Application of organocatalytic approach for the synthesis of piperidine-2-ones, useful building blocks for the preparation of antidepresants

Tato bakalářská práce pojednává o využití organokatalytického konceptu pro přípravu enantiomerně čistých substituovaných piperidin-2-onů ze snadno synteticky dostupných výchozích látek za katalýzy komerčně dostupnými sekundárními aminy. Substituované piperidin-2-ony byly připraveny v dobrých výtěžcích (49-99 %) a s vynikající enantioselektivitou (93-96 % ee). Byla provedena syntéza klíčového intermediátu pro přípravu antidepresiva (+)-femoxetinu, čímž byla syntéza formálně dokončena v úhrnném výtěžku 23 % s enantiomerním přebytkem 95 % ee.This bachelor thesis is focused on the application of organocatalytic approach for the synthesis of enantiomerically pure substitued piperidine-2-ones from synthetically easily avaiable starting materials and commercially avaiable secondary amine. Substitued piperidine-2-ones are prepared in good yields (49-99 %) and excellent enantioselectivities (93-96 % ee). The key-intermediate in synthesis of (+)-femoxetine is prepared and the synthesis is formally finalised in the overall yield 23 % and enantiomeric excess of 95 %.Department of Organic ChemistryKatedra organické chemieFaculty of SciencePřírodovědecká fakult

Unanticipated admissions to paediatric cardiac critical care after cardiac catheterisations.

OBJECTIVES: Cardiac catheterisation is commonly used for diagnosis and therapeutic interventions in paediatric cardiology. The inherent risk of the procedure can result in unanticipated admissions to critical care. Our goals were to provide a qualitative description of characteristics and evaluation of children admitted unexpectedly to the cardiac critical care unit (CCCU). METHODS: A retrospective single centre review of cardiac catheterisation procedures was done between 1 January, 2003 and 30 April, 2013. RESULTS: Of 9336 cardiac catheterisations performed, 146 (1.6%) were admitted from the catheterisation laboratory to the CCCU and met inclusion criteria. Of these 146 patients, 117 (1.3%) met criteria for unexpected admission and 29 (0.3%) were planned admissions. The majority admitted unexpectedly were below 1 year of age without co-morbidity aside from heart disease. Patients with planned admissions were significantly more likely to have single ventricle physiology, undergoing angiography or transferred for observation. Most unplanned admissions were triggered by interventional catheterisations or procedure-related complications. Patients received mechanical ventilation as the main CCCU management. Eighteen patients needed either cardiopulmonary resuscitation and/or extracorporeal membrane oxygenation during their catheterisation. About 106/117 (90.6%) patients survived to hospital discharge with no deaths in the planned admission group. CONCLUSIONS: Admission to CCCU following cardiac catheterisation was uncommon and tended to occur in younger children undergoing interventional procedures. Outcomes did not differ between patients experiencing planned and unplanned CCCU admission. Ongoing development of risk stratification tools may help to decrease unplanned CCCU admissions. Further studies are needed to determine whether unplanned admission following paediatric cardiac catheterisation should be utilised as a quality indicator

Interprofessional Collaboration in a New Model of Transitional Care for Families with Preterm Infants – The Health Care Professional's Perspective

Background: Families with preterm infants find life after hospital discharge challenging and need tailored support to thrive. The “Transition to Home (TtH)”-model offers structured, individual support for families with preterm infants before and after hospital discharge. TtH improves parental mental health and competence, promotes child development and fosters interprofessional collaboration (IPC). Aim: Evaluate the TtH-models’ structure and implementation process and its associated interprofessional collaboration from the healthcare professional’s (HCP) perspective. Methods: This qualitative explorative study thematically analyzed four focus group inter- views (n=28 HCP) and an open-ended questionnaire with general pediatricians (n=8). Results: The main themes of the thematic analysis were the benefits of the TtH-model, tailored parental support, the challenges of changing interprofessional collaboration, facil- itators and barriers to successfully implementing the model, and feasibility and health economic limits. HCP acknowledge that continuous family-centered care led by an advanced practice nurse (APN) supports, strengthens, and relieves families with preterm infants in the transition from hospital to home. Families in complex situations benefit most. The TtH- model incorporates key aspects of integrated care like shared decision-making, considering family preferences, and defining the APN as the family’s main contact. HCP want network collaboration but found communication, cooperation, and reorganization challenging in the new IPC process. IPC challenges and involving many HCP in family care can create parental oversupply, negatively affect treatment outcomes, and raise health care costs. Conclusion: These challenges need to be addressed to ensure sustainable implementation of the model. The roles and tasks of HCP should be clearly distinguished from each other, and HCP must have time to learn this new form of IPC. Learning requires time, effective communication strategies, and leadership support. Political action is also required to imple- ment new models of care, including regulating advanced practice roles and developing new financing models

Enhancing Parents’ Well-Being after Preterm Birth—A Qualitative Evaluation of the “Transition to Home” Model of Care

There are few programs available aimed at preventing short- and long-term negative consequences after preterm birth and covering the entire care continuum. The “Transition to Home (TtH)” model is such a program, offering structured, individual support for families with preterm infants before and after hospital discharge. This study gathers and examines the parents’ views of receiving support from an interprofessional team under the TtH model of care during hospitalization and after discharge. Using a qualitative explorative design, 39 semi-structured interviews with parents were analyzed thematically. From this analysis, three main themes were identified: (1) TtH and the relevance of continuity of care; (2) Enhancement of parents’ autonomy and self-confidence; (3) Perception of interprofessional collaboration. Within these themes, the most relevant aspects identified were continuity of care and the appointment of a designated health care professional to anchor the entire care continuum. Emotional support complemented by non-medical approaches, along with strength-based and family resource-oriented communication, also emerged as key aspects. Continuous, family-centered care and well-organized interprofessional collaboration promote the well-being of the family after a premature birth. If the aspects identified in this study are applied, the transition from hospital to home will be smoothened for the benefit of affected families

Hemodynamic and prognostic impact of the diastolic pulmonary arterial pressure in children with pulmonary arterial hypertension-a registry-based analysis

BACKGROUND: Diastolic pulmonary arterial pressure (dPAP) is regarded to be less sensitive to flow metrics as compared to mean PAP (mPAP), and was therefore proposed for the assessment of a precapillary component in patients with postcapillary pulmonary hypertension (PH). To analyze the diagnostic and prognostic impact of dPAP in patients with pure precapillary PH, we purposed to compare the correlation between dPAP and mPAP, as well as hemodynamically-derived calculations [ratio of PAP to systemic arterial pressure (PAP/SAP), pulmonary vascular resistance index (PVRI), transpulmonary gradient (TPG)], using both dPAP and mPAP, at rest and during acute vasoreactivity testing (AVT) in children with idiopathic or heritable pulmonary arterial hypertension (IPAH/HPAH). Furthermore, we aimed to assess the association of these metrics (at baseline and changes after AVT) with transplant-free survival. METHODS: We conducted a retrospective analysis of the TOPP (Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension) registry including 246 IPAH/HPAH patients. Of these, 45 children (18.3%) died, and 13 (5.3%) received lung transplantation during the observation period. RESULTS: dPAP and mPAP-derived variables showed almost linear relationship. Higher mPAP/mSAP, and dPAP-/mPAP-derived PVRI at rest was associated with time to death/transplantation. At maximum AVT-response, the decrease of dPAP and mPAP, diastolic pulmonary gradient (DPG) and TPG, as well as dPAP/dSAP and mPAP/mSAP was associated with time to death/transplantation, showing higher significance than corresponding baseline values. Remarkably, no predictive value was found for PVRI-reduction during AVT, neither dPAP- nor mPAP-derived. CONCLUSIONS: There is a strong relationship between dPAP and mPAP-derived variables. According to our results, hemodynamics during AVT (irrespectively of dPAP- or mPAP-derived) may have more prognostic implications than resting hemodynamics in children with IPAH/HPAH, except for PVRI

Evaluierung der Zugangsregelungen nach § 71b, § 71c, § 71d UG 2002

Seit rund 15 Jahren gibt es an öffentlichen Universitäten in Österreich quantitative Zugangsregelungen. Diese Zugangsregelungen sind gemäß § 143 Abs. 42 Universitätsgesetz 2002 zu evaluieren

Application of a modified clinical classification for pulmonary arterial hypertension associated with congenital heart disease in children: emphasis on atrial septal defects and transposition of the great arteries. An analysis from the TOPP registry

AimsA proportion of patients with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) do not fit in the current classification. We aimed to analyse the applicability of an adapted clinical classification of PAH-CHD to pediatric patients using the TOPP-1 registry (Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension) and focus on atrial septal defects (ASD) and transposition of the great arteries (TGA).Methods and resultsHemodynamic and clinical data of all patients with PAH-CHD in the TOPP cohort were reviewed. Patients were classified according to predefined ABCDE categories (A: Eisenmenger syndrome, B: left-to-right shunt, C: coincidental defects, including all ASDs, D: corrected CHD, E: TGA), or as complex CHD (group 5), by 2 independent investigators. In case of disagreement, a third reviewer could either settle a final decision, or the patient was deemed not classifiable. Survival curves were calculated for each group and compared to idiopathic PAH patients of the registry. A total of 223 out of 531 patients in the registry had PAH-CHD, and 193 were categorized to the following groups: A 39(20%), B 27(14%), C 62(32%) including 43 ASDs, D 58(30%), E 7(4%), whereas 6 patients were categorized as group 5, and 10 patients were unable to be classified. No survival difference could be demonstrated between the groups.ConclusionsThis modified classification seems to be more applicable to pediatric PAH-CHD patients than the previous classification, but some patients with PAH-CHD who never had a shunt remain unclassifiable. The role of ASD in pediatric PH should be reconsidered

Biventricular structural and functional responses to aortic constriction in a rabbit model of chronic right ventricular pressure overload

Objectives: Chronic right ventricular (RV) pressure overload results in pathologic RV hypertrophy and diminished RV function. Although aortic constriction has been shown to improve systolic function in acute RV failure, its effect on RV responses to chronic pressure overload is unknown. Methods: Adjustable vascular banding devices were placed on the main pulmonary artery and descending aorta. In 5 animals (sham group), neither band was inflated. In 9 animals (PAB group), only the pulmonary arterial band was inflated, with adjustments on a weekly basis to generate systemic or suprasystemic RV pressure at 28 days. In 9 animals, both pulmonary arterial and aortic devices were inflated (PAB+AO group), the pulmonary arterial band as for the PAB group and the aortic band adjusted to increase proximal systolic blood pressure by approximately 20 mm Hg. Effects on the functional performance were assessed 5 weeks after surgery by conductance catheters, followed by histologic and molecular assessment. Results: Contractile performance was significantly improved in the PAB+AO group versus the PAB group for both ventricles. Relative to sham-operated animals, both banding groups showed significant differences in myocardial histologic and molecular responses. Relative to the PAB group, the PAB+AO group showed significantly decreased RV cardiomyocyte diameter, decreased RV collagen content, and reduced RV expression of endothelin receptor type B, matrix metalloproteinase 9, and transforming growth factor beta genes. Conclusions: Aortic constriction in an experimental model of chronic RV pressure overload not only resulted in improved biventricular systolic function but also improved myocardial remodeling. These data suggest that chronically increased left ventricular afterload leads to a more physiologically hypertrophic response in the pressure-overloaded RV. (J Thorac Cardiovasc Surg 2012;144:1494-501)Deutsche Herzstiftung e.V., Frankfurt, German

Pulmonary-to-Systemic Arterial Shunt to Treat Children With Severe Pulmonary Hypertension

BACKGROUND: The placement of a pulmonary-to-systemic arterial shunt in children with severe pulmonary hypertension (PH) has been demonstrated, in relatively small studies, to be an effective palliation for their disease. OBJECTIVES: The aim of this study was to expand upon these earlier findings using an international registry for children with PH who have undergone a shunt procedure. METHODS: Retrospective data were obtained from 110 children with PH who underwent a shunt procedure collected from 13 institutions in Europe and the United States. RESULTS: Seventeen children died in-hospital postprocedure (15%). Of the 93 children successfully discharged home, 18 subsequently died or underwent lung transplantation (20%); the mean follow-up was 3.1 years (range: 25 days to 17 years). The overall 1- and 5-year freedom from death or transplant rates were 77% and 58%, respectively, and 92% and 68% for those discharged home, respectively. Children discharged home had significantly improved World Health Organization functional class (P < 0.001), 6-minute walk distances (P = 0.047) and lower brain natriuretic peptide levels (P < 0.001). Postprocedure, 59% of children were weaned completely from their prostacyclin infusion (P < 0.001). Preprocedural risk factors for dying in-hospital postprocedure included intensive care unit admission (hazard ratio [HR]: 3.2; P = 0.02), mechanical ventilation (HR: 8.3; P < 0.001) and extracorporeal membrane oxygenation (HR: 10.7; P < 0.001). CONCLUSIONS: A pulmonary-to-systemic arterial shunt can provide a child with severe PH significant clinical improvement that is both durable and potentially free from continuous prostacyclin infusion. Five-year survival is comparable to children undergoing lung transplantation for PH. Children with severely decompensated disease requiring aggressive intensive care are not good candidates for the shunt procedure