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The global burden of antibiotic resistance is tremendous and, without new anti-infective strategies, will continue to increase in the coming decades. Despite the growing need for new antibiotics, few pharmaceutical companies today retain active antibacterial drug discovery programmes. One reason is that it is scientifically challenging to discover new antibiotics that are active against the antibiotic-resistant bacteria of current clinical concern. However, the main hurdle is diminishing economic incentives. Increased global calls to minimize the overuse of antibiotics, the cost of meeting regulatory requirements and the low prices of currently marketed antibiotics are strong deterrents to antibacterial drug development programmes. New economic models that create incentives for the discovery of new antibiotics and yet reconcile these incentives with responsible antibiotic use are long overdue. DRIVE-AB is a €9.4 million public–private consortium, funded by the EU Innovative Medicines Initiative, that aims to define a standard for the responsible use of antibiotics and to develop, test and recommend new economic models to incentivize investment in producing new anti-infective agents.

Respiratory syncytial virus (RSV) is a major worldwide cause of morbidity and mortality in children under five years of age. Evidence-based management guidelines suggest that there is no effective treatment for RSV lower respiratory tract infection (LRTI) and that supportive care, ie, hydration and oxygenation, remains the cornerstone of clinical management. However, RSV treatments in development in the past decade include 10 vaccines and 11 therapeutic agents in active clinical trials. Maternal vaccination is particularly relevant because the most severe disease occurs within the first 6 months of life, when children are unlikely to benefit from active immunisation. We must optimise the implementation of novel RSV therapeutics by understanding the target populations, showing safety, and striving for acceptable pricing in the context of this worldwide health problem. In this Review, we outline the limitations of RSV LRTI management, the drugs in development, and the remaining challenges related to study design, regulatory approval, and implementation. © 2015 Elsevier Ltd.

Asthma treatment might improve when inhaled steroids are titrated on airway inflammation. Fractional exhaled nitric oxide (FeNO0.05), a marker of eosinophilic airway inflammation, can be measured at home.We assessed daily FeNO0.05 telemonitoring in the management of childhood asthma.Children with atopic asthma (n = 151) were randomly assigned to two groups: FeNO0.05 plus symptom monitoring, or monitoring of symptoms only. All patients scored asthma symptoms in an electronic diary over 30 weeks; 77 received a portable nitric oxide (NO) analyzer. Data were transmitted daily to the coordinating centers. Patients were phoned every 3 weeks and their steroid dose was adapted according to FeNO0.05 and symptoms, or according to symptoms. Children were seen at 3, 12, 21, and 30 weeks for examination and lung function testing. The primary end point was the proportion of symptom-free days in the last 12 study weeks.Telemonitoring was feasible with reliable FeNO0.05 data for 86% of days, and valid diary entries for 79% of days. Both groups showed an increase in symptom-free days, improvement of FEV1 and quality of life, and a reduction in steroid dose. None of the changes from baseline differed between groups. The difference in symptom-free days over the last 12 weeks was 0.3% (P = 0.95; 95% confidence interval, -10 to 11%). There was a trend for fewer exacerbations in the FeNO0.05 group.Thirty weeks of daily FeNO0.05 and symptom telemonitoring was associated with improved asthma control and a lower steroid dose. We found no added value of daily FeNO0.05 monitoring compared with daily symptom monitoring only.

This paper discusses the commercialization of science as an embedding process within a complex network of technical and social resources resources. We rely on a single in-depth case study over the commercialization and de-commercialization of Uppsala PET center in order to identify how PET radiotracers, our focal piece of science, are interfaced with other resources and how they are connected to the three settings of developing, producing and using. We find that the twists and turns in the innovation journey of the PET center depend on deep technical interfaces, problematic mixed interfaces that create conflicts between the involved actors, and shallow organizational interfaces

Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved. © 2012 John Wiley & Sons A/S.

There is a lack of high-quality evidence on what treatment should be used in children with properly characterised severe, therapy-resistant asthma. Data have to be largely extrapolated from trials in children with mild asthma, and adults with severe asthma. Therapeutic options can be divided into medications used in lower doses for children with less severe asthma, and those used in other paediatric diseases but not for asthma (for example, methotrexate). In the first category are high-dose inhaled corticosteroids (ICS) (≤ 2,000 μg · day(-1) fluticasone equivalent), oral prednisolone, the anti-immunoglobulin (Ig)E antibody omalizumab, high-dose long-acting β(2)-agonists, low-dose oral theophylline and intramuscular triamcinolone. If peripheral airway inflammation is thought to be a problem, the use of fine-particle ICS or low-dose oral corticosteroids may be considered. More experimental therapies include oral macrolides, cyclosporin, cytotoxic drugs such as methotrexate and azathioprine, gold salts, intravenous infusions of Ig, subcutaneous β(2)-agonist treatment and, in those sensitised to fungi, oral antifungal therapy with itraconazole or voriconazole. Those with recurrent severe exacerbations, particularly in the context of good baseline asthma control, are particularly difficult to treat; baseline control and lung function must be optimised with the lowest possible dose of ICS, and allergen triggers and exposures minimised. The use of high-dose ICS, leukotriene receptor antagonists or both at the time of exacerbations can be considered. There is no evidence regarding which therapeutic option to recommend. Better evidence is required for all these treatment options, underscoring the need for the international and co-ordinated approach which we have previously advocated.

Although most children with asthma are easy to treat with low doses of safe medications, many remain symptomatic despite every therapeutic effort. The nomenclature regarding this group is confusing, and studies are difficult to compare due to the proliferation of terms describing poorly defined clinical entities. In this review of severe asthma in children, the term problematic severe asthma is used to describe children with any combination of chronic symptoms, acute severe exacerbations and persistent airflow limitation despite the prescription of multiple therapies. The approach to problematic severe asthma may vary with the age of the child, but, in general, three steps need to be taken in order to separate difficult-to-treat from severe therapy-resistant asthma. First, confirmation that the problem is really due to asthma requires a complete diagnostic re-evaluation. Secondly, the paediatrician needs to systematically exclude comorbidity, as well as personal or family psychosocial disorders. The third step is to re-evaluate medication adherence, inhaler technique and the child's environment. There is a clear need for a common international approach, since there is currently no uniform agreement regarding how best to approach children with problematic severe asthma. An essential first step is proper attention to basic care.

Hintergrund: Im Rahmen der offenen, randomisierten Phase III-Studie ARTEMIS wurde Darunavir/Ritonavir (DRV/r) 800/100mg qd (n=343) mit Lopinavir( LPV/r) 800/200mg pro Tag( [qd or bid]; n=346) jeweils in Kombination mit Tenofovir/Emtricitabin bei nicht[for full text, please go to the a.m. URL], 10. Kongress für Infektionskrankheiten und Tropenmedizin (KIT 2010)

Several epidemiologic studies have suggested an association between childhood asthma and exposure to disinfection by-products (DBPs) in the swimming pool environment. In August 2007 a group of clinicians, epidemiologists, exposure scientists, pool operations experts, and analytical chemists met to discuss the literature on childhood asthma and swimming pools, and to develop recommendations for future research. In a review based on the results of that workshop, the authors state that current evidence, while suggestive, is inconclusive for an association with childhood asthma, and they point to several substantial data gaps that must be filled [EHP 117:500–507; Weisel et al.]. The authors articulate several variables that must be measured in more detail to properly characterize inhalation exposure to chemicals around pools. The review calls for a comprehensive assessment of a substantially larger number of chemicals in the pool area than the limited number of DBPs studied to date. Earlier epidemiologic studies suggested trichloramine as a DBP of interest, but one 2007 study revealed previously unknown volatile DBPs in the air surrounding swimming pools. The frequency and extent of exposure to chemicals around pools also must be studied. In research to date, only simple exposure indices have been used, including whether the pool was indoors or outdoors, specific disinfection treatment, whether the child swam in or was simply present at an indoor pool, and cumulative duration of swimming. But to evaluate the breathing rate and DBP dose delivered to the lungs, more detailed, validated assessments of activity levels are needed. To obtain these data, the authors recommend that future studies use prospective questionnaires in which participants report their pool use and activity levels over time as they occur. The authors also point to the need for studies that define asthma cases in a rigorous, reproducible way, utilizing the International Study of Asthma and Allergy in Children questionnaire. Previous studies have often used clinical diagnoses, but this may be insufficient for epidemiologic studies because asthma is a heterogeneous disease with no single reliable diagnostic test. Additional needs include development and validation of new biomarkers for asthmatic reactivity and studies designed to refine guidelines for proper pool maintenance and disinfection to reduce levels of DBPs. The authors conclude this research area requires studies across multiple disciplines. Once chemicals of interest are identified, studies of the mechanisms behind the possible association—such as oxidative stress, inflammation, and changes in lung permeability—may be useful. But long-range prospective studies starting in early childhood will be needed to better gauge the relationship between swimming pools and childhood asthma. Absent conclusive studies, the authors say children’s exposures should be minimized. Pool managers must be well educated about pool chemistry so they can understand the potential dangers of disinfectants and DBPs. Swimmers, too, must be educated about the need for proper pool hygiene (for example, showering before swimming and not urinating in the pool), as swimmer hygiene can affect the formation of DBPs and the amount of disinfectant used.

Services have become an increasingly important part of many organizations' expenditures. At the same time, organizational buyers view the purchase of business services to be highly complex. The specific characteristics of services influence the purchasing process in the sense that certain steps in the purchasing process become more important, more difficult, or just different in comparison with purchasing the process for goods. This paper investigates the phase of ex post evaluation of suppliers of business services. Based on a literature review on supplier evaluation models, we identify three types of quality that are important in evaluating the performance of service suppliers. We then conduct an embedded case study to identify which of these quality types are most important for services for which the buying company pursues are more transactional approach, versus services for which a more relational view is adopted. The results of this embedded case study indicate that functional service quality (i.e. quality of the service process) and relationship quality are less important for services that are bought via a transactionoriented purchasing strategy than for services bought by a relation-oriented purchasing strategy.

Background The PERSEO study (psychiatric emergency study and epidemiology) is a naturalistic, observational clinical survey in Italian acute hospital psychiatric units, called SPDCs (Servizio Psichiatrico Diagnosi e Cura; in English, the psychiatric service for diagnosis and management). The aims of this paper are: (i) to describe the epidemiological and clinical characteristics of patients, including sociodemographic features, risk factors, life habits and psychiatric diagnoses; and (ii) to assess the clinical management, subjective wellbeing and attitudes toward medications. Methods A total of 62 SPDCs distributed throughout Italy participated in the study and 2521 patients were enrolled over the 5-month study period. Results Almost half of patients (46%) showed an aggressive behaviour at admission to ward, but they engaged more commonly in verbal aggression (38%), than in aggression toward other people (20%). A total of 78% of patients had a psychiatric diagnosis at admission, most frequently schizophrenia (36%), followed by depression (16%) and personality disorders (14%), and no relevant changes in the diagnoses pattern were observed during hospital stay. Benzodiazepines were the most commonly prescribed drugs, regardless of diagnosis, at all time points. Overall, up to 83% of patients were treated with neuroleptic drugs and up to 27% received more than one neuroleptic either during hospital stay or at discharge. Atypical and conventional antipsychotics were equally prescribed for schizophrenia (59 vs 65% during stay and 59 vs 60% at discharge), while atypical drugs were preferred in schizoaffective psychoses (72 vs 49% during stay and 70 vs 46% at discharge) and depression (41 vs 32% during stay and 44 vs 25% at discharge). Atypical neuroleptics were slightly preferred to conventional ones at hospital discharge (52 vs 44%). Polypharmacy was in general widely used. Patient attitudes toward medications were on average positive and self-reported compliance increased during hospital stay. Conclusion Results confirm the widespread use of antipsychotics and the increasing trend in atypical drugs prescription, in both psychiatric in- and outpatients.