Although transforming growth factor-beta (TGF-␤) signaling negatively regulates branching morphogenesis in early lung development, few studies to date have addressed the role of this family of growth factors during late lung development. We describe here that the expression, tissue localization, and activity of components of the TGF-␤ signaling machinery are dynamically regulated during late lung development in the mouse and human. Pronounced changes in the expression and localization of the TGF-␤ receptors Acvrl1, Tgfbr1, Tgfbr2, Tgfbr3, and endoglin, and the intracellular messengers Smad2, Smad3, Smad4, Smad6, and Smad7 were noted as mouse and human lungs progressed through the canalicular, saccular, and alveolar stages of development. TGF-␤ signaling, assessed by phosphorylation of Smad2, was detected in the vascular and airway smooth muscle, as well as the alveolar and airway epithelium throughout late lung development. These data suggest that active TGF-␤ signaling is required for normal late lung development. Developmental Dynamics 237:259 -269, 2008.

Besides focussing on disease in the diagnostic process, emotional and strategic goals are hidden motives that play a critical role in clinical decision-making. They might even represent an initial factor in a cascade of interventions leading to overdiagnosis. How GPs might control these influences provides an important aspect for further research, practice and teaching.

Background: Collaborative care approaches between general practitioners (GPs) and pharmacists have received international recognition for medication optimization and deprescribing efforts. Although specialist providers have been shown to influence deprescribing, their profession so far remains omitted from collaborative care approaches for medication optimization. Similarly, while explorative studies on role perception and collaboration between GPs and pharmacists grow, interaction with specialists for medication optimization is neglected. Our qualitative study therefore aims to explore GPs', community pharmacists' and specialist providers' role perceptions of deprescribing, and to identify interpersonal as well as structural factors that may influence collaborative medication optimization approaches. Method: Seven focus-group discussions with GPs, community pharmacists and community specialists were conducted in Hesse and Lower Saxony, Germany. The topic guide focused on views and experiences with deprescribing with special attention to inter-professional collaboration. We conducted conventional content analysis and conceptualized emerging themes using the Theoretical Domains Framework. Results: Twenty-six GPs, four community pharmacists and three community specialists took part in the study. The main themes corresponded to the four domains 'Social/professional role and identity' (1), 'Social influences' (2), 'Reinforcement' (3) and´Environmental context and resources' (4) which were further described by beliefs statements, that is inductively developed key messages. For (1), GPs emerged as central medication managers while pharmacists and specialists were assigned confined or subordinated tasks in deprescribing. Social influences (2) encompassed patients' trust in GPs as a support, while specialists and pharmacists were believed to threaten GPs' role and deprescribing attempts. Reinforcements (3) negatively affected GPs' and pharmacists' effort in medication optimization by social reprimand and lacking reward. Environmental context (4) impeded deprescribing efforts by deficient reimbursement and resources as well as fragmentation of care, while informational and gate-keeping resources remained underutilized.

The aim of this systematic review was to identify generic instruments for drug discontinuation in patients with polypharmacy in the primary care setting.Methods: We systematically searched PubMed and EMBASE, 8 guideline databases (AWMF, NICE, NGC, SIGN, NHMRC, CPG, KCE), the Cochrane Library and grey literature (Google) in 2016 and 2017. Two independent researchers screened and analysed data. The drug discontinuation instruments of the included publications were described and classified.Results: We identified 16 relevant publications. Here we found complex algorithms as well as instruments composed of distinct sequential steps. Two guidelines are constructed as electronic web-applications. Instruments revealed diverging emphases on the stages of deprescribing, i.e. preparation, drug evaluation, decisionmaking and implementation. Accordingly, 3 types of instruments emerged: general frameworks, detailed drug assessment tools and comprehensive discontinuation guidelines. Conclusion:Diverse generic instruments exist for different areas of applications in regard to drug discontinuation. However, there is still a need for practical and userfriendly tools that support physicians in communicational aspects, visualise trade-offs and also enhance patient involvement.

Background Deprescribing is an important task for general practitioners (GPs) in the face of risky polypharmacy. The electronic tool "MediQuit" was developed to guide GPs and patients through a deprescribing consultation that entails a drug-selection phase, shared decision making, and advice on safe implementation. Objectives A pilot study was conducted to determine the target group of patients that is selected for consultation and to assess the impact, patient involvement, and feasibility of the tool. Methods This was an uncontrolled pilot study. GPs from two German regions were invited to use MediQuit in consultations with a view to deprescribing one drug, if appropriate. They selected patients on the basis of broad inclusion criteria. Collected data entailed participants' characteristics, patients' medication lists, deprescribed drugs, and feasibility assessments. Patients were contacted shortly after the consultation and again after 4 weeks. Results In total, 16 GPs agreed to participate, of whom ten actually performed deprescribing consultations. They selected 41 predominately older patients on excessive polypharmacy. Deprescribing was achieved in 70% of consultations in agreement with patients. Drugs deprescribed were symptom-lowering and preventive drugs (mainly anatomical therapeutic chemical classes A and C). GPs found MediQuit useful in initiating communication on this issue and enhancing deliberations for a deprescribing decision. The median consultation length was 15 min (interquartile range 10-20). At follow-up, GPs and patients infrequently disagreed on which drug(s) was discontinued, and GPs rated patient involvement higher than did patients themselves. Discussion MediQuit assists in identifying concrete deprescribing opportunities, patient involvement, and shared decision making. The three-step deprescribing procedure is well-accepted once initial organizational efforts are overcome. After revision, further studies are needed to enhance the quality of evidence on acceptance and effectiveness.