HBsAg and for anti-HBc, tested with two independent anti-HBc assays. 172 donations (4.1%) were HBsAg negative but repeatedly reactive with at least one of the two anti-HBc assays. Of these 172 samples, 86 were reactive with the first anti-HBc assay only, 13 were reactive with the second anti-HBc assay only and 73 (1.7% of the total screened donations) were "confirmed" positive with both anti-HBc assays. CONCLUSION: The prevalence of anti-HBc "confirmed" positive donations in the two Swiss blood donor populations studied was low (<2%) and we found only one HBV NAT positive (HBsAg positive) donation among more than 18000. Concerning blood product safety, an increase in the deferral rate of less than 2% of anti-HBc positive, potentially infectious donors, would in our opinion make routine anti-HBc testing of blood donations cost-effective. There is however still a need for more specific assays to avoid an unacceptably high deferral rate of "false" positive donors. In contrast, the introduction of HBV NAT in minipools gives minimal benefit due to the inadequate sensitivity of the assay. It remains to evaluate more extensively the value of individual donation NAT, alone or in addition to anti-HBc, as supplemental testing in the context of several Swiss blood donor populations.

Drug eluting and bare metal stents in people with and without diabetes: collaborative network meta-analysis

Objective To compare the effectiveness and safety of three types of stents (sirolimus eluting, paclitaxel eluting, and bare metal) in people with and without diabetes mellitus. Design Collaborative network meta-analysis. Data sources Electronic databases (Medline, Embase, the Cochrane Central Register of Controlled Trials), relevant websites, reference lists, conference abstracts, reviews, book chapters, and proceedings of advisory panels for the US Food and Drug Administration. Manufacturers and trialists provided additional data. Review methods Network meta-analysis with a mixed treatment comparison method to combine direct within trial comparisons between stents with indirect evidence from other trials while maintaining randomisation. Overall mortality was the primary safety end point, target lesion revascularisation the effectiveness end point. Results 35 trials in 3852 people with diabetes and 10 947 people without diabetes contributed to the analyses. Inconsistency of the network was substantial for overall mortality in people with diabetes and seemed to be related to the duration of dual antiplatelet therapy (P value for interaction 0.02). Restricting the analysis to trials with a duration of dual antiplatelet therapy of six months or more, inconsistency was reduced considerably and hazard ratios for overall mortality were near one for all comparisons in people with diabetes: sirolimus eluting stents compared with bare metal stents 0.88 (95% credibility interval 0.55 to 1.30), paclitaxel eluting stents compared with bare metal stents 0.91 (0.60 to 1.38), and sirolimus eluting stents compared with paclitaxel eluting stents 0.95 (0.63 to 1.43). In people without diabetes, hazard ratios were unaffected by the restriction. Both drug eluting stents were associated with a decrease in revascularisation rates compared with bare metal stents in people both with and without diabetes. Conclusion In trials that specified a duration of dual antiplatelet therapy of six months or more after stent implantation, drug eluting stents seemed safe and effective in people both with and without diabetes.

Effect of GH on human skeletal muscle lipid metabolism in GH deficiency

Adult-onset growth hormone (GH) deficiency (GHD) is associated with insulin resistance and decreased exercise capacity. Intramyocellular lipids (IMCL) depend on training status, diet, and insulin sensitivity. Using magnetic resonance spectroscopy, we studied IMCL content following physical activity (IMCL-depleted) and high-fat diet (IMCL-repleted) in 15 patients with GHD before and after 4 mo of GH replacement therapy (GHRT) and in 11 healthy control subjects. Measurements of insulin resistance and exercise capacity were performed and skeletal muscle biopsies were carried out to assess expression of mRNA of key enzymes involved in skeletal muscle lipid metabolism by real-time PCR and ultrastructure by electron microscopy. Compared with control subjects, patients with GHD showed significantly higher difference between IMCL-depleted and IMCL-repleted. GHRT resulted in an increase in skeletal muscle mRNA expression of IGF-I, hormone-sensitive lipase, and a tendency for an increase in fatty acid binding protein-3. Electron microscopy examination did not reveal significant differences after GHRT. In conclusion, variation of IMCL may be increased in patients with GHD compared with healthy control subjects. Qualitative changes within the skeletal muscle (i.e., an increase in free fatty acids availability from systemic and/or local sources) may contribute to the increase in insulin resistance and possibly to the improvement of exercise capacity after GHRT. The upregulation of IGF-I mRNA suggests a paracrine/autocrine role of IGF-I on skeletal muscle.

Impact of working memory training on memory performance in old-old adults

Memory impairments constitute an increasing objective and subjective problem with advancing age. The aim of the present study was to investigate the impact of working memory training on memory performance. The authors trained a sample of 80-year-old adults twice weekly over a time period of 3 months. Participants were tested on 4 different memory measures before, immediately after, and 1 year after training completion. The authors found overall increased memory performance in the experimental group compared to an active control group immediately after training completion. This increase was especially pronounced in visual working memory performance and, to a smaller degree, also in visual episodic memory. No group differences were found 1 year after training completion. The results indicate that even in old?old adults, brain plasticity is strong enough to result in transfer effects, that is, performance increases in tasks that were not trained during the intervention.

Antiretroviral treatment during pregnancy

OBJECTIVE: Virologic failure of HIV-positive patients is of special concern during pregnancy. We compared virologic failure and the frequency of treatment changes in pregnant and non-pregnant women of the Swiss HIV Cohort Study. METHODS: Using data on 372 pregnancies in 324 women we describe antiretroviral therapy during pregnancy. Pregnant women on HAART at conception (n = 131) were matched to 228 non-pregnant women (interindividual comparison) and to a time period of equal length before and after pregnancy (intraindividual comparison). Women starting HAART during pregnancy (n = 145) were compared with 578 non-pregnant women starting HAART. FINDINGS: The median age at conception was 31 years, 16% (n = 50) were infected through injecting drug use and the median CD4 cell count was 489 cells/microl. In the majority of pregnancies (n = 220, 59%), women had started ART before conception. When ART was started during pregnancy (n = 145, 39%), it was mainly during the second trimester (n = 100, 69%). Two thirds (n = 26) of 35 women starting in the third trimester were diagnosed with HIV during pregnancy. The risk of virologic failure tended to be lower in pregnant than in non-pregnant women [adjusted odds ratio 0.52 (95% confidence interval 0.25-1.09, P = 0.08)], but was similar in the intraindividual comparison (adjusted odds ratio 1.04, 95% confidence interval 0.48-2.28). Women starting HAART during pregnancy changed the treatment less often than non-pregnant women. CONCLUSION: Despite the physiological changes occurring during pregnancy, HIV infected pregnant women are not at higher risk of virologic failure.

Cardiovascular mortality and exposure to extremely low frequency magnetic fields: a cohort study of Swiss railway workers

BACKGROUND: Exposure to intermittent magnetic fields of 16 Hz has been shown to reduce heart rate variability, and decreased heart rate variability predicts cardiovascular mortality. We examined mortality from cardiovascular causes in railway workers exposed to varying degrees to intermittent 16.7 Hz magnetic fields. METHODS: We studied a cohort of 20,141 Swiss railway employees between 1972 and 2002, including highly exposed train drivers (median lifetime exposure 120.5 muT-years), and less or little exposed shunting yard engineers (42.1 muT-years), train attendants (13.3 muT-years) and station masters (5.7 muT-years). During 464,129 person-years of follow up, 5,413 deaths were recorded and 3,594 deaths were attributed to cardio-vascular diseases. We analyzed data using Cox proportional hazards models. RESULTS: For all cardiovascular mortality the hazard ratio compared to station masters was 0.99 (95%CI: 0.91, 1.08) in train drivers, 1.13 (95%CI: 0.98, 1.30) in shunting yard engineers, and 1.09 (95%CI: 1.00, 1.19) in train attendants. Corresponding hazard ratios for arrhythmia related deaths were 1.04 (95%CI: 0.68, 1.59), 0.58 (95%CI: 0.24, 1.37) and 10 (95%CI: 0.87, 1.93) and for acute myocardial infarction 1.00 (95%CI: 0.73, 1.36), 1.56 (95%CI: 1.04, 2.32), and 1.14 (95%CI: 0.85, 1.53). The hazard ratio for arrhythmia related deaths per 100 muT-years of cumulative exposure was 0.94 (95%CI: 0.71, 1.24) and 0.91 (95%CI: 0.75, 1.11) for acute myocardial infarction. CONCLUSION: This study provides evidence against an association between long-term occupational exposure to intermittent 16.7 Hz magnetic fields and cardiovascular mortality.

Comparison between intravitreal and orbital floor triamcinolone acetonide after phacoemulsification in patients with endogenous uveitis

PURPOSE: To compare the effect of intravitreal and orbital floor triamcinolone acetonide (TA) on macular edema, visual outcome, and course of postoperative inflammation after cataract surgery in uveitis patients. DESIGN: Prospective, randomized clinical trial. METHODS: Monocenter study (40 patients) with chronic endogenous uveitis who underwent phacoemulsification with intraocular lens implantation with either 4 mg intravitreal TA (n = 20) or 40 mg orbital floor TA (n = 20). The primary outcome was influence on cystoid macular edema (CME). Secondary outcome measures were best-corrected visual acuity (BCVA), anterior chamber cell grade, laser flare photometry, giant cell deposition, posterior capsule opacification (PCO), and intraocular pressure. RESULTS: Mean central foveal thickness decreased in the intravitreal TA group and increased in the orbital floor TA group (P < .001 at one and three months). CME improved in 50% of patients after intravitreal TA, whereas it was unchanged after orbital floor TA (difference between the groups at three months, P = .049). Mean BCVA (logarithm of the minimal angle of resolution) improved postoperatively (P < .001) from 0.76 and 0.74 to 0.22 and 0.23 in the intravitreal TA and orbital floor TA group, respectively. Anterior chamber cell count at one month was lower in the intravitreal TA than in the orbital floor TA group (P = .02). Laser flare photometry values and giant cell numbers were slightly higher after orbital floor TA than after intravitreal TA. The groups did not differ with respect to PCO rate and ocular hypertension. CONCLUSIONS: The CME improvement and anti-inflammatory effect after intravitreal TA was better than after orbital floor TA injection in cataract surgery in uveitis patients.

Limited value of cyclosporine A for the treatment of patients with uveitis associated with juvenile idiopathic arthritis

AIMS: Juvenile idiopathic arthritis (JIA) is often associated with severe chronic anterior uveitis (CAU), and immunosuppressive therapy may be required. In this study, the value of cyclosporine A (CsA) as monotherapy or as combination therapy for treating uveitis was studied in a large cohort of JIA children. METHODS: Multicentre retrospective study including 82 JIA children (girls n=60) suffering from unilateral or bilateral (n=55) CAU. The indication for CsA was active uveitis, although patients were on topical or systemic corticosteroids, MTX, or other immunosuppressive drugs. RESULTS: Inactivity of uveitis during the entire treatment period (mean 3.9 years) was obtained with CsA monotherapy in 6 of 25 (24%) patients, but more often when CsA was combined with the immunosuppressives (35/72 patients; 48.6%, P=0.037), or MTX (18/37 patients, 48.6%, P=0.065), which had already been given. With CsA (mean dosage 2.9 mg/kg), systemic immunosuppressive drugs and steroids could be reduced by >or=50% (n=19) or topical steroids reduced to

1509 - Johannes Calvin - 2009. Sein Wirken in Kirche und Gesellschaft. Essays zum 500. Geburtstag

Welche bleibenden Impulse haben Johannes Calvin und der Calvinismus Kirche und Gesellschaft bis heute gegeben? Mit dieser Frage beschäftigen sich anlässlich des 500. Geburtstags des Genfer Reformators die Autorinnen und die Autoren der vorliegenden Beiträge anhand ausgewählter theologischer und wirkungsgeschichtlicher Themen. Gleichzeitig bieten sie eine grundlegende und allgemein verständliche Einführung in Calvins Leben und Theologie, in seine kontinuierliche Relevanz für kirchliche, gesellschaftliche und politische Fragen sowie in die Geschichte der Reformation in der Schweiz und weltweit. Sie blenden dabei auch die kritischen Anfragen an Calvin nicht aus. Der im Auftrag des Schweizerischen Evangelischen Kirchenbunds herausgegebene Sammelband ist eine wissenschaftlich fundierte, leserfreundliche Einführung, die Fragestellungen anregt, Perspektiven eröffnet und Austausch ermöglicht. Mit Beiträgen von Philip Benedict, James D. Bratt, Emidio Campi, Eva-Maria Faber, Eric Fuchs, Wulfert de Greef, Christopher L. Elwood, Ulrich H. J. Körtner, Christian Link, Christian Moser, Andrew Pettegree, Christoph Strohm, Mario Turchetti

Further concerns about self-assessment: are medical students aware of their progress in clinical skills during clerkship

Background: Medical students do not accurately self-assess their competence. However, little is known about the awareness of change of competence over time. The aim of this study was to evaluate if students are aware of their progress. Summary of work: Twenty-two fourth year medical students had self- and expert-assessments of their clinical skills in musculoskeletal medicine in an OSCE like station (4 point Likert scale) at the beginning (t0) and end (t1) of their eight weeks clerkship in internal medicine. Thirteen students were assigned to the intervention of a 6x1 hour practical examination course; nine took part in the regular clinical clerkship activities only and served as controls. Summary of results/Conclusions: The intervention students significantly improved their skills (from 2.78 ± 0.36 to 3.30 ± 0.36, p<0.05) in contrast to the control students (from 3.11 ± 0.58 to 2.83 ± 0.49, n.s.). At t0, 19 students, at t1 21 out of 22 students underestimated their competence. Correlations between the change of self- and expert-assessment were r=0.43, p<0.05 (all), r=0.47, n.s. (control) and r=-0.12, n.s. (intervention), respectively. Take-home message: Medical students improving their clinical skills by an interactive course in addition to their regular clerkship activities are not aware of their progress