Addition of the nuclear export inhibitor selinexor to standard intensive treatment for elderly patients with acute myeloid leukemia and high risk myelodysplastic syndrome.

Treatment results of AML in elderly patients are unsatisfactory. In an open label randomized phase II study, we investigated whether addition of the XPO1 inhibitor selinexor to intensive chemotherapy would improve outcome in this population. 102 AML patients > 65 years of age (median 69 (65-80)) were randomly assigned to standard chemotherapy (3 + 7) with or without oral selinexor 60 mg twice weekly (both arms n = 51), days 1-24. In the second cycle, cytarabine 1000 mg/m2 twice daily, days 1-6 with or without selinexor was given. CR/CRi rates were significantly higher in the control arm than in the investigational arm (80% (95% C.I. 69-91%) vs. 59% (45-72%; p = 0.018), respectively). At 18 months, event-free survival was 45% for the control arm versus 26% for the investigational arm (Cox-p = 0.012) and overall survival 58% vs. 33%, respectively (p = 0.009). AML and infectious complications accounted for an increased death rate in the investigational arm. Irrespective of treatment, MRD status after two cycles appeared to be correlated with survival. We conclude that the addition of selinexor to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients. (Netherlands Trial Registry number NL5748 (NTR5902), www.trialregister.nl ).

Does the smell of alcohol make it harder to resist? The impact of olfactory cues on inhibitory control and attentional bias.

BACKGROUND: It is well known that, owing to associative processing, olfactory cues can impact memory, emotion and behaviour. Research also points to a link between the smells of particular substances and craving. Yet, to date, little research has investigated how smell may impact other cognitive processes that are known to drive alcohol consumption. AIM: To assess how exposure to alcohol-related (vodka) relative to neutral (citrus) olfactory cues impacts inhibitory control and attentional bias. METHOD: Participants took part in a go/no-go (Study 1) and Stroop task (Study 2) while wearing masks that were pre-treated with vodka or citrus oil of equivalent intensity. STUDY 1 RESULTS: Response error rates were higher in participants in the alcohol-related (versus neutral) olfactory condition, with no interaction between olfactory and visual cue. STUDY 2 RESULTS: Responses to alcohol-related versus neutral words were similar, while performance appeared significantly impaired among participants wearing alcohol (relative to citrus) infused masks. Conclusion The smell of alcohol may impair signal detection performance on the go/no-go and Stroop task. As inhibitory control and attentional processes are known to be associated with decisions to drink or exercise restraint, these results may have implications for our understanding of alcohol consumption and for tailoring interventions.

[Outcome of a survey on antibiotic prescribing in veterinary medicine]. / Ergebnisse einer Umfrage zur ­Verschreibung von Antibiotika in der ­Veterinärmedizin.

INTRODUCTION: As part of the national strategy on antibiotic resistance (StAR), a therapy guide for the prudent prescription of antimicrobial agents in animals was developed. To facilitate its implementation in the veterinary practice, the therapy recommendations contained therein have been translated to the user-friendly decision support AntibioticScout.ch. In this context, we conducted a non-representative survey to assess the level of awareness as well as usage of this guide and the AntibioticScout.ch decision support. Based on case studies with typical diseases in dogs, cats and cattle, it was shown that the veterinarians participating in the survey strive to handle antibiotics responsibly and to prescribe them with restraint. Nevertheless, the survey points to possible improvements in the antibiotic therapy. In particular, the StAR guidelines or AntibioticScout.ch can be useful to the practicing veterinarians for taking into account all relevant decision criteria in the optimal selection of a suitable antimicrobial agent.

INTRODUCTION: Dans le cadre de la stratégie nationale de résistance aux antibiotiques (StAR), un guide thérapeutique pour la prescription prudente d'agents antimicrobiens chez les animaux a été élaboré. Pour faciliter son application dans la pratique vétérinaire, les recommandations thérapeutiques qu'il contient ont été transférées dans l'aide à la décision conviviale en-ligne AntibioticScout.ch. Dans ce contexte, nous avons mené une enquête non représentative pour évaluer le niveau de connaissance et l'utilisation de ce guide de l'aide à la decision AntibioticScout.ch. Sur la base d'études de cas portant sur des maladies typiques des chiens, des chats et des bovins, il a été démontré que les vétérinaires participant à l'enquête s'efforcent d' utiliser les antibiotiques de manière responsable et de les prescrire avec modération. Néanmoins, l'enquête met en évidence les améliorations possibles de la thérapie antibiotique. Le guide thérapeutique StAR ou AntibioticScout.ch peut être particulièrement utile à la profession vétérinaire pour prendre en compte tous les critères de décision pertinents dans la sélection optimale d'un agent antimicrobien approprié.

[Survey on the use of antibiotics in exotic pets among Swiss veterinarians]. / Umfrage bei Schweizer Tierärzte/-innen über den Einsatz von Antibiotika bei exotischen Heimtieren.

INTRODUCTION: Monitoring programs and guidelines on the use of antibiotics and antibiotic resistance in human and veterinary medicine have been developed worldwide to promote the prudent use of antibiotics in recent years. However, such information on the use of antibiotics in exotic pets is absent. This fact must be taken into account, since the number of exotic pet patients is constantly increasing and the administration of antibiotics is particular challenging due to the diversity of species and the differences in physiology. The present study reports the results of a survey of frequently used antibiotics and the criteria of antibiotic usage in exotic pets (rabbits, rodents, birds and reptiles) among Swiss veterinarians. These data should form the basis for the development of antibiotic usage guidelines in exotic pets. A total of 61 veterinarians returned the questionnaire. The most important decision-making criteria for antibiotic treatment and antibiotic selection were clinical symptoms (55/59, 93% for antibiotic treatment and 40/59, 68% for antibiotic selection), experience (41/59, 69% and 36/59, 61%, respectively) and textbooks (39/59, 66% and 40/59, 68%). The most important decision-making criteria for dosage and duration of therapy were textbooks (59/59, 100%) and experience (31/59, 53%). The use of a microbial culture was used as a decision criterion for both antibiotic treatment and antibiotic selection by 39% of the participants, sensitivity testing was chosen as a decision criterion by 37% for antibiotic treatment and by 46% for antibiotic selection. Fluoroquinolones were used most frequently, 46/56 (82% of the participants) for rabbits, 49/57 (86%) for rodents, 36/37 (97%) for reptiles and 38/46 (83%) for birds. The vast majority of veterinarians (57/58, 98%) would consult a guide for the use of antibiotics. The frequent use of critical antibiotics in exotic pets underscores the need for a guide to the prudent use of antibiotics. The positive influence of such guidelines has already been proven in dogs and cats.

INTRODUCTION: Pour promouvoir une utilisation prudente des antibiotiques, des programmes de surveillance et des lignes directrices sur l'utilisation des antibiotiques et la résistance aux antibiotiques en médecine humaine et vétérinaire ont été élaborés dans le monde entier ces dernières années. Cependant, il n'existe actuellement aucune information de ce type en ce qui concerne les nouveaux animaux de compagnie ainsi que des informations exhaustives sur l'utilisation d'antibiotiques dans la pratique vétérinaire. Ce fait doit être pris en compte, d'autant plus que le nombre d'nouveaux animaux de compagnie est en constante augmentation dans la patientèle et que l'administration d'antibiotiques est un défi particulier en raison de la diversité des espèces et des différences de physiologie. Dans la présente étude, une enquête a été menée pour avoir un aperçu des antibiotiques fréquemment utilisés et de leurs critères d'utilisation chez les nouveaux animaux de compagnie (lapins, rongeurs, oiseaux et reptiles) auprès de vétérinaires suisses. Ces données sont destinées à servir de base à l'élaboration d'un guide sur les antibiotiques pour les animaux exotiques. Au total 61 vétérinaires ont répondu au questionnaire. Les critères de décision les plus importants pour le traitement antibiotique et la sélection d'un antibiotique étaient les symptômes (55/59, 93% pour le traitement antibiotique et 40/59, 68% pour la sélection de l'antibiotique), l'expérience (41/59, 69% et 36/59, 61%, respectivement) et la littérature spécialisée (39/59, 66% et 40/59, 68%). Les critères de décision les plus importants pour e dosage et la durée du traitement étaient la littérature spécialisée (59/59, 100%) et l'expérience (31/59, 53%). L'utilisation d'une culture bactériologique a été donnée par 39% des participants comme critère de décision à la fois pour le traitement antibiotique et le choix de l'antibiotique et un antibiogramme a été choisi par 37% comme critère de décision pour le traitement antibiotique et 46% pour le choix de l'antibiotique. Il a été constaté que les fluoroquinolones sont utilisées le plus fréquemment, chez 46/56 (82% des participants) pour les lapins, 49/57 (86%) pour les rongeurs, 36/37 (97%) pour les reptiles et 38/46 (83%) pour les oiseaux. La grande majorité des vétérinaires (57/58, 98%) a déclaré qu'ils consulteraient un guide pour l'utilisation des antibiotiques. L'utilisation fréquente d'antibiotiques critiques chez les nouveaux animaux de compagnie souligne la nécessité d'un guide sur l'utilisation prudente des antibiotiques. L'influence positive de ces recommandations a déjà été prouvée pour les chiens et les chats.

[Antibiotic-resistant bacteria in dogs and cats: recommendations for -owners]. / Antibiotikaresistente Bakterien bei Hund und Katze: Empfehlungen für Halterinnen und Halter.

INTRODUCTION: Antibiotic-resistant bacteria are of increasing importance in human and veterinary medicine. Also, small animal clinics and practices are facing patients carrying antibiotic-resistant bacteria. What risk do these animals pose for animal owners? How can the risk of transmission to humans be reduced? A working group of human and veterinary medicine experts developed a guide for dog or cat owners with pets carrying antibiotic-resistant bacteria. The guide contains background information on the most important antibiotic-resistant bacteria in dogs and cats, namely methicillin-resistant staphylococci and extended spectrum beta-lactamase (ESBL)- and carbapenemase-producing Enterobacteriaceae. Measures are listed to reduce the risk of transmission to humans. This review explains the pathophysiology, occurrence and risk factors of these bacteria in dogs, cats and humans. Recommended measures are outlined.

INTRODUCTION: Les germes résistants aux antibiotiques revêtent une importance croissante en médecine humaine et vétérinaire. Les cliniques et pratiques pour petits animaux sont également confrontées à des patients chez lesquels des germes résistants aux antibiotiques ont été détectés. Quel risque ces animaux présentent-ils pour les propriétaires d'animaux? Comment réduire le risque de transmission à l'homme? Un groupe de travail composé d'experts en médecine humaine et vétérinaire a élaboré un guide pour les propriétaires dont les chiens ou les chats sont porteurs de germes résistants aux antibiotiques. Le guide contient des informations générales sur les germes résistants aux antibiotiques les plus importants chez les chiens et les chats, à savoir les staphylocoques résistants à la méthicilline et les entérobactéries productrices de bêta-lactamases à spectre étendu (BLSE) et de carbapénémases. Des mesures sont également répertoriées pour réduire le risque de transmission de ces germes à l'homme. Cette revue explique les informations de base sur les propriétés des germes et leur occurrence, les facteurs de risque chez les chiens, les chats et les humains, et explique les mesures recommandées.

[The reclassification assistant: Drug reclassification made easy]. / Umwidmungs-Assistent: Arzneimittelumwidmung leicht gemacht.

INTRODUCTION: In Switzerland, just over 700 veterinary medicinal products are authorized. Nevertheless, in practice veterinarians are often confronted with extraordinary situations in which a suitable veterinary medicinal product is not authorized, unavailable or otherwise not applicable. For livestock and horses in particular, this poses a challenge for pharmacotherapy due to food safety regulations. In these cases, the reclassification assistant can be used to determine whether and how a medicinal product containing the appropriate drug can be reclassified and correctly applied in food-producing animals. The users will be guided step by step with selectable options through the online assistant. If the desired reclassification is permitted in the legal framework, information on the withdrawal periods to be observed for the chosen medicinal product will be provided. This online assistant follows an algorithm based on the reclassification cascade and applicable food safety regulations.

INTRODUCTION: En Suisse, un peu plus de 700 médicaments vétérinaires sont autorisés. Néanmoins, dans la pratique, les vétérinaires sont souvent confrontés à des situations extraordinaires dans lesquelles un médicament vétérinaire approprié n'est ni autorisé, ni disponible, ni utilisable pour d'autres raisons. En particulier pour le bétail et les chevaux, cela pose un défi pour la pharmacothérapie en raison de la réglementation sur la sécurité alimentaire. Dans ces cas, l'assistant de reconversion peut être utilisé pour déterminer si et comment un médicament contenant le principe actif approprié peut être reconverti et correctement appliqué. Les utilisateurs seront guidés pas à pas avec des options sélectionnables via l'assistant en ligne. Si la reconversion souhaitée est autorisée dans le cadre légal, des informations sur les délais d'attente à respecter pour le médicament choisi seront fournies. Cet assistant en ligne suit un algorithme basé sur la cascade de reconversion les réglementations applicables en matière de sécurité alimentaire.

[AntibioticScout.ch: Decision support for the prudent use of antimicrobials: Application in cattle]. / AntibioticScout.ch: Entscheidungshilfe für den umsichtigen Einsatz von antimikrobiellen Wirkstoffen: Anwendung beim Rind.

INTRODUCTION: The administration of antibiotics in livestock has been criticized for many years, in particular because of an inappropriate use and the appearance of antibiotic residues in the environment, which can promote the emergence and spread of resistant bacteria. However, antibiotics are essential for the successful and sustainable control of bacterial pathogens. With the aim of optimizing the use of antibiotics in food animals and minimizing the prevalence of resistant bacteria, AntibioticScout. ch provides a decision aid for the prudent use of antimicrobial drugs. This approach emphasizes the importance of supportive therapy and the hallmarks of preventive concepts. Procedures to improve animal health and animal welfare in accordance with the principles of good veterinary practice are primary and effective tools to reduce the use of antimicrobial drugs. The necessary reduction in the use of antibiotics must, therefore, be accompanied by appropriate management strategies in animal husbandry. In particular, hygiene, animal welfare and biosecurity measures are crucial to ensure an optimal health status in farm animals.

INTRODUCTION: On discute depuis des années de l'usage des antibiotiques dans l'élevage des animaux de rente, en particulier en ce qui concerne leur utilisation incorrecte et la charge environnementale liée à des résidus d'antibiotiques susceptibles de favoriser l'apparition et la propagation de résistances. Toutefois les antibiotiques sont essentiels pour assurer une lutte efficace et durable contre les maladies d'origine bactérienne. Dans le but d'optimiser l'usage des antibiotiques dans l'élevage des animaux de rente et, par conséquence, de réduire le développement de résistances, AntibioticScout.ch propose une aide à la décision pour un usage prudent de ces substances ("prudent use"). Parallèlement, on attire l'attention sur les traitements adjuvants et sur les mesures de prévention. Des mesures visant à améliorer la santé et le bien-être des animaux en tenant compte des fondements d'une bonne pratique vétérinaire sont des instruments efficaces pour réduire l'usage des antibiotiques. Cette réduction indispensable doit donc être combinée avec des mesures de gestion adéquates dans les élevages. Ce sont en particulier l'hygiène et les conditions d'élevage correctes ainsi que la mise en place de mesures de biosécurité qui sont décisives pour l'optimisation de la santé des troupeaux.

[AntibioticScout.ch: A decision supporting tool for antimicrobial stewardship: application to companion animal medicine]. / AntibioticScout.ch: Eine Entscheidungshilfe für den umsichtigen Einsatz von antimikrobiellen Wirkstoffen: Anwendung in der Kleintiermedizin.

INTRODUCTION: Bacterial resistances to antimicrobial drugs pose serious public health challenges. The observed increase of resistances is attributed to the uncontrolled, massive and often unnecessary administration of antibiotics both in human and veterinary medicine. To support the responsible use of antimicrobials in animals and help veterinarians selecting the most suitable antimicrobial drugs, we developed the AntibioticScout.ch as a comprehensive decision supporting tool providing online access to the current knowledge of rational antibiotic prescription practices. User-friendly search functions allow for the fast and efficient retrieval of information that is structured in this database by animal species, organ systems and therapeutic indications. In addition, an online form allows to report treatment failures in order to identify problematic cases as well as ensuing risks and take appropriate mitigation measures. The present report describes the workflow of this decision support system applied to the prudent use of antimicrobials in companion animal medicine.

INTRODUCTION: Les résistances bactériennes face aux substances antimicrobiennes placent le système de santé face à de grands défis. L'augmentation des résistances est attribuée à une utilisation mal dirigée, massive et souvent inutile d'antibiotiques tant en médecine humaine qu'en médecine vétérinaire. Afin d'encourager une utilisation responsable des substances antimicrobiennes en médecine vétérinaire et pour soutenir les vétérinaires lors du choix de l'antibiotique adapté, on a créé, avec AntibioticScout. ch, une aide à la décision de grande envergure qui permet de recourir à chaque instant aux principes de prescription reconnus de la médecine fondée sur les faits (Evidence Based Medicine). La banque de données est structurée par espèces animales, systèmes d'organes et indications et un moteur de recherche intuitif garantit de trouver rapidement et efficacement les informations. D'autre part un formulaire en ligne pour l'annonce d'une inefficacité est proposé afin de reconnaitre les cas à problèmes et les risques en vue d'améliorer l'aide au diagnostic. La présente contribution pour but de démontrer l'utilisation d'AntibioticScout pour un usage prudent des antibiotiques en médecine des petits animaux.

Assessment of imatinib as first-line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study IV and impact of non-CML determinants.

Chronic myeloid leukemia (CML)-study IV was designed to explore whether treatment with imatinib (IM) at 400 mg/day (n=400) could be optimized by doubling the dose (n=420), adding interferon (IFN) (n=430) or cytarabine (n=158) or using IM after IFN-failure (n=128). From July 2002 to March 2012, 1551 newly diagnosed patients in chronic phase were randomized into a 5-arm study. The study was powered to detect a survival difference of 5% at 5 years. After a median observation time of 9.5 years, 10-year overall survival was 82%, 10-year progression-free survival was 80% and 10-year relative survival was 92%. Survival between IM400 mg and any experimental arm was not different. In a multivariate analysis, risk group, major-route chromosomal aberrations, comorbidities, smoking and treatment center (academic vs other) influenced survival significantly, but not any form of treatment optimization. Patients reaching the molecular response milestones at 3, 6 and 12 months had a significant survival advantage. For responders, monotherapy with IM400 mg provides a close to normal life expectancy independent of the time to response. Survival is more determined by patients' and disease factors than by initial treatment selection. Although improvements are also needed for refractory disease, more life-time can currently be gained by carefully addressing non-CML determinants of survival.

Inability to work and need for disability pension among long-term survivors of hematopoietic stem cell transplantation.

Return to work is critical goal following HSCT. However, late effects may impede return to normal activity after HSCT. In the case of inability to work, patients may need a work disability pension to ensure a reasonable livelihood. This study evaluated inability to work and need for disability pension among long-term survivors and analyzed possible determinants of need for social support. This retrospective, single-center study included all HSCT patients surviving ⩾5 years seen at the outpatient clinic between January 2013 and August 2015. There were 203 patients, median age at HSCT 35 years, and 50 years at time of study; median time between HSCT and study control was 12 years; 178 had allo-HSCT, 187 had a malignant disease. At time of study, 156 (77%) were working full or part-time, 47 (23%) were not working. In total, 76 (37%) survivors were receiving a work disability pension compared to 3.17% of the Swiss working population. Patients with a disability pension were significantly older at HSCT, were more often living alone, had more active physical and mental late effects, and higher score of fatigue compared to patients without. These findings underline the importance of screening for employment and the social consequences of non-employment in long-term survivors after HSCT.

Epidemiological and Molecular Analysis of an Outbreak of Highly Pathogenic Avian Influenza H5N8 clade 2.3.4.4 in a German Zoo: Effective Disease Control with Minimal Culling.

Outbreaks of highly pathogenic avian influenza A virus (HPAIV) subtype H5N8, clade 2.3.4.4, were first reported in January 2014 from South Korea. These viruses spread rapidly to Europe and the North American continent during autumn 2014 and caused, in Germany, five outbreaks in poultry holdings until February 2015. In addition, birds kept in a zoo in north-eastern Germany were affected. Only a few individual white storks (Ciconia ciconia) showed clinical symptoms and eventually died in the course of the infection, although subsequent in-depth diagnostic investigations showed that other birds kept in the same compound of the white storks were acutely positive for or had undergone asymptomatic infection with HPAIV H5N8. An exception from culling all of the 500 remaining zoo birds was granted by the competent authority. Restriction measures included grouping the zoo birds into eight epidemiological units in which 60 birds of each unit tested repeatedly negative for H5N8. Epidemiological and phylogenetical investigations revealed that the most likely source of introduction was direct or indirect contact with infected wild birds as the white storks had access to a small pond frequented by wild mallards and other aquatic wild birds during a period of 10 days in December 2014. Median network analysis showed that the zoo bird viruses segregated into a distinct cluster of clade 2.3.4.4 with closest ties to H5N8 isolates obtained from mute swans (Cygnus olor) in Sweden in April 2015. This case demonstrates that alternatives to culling exist to rescue valuable avifaunistic collections after incursions of HPAIV.

[AntibioticScout: Online tool for antimicrobial stewardship in veterinary medicine]. / AntibioticScout: Online-Entscheidungshilfe für den umsichtigen Einsatz von antimikrobiellen Wirkstoffen.

INTRODUCTION: Resistances to antimicrobials pose serious public health challenges. This issue concerns both human and veterinary medicine and can only be solved by a multidisciplinary approach. A comprehensive concept is, therefore, being worked out within the StAR (strategy antibiotic resistance) program in order to preserve the effectiveness of antibiotics for humans as well as animals. In this context, the AntibioticScout (www.AntibioticScout. ch) offers a new online tool for the prudent use of antibiotics in veterinary medicine. By involving all stakeholders, the guidelines included in the AntibioticScout will result in a nationwide accepted standard for the treatment of bacterial infections in animals. An additional system for the rapid reporting of cases of suspected lack of efficacy of antimicrobials is integrated to allow early detection of emerging resistance and the immediate launch of risk mitigation measures. A first version of the AntibioticScout for the treatment of dogs, cats and horses is available by the end of 2016. All stakeholders are now invited to contribute to the development of the AntibioticScout decision support.

INTRODUCTION: Les résistances face aux substances antimicrobiennes placent le système de santé face à de grands défis. Ce problème touche aussi bien la médecine humaine que vétérinaire et ne peut être réglé que de façon transversale. C'est pour cette raison qu'a été développé, avec le programme StAR (Strategie Antibiotikaresistenzen), un concept global pour assurer à long terme l'efficacité des antibiotiques aussi bien chez les hommes que chez les animaux. Dans ce contexte, nous mettons à disposition, avec le développement d'AntibioticScout (www.AntibioticScout. ch), un nouvel outil en ligne pour soutenir un usage responsable des antibiotiques en médecine vétérinaire. Avec le concours de représentants de tous les milieux intéressés, il s'agit de développer les lignes directrices d'un standard accepté au plan national pour le traitement des infections bactériennes chez les animaux et de le mettre à disposition dans AntibioticScout. En outre un système d'annonce immédiate en cas d'inefficacité sera mis en place, afin de repérer précocement les risques et de prendre les mesures correspondantes. Une première version d'AntibioticScout pour le traitement des chiens, chats et chevaux est disponible dès fin 2016. Tous les cercles intéressés sont dès maintenant invités à contribuer au développement d'Antibiotic Scout.

Smells like inhibition: The effects of olfactory and visual alcohol cues on inhibitory control.

RATIONALE: How the smell of alcohol impacts alcohol-related thoughts and behaviours is unclear, though it is well-documented that alcohol-related stimuli and environments may trigger these. OBJECTIVES: The current study, therefore, aimed to investigate the priming effects of both visual and olfactory alcohol cues on inhibitory control. METHOD: Forty individuals (M age = 23.65, SD = 6.52) completed a go/no-go association task (GNAT) which measured reaction times, response accuracy and false alarm rates whilst being exposed to alcohol-related (or neutral) olfactory and visual cues. RESULTS: Alcohol-related visual cues elicited lower false alarm rates, slower reaction times and higher accuracy rates relative to neutral pictorial cues. False alarm rates were significantly higher for those exposed to alcohol as opposed to neutral olfactory cues. CONCLUSIONS: By highlighting that exposure to alcohol-related olfactory cues may impede response inhibition, the results indicate that exposure to such stimuli may contribute to the activation of cognitive responses which may drive consumption.

Secondary malignancies in chronic myeloid leukemia patients after imatinib-based treatment: long-term observation in CML Study IV.

Treatment of chronic myeloid leukemia (CML) has been profoundly improved by the introduction of tyrosine kinase inhibitors (TKIs). Long-term survival with imatinib is excellent with a 8-year survival rate of ∼88%. Long-term toxicity of TKI treatment, especially carcinogenicity, has become a concern. We analyzed data of the CML study IV for the development of secondary malignancies. In total, 67 secondary malignancies were found in 64 of 1525 CML patients in chronic phase treated with TKI (n=61) and interferon-α only (n=3). The most common malignancies (n⩾4) were prostate, colorectal and lung cancer, non-Hodgkin's lymphoma (NHL), malignant melanoma, non-melanoma skin tumors and breast cancer. The standardized incidence ratio (SIR) for all malignancies excluding non-melanoma skin tumors was 0.88 (95% confidence interval (0.63-1.20)) for men and 1.06 (95% CI 0.69-1.55) for women. SIRs were between 0.49 (95% CI 0.13-1.34) for colorectal cancer in men and 4.29 (95% CI 1.09-11.66) for NHL in women. The SIR for NHL was significantly increased for men and women. An increase in the incidence of secondary malignancies could not be ascertained. The increased SIR for NHL has to be considered and long-term follow-up of CML patients is warranted, as the rate of secondary malignancies may increase over time.

Towards improving service delivery in screening and intervention services in community pharmacies: a case study of an alcohol IBA service.

BACKGROUND: Previous studies have demonstrated positive outcomes from a range of pharmacy public health services, but barriers to delivery remain. This paper explores the processes of delivering an alcohol screening and intervention service, with a view to improving service delivery. METHODS: A mixed-methods, multi-perspective approach was used, comprising in-pharmacy observations and recording of service provision, follow-up interviews with service users and interactive feedback sessions with service providers. RESULTS: Observations and recordings indicate that staff missed opportunities to offer the service and that both availability and delivery of the service were inconsistent, partly owing to unavailability of trained staff and service restrictions. Most service users gave positive accounts of the service and considered pharmacies to be appropriate places for this service. Respondents also described positive impacts, ranging from thinking more about alcohol consumption generally to substantial reductions in consumption. Key facilitators to service provision included building staff confidence and service champions. Barriers included commissioning issues and staff perception of alcohol as a sensitive topic. CONCLUSIONS: Findings support expansion of pharmacies' role in delivering public health services and highlight benefits of providing feedback to pharmacy staff on their service provision as a possible avenue for service improvement.

Combination therapy for multidrug-resistant cytomegalovirus disease.

Multidrug-resistant (MDR) cytomegalovirus (CMV) emerged after transient responses to ganciclovir, foscarnet, and cidofovir in a CMV-seropositive recipient who underwent allogeneic hematopoietic stem cell transplantation from a CMV-seronegative donor. Experimental treatments using leflunomide and artesunate failed. Re-transplantation from a CMV-seropositive donor supported by adoptive transfer of pp65-specific T cells and maribavir was followed by lasting suppression. This case illustrates that successful MDR CMV therapy may require individualized multidisciplinary approaches.

Synergistic effect of sorafenib and cGvHD in patients with high-risk FLT3-ITD+AML allows long-term disease control after allogeneic transplantation.

The multikinase inhibitor sorafenib has shown a strong anti-leukemic effect in FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML); however, remission is often transient. To better understand the role of sorafenib, we performed a retrospective analysis of all patients who received sorafenib in combination with allogeneic hematopoietic stem cell transplantation (HSCT) at our center. Seventeen patients with FLT3-ITD positive AML were treated with sorafenib in combination with allogeneic HSCT. Seven patients received sorafenib therapy pre- and posttransplant, and 10 patients were given sorafenib only posttransplant. Median duration of sorafenib treatment was 13 months (range 1-42); median dose was 600 mg (range 100-1200). Fourteen patients (82 %) achieved a complete remission (CR), while 5 patients (29 %) eventually developed progressive disease. Developing chronic graft-versus-host disease (GvHD) had a strong protective influence on the risk of sorafenib resistance (p = 0.028, HR 0.08, 95 % CI 0.01-0.76). In a total of 8 patients, sorafenib had to be stopped, paused or dose-reduced due to toxicity. In 5 patients with pronounced toxicity, we switched to an alternating dosing schedule with 1 month on/1 month off sorafenib. These patients subsequently remained in sustained complete molecular remission, with a median follow-up of 20 months. Our data indicate that sorafenib can achieve high rates of sustained remission in high-risk patients treated in combination with HSCT.

Lower dose anti-thymocyte globulin for GvHD prophylaxis results in improved survival after allogeneic stem cell transplantation.

In vivo T-cell depletion with anti-thymocyte globulin (ATG) can attenuate GvHD but may increase infection and relapse risks. ATG-Fresenius (ATG-F) at a dose of 60 mg/kg was standard GvHD prophylaxis in unrelated donor hematopoietic stem cell transplantation (HSCT) at our institution. We changed to an incremental reduced dose regimen of 35 mg/kg and extended ATG prophylaxis to include older matched-related donor transplants considered to be at higher risk of GvHD. A total of 265 adults with hematological malignancies receiving a first allogeneic HSCT after myeloablative conditioning between 2009 and 2014 were analyzed in this cohort study. Patients had either received higher dose (n=32) or lower dose ATG-F (n=88) or no ATG (n=145). ATG-F was associated with slower engraftment and less chronic GvHD, whereas no effect was noted on acute grade II-IV GvHD and relapse incidence. Transplant-related mortality (TRM) was lower and survival higher with lower dose, but not with higher dose ATG-F. Both ATG-F groups were associated with more viral reactivation, viral disease and bacterial blood stream infection, but not invasive fungal infection, and with slower immune reconstitution. The recently adopted strategy of using lower doses of ATG-F in unrelated and older age-related donor HSCT appears to reduce TRM without increasing disease relapse, leading to slightly enhanced survival.