Nursing care for patient with Crohn's disease in the surgical department

U radu se prikazuje vanjskotrgovinska razmjena Republike Hrvatske od 2012. do 2016. godine. Glavne komponente vanjskotrgovinske razmjene su, izvoz i uvoz, a njihov odnos iskazuje se na vanjskotrgovinskoj bilanci, u pozitivnom iznosu kao suficit, u negativnom kao deficit. Rad prikazuje kretanje izvoza i uvoza u apsolutnim iznosima i strukturu vanjskotrgovinske bilance te daje pregled vanjskotrgovinske razmjene s najvažnijim zemljama partnerima Republike Hrvatske. Činjenica je da sve zemlje teže ostvarivanju suficita, stoga se u radu naglašava važnost i mogućnosti stimuliranja izvoza u Republici Hrvatskoj. Metodom intervjua, na primjeru iz prakse jednog izvoznika, prikazani su problemi s kojima se susreće u poslovanju.This thesis discusses foreign trade in the Republic of Croatia since 2012 until 2016. Relations in the foreign trade are determined by Croatia's foreign trade policy. Key foreign trade components have been defined, as well as import and export. Their relations are shown in the foreign trade balance, in the positive amount as surplus and in the negative as deficit. This thesis shows the movement of exports and imports in absolute terms and structure of foreign trade balance and it gives an overview of foreign trade with the most important Croatia's partner countries. It is a fact that all countries seek to achieve a surplus, therefore, the importance and the possibility of export stimulation has been emphasized. This paper shows, in an interview, all the problems that a Croatian exporter has had during his business experience

Clinical experience and management of adverse events in patients with advanced ALK-positive non-small-cell lung cancer receiving alectinib.

Alectinib is a preferred first-line therapy for patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) in several national clinical practice guidelines. The randomized, global, phase III ALEX study has demonstrated significant improvement in progression-free survival for alectinib over crizotinib in treatment-naive ALK-positive NSCLC. It was also the first study to show clinically meaningful improvement in overall survival for a next-generation ALK tyrosine kinase inhibitor relative to crizotinib. The J-ALEX and ALESIA phase III studies confirmed the clinical benefit of alectinib relative to crizotinib in the first-line ALK-positive NSCLC treatment setting in Japanese and Asian patients, respectively. Across these pivotal phase III trials, alectinib had a manageable, well-characterized safety profile. Here, we review the safety and tolerability of long-term alectinib treatment in patients with advanced ALK-positive NSCLC and provide guidance for physicians, based on clinical experience, on the management of the most frequently reported adverse events (AEs). Most AEs associated with alectinib can be managed by dose reduction. Some alectinib-related AEs are not yet fully characterized, including myalgia and peripheral oedema and deciphering their underlying mechanism of action could enhance their management. With longer-term follow-up, the safety profile of alectinib continues to remain consistent in the ALEX study, with no new safety signals observed. Safety and tolerability data from the first-line phase III alectinib trials are also consistent with those observed in clinical trials of alectinib in later-line settings. These results add to the weight of evidence recommending alectinib as a preferred therapy for treatment-naive advanced ALK-positive NSCLC

Final efficacy and safety data, and exploratory molecular profiling from the phase III ALUR study of alectinib versus chemotherapy in crizotinib-pretreated ALK-positive non-small-cell lung cancer

Background: At the primary data cut-off, the ALUR study demonstrated significantly improved progression-free survival (PFS) and central nervous system (CNS) objective response rate (ORR) with alectinib versus chemotherapy in pretreated, advanced anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer. We report final efficacy and safety data, and exploratory molecular profiling. Patients and methods: Patients who received prior platinum-doublet chemotherapy and crizotinib were randomized 2 : 1 to receive alectinib 600 mg twice daily (n = 79) or chemotherapy (pemetrexed 500 mg/m(2) or docetaxel 75 mg/m(2), every 3 weeks; n = 40) until progressive disease, death or withdrawal. The primary endpoint was investigator-assessed PFS. Secondary endpoints included ORR, CNS ORR and safety. Plasma samples were collected at baseline, then every 6 weeks until progressive disease; molecular factors detected by next-generation sequencing were correlated with outcomes. Results: Investigator-assessed PFS was significantly longer with alectinib than chemotherapy (median 10.9 versus 1.4 months; hazard ratio 0.20, 95% confidence interval 0.12-0.33; P < 0.001). ORR was 50.6% with alectinib versus 2.5% with chemotherapy (P < 0.001). In patients with measurable CNS metastases at baseline, CNS ORR was 66.7% with alectinib versus 0% with chemotherapy (P < 0.001). No new safety signals were seen. ALK rearrangement was identified in 69.5% (n = 41/59) of baseline plasma samples. Confirmed partial responses were observed with alectinib in 6/11 patients with a secondary ALK mutation and 4/6 patients with a non-EML4-ALK (where EML4 is echinoderm microtubule-associated protein-like 4) fusion. Detection of mutant TP53 in baseline plasma resulted in numerically shorter PFS with alectinib (hazard ratio 1.88, 95% confidence interval 0.9-3.93). Conclusions: Final efficacy data from ALUR confirmed the superior PFS, ORR and CNS ORR of alectinib versus chemotherapy in pretreated, advanced ALK-positive non-small-cell lung cancer. Alectinib prolonged PFS versus chemotherapy in patients with wild-type or mutant TP53; however, alectinib activity was considerably decreased in patients with mutant TP53

Safety and Efficacy of Bevacizumab Plus Standard-of-Care Treatment Beyond Disease Progression in Patients With Advanced Non-Small Cell Lung Cancer: The AvaALL Randomized Clinical Trial

Importance: Bevacizumab treatment beyond progression has been investigated in breast and metastatic colorectal cancers. Avastin in All Lines Lung (AvaALL) is the first randomized phase 3 study of bevacizumab across multiple lines of treatment beyond progression in non-small cell lung cancer (NSCLC). Objective: To assess the efficacy and safety of continuous bevacizumab treatment beyond first progression in NSCLC. Design, Setting, and Participants: AvaALL was a randomized, open-label, phase 3b trial, conducted from 2011 to 2015 in 123 centers worldwide. Patients with nonsquamous NSCLC previously treated with first-line bevacizumab plus platinum-doublet chemotherapy and at least 2 cycles of bevacizumab maintenance were randomized (1:1) at first progression to receive bevacizumab plus standard of care (SOC) or SOC alone. Interventions: Patients received bevacizumab (7.5 or 15 mg/kg intravenously every 21 days) and/or investigator&apos;s choice of SOC. For subsequent lines, patients treated with bevacizumab received SOC with or without bevacizumab; the SOC arm received SOC only. Main Outcomes and Measures: The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival from first to second (PFS2) and third progression (PFS3), time to second (TTP2) and third progression (TTP3), and safety. Results: Between June 2011 and January 2015, 485 patients (median age, 63.0 years [range, 26-84 years]; 293 [60.4%] male) were randomized. Median OS was not significantly longer with bevacizumab plus SOC vs SOC alone: 11.9 (90% CI, 10.2-13.7) vs 10.2 (90% CI, 8.6-11.9) months (hazard ratio [HR], 0.84; 90% CI, 0.71-1.00; P =.104). Median PFS2 was numerically longer with bevacizumab plus SOC vs SOC alone: 5.5 (90% CI, 4.2-5.7) vs 4.0 (90% CI, 3.4-4.3) months (HR, 0.83; 90% CI, 0.70-0.98; P =.06). Median PFS3 appeared longer with bevacizumab plus SOC vs SOC alone: 4.0 (90% CI, 2.9-4.5) vs 2.6 (90% CI, 2.3-2.9) months (HR, 0.63; 90% CI, 0.49-0.83), as did TTP2 and TTP3. Grade 3/4 adverse events were more frequent with bevacizumab plus SOC (186 [76.5%]) vs SOC alone (140 [60.3%]). No new safety signals were observed. Conclusions and Relevance: The primary end point was not met; however, OS was underpowered according to initial statistical assumptions. Continued therapy beyond first progression led to improved PFS3 (but not PFS2), TTP2, and TTP3. Although a result with P =.06 for PFS2 would conventionally be considered significant at a specified 2-sided α of.10, in the absence of adjustments for multiplicity, this result could be a chance finding. No new safety signals were identified with bevacizumab treatment beyond progression. © 2018 American Medical Association. All rights reserved