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31.
Incidence and control of steroid-induced hyperglycaemia in hospitalised patients at a tertiary care centre for lung diseases
Matej Dobravc Verbič, Jasna Gruban, Mojca Kerec Kos, 2021, original scientific article

Abstract: Background The aim of this study was to determine the incidence of steroid-induced hyperglycaemia (SIH) in patients hospitalised at the tertiary centre for lung diseases, to assess glycaemic control during hospitalisation, and to determine the factors associated with the control of SIH. Methods A 4-month retrospective study was conducted. All patients who received systemic glucocorticoids for%%%2 days during hospitalisation, with%%%2 elevated blood glucose (BG) readings, were included in the analysis. SIH control was determined by mean BG levels, the number and proportion of elevated and pronouncedly elevated BG readings, and the number of hypoglycaemic events. Results 60 of 283 patients (21.2%) developed SIH, of which 55 patients were included in further analysis. Mean fasting and daytime BG levels were 7.8%%%2.9 mmol/l and 10.9%%%2.2 mmol/l, respectively. 41/55 patients (74.5%) had elevated average BG levels. 45/55 patients (81.8%) had%>%5 readings or%>%20% of all readings exceeding hyperglycaemia threshold, and 33/55 patients (60.0%) had pronouncedly elevated BG levels on more than one occasion. 6/55 patients (10.9%) experienced more than one hypoglycaemic event or a severe hypoglycaemia. Only 9/55 patients (16.4%) achieved adequate SIH control according to all defined criteria. Pre-existing diabetes and longer duration of hospital treatment with low glucocorticoid dose were significantly associated with poorer glycaemic control (p%<%0.001 and p%=%0.003, respectively). Conclusions Appropriate SIH management was demonstrated to be challenging. According to the defined criteria, adequate glycaemic control during hospitalisation was not achieved in the large majority of patients with SIH.
Keywords: hyperglycaemia, glucocorticoids, acetylcholine, blood glucose levels, antidiabetic therapy, steroid diabetes
Published in DiRROS: 10.03.2021; Views: 1028; Downloads: 277
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32.
GLCCI1 polymorphism rs37973 and asthma treatment response to inhaled corticosteroids
Matija Rijavec, Mateja Žavbi, Anton Lopert, Matjaž Fležar, Peter Korošec, 2018, original scientific article

Abstract: Background. Asthma treatment response is highly variable and pharmacogenetic markers that predict treatment response would be one step closer to personalized treatment. GWAS studies have shown that polymorphisms GLCCI1 could be associated with asthma treatment response to inhaled corticosteroids (ICS). Materials and methods. We genotyped rs37973 of GLCCI1 in 208 adult asthma patients treated with ICS. Change in % predicted FEV1 was analysed after short-term (3 months) and after long-term (at least 3 years) treatment. Treatment success was defined as good when FEV1 decreased less than 30 ml/year. Results. After 3 months of treatment, change of % predicted FEV1 was higher in patients with GG genotype than in patients with AG+AA genotype, and this genotype dependent difference was only evident in non-smokers. Similar results were found after at least 3 years of treatment when all patients were analysed, in non-smokers and patients with atopy. Even though, no differences in treatment success (good vs. poor response) were observed when analysing the entire group of patients, genotype dependent treatment success was highly influenced by smoking and atopy. GG genotype was overrepresented in non-smokers and patients with atopy with good response. Conclusions. Rs37973 was associated with short- and long-term treatment response; however, there was a great influence of smoking and atopy on pharmacogenetic association. Furthermore, we found GG genotype to be associated with better treatment response, what is contrary to results found in GWAS.
Keywords: asthma -- diagnosis -- therapy, pharmacogenetics, genetic polymorphism, smoking, inhaled corticosteroids, atopy, GLCCI1, FEV1, rs37973
Published in DiRROS: 16.12.2020; Views: 1529; Downloads: 409
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33.
The clinical relevance of oliguria in the critically ill patient : analysis of a large observational database
Jean Louis Vincent, Andrew Ferguson, Peter Pickkers, Stephan M. Jakob, Ulrich Jaschinski, Ghaleb A. Almekhlafi, Marc Leone, Majid Mokhtari, Luis E. Fontes, Philippe R. Bauer, Yasser Sakr, 2020, original scientific article

Abstract: Background: Urine output is widely used as one of the criteria for the diagnosis and staging of acute renal failure, but few studies have specifically assessed the role of oliguria as a marker of acute renal failure or outcomes in general intensive care unit (ICU) patients. Using a large multinational database, we therefore evaluated the occurrence of oliguria (defined as a urine output < 0.5 ml/kg/h) in acutely ill patients and its association with the need for renal replacement therapy (RRT) and outcome. Methods: International observational study. All adult (> 16 years) patients in the ICON audit who had a urine output measurement on the day of admission were included. To investigate the association between oliguria and mortality, we used a multilevel analysis. Results: Of the 8292 patients included, 2050 (24.7%) were oliguric during the first 24 h of admission. Patients with oliguria on admission who had at least one additional 24-h urine output recorded during their ICU stay (n = 1349) were divided into three groups: transient-oliguria resolved within 48 h after the admission day (n = 390 [28.9%]), prolonged-oliguria resolved > 48 h after the admission day (n = 141 [10.5%]), and permanent-oliguria persisting for the whole ICU stay or again present at the end of the ICU stay (n = 818 [60.6%]). ICU and hospital mortality rates were higher in patients with oliguria than in those without, except for patients with transient oliguria who had significantly lower mortality rates than non-oliguric patients. In multilevel analysis, the need for RRT was associated with a significantly higher risk of death (OR = 1.51 [95% CI 1.19%1.91], p = 0.001), but the presence of oliguria on admission was not (OR = 1.14 [95% CI 0.97%1.34], p = 0.103). Conclusions: Oliguria is common in ICU patients and may have a relatively benign nature if only transient. The duration of oliguria and need for RRT are associated with worse outcome.
Keywords: critical care, critical illness, urine, oliguria, kidney, renal insufficiency, kidney diseases, acute kidney failure, mortality, urine output, renal replacement therapy
Published in DiRROS: 18.11.2020; Views: 1725; Downloads: 1077
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34.
Sequential afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer : final analysis of the GioTag study
Maximilian J Hochmair, Alessandro Morabito, Desiree Hao, Cheng-Ta Yang, Ross A Soo, James C-H Yang, Rasim Gucalp, Balazs Halmos, Angela Märten, Tanja Čufer, 2020, original scientific article

Abstract: Aim: Final overall survival (OS) and time on treatment analysis of patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) who received sequential afatinib and osimertinib. Patients & methods: Patients (n = 203) had T790M-positive disease following first-line afatinib and started osimertinib treatment >/=10 months before data entry. Primary outcome was time on treatment; OS analysis was exploratory. Results: Median time on treatment with afatinib and osimertinib was 27.7 months (90% CI: 26.7-29.9). Median OS was 37.6 months (90% CI: 35.5-41.3); median OS was 41.6 and 44.8 months in Del19-positive patients and Asian patients, respectively. Conclusion: In real-world clinical practice, sequential afatinib and osimertinib was associated with encouraging outcomes in patients with EGFR mutation-positive NSCLC, especially in Del19-positive patients and Asian patients.
Keywords: non-small cell lung carcinoma -- therapy, drug therapy, afatinib, osimertinib, GioTag study
Published in DiRROS: 18.11.2020; Views: 1585; Downloads: 1286
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35.
Continuous glucose monitoring use and glucose variability in pre-school children with type 1 diabetes
Klemen Dovč, Kevin Cargnelutti, Anže Šturm, Julij Šelb, Nataša Bratina, Tadej Battelino, 2018, original scientific article

Abstract: Aims. The objective of this nationwide population-based cohort study was to evaluate the correlation between continuous glucose monitoring (CGM) use and glucose variability in pre-schoolers with type 1 diabetes. Methods. We analysed data from the Slovenian National Registry. The primary endpoint was the difference in glucose variability between periods, during which participants were using CGM and periods, during which CGM was not used, over 5 years. Results. A total of 40 children <8 years old were followed for an estimated observational period of 116 patient/years. Mean age at CGM initiation was 3.5 (±1.7) years. Both standard deviation of mean glucose [3.6 mmol/L (3.2–3.9) with CGM and 4.3 mmol/L (3.8–4.7) without CGM, p < 0.001] and coefficient of variation [44.0% (40.4–47.0) with CGM and 46.1% (42.3–49.4) without CGM, p = 0.021] were lower during the periods, when CGM was used. Frequent CGM use (>5 days/week) was associated with a 0.4% [4.4 mmol/mol] reduction in glycated haemoglobin level (7.6% compared to 7.2%, p = 0.047). Conclusions. Our results indicate that the use of CGM was associated with reduced glucose variability during a 5 year follow-up period among pre-schoolers with type 1 diabetes.
Keywords: continuous glucose monitoring, type 1 diabetes, children, insulin therapy
Published in DiRROS: 12.11.2020; Views: 1398; Downloads: 871
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36.
Sequential treatment with afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer : an observational study
Maximilian J Hochmair, Alessandro Morabito, Desiree Hao, Cheng-Ta Yang, Ross A Soo, James C-H Yang, Rasim Gucalp, Balazs Halmos, Lara Wang, Amanda Golembesky, Angela Märten, Tanja Čufer, 2018, original scientific article

Abstract: Aim: To assess outcomes in patients with EGFR mutation-positive (Del19, L858R) non-small-cell lung cancer receiving sequential afatinib and osimertinib in a real-world clinical setting. Materials & methods: In this retrospective, observational, multicenter study, patients (n = 204) had T790M-positive disease following first-line afatinib and started osimertinib treatment [>/=]10 months prior to data entry. Primary outcome was time on treatment. Results: Overall median time on treatment was 27.6 months (90% CI: 25.9-31.3), 30.3 months (90% CI: 27.6-44.5) in Del19-positive patients and 46.7 months (90% CI: 26.8-not reached) in Asians. The 2-year overall survival was 78.9%. Conclusion: In real-world clinical practice, sequential afatinib and osimertinib facilitates prolonged, chemotherapy-free treatment in patients with T790M acquired resistance, and is a potentially attractive strategy, especially for Del19-positive tumors.
Keywords: lung neoplasms -- therapy, non-small-cell lung cancer, afatinib, osimertinib, epidermal growth factor receptor, EGFR, observational study
Published in DiRROS: 09.11.2020; Views: 1583; Downloads: 944
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37.
Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling : a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials
2019, original scientific article

Abstract: Background: Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles, or by giving individual drugs sequentially at full dose rather than in lower-dose concurrent treatment schedules, might enhance efficacy. Methods: To clarify the relative benefits and risks of dose-intense and standard-schedule chemotherapy in early breast cancer, we did an individual patient-level meta-analysis of trials comparing 2-weekly versus standard 3-weekly schedules, and of trials comparing sequential versus concurrent administration of anthracycline and taxane chemotherapy. The primary outcomes were recurrence and breast cancer mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded dose-intense versus standard-schedule first-event rate ratios (RRs). Findings: Individual patient data were provided for 26 of 33 relevant trials identified, comprising 37,298 (93%) of 40,070 women randomised. Most women were aged younger than 70 years and had node-positive disease. Total cytotoxic drug usage was broadly comparable in the two treatment arms; colony-stimulating factor was generally used in the more dose-intense arm. Combining data from all 26 trials, fewer breast cancer recurrences were seen with dose-intense than with standard-schedule chemotherapy (10-year recurrence risk 28.0% vs 31.4%; RR 0.86, 95% CI 0.82-0.89; p<0.0001). 10-year breast cancer mortality was similarly reduced (18.9% vs 21.3%; RR 0.87, 95% CI 0.83-0.92; p<0.0001), as was all-cause mortality (22.1% vs 24.8%; RR 0.87, 95% CI 0.83-0.91; p<0.0001). Death without recurrence was, if anything, lower with dose-intense than with standard-schedule chemotherapy (10-year risk 4.1% vs 4.6%; RR 0.88, 95% CI 0.78-0.99; p=0.034). Recurrence reductions were similar in the seven trials (n=10,004) that compared 2-weekly chemotherapy with the same chemotherapy given 3-weekly (10-year risk 24.0% vs 28.3%; RR 0.83, 95% CI 0.76-0.91; p<0.0001), in the six trials (n=11,028) of sequential versus concurrent anthracycline plus taxane chemotherapy (28.1% vs 31.3%; RR 0.87, 95% CI 0.80-0.94; p=0.0006), and in the six trials (n=6532) testing both shorter intervals and sequential administration (30.4% vs 35.0%; RR 0.82, 95% CI 0.74-0.90; p<0.0001). The proportional reductions in recurrence with dose-intense chemotherapy were similar and highly significant (p<0.0001) in oestrogen receptor (ER)-positive and ER-negative disease and did not differ significantly by other patient or tumour characteristics. Interpretation: Increasing the dose intensity of adjuvant chemotherapy by shortening the interval between treatment cycles, or by giving individual drugs sequentially rather than giving the same drugs concurrently, moderately reduces the 10-year risk of recurrence and death from breast cancer without increasing mortality from other causes.
Keywords: breast neoplasms, women, drug therapy, clinical protocols, meta-analysis, breast cancer, chemotherapy, treatment schedule, randomized trials
Published in DiRROS: 22.10.2020; Views: 1413; Downloads: 1184
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38.
ARIA pharmacy 2018 "Allergic rhinitis care pathways for community pharmacy"
Sinthia Bosnic-Anticevitch, Elisio Costa, Enrica Menditto, Olga Lourenço, Ettore Novellino, Slawomir Bialek, Vitalis Briedis, Roland Buonaiuto, Henry Chrystyn, Biljana Cvetkovski, Mihaela Zidarn, 2019, review article

Abstract: Pharmacists are trusted health professionals. Many patients use over-the-counter (OTC) medications and are seen by pharmacists who are the initial point of contact of allergic rhinitis management in most countries. The role of pharmacists in integrated care pathways (ICPs) for allergic diseases is important. This paper builds on existing studies and provides tools intended to help pharmacists provide optimal advice/interventions/strategies to patients with rhinitis. The ARIA-pharmacy ICP includes a diagnostic questionnaire specifically focusing attention on key symptoms and markers of the disease, a systematic Diagnosis Guide (including differential diagnoses) and a simple flowchart with proposed treatment for rhinitis and asthma multimorbidity. Key prompts for referral within the ICP are included. The use of technology is critical to enhance the management of AR. However, the ARIA-pharmacy ICP should be adapted to local health care environments/situations as regional (national) differences exist in pharmacy care.
Keywords: asthma -- guideline, allergic rhinitis -- Guideline, pharmacists, drug therapy, nonprescription drugs, critical pathways, allergic diseases
Published in DiRROS: 09.10.2020; Views: 1396; Downloads: 383
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