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Aromatase inhibitors (AIs) have been considered first-line therapy for patients with hormone-dependent breast cancer due to their high efficacy and good tolerability. However, AIs are not free of adverse events, and studies show that therapy with AIs is associated with an increased risk of cardiovascular events and the development of insulin resistance and diabetes. We searched the Cochrane Central Register of Controlled Trials, PubMed and EMBASE up to 27 October 2020 for the prevalence of cardiovascular and/or metabolic adverse effects during treatment with AIs in postmenopausal women with breast cancer. A meta-analysis was performed using a random effects model. Odds ratios and 95% confidence intervals were calculated and illustrated using forest plot charts. We performed separate analyses depending on trial design. Twenty two studies met the inclusion criteria. AIs were associated with a higher risk of cardiovascular events, especially when we compared study arms in which AIs were used (alone or in sequence with TAM) with the arms in which TAM was used alone (OR = 1.16; 95%CI 1.04–1.30) or when comparing patients taking AIs alone to patients taking TAM alone or in sequence with AIs (OR = 1.24; 95%CI 1.11–1.38). A pooled analysis of five trials comparing adjuvant AIs to TAM showed the odds for arterial hypertension being 1.31 times higher for patients taking AIs; however, this did not reach statistical significance (OR = 1.31; 95%CI 0.47–3.65). We have not shown an increased risk of dyslipidemia or weight gain with the use of AIs. Our results suggest that postmenopausal women with breast cancer treated with AIs have an increased risk of cardiovascular events in comparison with TAM, potentially due more to a cardioprotective effect of the latter than the cardiotoxicity of AIs. We were unable to prove a similar association for hypertension, dyslipidemia, hyperglycemia or weight gain. Further high-quality RCTs and post-marketing safety observational studies are needed to definitively evaluate the impact of AIs on metabolic disorders in breast cancer patients.

Background: Current management of ulcerative colitis (UC) is aimed to treat active disease and to maintain remission. For patients in whom conventional treatment is no longer effective, biological or small molecule therapy may be an option. The aim was to assess the cost-effectiveness of induction and maintenance treatment up to 1 year of UC with infliximab (IFX), adalimumab (ADA), golimumab, vedolizumab (VDZ) and tofacitinib (TFB) compared with standard of care (SoC) in Poland. Methods: A hybrid decision tree/Markov model was used to estimate the expected costs and effects of four biologics, TFB and placebo in patients with the diagnosis of moderate to severe UC who had an inadequate response, lost response, or were intolerant to a conventional therapy. Prior exposure to anti-TNF was considered. At the beginning of the maintenance phase, the decision to continue biological therapy was determined by the achievement of response at the end of induction. Efficacy data were obtained from a network meta-analysis using placebo as the common comparator. Costs were presented in 2018 Polish zloty (PLN) and outcomes included quality-adjusted life-years (QALYs). The analysis was performed from the Polish public payer’s perspective and lifetime horizon was set. Results: In anti-TNF naïve, IFX and VDZ were characterized by the most favourable incremental cost-effectiveness ratios (ICURs) compared with SoC, PLN211,250.78 and PLN361,694.61/QALY (€49,589.38 and €84,904.84/QALY), respectively. In anti-TNF-exposed population the most effective treatment was TFB. Both ADA and VDZ were more effective than SoC; however, ICUR values were much above the cost-effectiveness threshold. The incorporation of biosimilars reversed the ranking of treatments in relation to the growing ICUR. Conclusion: Although ICUR values for all biological therapies exceeded the acceptability threshold in Poland, for anti-TNF-naïve UC patients IFX and for anti-TNF-exposed UC patients VDZ are currently the most cost-effective alternatives.

P-glycoprotein encoded by the ABCB1 gene constitutes a molecular barrier in the small and large bowel epithelium, and its different expression may influence susceptibility to inflammatory bowel disease (IBD). We aimed to assess the contribution of the C3435T polymorphism to disease risk in the Polish population. A total of 100 patients (50 Crohn’s disease (CD), 50 ulcerative colitis (UC)) and 100 healthy controls were genotyped for the single nucleotide polymorphism (SNP) C3435T by using the PCR-RFLP method. Patients were classified on the basis of disease phenotype and the specific treatment used. A meta-analysis was carried out of our results and those from previously published Polish studies. There was no significant difference in allele and genotype frequencies in IBD patients compared with controls. For CD patients, a lower frequency of TT genotype in those with colonic disease, a lower frequency of T allele, and a higher frequency of C allele in those with luminal disease were observed, whereas for UC patients, a lower frequency of CT genotype was observed in those with left-sided colitis. A meta-analysis showed a tendency towards higher prevalence of CC genotype in UC cases. These results indicate that the C3435T variants may confer a risk for UC and influence disease behaviour.

The most abundant interneurons in the primate striatum are those expressing the calcium-binding protein calretinin (CR). The present immunohistochemical study provides detailed assessments of their morphological traits, number, and topographical distribution in normal monkeys (Macaca fascicularis) and in monkeys rendered parkinsonian (PD) by MPTP intoxication. In primates, the CR+ striatal interneurons comprise small (8–12 μm), medium (12–20 μm) and large-sized (20–45 μm) neurons, each with distinctive morphologies. The small CR+ neurons were 2–3 times more abundant than the medium-sized CR+ neurons, which were 20–40 times more numerous than the large CR+ neurons. In normal and PD monkeys, the density of small and medium-sized CR+ neurons was twice as high in the caudate nucleus than in the putamen, whereas the inverse occurred for the large CR+ neurons. Double immunostaining experiments revealed that only the large-sized CR+ neurons expressed choline acetyltransferase (ChAT). The number of large CR+ neurons was found to increase markedly (4–12 times) along the entire anteroposterior extent of both the caudate nucleus and putamen of PD monkeys compared to controls. Comparison of the number of large CR−/ChAT+ and CR+/ChAT+ neurons together with experiments involving the use of bromo-deoxyuridine (BrdU) as a marker of newly generated cells showed that it is the expression of CR by the large ChAT+ striatal interneurons, and not their absolute number, that is increased in the dopamine-depleted striatum. These findings reveal the modulatory role of dopamine in the phenotypic expression of the large cholinergic striatal neurons, which are known to play a crucial role in PD pathophysiology.

BackgroundMany atrial fibrillation patients eligible for oral anticoagulants are unaware of the presence of AF, and improved detection is necessary to facilitate thromboprophylaxis against stroke.ObjectiveTo assess the effectiveness of screening for AF compared to no screening and to compare efficacy outcomes of different screening strategies.Materials and methodsCochrane Central Register of Controlled Trials, EMBASE and MEDLINE from Jan 1, 2000 -Dec 31, 2015 were searched. Studies employing systematic or opportunistic screening and using ECG or pulse palpation in populations age ≥40 years were included. Data describing study and patient characteristics and number of patients with new AF were extracted. The outcome was the incidence of previously undiagnosed AF.ResultsWe identified 25 unique (3 RCTs and 22 observational) studies (n = 88 786) from 14 countries. The incidence of newly detected AF due to screening was 1.5% (95% CI 1.1 to 1.8%). Systematic screening was more effective than opportunistic: 1.8% (95% CI 1.4 to 2.3%) vs. 1.1% (95% CI 0.6 to 1.6%), pConclusionsActive screening for AF, whether systematic or opportunistic, is effective beginning from 40 years of age. The organisation of screening process may be more important than technical solutions used for heart rhythm assessment.

W opracowaniu podjęto temat sektorów deficytowych i nadwyżkowych na rynku pracy w województwie śląskim. Zasadniczym celem badania była charakterystyka obecnego stanu elementarnych grup zawodów ze względu na ich deficytowość lub nadwyżkowość. Ocenę sektorową przeprowadzono w oparciu o grupy elementarne, ustalone w aktualnej klasyfikacji zawodów na potrzeby rynku pracy. W badaniu przyjęto dynamiczne ujęcie problemu przez analizę wskaźników intensywności deficytu (nadwyżki) i salda ruchu bezrobotnych dla grup elementarnych w kilku kolejnych półroczach. Analiza sektorowa wykazała, iż większość grup elementarnych cechowała się nadwyżkowymi wartościami wskaźnika intensywności oraz głównie dodatnimi saldami ruchu bezrobotnych w całym okresie badawczym. Uzyskane wyniki świadczą o istnieniu zdecydowanej przewagi liczebnej sektorów nadwyżkowych. Jako istotny sektor deficytowy zaznaczyła się grupa lekarzy specjalistów. Najliczniejsze sektory deficytowe wystąpiły w grupie wielkiej robotników przemysłowych i rzemieślników. Nadwyżkowość większości analizowanych grup elementarnych i niekorzystne tendencje na rynku pracy umożliwiły wskazanie dużej liczby sektorów szczególnie nadwyżkowych. Instytucje odpowiedzialne za poprawę sytuacji na rynku pracy powinny zatem w większym stopniu skupić się na przekwalifikowaniu pracowników z tych sektorów i stworzeniu warunków do rozwoju przedsiębiorczości młodych ludzi.