Osteoporosis treatment with denosumab in routine clinical practice in Poland

Introduction: The receptor activator for nuclear factor k B ligand (RANKL) inhibitor denosumab is approved for the treatment of osteoporosis in postmenopausal women and men at increased fracture risk. The objectives were to describe the characteristics of patients with osteoporosis initiating denosumab in Polish clinical practice and their clinical management during the first 12 months of denosumab treatment. Material and methods: This prospective, observational study enrolled denosumab-naïve women and men in Poland with osteoporosis, who had received at least one denosumab injection in the 8 weeks prior to enrolment. Patients were enrolled from specialist osteoporosis treatment centres, and orthopaedic, rheumatological, and family doctor centres. Outcomes included patient characteristics, denosumab treatment patterns, bone mineral density (BMD), and fracture; all analyses were descriptive. Results: The study enrolled 463 patients; most (96%) were women, aged ≥ 65 years (84%), with prior fractures (88%). Approximately two-thirds of the women had received prior osteoporosis therapy, with the main reasons for discontinuation being adverse events (75%) and lack of effect (73%). Across all patients, the most common reasons for prescribing denosumab were low bone mineral density (BMD/T-score) (93%) and history of osteoporotic fracture (78%). Mean BMD at denosumab initiation ranged from T-score –3.00 (lumbar spine) to T-score –2.6 (total hip), and BMD increased by 2.8–6.2% at month 12. Most patients completed follow-up (86%) and were due to receive a third denosumab injection (81%). Conclusion: The article presents detailed sociodemographic and disease-related characteristics of patients who routinely implemented denosumab therapy. Most of them continued denosumab for at least 12 months, with increased BMD T-scores

Comparative two time-point proteome analysis of the plasma from preterm infants with and without bronchopulmonary dysplasia

Background: In this study, we aimed to analyze differences in plasma protein abundances between infants with and without bronchopulmonary dysplasia (BPD), to add new insights into a better understanding of the pathogenesis of this disease. Methods: Cord and peripheral blood of neonates (≤ 30 weeks gestational age) was drawn at birth and at the 36th postmenstrual week (36 PMA), respectively. Blood samples were retrospectively subdivided into BPD(+) and BPD(−) groups, according to the development of BPD. Results: Children with BPD were characterized by decreased afamin, gelsolin and carboxypeptidase N subunit 2 levels in cord blood, and decreased galectin-3 binding protein and hemoglobin subunit gamma-1 levels, as well as an increased serotransferrin abundance in plasma at the 36 PMA. Conclusions: BPD development is associated with the plasma proteome changes in preterm infants, adding further evidence for the possible involvement of disturbances in vitamin E availability and impaired immunological processes in the progression of prematurity pulmonary complications. Moreover, it also points to the differences in proteins related to infection resistance and maintaining an adequate level of hematocrit in infants diagnosed with BPD

Comparison of whole genome expression profile between preterm and full-term newborns

Objectives: Evaluate the time dependent expression of genes in preterm neonates and verify the influence of ontogenic maturation and the environmental factors on the gene expression after birth. Material and methods: The study was carried out on 20 full-term newborns and 62 preterm newborns (mean birth weight = 1002 [g] (SD: 247), mean gestational age = 27.2 weeks (SD: 1.9)). Blood samples were drawn from all the study participants at birth and at the 36th week postmenstrual age from the preterm group to assess whole genome expression in umbilical cord blood and in peripheral blood leukocytes, respectively. (SurePrint G3 Human Gene Expression v3, 8x60K Microarrays (Agilent)). Results: A substantial number of genes was found to be expressed differentially at the time of birth and at 36 PMA in comparison to the term babies with more genes being down-regulated than up-regulated. However, the fold change in the majority of cases was < 2.0. Extremely preterm and very preterm infants were characterized by significantly down-regulated cytokine and chemokine related pathways. The number of down-regulated genes decreased and number of up-regulated genes increased at 36 PMA vs. cord blood. There were no specific gene expression pathway profiles found within the groups of different gestational ages. Conclusions: Preterm delivery is associated with a different gene expression profile in comparison to term delivery. The gene expression profile changes with the maturity of a newborn measured by the gestational age

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Geographic information system for mobile devices Design and implementation

Celem niniejszej pracy magisterskiej było zaprojektowanie mobilnego systemu informacji przestrzennej i przedstawienie jego przykładowej implementacji. Został stworzony projekt architektury oprogramowania oraz omówiono decyzje, które zostały podjęte w celu rozwiązania napotkanych problemów projektowych, a także wybrane technologie. Przedstawiony system składa się z dwóch modułów: aplikacji serwerowej oraz programu klienta, działającego na urządzeniu mobilnym – smartfonie.Dla aplikacji serwerowej została wybrana platforma Google App Engine. Jest to model chmury obliczeniowej Platforma jako Usługa, udostępniający programistom niezbędne narzędzia do tworzenia oprogramowania, hosting stron www, wirtualne środowisko uruchomieniowe oraz skalowalną, rozproszoną i nierelacyjną bazę danych. Część ta została stworzona w języku programowania Java.Przygotowano aplikację klienta dla telefonów komórkowych z zainstalowanym systemem operacyjnym Android. Jest to rozwiązanie wpierane przez firmę Google, które łatwo zintegrować z usługami Google App Engine. Udostępniony protokół GCM sprawił, że komunikacja serwera z tymi urządzeniami jest szybka, a dodatkowo bezpłatna. Oprogramowanie dla tej platformy zostało stworzone w języku programowania Java.Przedstawiony projekt może stanowić szkielet dla bardziej wyspecjalizowanych rozwiązań, a omówiona architektura pozwala na dodawanie nowych funkcjonalności.The purpose of present M. A. thesis was to design and implement geographic information system for mobile devices. It contains project of software architecture and discussion of decisions that have been made to solve problems during design. The dissertation presents technologies and explains the reasons for which they are used in the implementation. The present system contains of two modules: server-side application and client created for smart phones.Google App Engine is the platform selected for server-side application to be implemented. It is platform as a service cloud computing solution, that offers tools for developers, automatic scaling for applications, virtual runtime environment, web hosting and scalable, distributed, non relational database. This part was developed in the Java programming language. Client application was implemented for mobile phones running the Android operating system. It is solution fostered by Google company and can easily integrate with Google App Engine. Furthermore, published GCM protocol made the serve communication with these devices fast and free of charges. Software created for this platform was developed in the Java programming language.The proposed project can be used as a framework for more specialized solutions and architecture discussed in the paper allows to extend it with new functionality

Analiza obrazu klinicznego niedoczynności tarczycy u kobiet w okresie menopauzy

The objective of this retrospective study was to analyze the clinical picture of hypothyroidism in women, inrelation to their menopausal status. Materials and methods: A total of 694 female ambulatory patients were divided into 3 groups: group I – 258menstruating patients aged up to 45, group II – 124 perimenopausal patients aged between 46 and 52, group III– 312 postmenopausal patients aged over 52. Medical documentation of the patients with hypothyroidism wasevaluated in terms of the selected features of their medical history and clinical picture of the disease. Results: The main cause of hypothyroidism was the chronic autoimmune thyroid gland inflammation; ingroup I it concerned 62.8% of patients, in the remaining two groups it was 50.0% and 51.6%, respectively. Analysing the prevalence of clinical symptoms it was found that the most frequent ones were: weight gain (18.6%),weakness (16.3%) and drowsiness (14.7%). In group II the prevailing symptoms were: hypertension (37.1%),weight gain (21.8%), drowsiness and weakness (12.1%) whereas in group III hypertension (60.3%), symptoms ofischemic heart disease (24.4%) and weight gain (14.4%) were dominant. Mean daily doses of levothyroxine usedin the 3 groups of patients were 90 μg, 81 μg ,74 μg, respectively. In women from groups II and III, a lipid balancedisorder (hypercholesterolemia) was observed significantly more often than in younger patients. Conclusions: Hyperthyroidism was diagnosed most frequently in postmenopausal women. The main causeof hypothyroidism was the chronic autoimmune thyroid gland inflammation. In postmenopausal women unusualclinical symptoms of hyperthyroidism dominated, which resulted from the coexistence of other diseases,mainly cardiovascular disorders. A 24-hour long-dose of levothyroxine in postmenopausal women was lower ascompared to menstruating women. Hypercholesterolemia was a considerably frequent element of the clinicalpicture of hypothyroidism in postmenopausal women

An iTRAQ-based quantitative proteomic analysis of plasma proteins in preterm newborns with retinopathy of prematurity

Purpose: Retinopathy of prematurity (ROP) is a vision-threatening complication of a premature birth, in which the etiology still remains unclear. Importantly, the molecular processes that govern these effects can be investigated in a perturbed plasma proteome composition. Thus, plasma proteomics may add new insights into a better understanding of the pathogenesis of this disease. Methods: The cord and peripheral blood of neonates (≤30 weeks gestational age) was drawn at birth and at the 36th postmenstrual week (PMA), respectively. Blood samples were retrospectively subdivided into ROP(+) and ROP(−) groups, according to the development of ROP. Results: The quantitative analysis of plasma proteome at both time points revealed 30 protein abundance changes between ROP(+) and ROP(−) groups. After standardization to gestational age, children who developed ROP were characterized by an increased C3 complement component and fibrinogen level at both analyzed time points. Conclusions: Higher levels of the complement C3 component and fibrinogen, present in the cord blood and persistent to 36 PMA, may indicate a chronic low-grade systemic inflammation and hypercoagulable state that may play a role in the development of ROP