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Background: In contemporary clinical practice, carotid artery stenting (CAS) is increasingly becoming a multispecialty field, joining operators of various training backgrounds, which bring forth their unique expertise, patient management philosophies, and procedural preferences. The best practices and approaches, however, are still debated. Therefore, real-world insights on different operator preferences and related outcomes are of utmost value, yet still rather scarce in the available literature., Methods: Using the data collected in the ROADSAVER observational, European multicenter CAS study, a prespecified comparative analysis evaluating the impact of the operator's specialization was performed. We used major adverse event (MAE) rate at 30-day follow-up, defined as the cumulative incidence of any death or stroke, and its components as outcome measures., Results: A total of 1965 procedures were analyzed; almost half 878 (44.7%) were performed by radiologists (interventional/neuro), 717 (36.5%) by cardiologists or angiologists, and 370 (18.8%) by surgeons (vascular/neuro). Patients treated by surgeons were the oldest (72.9±8.5), while radiologists treated most symptomatic patients (58.1%) and more often used radial access (37.2%). The 30-day MAE incidence achieved by cardiologists/angiologists was 2.0%, radiologists 2.5%, and surgeons 1.9%; the observed differences in rates were statistically not-significant (P=0.7027), even when adjusted for baseline patient/lesion and procedural disparities across groups. The corresponding incidence rates for death from any cause were 1.0%, 0.8%, and 0.3%, P=0.4880, and for any stroke: 1.4%, 2.3%, and 1.9%, P=0.4477, respectively., Conclusions: Despite the disparities in patient selection and procedural preferences, the outcomes achieved by different specialties in real-world, contemporary CAS practice remain similar when using modern devices and techniques.

Background: Plant-based diets are not inherently healthy. Similar to omnivorous diets, they may contain excessive amounts of sugar, sodium, and saturated fats, or lack diversity. Moreover, vegans might be at risk of inadequate intake of certain vitamins and minerals commonly found in foods that they avoid. We developed the VEGANScreener, a tool designed to assess the diet quality of vegans in Europe., Methods: Our approach combined best practices in developing diet quality metrics with scale development approaches and involved the following: (a) narrative literature synthesis, (b) evidence evaluation by an international panel of experts, and (c) translation of evidence into a diet screener. We employed a modified Delphi technique to gather opinions from an international expert panel., Results: Twenty-five experts in the fields of nutrition, epidemiology, preventive medicine, and diet assessment participated in the first round, and nineteen participated in the subsequent round. Initially, these experts provided feedback on a pool of 38 proposed items from the literature review. Consequently, 35 revised items, with 17 having multiple versions, were suggested for further consideration. In the second round, 29 items were retained, and any residual issues were addressed in the final consensus meeting. The ultimate screener draft encompassed 29 questions, with 17 focusing on foods and nutrients to promote, and 12 addressing foods and nutrients to limit. The screener contained 24 food-based and 5 nutrient-based questions., Conclusions: We elucidated the development process of the VEGANScreener, a novel diet quality screener for vegans. Future endeavors involve contrasting the VEGANScreener against benchmark diet assessment methodologies and nutritional biomarkers and testing its acceptance. Once validated, this instrument holds potential for deployment as a self-assessment application for vegans and as a preliminary dietary screening and counseling tool in healthcare settings.

Purpose: To assess the current use of drug-eluting devices for peripheral arterial disease (PAD) among interventional radiologists following the controversy caused by the 2018 meta-analysis suggesting an increased mortality risk for paclitaxel-eluting devices., Methods: An anonymous survey was sent to 7035 CIRSE members via email; only complete responses were included and statistically analysed., Results: Three hundred and seven members (4.4%) completed the survey. Among these, 95.8% indicated that they personally perform peripheral vascular procedures. Thirty-eight percentage of respondents did not see any change of practice since 2018, while 47% reported that the use of drug-eluting devices decreased; for 13%, the use stopped altogether, while it increased in 3% of responses. 45.6% of respondents also felt the impact of the controversy in terms of pricing, availability or directives from hospital administration. A large majority of respondents (83.7%) who perform peripheral vascular procedures consider the use of these devices as safe, 12.9% were undecided and 3.4% did not consider them as safe. Among the respondents who do not perform endovascular procedures, 77% considered these devices as safe and 23% were undecided., Conclusion: Although the 2018 meta-analysis had a disruptive impact on the use of drug-eluting devices in PAD, with the increasing body of evidence available, a majority of respondents continue to believe in the safety of these devices for use in femoropopliteal disease., (© 2023. The Author(s).)

In the current classification of the World Health Organization (WHO), bone marrow mastocytosis (BMM) is a provisional variant of indolent systemic mastocytosis (ISM) defined by bone marrow involvement and absence of skin lesions. However, no additional diagnostic criteria for BMM have been proposed. Within the registry dataset of the European Competence Network on Mastocytosis, we compared characteristics and outcomes of 390 patients with BMM and 1175 patients with typical ISM. BMM patients were significantly older, predominantly male, had lower tryptase and lower burden of neoplastic mast cells, and displayed a higher frequency of allergic reactions, mainly triggered by Hymenoptera, than patients with typical ISM. The estimated 10-year progression-free survival of BMM and typical ISM was 95.9% and 92.6%, respectively. In BMM patients defined by WHO-based criteria, the presence of one B-Finding and tryptase level ≥125 ng/mL were identified as risk factors for progression in multivariate analyses. BMM patients without any of these risk factors were found to have better progression-free survival (p < 0.05) and better overall survival (p < 0.05) than other ISM patients. These data support the proposal to define BMM as a separate SM variant characterized by SM criteria, absence of skin lesions, absence of B-Findings, and tryptase levels <125 ng/mL., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Wheat is one of the most commonly consumed foods and a known elicitor of anaphylaxis in children and adults. Reactions in adults are often cofactor dependent and characterized by a prolonged time between food intake and the onset of symptoms making the diagnosis of wheat anaphylaxis challenging., Objective: To characterize a cohort of patients with the history of wheat anaphylaxis to better understand this atypical phenotype of anaphylaxis., Methods: Data from the European Anaphylaxis Registry from 2007 to 2019 (n = 10,636) including 250 patients (213 adults and 37 children) with a history of anaphylaxis caused by wheat were analyzed., Results: Wheat was the most common food elicitor of anaphylaxis in adults in the registry in Central Europe. Reactions to wheat in adults were frequently associated with exercise as a cofactor (82.8%) and partially delayed (57.5%). Only 36.9% of patients had atopic comorbidities, which was uncommonly low for adult patients allergic to other kinds of foods (63.2%). Anaphylaxis to wheat presented frequently with cardiovascular symptoms (86.7%) including severe symptoms such as loss of consciousness (41%) and less often with respiratory symptoms (53.6%). The reactions to wheat were more severe than reactions to other foods (odds ratio [OR] = 4.33), venom (OR = 1.58), or drugs (OR = 2.11)., Conclusions: Wheat is a relevant elicitor of anaphylaxis in adults in Central Europe. Wheat anaphylaxis is highly dependent on the presence of cofactors and less frequently associated with atopic diseases compared with other food allergies. More data on mechanisms of wheat-induced anaphylaxis are required to develop preventive measures for this potentially life-threatening disease., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Aims: Prior analyses disclosed variations in antiplatelet drug response and clinical outcomes between smokers and non-smokers, thus the safety and efficacy of any dual antiplatelet therapy (DAPT) de-escalation strategy may differ in relation to smoking status. Hence, we assessed the impact of smoking on clinical outcomes and adenosine diphosphate-induced platelet aggregation following guided de-escalation of DAPT in invasively managed acute coronary syndrome (ACS) patients., Methods and Results: The multicentre TROPICAL-ACS trial randomized 2610 biomarker-positive ACS patients 1:1 to standard treatment with prasugrel for 12 months (control group) or a platelet function testing guided de-escalation of DAPT. Current smokers (n = 1182) showed comparable event rates between study groups [6.6% vs. 6.6%; hazard ratio (HR) 1.0, 95% confidence interval (CI) 0.64-1.56, P > 0.99]. In non-smokers (n = 1428), a guided DAPT de-escalation was associated with a lower 1-year incidence of the primary endpoint [cardiovascular death, myocardial infarction, stroke, or bleeding ≥ Grade 2 according to Bleeding Academic Research Consortium (BARC) criteria] compared with control group patients (7.9% vs. 11.0%; HR 0.71, 95% CI 0.50-0.99, P = 0.048). This reduction was mainly driven by a lower rate of BARC ≥ Grade 2 bleedings (5.2% vs. 7.7%; HR 0.68, 95% CI 0.45-1.03, P = 0.066). There was no significant interaction of smoking status with treatment effects of guided DAPT de-escalation (Pint = 0.23). Adenosine diphosphate-induced platelet aggregation values were higher in current smokers [median 28 U, interquartile range (IQR: 20-40)] vs. non-smoker [median 24 U (16-25), P < 0.0001] in the control group and in current smokers [median 42 U, IQR (27-68)] vs. non-smoker [median 37 U, IQR (25-55), P < 0.001] in the monitoring group., Conclusion: Guided DAPT de-escalation appears to be equally safe and effective in smokers and non-smokers. Regardless of smoking status and especially for those patients deemed unsuitable for 1 year of potent platelet inhibition this DAPT strategy might be used as an alternative antiplatelet treatment regimen., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: Patients with a history of anaphylaxis are at risk of future anaphylactic reactions. Thus, secondary prevention measures are recommended for these patients to prevent or attenuate the next reaction., Methods: Data from the Anaphylaxis Registry were analyzed to identify secondary prevention measures offered to patients who experienced anaphylaxis. Our analysis included 7788 cases from 10 European countries and Brazil., Results: The secondary prevention measures offered varied across the elicitors. A remarkable discrepancy was observed between prevention measures offered in specialized allergy centers (84% of patients were prescribed adrenaline autoinjectors following EAACI guidelines) and outside the centers: Here, EAACI guideline adherence was only 37%. In the multivariate analysis, the elicitor of the reaction, age of the patient, mastocytosis as comorbidity, severity of the reaction, and reimbursement/availability of the autoinjector influence physician's decision to prescribe one., Conclusions: Based on the low implementation of guidelines concerning secondary prevention measures outside of specialized allergy centers, our findings highlight the importance of these specialized centers and the requirement of better education for primary healthcare and emergency physicians., (© 2019 The Authors. Allergy published by John Wiley & Sons Ltd.)

Purpose: To report the clinical effect of a drug-eluting stent on femoropopliteal occlusive disease in patients with long lesions. Materials and Methods: The global IMPERIAL Long Lesion substudy ( ClinicalTrials.gov identifier NCT02574481) is a prospective, single-arm, multicenter trial of the Eluvia Drug-Eluting Vascular Stent for treating femoropopliteal lesions >140 mm and ≤190 mm in length. Fifty patients (mean age 68.2 years; 32 men) with long lesions (mean length 162.8±34.7 mm) were enrolled; 20 patients had diabetes. Fourteen of the lesions were severely calcified and 16 were occluded. Primary patency (duplex ultrasound peak systolic velocity ratio ≤2.4 in the absence of clinically-driven target lesion revascularization or bypass of the target lesion) and major adverse events [30-day all-cause death and 1-year target limb major amputation or target lesion revascularization (TLR)] were assessed at 12 months. Results: At 12 months, no deaths, target limb amputations, or stent thrombosis had occurred. The Kaplan-Meier estimate of primary patency was 91.0% (95% CI 82.5% to 99.6%). The MAE-free rate at 12 months was 93.5% due to 3 clinically-driven TLRs. The corresponding Kaplan-Meier estimate of freedom from TLR was 93.9% (95% CI 87.2% to 100%). Conclusion: The IMPERIAL Long Lesion substudy demonstrated excellent patency and safety through 1 year among patients with long femoropopliteal occlusive disease treated with the Eluvia stent.

There is considerable evidence that biodiversity promotes multiple ecosystem functions (multifunctionality), thus ensuring the delivery of ecosystem services important for human well-being. However, the mechanisms underlying this relationship are poorly understood, especially in natural ecosystems. We develop a novel approach to partition biodiversity effects on multifunctionality into three mechanisms and apply this to European forest data. We show that throughout Europe, tree diversity is positively related with multifunctionality when moderate levels of functioning are required, but negatively when very high function levels are desired. For two well-known mechanisms, 'complementarity' and 'selection', we detect only minor effects on multifunctionality. Instead a third, so far overlooked mechanism, the 'jack-of-all-trades' effect, caused by the averaging of individual species effects on function, drives observed patterns. Simulations demonstrate that jack-of-all-trades effects occur whenever species effects on different functions are not perfectly correlated, meaning they may contribute to diversity-multifunctionality relationships in many of the world's ecosystems.

We comment on an unusual strain of Microsporum (M.) audouinii. It was isolated from tinea corporis of a boy who lived in Germany and most likely had acquired his infection during a stay on a farm with animal husbandry in Poland. The strain showed features of M. canis (plenty of markedly rough-walled macroconidia, growth on rice, positive hair perforation) as well as of M. audouinii (white thallus, long macroconidia with central constriction) and in vitro it degraded hair of various mammals. Because its ribosomal internal transcribed spacer region showed 99.9% homology to a M. audouinii reference strain it was finally identified as M. audouinii. We relate these findings with recent observations of M. audouinii causing tinea in Europe. This appraisal suggests that irrespective of an identical ribosomal ITS region distinct M. audouinii strains can display a spectrum of morphological and physiological features that is broader than currently outlined in mycological textbooks. Certain unusual characteristics like an enhanced capacity to utilise keratins may even be associated with unexpected transmission routes. Above all sporadic M. audouinii infections in Europe that bear no relation to an endemic area should be analysed from this perspective., (© 2015 Blackwell Verlag GmbH.)

Aim: Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome these limitations and screened all DCM disease genes in a large cohort., Methods and Results: In this multi-centre, multi-national study, we have enrolled 639 patients with sporadic or familial DCM. To all samples, we applied a standardized protocol for ultra-high coverage next-generation sequencing of 84 genes, leading to 99.1% coverage of the target region with at least 50-fold and a mean read depth of 2415. In this well characterized cohort, we find the highest number of known cardiomyopathy mutations in plakophilin-2, myosin-binding protein C-3, and desmoplakin. When we include yet unknown but predicted disease variants, we find titin, plakophilin-2, myosin-binding protein-C 3, desmoplakin, ryanodine receptor 2, desmocollin-2, desmoglein-2, and SCN5A variants among the most commonly mutated genes. The overlap between DCM, hypertrophic cardiomyopathy (HCM), and channelopathy causing mutations is considerably high. Of note, we find that >38% of patients have compound or combined mutations and 12.8% have three or even more mutations. When comparing patients recruited in the eight participating European countries we find remarkably little differences in mutation frequencies and affected genes., Conclusion: This is to our knowledge, the first study that comprehensively investigated the genetics of DCM in a large-scale cohort and across a broad gene panel of the known DCM genes. Our results underline the high analytical quality and feasibility of Next-Generation Sequencing in clinical genetic diagnostics and provide a sound database of the genetic causes of DCM., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Background: Data on treatment satisfaction in European men and women with chronic constipation are limited., Aim: To assess satisfaction with current treatment among European men and women with chronic constipation., Methods: An internet-based survey was conducted in 2009 in 10 European countries: Austria, Germany, France, Ireland, Italy, Spain, Switzerland, the UK, Belgium and the Netherlands. Participants had self-reported chronic constipation (<3 bowel movements/week and ≥1 symptoms for ≥6 months of: pain during defecation; lumpy/hard faeces; and feeling of incomplete evacuation). Demographic data and disease history were collected. For participants using laxatives, drug name/class, satisfaction with treatment and interest in other treatments were collected., Results: Of the 1941 participants screened, 1355 had chronic constipation and met the inclusion criteria (chronic constipation population). The majority of the chronic constipation population who disclosed their sex (n = 811) were women (82%). Sixty-eight per cent of respondents (n = 855/1255) reported using laxatives, with the proportion of laxative users differing between subsets. Twenty-eight per cent (n = 225/793) were (very) satisfied with their treatment, whereas 44% (n = 345/793) were neutral and 28% (n = 223/793) (very) dissatisfied. There was no relationship between type of laxative and degree of (dis)satisfaction. Interest in other treatments was high with 83% (n = 686/827) of respondents 'absolutely' or 'probably' interested. Respondents dissatisfied with their treatment were more likely to be interested in other treatments., Conclusions: Laxative-use is common for chronic constipation. In this large survey, 28% of participants were dissatisfied with their treatment, with the majority interested in other treatments., (© 2012 Blackwell Publishing Ltd.)

Aims: To investigate which motives young adolescents indicate for first-time alcohol consumption and whether these motives are linked to risky drinking., Methods: Logistic regressions were used based on a nationally representative sample of 1,654 11- to 14-year-olds who had consumed alcohol at least once., Results: 'To toast' (42.5%), 'to find out what effect it would have' (36.4%), and 'to have more fun at a party' (31.0%) were most frequently indicated as motives. Boys indicated curiosity about the effect more often than girls who instead more frequently indicated coping motives. Those who had their first drink 'to have more fun at a party' or 'because it was exciting' had a higher likelihood of risky drinking. Moreover, those who indicated depression as a motive were three times more likely to have 5 or more drinks on a single occasion., Conclusions: Information on young people's motives for first-time drinking appears to play a significant role in primary prevention, e.g. to prevent risky drinking or alcohol-related problems later in life by postponing alcohol use., (Copyright © 2011 S. Karger AG, Basel.)

Purpose: To determine the clinical outcome and the success of stent application for high-grade lesions of the infrapopliteal arteries compared with treatment with percutaneous transluminal angioplasty (PTA) in critical limb ischemia (CLI)., Materials and Methods: In this ethics board-approved randomized prospective study, PTA or stent application was performed on 131 lesions in 88 patients with CLI. The primary end points were clinical improvement after endovascular treatment and limb salvage rate. Secondary end points were defined by the minimal lumen diameter (MLD) before and after the revascularization procedure, percentage of residual diameter stenosis (DS), binary restenosis rate (>50% DS and >70% DS), and incidence of target lesion revascularization at 9-month follow-up., Results: At 3 months, the clinical status in the PTA group was less improved than that in the stent group (P = .008). At 9 months, there had been five minor and two major amputations in the PTA group and five major and five minor amputations in the stent group. MLD was significantly larger and the percentage of DS was significantly less in the stent group at completion angiography. At 9 months, the angiographic control showed better trends for the stent group in comparison to the PTA group despite that no significant differences were detected (MLD, 1.19 mm ± 0.92 vs 1.02 mm ± 1.02; DS, 38.68% ± 25.47 vs 43.31% ± 28.37)., Conclusion: Infrapopliteal stent application is an effective treatment modality in CLI. The PTA and stent groups were essentially equal at 3 and 9 months except for the difference in clinical improvement in the stent group at 3 months., (RSNA, 2011)

Background: Although constipation can be a chronic and severe problem, it is largely treated empirically. Evidence for the efficacy of some of the older laxatives from well-designed trials is limited. Patients often report high levels of dissatisfaction with their treatment, which is attributed to a lack of efficacy or unpleasant side-effects. Management guidelines and recommendations are limited and are not sufficiently current to include treatments that became available more recently, such as prokinetic agents in Europe., Purpose: We present an overview of the pathophysiology, diagnosis, current management and available guidelines for the treatment of chronic constipation, and include recent data on the efficacy and potential clinical use of the more newly available therapeutic agents. Based on published algorithms and guidelines on the management of chronic constipation, secondary pathologies and causes are first excluded and then diet, lifestyle, and, if available, behavioral measures adopted. If these fail, bulk-forming, osmotic, and stimulant laxatives can be used. If symptoms are not satisfactorily resolved, a prokinetic agent such as prucalopride can be prescribed. Biofeedback is recommended as a treatment for chronic constipation in patients with disordered defecation. Surgery should only be considered once all other treatment options have been exhausted., (© 2011 Blackwell Publishing Ltd.)

Aims: Alcohol consumption seems to be the best predictor of drunkenness and evidence suggests that individual and country factors influence the perception of drunkenness. This study examines if the relationship between volume of alcohol consumption and perceived drunkenness varies across European countries in samples of adolescents., Methods: Data came from the 2007 European School Survey Project on Alcohol and other Drugs (ESPAD). The analytical sample consisted of n = 60,114 (93%) 15-16-year-old students in 24 countries reporting alcohol consumption on the last drinking occasion. At the individual level, perceived drunkenness on the last drinking occasion was measured with a 10-point scale, alcohol consumption on the last drinking occasion with a beverage-specific quantity index. Six individual characteristics were assessed and used as control variables. At the country level, a total of five country-level variables were included in the study. Data were analysed using multilevel regression models simultaneously considering both individual level (Level 1) and group (country) level (Level 2) variables., Results: The relationship between alcohol consumption and perceived drunkenness varied across countries. This variation could partly be explained by drinking patterns and geographical region., Conclusion: The perception of the effects of alcohol in terms of drunkenness seems to vary across countries. Future studies should develop sound indicators of cultural differences accounting for this variation.

Purpose: Vascular closure devices are routinely used after many vascular interventional radiology procedures. However, there have been no major multicenter studies to assess the safety and effectiveness of the routine use of closure devices in interventional radiology., Methods: The CIRSE registry of closure devices with an anchor and a plug started in January 2009 and ended in August 2009. A total of 1,107 patients were included in the registry., Results: Deployment success was 97.2%. Deployment failure specified to access type was 8.8% [95% confidence interval (95% CI) 5.0-14.5] for antegrade access and 1.8% (95% CI 1.1-2.9) for retrograde access (P = 0.001). There was no difference in deployment failure related to local PVD at the access site. Calcification was a reason for deployment failure in only <0.5% of patients. Postdeployment bleeding occurred in 6.4%, and most these (51.5%) could be managed with light manual compression. During follow-up, other device-related complications were reported in 1.3%: seven false aneurysms, three hematoma >5.9 cm, and two vessel occlusions., Conclusion: The conclusion of this registry of closure devices with an anchor and a plug is that the use of this device in interventional radiology procedures is safe, with a low incidence of serious access site complications. There seems to be no difference in complications between antegrade and retrograde access and other parameters.

Objective: Opioid therapy is frequently associated with treatment-limiting constipation. Naloxone is an opioid antagonist with low oral systemic bioavailability. This Phase III clinical trial assessed the safety and efficacy of an oral fixed-ratio combination of oxycodone prolonged-release (PR) and naloxone PR compared with oxycodone PR in relieving opioid-induced constipation., Study Design: This double-blind, multicenter trial was conducted in specialist and primary care centers in four European countries in an out-patients setting. The study included 322 adult patients with moderate-to-severe, noncancer pain requiring opioid therapy in a range of >or=20 mg/day and

Purpose: To investigate the short term and 6 month outcomes of a recently introduced iliac stent (the Medtronic AVE Flexible Iliac Bridge Stent)., Method: One hundred and sixteen patients, 122 limbs from 6 European sites with atherosclerotic occlusive disease were included if they either had a full occlusion or there was a residual gradient >10 mmHg following PTA. Clinical, haemodynamic and Duplex outcomes were recorded to 6 months., Results: After stent placement there was no residual stenosis >30 and 8.1% of segments had a residual resting gradient of >10 mmHg. There were three local complications and three deaths at 30 days. Primary patency at 30 days and 6 months was 94.1 and 82.7%. Marked clinical improvement occurred in 87.6 and 86.2% at 30 days and 6 months., Conclusion: The Medtronic AVE iliac stent has good 30 day and 6 months outcomes supporting the effective use of this device in occlusive disease.

Background: Transplantation of allogeneic haemopoietic stem cells can cure several primary immunodeficiencies. This European report focuses on the long-term results of such procedures done between 1968 and December, 1999, for primary immunodeficiencies., Methods: The report includes data from 37 centres in 18 countries, which participated in a European registry for stem-cell transplantation in severe combined immuno deficiencies (SCID) and in other immunodeficiency disorders (non-SCID). 1082 transplants in 919 patients were studied (566 in 475 SCID patients, 512 in 444 non-SCID patients; four procedures excluded owing to insufficient data). Minimum follow-up of 6 months was required., Findings: In SCID, 3-year survival with sustained engraftment was significantly better after HLA-identical than after mismatched transplantation (77% vs 54%; p=0.002) and survival improved over time. In HLA-mismatched stem-cell transplantation, B(-) SCID had poorer prognosis than B(+) SCID. However, improvement with time occurred in both SCID phenotypes. In non-SCID, 3-year survival after genotypically HLA-matched, phenotypically HLA-matched, HLA-mismatched related, and unrelated-donor transplantation was 71%, 42%, 42%, and 59%, respectively (p=0.0006). Acute graft versus host disease predicted poor prognosis whatever the donor origin except in related HLA-identical transplantation in SCID., Interpretation: The improvement in survival over time indicates more effective prevention and treatment of disease-related and procedure-related complications--eg, infections and graft versus host disease. An important factor is better prevention of graft versus host disease in the HLA-non-identical setting by use of more efficient methods of T-cell depletion. For non-SCID, stem-cell transplantation can provide a cure, and grafts from unrelated donors are almost as beneficial as those from genetically HLA-identical relatives.

Treatment of chronic granulomatous disease (CGD) with myeloablative bone marrow transplantation is considered risky. This study investigated complications and survival according to different risk factors present at transplantation. The outcomes of 27 transplantations for CGD, from 1985 to 2000, reported to the European Bone Marrow Transplant Registry for primary immunodeficiencies were assessed. Most transplant recipients were children (n = 25), received a myeloablative busulphan-based regimen (n = 23), and had unmodified marrow allografts (n = 23) from human leukocyte antigen (HLA)-identical sibling donors (n = 25). After myeloablative conditioning, all patients fully engrafted with donor cells; after myelosuppressive regimens, 2 of 4 patients fully engrafted. Severe (grade 3 or 4) graft-versus-host disease (GVHD) disease developed in 4 patients: 3 of 9 with pre-existing overt infection, 1 of 2 with acute inflammatory disease. Exacerbation of infection during aplasia was observed in 3 patients; inflammatory flare at the infection site during neutrophil engraftment in 2: all 5 patients belonged to the subgroup of 9 with pre-existing infection. Overall survival was 23 of 27, with 22 of 23 cured of CGD (median follow-up, 2 years). Survival was especially good in patients without infection at the moment of transplantation (18 of 18). Pre-existing infections and inflammatory lesions have cleared in all survivors (except in one with autologous reconstitution). Myeloablative conditioning followed by transplantation of unmodified hemopoietic stem cells, if performed at the first signs of a severe course of the disease, is a valid therapeutic option for children with CGD having an HLA-identical donor.

Objective: This 1-year study compared the cost effectiveness of omeprazole and ranitidine when used as initial therapy in an intermittent treatment strategy for the management of patients with symptomatic gastro-oesophageal reflux disease with or without erosive oesophagitis., Design and Setting: A prospective health economic analysis was conducted alongside an international multicentre randomised, double-blind clinical study. The economic analysis was performed from a societal perspective., Patients: A total of 704 patients in the UK, the Republic of Ireland, Germany, France, Italy and Spain were randomised to 1 of the 3 treatment groups., Interventions: Patients were randomised to receive either omeprazole 20 mg once daily, omeprazole 10 mg once daily or ranitidine 150 mg twice daily. Initial treatment failure resulted in dose titration and drug switching from ranitidine to omeprazole, and subsequently open maintenance treatment., Main Outcome Measures and Results: The estimated mean direct medical costs (medication and number of visits and endoscopies) were found to be lower for both dosages of omeprazole than for ranitidine in all countries except Germany. However, none of the differences were statistically significant. The differences between omeprazole 10 mg and omeprazole 20 mg were small and nonsignificant. With regard to numbers of symptom-free days, both omeprazole 20 mg and omeprazole 10 mg were found to be more effective than ranitidine. However, none of the differences were statistically significant., Conclusions: Following a pragmatic interpretation, incorporating intermediate short term results, the results in this study give no support to the notion that a step-up approach, either as dose titration from omeprazole 10 mg to omeprazole 20 mg or as drug switching from ranitidine to omeprazole, will result in cost savings and thereby be cost effective.

We have performed a retrospective analysis of the development of T- and B-cell functions after HLA-nonidentical T-cell-depleted bone marrow transplantation (BMT) performed in 193 patients with severe combined immunodeficiency (SCID) at 18 European centers between December 1982 and December 31, 1993. One hundred sixteen of 193 patients were alive with evidence of engraftment 6 months after BMT. Development of T-cell function occurred earlier than B-cell function and was achieved more frequently up to the time of last follow-up. The median time to achieve normal T-cell function was 8.7 months, whereas the median time to achieve normal B-cell function was 14.9 months. Twenty-four patients died later than 6 months post-BMT, mainly due to chronic graft-versus-host disease (cGVHD) and/or viral infection. Absence of T-cell reconstitution 6 months after BMT, unlike absence of B-cell reconstitution, was associated with a poor outcome. Two additional factors were associated with a poor outcome: presence of cGVHD 6 months after BMT and B- SCID versus B+ SCID. However, two of these three factors remained as significant prognostic factors in a multivariate analysis: the absence of T-cell function and the presence of cGVHD 6 months after BMT. Analysis of the factors influencing the development of immune reconstitution showed that T- and B-cell functions occurred earlier and more frequently in B+ SCID versus B- SCID patients. Acute GVHD was associated with a slower development of T-cell function at 6 months, and cGVHD had a negative influence on the development of T-cell function afterwards, but neither acute nor chronic GVHD was found to influence the development of B-cell function. Once engraftment occurred, whether patients had or had not received Busulfan in the conditioning regimen did not influence the kinetics and quality of T-cell function development. In a multivariate study, two factors were found to influence the T-cell function 6 months after BMT: type of SCID and acute GVHD. The results of this retrospective analysis should lead to new protocols adapted to SCID disease, considering that disease-related as well as BMT-related parameters influence the development of immune function and thereby long-term outcome after HLA-nonidentical T-cell-depleted BMT.

Aims: To investigate quality of life in patients with gastro-oesophageal reflux disease., Patients: A series of 704 patients were randomised to treatment with ranitidine 150 mg bd, omeprazole 10 mg om or omeprazole 20 mg om for 2 weeks. Asymptomatic/mildly symptomatic patients were followed for 12 months., Methods: The Psychological General Well-Being index and the Gastrointestinal Symptom Rating Scale were completed before and during short-term and intermittent treatment., Results: The quality of life response rate was > 80%. The majority of the patients receiving omeprazole 20 mg om (55%) had symptom relief after 2 weeks despite the fact that more patients on ranitidine required 4 weeks' treatment and an increased dose. There was no difference in the reflux dimension of Gastrointestinal Symptom Rating Scale between treatments in the initial treatment phase, but the total Gastrointestinal Symptom Rating Scale score improved significantly more on omeprazole 10 mg om than on ranitidine 150 mg bd (p = 0.006). Both doses of omeprazole improved the total Psychological General Well-Being score more than ranitidine (omeprazole 10 mg om versus ranitidine 150 mg bd, p = 0.005, omeprazole 20 mg om versus ranitidine 150 mg bd, p = 0.031). During follow-up, relapsing patients returned to pre-treatment symptom and well-being scores, but these dimensions were restored after treatment., Conclusion: The quality of life is impaired in patients presenting with reflux symptoms. Irrespective of whether the patients presented with endoscopy positive or endoscopy negative reflux disease, treatment on demand improved the quality of life.