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Background & Aims Based on positive results from small single center studies, granulocyte-colony stimulating factor (G-CSF) is being widely used for the treatment of patients with acute-on-chronic liver failure (ACLF). Herein, we aimed to evaluate the safety and efficacy of G-CSF in patients with ACLF. Methods In this multicenter, prospective, controlled, open-label phase II study, 176 patients with ACLF (EASL-CLIF criteria) were randomized to receive G-CSF (5 μg/kg daily for the first 5 days and every third day thereafter until day 26) plus standard medical therapy (SMT) (n = 88) or SMT alone. The primary efficacy endpoint was 90-day transplant-free survival analyzed by Cox regression modeling. The key secondary endpoints were overall and transplant-free survival after 360 days, the development of ACLF-related complications, and the course of liver function scores during the entire observation period. Results Patients treated with G-CSF had a 90-day transplant-free survival rate of 34.1% compared to 37.5% in the SMT group (hazard ratio [HR] 1.05; 95% CI 0.711–1.551; p = 0.805). Transplant-free and overall survival at 360 days did not differ between the 2 arms (HR 0.998; 95% CI 0.697–1.430; p = 0.992 and HR 1.058; 95% CI 0.727–1.548; p = 0.768, respectively). G-CSF did not improve liver function scores, the occurrence of infections, or survival in subgroups of patients without infections, with alcohol-related ACLF, or with ACLF defined by the APASL criteria. Sixty-one serious adverse events were reported in the G-CSF+SMT group and 57 were reported in the SMT group. In total, 7 drug-related serious adverse reactions occurred in the G-CSF group. The study was prematurely terminated due to futility after conditional power calculation. Conclusions In contrast to previous findings, G-CSF had no significant beneficial effect on patients with ACLF in this multicenter controlled trial, which suggests that it should not be used as a standard treatment for ACLF. ClinicalTrials.gov number NCT02669680 Lay summary Granulocyte-colony stimulating factor was considered as a novel treatment for acute-on-chronic liver failure (ACLF). We performed the first randomized, multicenter, controlled phase II trial, which showed that G-CSF did not improve survival or other clinical endpoints in patients with ACLF. Therefore, G-CSF should not be used to treat liver disease outside clinical studies.

Whether α4β2 nicotinic acetylcholine receptor (α4β2-nAChR) expression is reduced in early Alzheimer’s disease is controversial. Using (-)-[18F]Flubatine PET, Sabri, Meyer et al. report α4β2-nAChR deficiency in mild Alzheimer’s dementia, especially within the basal forebrain-cortical and septohippocampal cholinergic projections. Reduced α4β2-nAChR availability correlates with impaired episodic memory and executive function/working memory., In early Alzheimer’s dementia, there is a need for PET biomarkers of disease progression with close associations to cognitive dysfunction that may aid to predict further cognitive decline and neurodegeneration. Amyloid biomarkers are not suitable for that purpose. The α4β2 nicotinic acetylcholine receptors (α4β2-nAChRs) are widely abundant in the human brain. As neuromodulators they play an important role in cognitive functions such as attention, learning and memory. Post-mortem studies reported lower expression of α4β2-nAChRs in more advanced Alzheimer’s dementia. However, there is ongoing controversy whether α4β2-nAChRs are reduced in early Alzheimer’s dementia. Therefore, using the recently developed α4β2-nAChR-specific radioligand (−)-18F-flubatine and PET, we aimed to quantify the α4β2-nAChR availability and its relationship to specific cognitive dysfunction in mild Alzheimer’s dementia. Fourteen non-smoking patients with mild Alzheimer’s dementia, drug-naïve for cholinesterase therapy, were compared with 15 non-smoking healthy controls matched for age, sex and education by applying (−)-18F-flubatine PET together with a neuropsychological test battery. The one-tissue compartment model and Logan plot method with arterial input function were used for kinetic analysis to obtain the total distribution volume (VT) as the primary, and the specific binding part of the distribution volume (VS) as the secondary quantitative outcome measure of α4β2-nAChR availability. VS was determined by using a pseudo-reference region. Correlations between VT within relevant brain regions and Z-scores of five cognitive functions (episodic memory, executive function/working memory, attention, language, visuospatial function) were calculated. VT (and VS) were applied for between-group comparisons. Volume of interest and statistical parametric mapping analyses were carried out. Analyses revealed that in patients with mild Alzheimer’s dementia compared to healthy controls, there was significantly lower VT, especially within the hippocampus, fronto-temporal cortices, and basal forebrain, which was similar to comparisons of VS. VT decline in Alzheimer’s dementia was associated with distinct domains of impaired cognitive functioning, especially episodic memory and executive function/working memory. Using (−)-18F-flubatine PET in patients with mild Alzheimer’s dementia, we show for the first time a cholinergic α4β2-nAChR deficiency mainly present within the basal forebrain-cortical and septohippocampal cholinergic projections and a relationship between lower α4β2-nAChR availability and impairment of distinct cognitive domains, notably episodic memory and executive function/working memory. This shows the potential of (−)-18F-flubatine as PET biomarker of cholinergic α4β2-nAChR dysfunction and specific cognitive decline. Thus, if validated by longitudinal PET studies, (−)-18F-flubatine might become a PET biomarker of progression of neurodegeneration in Alzheimer’s dementia.

Zusammenfassung Hintergrund : Der „Food Allergy Quality of Life Questionnaire – Adult Form“ (FAQLQ-AF) ist der erste frei verfugbare Fragebogen zur Erfassung der gesundheitsbezogenen Lebensqualitat (health-related quality of life; HRQL) bei Erwachsenen mit Nahrungsmittelallergie (NMA). Wir prasentieren Daten zur Validierung der deutschsprachigen Version sowie zur HRQL bei Patienten mit birkenpollenassoziierter NMA. Patienten und Methodik : Die niederlandische Version des FAQLQ-AF (Skala 1–7, kein – extremer Einfluss) wurde ins Deutsche ubersetzt. Dreiundsiebzig Patienten mit anamnestisch vorhandener birkenpollenassoziierter NMA (52 Frauen, medianes Alter 43 Jahre) beantworteten Fragen zu Auslosern und Symptomen der NMA sowie den FAQLQ-AF. Konstruktvaliditat, diskriminative Validitat sowie interne Konsistenz des FAQLQ-AF wurden gemessen. Ergebnisse : Haufigste auslosende Nahrungsmittel waren: Apfel (78 %), Haselnusse (75 %), Sojadrinks (55 %) und Karotten (52 %). Ausschlieslich ein orales Allergiesyndrom (OAS) gaben 30 % an, 64 % ein OAS mit weiteren Symptomen, 6 % nur weitere Nicht-OAS-Symptome. Der deutschsprachige FAQLQ-AF zeigte eine sehr gute Konstruktvaliditat (Korrelation mit food allergy independent measure [FAIM]: r = 0,81; p < 0,001) und eine exzellente interne Konsistenz (Cronbachs α = 0,98). Der mittlere FAQL-AF Gesamtwert lag bei 3,7 (± 1,6). Der deutschsprachige FAQLQ-AF zeigte bei Frauen, alteren Patienten und solchen mit vielfaltigen relevanten Nahrungsmittelallergenen eine starkere Beeintrachtigung der HRQL. Schlussfolgerung : Der deutschsprachige FAQLQ-AF ist ein zuverlassiges und valides Messinstrument um die HRQL bei Patienten mit birkenpollenassoziierter NMA zu messen.

Background Right ventricular (RV) dysfunction predicts adverse outcome in peripartum cardiomyopathy (PPCM). We recently demonstrated beneficial effects associated with the prolactin release inhibitor bromocriptine at different doses when added to standard heart failure therapy in PPCM. Here, we evaluated for the first time the therapeutic potential of bromocriptine particularly in PPCM patients with RV involvement. Methods In this study, 40 patients with PPCM were included, of whom 24 patients had reduced RV ejection fraction (RVEF

Summary Background The “Food Allergy Quality of Life Questionnaire – Adult Form” (FAQLQ-AF) is the first freely available questionnaire for the assessment of health-related quality of life (HRQL) in adults with food allergy (FA). We present validation data for the German version as well as data on HRQL in patients with birch pollen-associated FA. Patients and Methods The Dutch FAQLQ-AF (scale from 1–7, no impairment – maximum impairment) was translated into German. Subsequently, 73 consecutive patients with a history of birch pollen-associated FA (52 women, median age 43 years) were surveyed using questions regarding triggers and symptoms of their FA as well as questions contained in the FAQLQ-AF. Construct validity, internal consistency, and discriminative ability were analyzed. Results The foods most frequently reported to elicit allergic reactions included apple (78 %), hazelnut (75 %), soy drinks (55 %), and carrot (52 %). Thirty percent of patients exclusively reported symptoms consistent with oral allergy syndrome (OAS). Sixty-four percent reported OAS combined with systemic symptoms, and only 6 % were exclusively affected by non-OAS symptoms. The German FAQLQ-AF showed good construct validity (correlation with the food allergy-independent measure: r = 0.81; p

Aims An anti-angiogenic cleaved prolactin fragment is considered causal for peripartum cardiomyopathy (PPCM). Experimental and first clinical observations suggested beneficial effects of the prolactin release inhibitor bromocriptine in PPCM. ................................................................................................................................................................................................... Methods and results In this multicentre trial, 63 PPCM patients with left ventricular ejection fraction (LVEF) < _35% were randomly assigned to short-term (1W: bromocriptine, 2.5mg, 7 days) or long-term bromocriptine treatment (8W: 5 mg for 2weeks followed by 2.5mg for 6weeks) in addition to standard heart failure therapy. Primary end point was LVEF change (delta) from baseline to 6months assessed bymagnetic resonance imaging. Bromocriptinewas well tolerated. Left ventricular ejection fraction increased from 28± 10% to 49± 12% with a delta-LVEF ofþ21± 11% in the 1W-group, and from 27± 10% to 51 ± 10% with a delta-LVEF ofþ24± 11% in the 8W-group (delta-LVEF: P = 0.381). Full-recovery (LVEF > _50%) was present in 52% of the 1W- and in 68% of the 8W-groupwith no differences in secondary end points between both groups (hospitalizations for heart failure: 1W: 9.7% vs. 8W: 6.5%, P = 0.651). The risk within the 8W-group to fail full-recovery after 6months tended to be lower.No patient in the study needed heart transplantation, LV assist device or died. ................................................................................................................................................................................................... Conclusion Bromocriptine treatment was associated with high rate of full LV-recovery and low morbidity and mortality in PPCM patients compared with other PPCM cohorts not treated with bromocriptine. No significant differences were observed between 1W and 8W treatment suggesting that 1-week addition of bromocriptine to standard heart failure treatment is already beneficial with a trend for better full-recovery in the 8W group.

Background Conflicting results exist on the effect of allergen immunotherapy (AIT) on pollen-related food allergy. We aimed to investigate the efficacy of one-year AIT with the folding variant (FV) of recombinant (r) Bet v 1 on birch-related soya allergy. Methods Of 138 subjects with Bet v 1 sensitization, 82 were positive at double-blind placebo-controlled food challenge (DBPCFC) with soya. A total of 56 of 82 were randomized in the ratio of 2:1 (active: placebo). Per-protocol population (PPP) had received ≥150 μg of allergen or placebo preparation. Outcome measures: lowest observed adverse effect levels (LOAEL), postinterventional occurrence of objective signs (objS) at any dose level, sIgE/IgG4 against Bet v 1 and Gly m 4. Between-group changes were investigated (ancova, Mann–Whitney U-test, Fisher exact test). Results Baseline characteristics including LOAELs were comparable in both groups with objS and subjS occurring in 82% and 95% of active (n = 38) vs 78% and 83% of placebo group (n = 18). After AIT, objS occurred in 24% and 47%, respectively. LOAEL group differences showed a beneficial tendency (P = 0.081) for LOAELobjective in PPP (30 active, 15 placebo). sIgG4 raised only in active group (Bet v 1: P = 0.054, Gly m 4: P = 0.037), and no relevant changes occurred for sIgE. Only 56% of the intended sample size was recruited. Conclusion For the first time, we present data on the effect of rBet v 1-FV on birch-related soya allergy. rBet v 1-FV AIT induced significant immunogenic effects. Clinical assessment showed a tendency in favour of the active group but did not reach statistical significance.

cope : The BASALIT clinical trial (EudraCT 2009-011737-27) investigated efficacy of birch allergen immunotherapy on lowest observed adverse effect levels (LOAEL) after soy food challenge in patients with birch-associated and Gly m 4 allergen-mediated soy allergy. Thus, consistently stable Gly m 4 levels were required in standardised challenge meals. Methods and results : Soy meal included soy protein isolate (SPI, 88% total protein). A Gly m 4-specific ELISA was developed and validated. 6 SPI and 24 meal batches were analysed for Gly m 4. (Repeated-measures) analyses of variance were done to identify potential changes between batches/ in time. Gly m 4 was below the ELISA detection limit (2 ng/ml) in placebo batches. With

Background: Multicentre trials investigating food allergies by double blind placebo controlled food challenges (DBPCFC) need standardized procedures, challenge meals and evaluation criteria. We aimed at developing a standardized approach for identifying patients with birch related soy allergy by means of DBPCFC to soy, including determination of threshold levels, in a multicentre setting. Methods: Microbiologically stable soy challenge meals were composed of protein isolate with consistent Gly m 4 levels. Patients sensitized to main birch allergen Bet v 1 and concomitant sensitization to its soy homologue Gly m 4 underwent DBPCFC. Outcome was defined according to presence and/or absence of ten objective signs and intensity of eight subjective symptoms as measured by visual analogue scale (VAS). Results: 138 adult subjects (63.8% female, mean age 38 years) underwent DBPCFC. Challenge meals and defined evaluation criteria showed good applicability in all centres involved. 45.7% presented with objective signs and 65.2% with subjective symptoms at soy challenge. Placebo challenge meals elicited non-cardiovascular objective signs in 11.6%. In 82 (59.4%) subjects DBPCFC was judged as positive. 70.7% of DPBCFC+ showed objective signs and 85.4% subjective symptoms at soy challenge. Subjective symptoms to soy challenge meal in DBPCFC+ subjects started at significantly lower dose levels than objective signs (p

Abstract. Introduction: Feelings of stigmatization can strongly influence quality of life in individuals with chronic skin diseases. The Short-Form of the Questionnaire on Experience with Skin Complaints (SF-QES) differentiates four factors of stigmatization: self-esteem and retreat, experienced refusal, concealment, and composure. The current study aimed to investigate the construct validity of the SF-QES. Method: The analysis was based on the complete SF-QES records of a clinical psoriasis trial, which yielded 1,005 records at baseline, 1,010 records at the end of therapy, and 885 and 827 records, respectively, at two follow-ups. Factor analyses and corresponding structural equation models (SEMs) using robust maximum likelihood estimation (RML) were applied. Additionally, the responsiveness of the scales to judgments of treatment success and two different interventions were compared. Results: The factor analyses provided results that widely agreed with the supposed four factors. SEM, however, showed moderately insufficient fit for this model, but supported five factors and the discrimination between affected self-esteem and retreat. The retreat scale was clearly most responsive to treatment success and intervention type. Conclusion: The construct validity of the SF-QES was largely supported, but the factor retreat should be separated from affected self-esteem and is most sensitive to physical intervention.

Background Hepatocellular carcinoma (HCC) is the fifth most common global cancer. When HCC is diagnosed early, interventions such as percutaneous ethanol injection (PEI), percutaneous acetic acid injection (PAI), or radiofrequency (thermal) ablation (RF(T)A) may have curative potential and represent less invasive alternatives to surgery. Objectives To evaluate the beneficial and harmful effects of PEI or PAI in adults with early HCC defined according to the Milan criteria, that is, one cancer nodule up to 5 cm in diameter or up to three cancer nodules up to 3 cm in diameter compared with no intervention, sham intervention, each other, other percutaneous interventions, or surgery. Search methods We searched the Cochrane Hepato-Biliary Group Controlled Trials Register (July 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 6), MEDLINE (1946 to July 2014), EMBASE (1976 to July 2014), and Science Citation Index Expanded (1900 to July 2014). We handsearched meeting abstracts of six oncological and hepatological societies and references of articles to July 2014. We contacted researchers in the field. Selection criteria We considered randomised clinical trials comparing PEI or PAI versus no intervention, sham intervention, each other, other percutaneous interventions, or surgery for the treatment of early HCC regardless of blinding, publication status, or language. We excluded studies comparing RFA or combination of different interventions as such interventions have been or will be addressed in other Cochrane Hepato-Biliary Group systematic reviews. Data collection and analysis Two review authors independently selected trials for inclusion, and extracted and analysed data. We calculated the hazard ratios (HR) for median overall survival and recurrence-free survival using the Cox regression model with Parmar's method. We reported type and number of adverse events descriptively. We assessed risk of bias by The Cochrane Collaboration domains to reduce systematic errors and risk of play of chance by trial sequential analysis to reduce random errors. We assessed the methodological quality with GRADE. Main results We identified three randomised trials with 261 participants for inclusion. The risk of bias was low in one and high in two trials. Two of the randomised trials compared PEI versus PAI; we included 185 participants in the analysis. The overall survival (HR 1.47; 95% confidence interval (CI) 0.68 to 3.19) and recurrence-free survival (HR 1.42; 95% CI 0.68 to 2.94) were not statistically significantly different between the intervention groups of the two trials. Trial sequential analysis for the comparison PEI versus PAI including two trials revealed that the number of participants that were included in the trials were insufficient in order to judge a relative risk reduction of 20%. Data on the duration of hospital stay were available from one trial for the comparison PEI versus PAI showing a significantly shorter hospital stay for the participants treated with PEI (mean 1.7 days; range 2 to 3 days) versus PAI (mean 2.2 days; range 2 to 5 days). Quality of life was not reported. There were only mild adverse events in participants treated with either PEI or PAI such as transient fever, flushing, and local pain. One randomised trial compared PEI versus surgery; we included 76 participants in the analyses. There was no significant difference in the overall survival (HR 1.57; 95% CI 0.53 to 4.61) and recurrence-free survival (HR 1.35; 95% CI 0.69 to 2.63). No serious adverse events were reported in the PEI group while three postoperative deaths occurred in the surgery group. In addition to the three randomised trials, we identified one quasi-randomised study comparing PEI versus PAI. Due to methodological flaws of the study, we extracted only the data on adverse events and presented them in a narrative way. We found no randomised trials that compared PEI or PAI versus no intervention, best supportive care, sham intervention, or other percutaneous local ablative therapies excluding RFTA. We found also no randomised clinical trials that compared PAI versus other interventional treatments or surgery. We identified two ongoing randomised clinical trials. One of these two trials compares PEI versus surgery and the other PEI versus transarterial chemoembolization. To date, it is unclear whether the trials will be eligible for inclusion in this meta-analysis as the data are not yet available. This review will not be updated until new randomised clinical trials are published and can be used for analysis. Authors' conclusions PEI versus PAI did not differ significantly regarding benefits and harms in people with early HCC, but the two included trials had only a limited number of participants and one trial was judged a high risk of bias. Thus, the current evidence precludes us from making any firm conclusions. There was also insufficient evidence to determine whether PEI versus surgery (segmental liver resection) was more effective, because conclusions were based on a single randomised trial. While some data from this single trial suggested that PEI was safer, the high risk of bias and the lack of any confirmatory evidence make a reliable assessment impossible. We found no trials assessing PEI or PAI versus no intervention, best supportive care, or sham intervention. There is a need for more randomised clinical trials assessing interventions for people with early stage HCC. Such trials should be conducted with low risks of systematic errors and random errors.

Objective: To determine whether the Bath Ankylosing Spondylitis Functional Index (BASFI) is applicable in older patients with ankylosing spondylitis and whether it shows major differences between younger and older patients with ankylosing spondylitis. Design: BASFI total scores and every BASFI item of 202 patients with ankylosing spondylitis aged ≥60 yr (group A) and 267 patients with ankylosing spondylitis aged ≤40 yr (group B) were calculated. The results were compared with the results of the Health Assessment Questionnaire for the Spondyloarthropathies. Results: The BASFI scores had a median of 4.2 in group A and 2.6 in group B. Marked differences between the age groups were found for every item of the BASFI. Internal consistency was high in both groups. The Spearman correlation coefficient between BASFI and the Health Assessment Questionnaire for the Spondyloarthropathies was r s(A) = 0.83 in group A and r s(B) = 0.78 in group B. Conclusion: The data suggest that the BASFI is also applicable to older patients experiencing AS. There is a significant difference in the BASFI score between younger and older patients with ankylosing spondylitis.

Fragestellung Der Einsatz des 36 Item Short-Form Health Survey (SF-36) in Kliniken ist problematisch, da einige Formulierungen in dem Fragebogen explizit auf den hauslichen bzw. beruflichen Kontext bezogen und damit in einer Klinik sehr unpassend sind. Um diesem bereits bekannten Problem zu begegnen, entfernten wir aus drei einleitenden Formulierungen die fur einen Klinikkontext klar unpassenden Ausdrucke-insgesamt 23 Worter-und erstellten so eine modifizierte Version des SF-36, den SF-36m. In der vorliegenden Arbeit werden in erster Linie zwei Fragen untersucht: Inwieweit beseitigt die angedeutete Modifikation die beschriebenen Probleme bei Applikation des SF-36 in Kliniken, und inwieweit sind SF-36 und SF-36m noch aquivalent?

Material and Methods: Patients were randomized 1:1:1 to receive either SOF+RBV for 16 or 24 weeks or SOF+PEG/RBV for 12 weeks and stratified by HCV genotype and cirrhosis status. All patients received SOF 400mg daily and RBV 1000–1200mg in a divided daily dose. PEG was administered as 180mg weekly injection. The primary end point was sustained virologic response 12 weeks after treatment (SVR12). Results: Of 592 patients randomized and treated, 92% had GT3 HCV, 67% were male, 84% white, 53% treatment experienced, 62% had non-CC IL28B genotypes, and 37% had cirrhosis. GT2 treatmentexperienced patients with cirrhosis had high SVR12 rates in all treatment groups: 87% of those receiving SOF+RBV for 16 weeks, 100% of those receiving SOF+RBV for 24 weeks, and 94% of those receiving SOF+PEG/RBV for 12 weeks. Among GT3 patients, SVR12 rates were highest in those receiving SOF+PEG/RBV for 12 weeks (93%) as compared to SOF+RBV for 24 (84%, p 0.008) or 16 weeks (71%, p < 0.001) (Table). The most common adverse events in all arms were fatigue, headache, insomnia, and nausea. Overall, 6 (1%) patients discontinued treatment due to adverse events; one of them was treated with SOF+PEG/RBV.

Background Hepatocellular carcinoma is the fifth most common cancer worldwide. Percutaneous interventional therapies, such as radiofrequency (thermal) ablation (RFA), have been developed for early hepatocellular carcinoma. RFA competes with other interventional techniques such as percutaneous ethanol injection, surgical resection, and liver transplantation. The potential benefits and harms of RFA compared with placebo, no intervention, chemotherapy, hepatic resection, liver transplantation, or other interventions are unclear. Objectives To assess the beneficial and harmful effects of RFA versus placebo, no intervention, or any other therapeutic approach in patients with hepatocellular carcinoma. Search methods We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and ISI Web of Science to September 2012. We handsearched meeting abstracts from ASCO, ESMO, AASLD, EASL, APASL, and references of articles. We also contacted researchers in the field (last search September 2012). Selection criteria We considered for inclusion randomised clinical trials investigating the effects of RFA versus placebo, no intervention, or any other therapeutic approach on hepatocellular carcinoma patients regardless of blinding, language, and publication status. Data collection and analysis Two review authors independently performed the selection of trials, assessment of risk of bias, and data extraction. We contacted principal investigators for missing information. We analysed hazard ratios (HR) as relevant effect measures for overall survival, two-year survival, event-free survival, and local recurrences with 95% confidence intervals (CI). In addition, we analysed dichotomous survival outcomes using risk ratios (RR). We used trial sequential analysis to control the risk of random errors ('play of chance'). Main results We identified no trials comparing RFA versus placebo, no intervention, or liver transplantation. We identified and included 11 randomised clinical trials with 1819 participants that included four comparisons: RFA versus hepatic resection (three trials, 578 participants); RFA versus percutaneous ethanol injection (six trials, 1088 participants) including one three-armed trial that also investigated RFA versus acetic acid injection; RFA versus microwave ablation (one trial, 72 participants); and RFA versus laser ablation (one trial, 81 participants). Ten of the eleven included trials reported on the primary outcome of this review, overall survival. Rates of major complications or procedure-related deaths were reported in 10 trials. The overall risk of bias was considered low in five trials and high in six trials. For a subgroup analysis, we included only low risk of bias trials. Regarding the comparison RFA versus hepatic resection, there was moderate-quality evidence from two low risk of bias trials that hepatic resection seems more effective than RFA regarding overall survival (HR 0.56; 95% CI 0.40 to 0.78) and two-year survival (HR 0.38; 95% CI 0.17 to 0.84). However, if we included a third trial with high risk of bias, the difference became insignificant (overall survival: HR 0.71; 95% CI 0.44 to 1.15). With regards to the outcomes event-free survival and local progression, hepatic resection also yielded better results than RFA. However, the number of complications was higher in surgically treated participants (odds ratio (OR) 8.24; 95% CI 2.12 to 31.95). RFA seemed superior to percutaneous ethanol or acetic acid injection regarding overall survival (HR 1.64; 95% CI 1.31 to 2.07). The RR for mortality was also in favour of RFA, but did not reach statistical significance (150/490 (30.6%) people in the percutaneous ethanol or acetic acid group versus 119/496 (24.0%) people in the RFA group; RR 1.76; 95% CI 0.97 to 3.22). The proportion of adverse events did not differ significantly between RFA and percutaneous ethanol or acetic acid injection (HR 0.70; 95% CI 0.33 to 1.48). Trial sequential analyses revealed that the number of participants in the included trials was insufficient and that more trials are needed to assess the effects of RFA versus other interventions. Authors' conclusions The effects of RFA versus no intervention, chemotherapeutic treatment, or liver transplantation are unknown. We found moderate-quality evidence that hepatic resection is superior to RFA regarding survival. However, RFA might be associated with fewer complications and a shorter hospital stay than hepatic resection. We found moderate-quality evidence showing that RFA seems superior to percutaneous ethanol injection regarding survival. There were too sparse data to recommend or refute ablation achieved by techniques other than RFA. More randomised clinical trials with low risk of bias and low risks of random errors assessing the effect of RFA are needed.

To evaluate the effect of combination of ranibizumab and laser photocoagulation to peripheral retinal areas of nonperfusion in patients with non-ischemic central retinal vein occlusion (CRVO) without neovascularizations. This prospective, proof of concept study randomized 22 CRVO patients into two arms. The RL group (ranibizumab + laser; n = 10) received ranibizumab with additive laser photocoagulation; the control R group (n = 12) was treated with ranibizumab only. All patients received three initial monthly ranibizumab injections followed by PRN regimen. Changes in best corrected visual acuity (BCVA) and in central retinal thickness (CRT) were documented over 6 months. Median of BCVA improved in the RL group from 65 ETDRS letters (interquartile range IQR = 10 letters) at baseline to 70 (IQR = 23.2) letters at month 6. In the control group BCVA remained stable [baseline: 61 (IQR = 19.5) and month 6: 61 (IQR = 22) letters]. CRT decreased between baseline and final visit in the RL group from 547 (IQR = 513) μm to 246.5 (IQR = 346.3) μm, and in the control group from 637.5 (IQR = 344) μm to 423 (IQR = 737) μm. More pronounced improvements in BCVA were seen in the RL group (medians = 14 vs. 6.5 letters) although the observed group differences were not statistically significant due to small samples. The selective laser photocoagulation of peripheral areas of nonperfusion seems to lead to additional visual improvement in patients with CRVO. A larger replication trial is necessary to confirm the results of this proof of concept study.

The pathogenetic role of the central serotonin transporters (SERT) in obsessive-compulsive disorder (OCD) has been investigated in vivo by positron emission tomography (PET) or single-photon emission computed tomography (SPECT) studies with inconsistent results. This might reflect methodological differences but possibly also the pathophysiological heterogeneity of the disorder, i.e. the age at onset of OCD. The aim of our study was to compare the SERT availability in patients with OCD to healthy controls (HC) taking into account the onset type, other factors and covariates (e.g. SERT genotype, age, depression level, gender). We studied 19 drug-naïve OCD patients (36±13 years, 8 females) with early onset (EO-OCD, n=6) or with late onset (LO-OCD, n=13), and 21 HC (38±8 years, 9 females) with PET and the SERT-selective radiotracer [11C]DASB. Statistical models indicated that a variety of covariates and their interaction influences SERT availability as measured by distribution volume ratios (DVR). These models revealed significant effects of onset type on DVR with lower values in the LO-OCD (starting at an age of 18 years) compared with EO-OCD and HC in limbic (e.g., the amygdala), paralimbic brain areas (the anterior cingulate cortex), the nucleus accumbens and striatal regions, as well as borderline significance in the thalamus and the hypothalamus. The putamen, the nucleus accumbens and the hypothalamus were found with significant interaction between two SERT gene polymorphisms (SERT-LPR and VNTR). These findings suggest that late but not early onset of OCD is associated with abnormally low SERT availability. In part, functional polymorphisms of the SERT gene might determine the differences.

Complete ST-segment resolution (STR) is associated with favorable prognosis in ST-elevation myocardial infarction (STEMI). The optimal reperfusion strategy in patients with STEMI presenting early after symptom-onset is still a matter of debate. So far, there are only a few studies comparing the effect of facilitated and primary percutaneous coronary intervention (PCI) on early myocardial reperfusion assessed by STR. The objective of this meta-analysis was, therefore, to evaluate the extent of early STR and subsequent prognosis in facilitated versus primary PCI. From 1990 to 2008, we identified 14 trials of patients with STEMI reporting STR data assigned to facilitated or primary PCI. The primary endpoint of this pooled analysis was STR before and after PCI. Clinical efficacy outcomes included short-term all-cause mortality at 30–90 days and mortality after 6 months. Together, these 14 trials randomly assigned 6,439 patients (3,605 to facilitated PCI, 2,834 to primary PCI). The facilitation agents were platelet glycoprotein IIb/IIIa inhibitors in nine (1,589 patients), fibrinolysis in three (1,037 patients), and the combination of platelet glycoprotein IIb/IIIa inhibitors plus reduced-dose fibrinolysis in three trials (979 patients). STR data were available in 4,105 patients (2,215 facilitated PCI, 1,890 primary PCI). Patients undergoing facilitated PCI were significantly more likely to achieve STR before catheterization and after PCI [OR pre-PCI 1.59 (CI 1.3, 1.90); OR post-PCI 1.69 (CI 1.28, 2.24)]. Despite this significantly improved surrogate parameter of effective myocardial reperfusion, mortality was similar between groups [OR 1.11 (CI 0.84, 1.45)]. Prehospital initiated facilitated PCI results in a higher percentage of complete STR before and after PCI when compared with primary PCI. However, this enhanced early reperfusion did not significantly improve the outcome after facilitated PCI. Therefore, the current data suggest that facilitated PCI does not offer an advantage over primary PCI. The results from ongoing clinical trials in STEMI patients presenting early (

There is a lack of sufficiently large randomized trials evaluating the effectiveness of saline spa balneophototherapy compared to ultraviolet B (UVB) only.The study aimed to evaluate whether highly concentrated saline spa water baths followed by UVB (HC-SSW-UVB) are superior to UVB only in moderate to severe psoriasis.One hundred and sixty (160) adults with a Psoriasis Area and Severity Index (PASI) of10 from 4 German spa centers were randomly allocated to HC-SSW-UVB (local sodium chloride concentration between 25% and 27%) or UVB only 3 a week until remission (PASI5) or for a maximum of 6 weeks. Reduction of PASIor = 50% (PASI-50) at the end of the intervention period was defined as primary outcome. Only persons receiving at least 1 intervention were included into the primary analysis.Participants allocated to HC-SSW-UVB attained to a statistically significantly higher rate of PASI-50 than patients allocated to UVB only (68/79 [86%] versus 38/71 [54%]; p0.001; number needed to treat, 3.1; 95% confidence interval, 2.1-6.0). Postintervention analysis did not yield a clear hint of a persisting effect.The study indicates that HC-SSW-UVB are superior to routine UVB at the end of a 6-week treatment course.

Objectives: To evaluate whether mild water-filtered near infrared whole-body hyperthermia (NI-WBH) produces an additional benefit when applied as an adjunct to a standard multimodal rehabilitation (MR) compared with MR only in patients with fibromyalgia (FM). Methods: One hundred thirty-nine patients of a German inpatient rehabilitation hospital meeting the ACR 1990 criteria for FM were randomly allocated to NI-WBH (heating-up to 38.1 degrees C body core temperature followed by a 15 min heat retention period) and MR or MR only, twice a week over 3 weeks. Main outcome measures were affective and sensory pain assessed by a German version of the McGill Pain Questionnaire, measured at baseline, postintervention, 3 and 6 months postintervention and analyzed by intention to treat. Results: Repeated measures analysis of covariance showed significant differences between groups for both primary outcome measures in favor of NI-WBH and MR compared with MR only (P < 0.001 for affective pain, P = 0.001 for sensory pain). Secondary analyses on pain intensity, FM-related quality of life and tender point assessment yielded similar results. Moderate effect sizes were observed for all outcome measures considered (range, 0.41 to 0.75). NI-WBH related side effects were observed in 14 of 69 participants (20%) but all disappeared in less than 30 minutes. Discussion: The study indicates that NI-WBH is a worthwhile adjunct to MR in the treatment of FM.

Background Subcutaneous carbon dioxide insufflations are a safe and inexpensive treatment modality in complementary medicine and are used mainly in musculoskeletal pain and vascular conditions. However, no rigorous trial exists on their efficacy. Aims To evaluate whether patients with acute non specific neck pain get pain free sooner, if treated with subcutaneous carbon dioxide insufflations compared to sham ultrasound. Methods One hundred and twenty-six persons from one German general practice with acute non specific neck pain less than 7 days and a current pain intensity ⩾40 mm on a 100 mm visual analogue scale were included into the trial. Participants received either a maximum number of nine subcutaneous carbon dioxide insufflations or a maximum number of nine sham ultrasound administered by four therapists in a randomized order, thrice weekly. Main outcome measure was time to neck pain relief during a 28 days follow-up period from baseline analyzed by intention to treat. Results Twenty-seven of 63 patients (43%) got neck pain free in the subcutaneous carbon dioxide insufflations group compared to 29 of 63 (46%) in the sham ultrasound group. Median time to neck pain relief was 28 days in both groups ( p = .77; logrank test). Secondary analyses yielded similar results. Conclusions The study indicates that subcutaneous carbon dioxide insufflations are not superior to sham ultrasound for treating patients with acute non specific neck pain. Because course of pain did not differ from the one expected from self limitation, it is likely that non specific effects played only a minor role, if any, in both interventions.

This study investigates the effects of radon (plus CO2) baths on RA in contrast to artificial CO2 baths in RA rehabilitation using a double-blinded trial enrolling 134 randomised patients of an in-patient rehabilitative programme (further 73 consecutive non-randomised patients are not reported here). The outcomes were limitations in occupational context/daily living (main outcome), pain, medication and further quantities. These were measured before the start, after the end of treatment and quarterly in the year thereafter. Repeated-measures analysis of covariance (RM-ANCOVA) of the intent-to-treat population was performed with group main effects (GME) and group × course interactions (G × C) reported. Hierarchically ordered hypotheses ensured the adherence of the nominal significance level. The superiority of the radon treatment was found regarding the main outcome (RM-ANCOVA until 12 months: p GME = 0.15, p GxC = 0.033). Consumption of steroids (p GME = 0.064, p G × C = 0.025) and NSAIDs (p GME = 0.035, p G × C = 0.008) were significantly reduced. The results suggest beneficial long-term effects of radon baths as adjunct to a multimodal rehabilitative treatment of RA.

To determine for patients with ankylosing spondylitis (AS) which factors are associated with disability and restricted body function.In 1538 patients with AS, occiput-to-wall distance, chest expansion, cervical rotation, finger-floor distance, and modified Schober test were measured cross-sectionally, and for each measure the patient's respective percentile was calculated. The mean of the 5 percentiles was summarized in the mobility restriction score (MRS). In addition, patients answered questions on disease progression and completed the Bath AS Functional Index (BASFI) questionnaire. All data were coded into 40 variables, used as independent variables in multiple regression analyses to identify factors associated with BASFI and MRS.Finger-to-floor distance (beta positive, +), cervical rotation (-), time since first AS symptoms (-), age (+), height loss (+), maximum height (-), delay in diagnosis (+), hip replacement (+), regular practice of sports (-), chest expansion (-), sex (worse BASFI in females), exposure to cold and dampness (+), and regular participation in AS group physical exercises (+) were significantly associated with worse BASFI. Significantly associated factors for worse MRS were height loss (+), sex (higher MRS in males), active inflammation of the cervical region (+), age (+), maximum height (-), active inflammation of the hip region (+), involvement of shoulders (+), time since first AS symptoms (+), urethritis (-), regular practice of sports (-), involvement of feet (-), and hip replacement (+). The models explain 47% of the variance observed for both the BASFI and MRS.The amount of variance explained for both BASFI and MRS is rather high. The results apply primarily to groups of patients, but are insufficient to guide clinical decisions in individual patients. These findings contribute to our understanding of factors influencing disability and restriction in body function in AS.

The aim of this study was to analyze the effect of radon therapy on pain in rheumatic diseases. MEDLINE and MedKur databases were searched for the terms radon plus therapy, rheum, arthritis, and osteo. Radon therapy centers and experts in the field were contacted, proceedings hand-searched, and bibliographies checked for references of potential importance. Included were all prospective randomized controlled clinical trials that compared clinical effects of radon therapy with other interventions in patients with rheumatic diseases and studied pain intensity. Information concerning patients, interventions, results, and methodology were extracted in a standardized manner by all authors independently and summarized descriptively. Reports on pain reduction were pooled for meta-analysis. Five clinical trials with a total of 338 patients and comparing the effect on pain of radon baths (three trials) or radon speleotherapy (two trials) with control intervention in degenerative spinal disease (two trials), rheumatoid arthritis (one trial) and ankylosing spondylitis (two trials) met the inclusion criteria. In meta-analysis, the pooled data showed no difference immediately after treatment (P=0.13) but significantly better pain reduction in the radon group than the control group at 3 months (P=0.02) and 6 months (P=0.002) after treatment. The existing trials suggest a positive effect of radon therapy on pain in rheumatic diseases. With respect to the potential clinical effect and given the increasing public interest in radon therapy, there is an urgent need for further randomized controlled clinical investigations with long-term follow-up.