Prioritization of implementation barriers related to integrated care models in Central and Eastern European countries.

The importance of integrated care will increase in future health systems due to aging populations and patients with chronic multimorbidity, however, such complex healthcare interventions are often developed and implemented in higher income countries. For Central and Eastern European (CEE) countries it is important to investigate which integrated care models are transferable to their setting and facilitate the implementation of relevant models by identifying barriers to their implementation. This study investigates the relative importance of integrated care models and the most critical barriers for their implementation in CEE countries. Experts from Croatia, Hungary, Poland, Romania and Serbia were invited to complete an online survey within the SELFIE H2020 project. 81 respondents completed the survey. Although experts indicated that some integrated care models were already being implemented in CEE countries, the survey revealed a great need for further improvement in the integration of care, especially the managed care of oncology patients, coordinated palliative care of terminally ill patients, and nursing care of elderly with multimorbidity. Lack of long-term financial sustainability as well as of dedicated financing schemes were seen the most critical implementation barriers, followed by the lack of integration between health and social care providers and insufficient availability of human resources. These insights can guide future policy making on integrated care in CEE countries.

Aromatase Inhibitors and Risk of Metabolic and Cardiovascular Adverse Effects in Breast Cancer Patients-A Systematic Review and Meta-Analysis.

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.

C3435T Polymorphism of the ABCB1 Gene in Polish Patients with Inflammatory Bowel Disease: A Case-Control and Meta-Analysis Study.

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.

Infliximab, adalimumab, golimumab, vedolizumab and tofacitinib in moderate to severe ulcerative colitis: comparative cost-effectiveness study in Poland.

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.

A panel of stomach-specific biomarkers (GastroPanel®) for the diagnosis of atrophic gastritis: A prospective, multicenter study in a low gastric cancer incidence area.

BACKGROUND: Analysis of serum biomarkers for the assessment of atrophic gastritis (AG), considered as gastric precancerous lesion, is of growing interest and recommended by current guidelines. Our aim was to evaluate the diagnostic performance of a panel of biomarkers (GastroPanel®) for the detection of AG in France, a country of a low gastric cancer (GC) incidence. MATERIAL AND METHODS: In this prospective, multicenter, cross-sectional study, consecutive patients considered at increased risk of GC and undergoing upper endoscopy with gastric biopsies were included. Blood samples were collected for the analysis of GastroPanel® (association of Pepsinogens I and II, Gastrin-17, and Helicobacter pylori serology) using ELISA. The results of GastroPanel® were compared to the results of histology considered as the reference. RESULTS: Between 2016 and 2019, 344 patients (148 cases with AG, 196 controls without AG) were included. Sensitivity, specificity, positive, and negative predictive values for the detection of AG by GastroPanel® were of 39.9% (95% CI 31.9; 48.2), 93.4% (95% CI 88.9; 96.4), 81.9 (95% CI 71.1; 90.0), and 67.3 (95% CI 61.4; 72.8), respectively. The sensitivity was significantly higher for the detection of severe AG [60.8% (95% CI 46.1; 74.6) P = .015] and corpus AG [61.0% (95% CI 49.2; 72.0), P = .004]. Diagnostic performances of GastroPanel® tended to be better than those of Pepsinogen I alone, but the difference did not reach statistical significance (P = .068). CONCLUSION: Serum pepsinogen and GastroPanel® tests show promising results for the detection of AG, especially of corpus AG and severe AG, in patients at high risk of GC in France.

Gastric Cancer: Where Are We Heading?

BACKGROUND: Despite its decreasing incidence, gastric cancer (GC) remains one of the leading cancers in the world and an important global healthcare problem due to its overall high prevalence and high mortality rate. SUMMARY: GC is a consequence of Helicobacter pylori infection in 90% of cases, while in 10% Epstein Barr Virus may be responsible. Moreover, some recent epidemiological data suggest an increasing incidence in some young patients groups possibly due to autoimmunity, and if this tendency is confirmed, it may change the epidemiology of GC in the future. The pathogenesis of GC is mainly related to H. pylori infection, but recent data indicate the possible role of other bacteria and their metabolites, like N-nitrosocompounds or acetaldehyde, interfering during the last steps of carcinogenesis. The new molecular classifications of GCs show a great heterogeneity of this neoplasia, which may in the future help to define personalized treatment strategies for the patients. Early detection and proper surveillance of high risk patients should be our major objectives. Key Messages: GC is still an important healthcare problem, with its several aspects which remain the major challenges for the future.

Faecal calprotectin as a diagnostic marker of inflammatory bowel disease in patients with gastrointestinal symptoms: meta-analysis.

Colonoscopy is the standard medical procedure to identify inflammatory bowel disease (IBD) in patients with gastrointestinal symptoms. Noninvasive measurement of faecal calprotectin concentration may replace colonoscopy in this indication. The study aimed to assess efficacy of faecal calprotectin as a diagnostic marker of IBD in patients with symptoms suggestive of such diagnosis. Meta-analysis of diagnostic accuracy studies was performed. Cochrane, EMBASE and MEDLINE databases were searched until December 2018. Inclusion criteria comprised experimental and observational studies, adults with gastrointestinal symptoms, calprotectin as index and colonoscopy as reference test, presence of data on/enabling the calculation of diagnostic accuracy parameters. For each study, sensitivity and specificity of faecal calprotectin were analysed as bivariate data. Nineteen studies were identified. The total number of patients was 5032. Calculated pooled sensitivity and specificity were 0.882 [95% confidence interval (CI), 0.827-0.921] and 0.799 (95% CI, 0.693-0.875), respectively. Following faecal calprotectin incorporation in the diagnostic work-up of 100 people with suspected IBD, 18 non-IBD patients will have a colonoscopy performed and one patient with the disease will not be referred for this examination. Faecal calprotectin concentration measurement is a useful screening test to rule out IBD, at the same time reducing the need for colonoscopy by 66.7%.

Effectiveness of screening for atrial fibrillation and its determinants. A meta-analysis.

BACKGROUND: Many atrial fibrillation patients eligible for oral anticoagulants are unaware of the presence of AF, and improved detection is necessary to facilitate thromboprophylaxis against stroke. OBJECTIVE: To assess the effectiveness of screening for AF compared to no screening and to compare efficacy outcomes of different screening strategies. MATERIALS AND METHODS: Cochrane 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. RESULTS: We 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%), p<0.05, GP-led screening than community based: 1.9% (95% CI 1.4 to 2.4%) vs. 1.1% (95% CI 0.7 to 1.6%), p<0.05, and repeated heart rhythm measurements than isolated assessments of rhythm: 2.1% (95% CI 1.5-2.8) vs. 1.2% (95% CI 0.8-1.6), p<0.05. Only heart rhythm measurement frequency had statistical significance in a multivariate meta-regression model (p<0.05). CONCLUSIONS: Active 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.

The importance of the polymorphisms of the ABCB1 gene in disease susceptibility, behavior and response to treatment in inflammatory bowel disease: A literature review.

Crohn's disease (CD) and ulcerative colitis (UD) are the 2 common clinical subtypes of idiopathic inflammatory bowel disease (IBD) characterized by chronic inflammation of the gastrointestinal tract. The multifactorial etiology and pathogenesis of IBD is still unknown; however, the interaction between genetic, environmental and immunological factors seems to be crucial. A member of the adenosine triphosphate (ATP)-binding cassette family, P-glycoprotein, encoded by the human ABCB1 gene, is among the most extensively studied transporters involved in drug disposition and effects. Single nucleotide polymorphisms (SNPs) located in exons 21, 26 and 12, i.e., G2677T/A, C3435T and C1236T, are of the greatest clinical importance. Functional defects of the intestinal epithelial barrier due to the lack of P-glycoprotein expression may constitute possible reasons for the development of colitis. Given that several drugs central to the therapy of IBD are also P-glycoprotein substrates, it has been hypothesized that its altered expression in IBD patients could modify the response to medical treatment. Nevertheless, there are conflicting reports of an association between these 3 SNPs and IBD. This article aims to review all relevant studies investigating the role of the polymorphisms of the ABCB1 gene in disease susceptibility, behavior and response to treatment in IBD.

Stool patterns and symptoms of disordered anorectal function in patients with inflammatory bowel diseases.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) typically clinically manifest with symptoms like chronic diarrhea, cramps, abdominal pain, and rectal bleeding. However, symptoms of abnormal anorectal function seem to be of equal importance, regardless of the presence or absence of perianal disease. OBJECTIVES: The aim of this study was to assess stool patterns and the prevalence of symptoms of disordered anorectal function, particularly urgency and fecal incontinence, and their severity in patients with inflammatory bowel diseases (IBDs). MATERIAL AND METHODS: Thirty-three patients with CD and 38 patients with UC completed a questionnaire. A push/strain maneuver was performed on all patients and 20 controls. RESULTS: Thirty-three patients had more than 3 bowel movements a day; 44 had loose/watery stools. Two patients had fewer than 3 bowel movements a week, 8 had hard/lumpy stools, and 3 used laxatives. Excessive straining and incomplete evacuation were reported by 17 and 38 patients, respectively. Fifty-two patients complained of urgency and 32 of tenesmus. Significantly, more UC patients than CD patients had urgency at least once a day (p < 0.04). The following symptoms were reported by patients in the following numbers: fecal incontinence (31), passive (20) and urge incontinence (16), incontinence to gas (24), as well as liquid (33) and solid stool (7). Stool/gas discrimination was defective in 28 patients. Eleven patients had to wear pads. Everyday functioning was worsened because of urgency/tenesmus in 39 patients and because of fecal incontinence in 28 patients. The push/strain maneuver was abnormal in 12 patients with CD, 15 patients with UC and 1 control subject. The differences between the 2 study groups and the controls were significant (p < 0.03 and p < 0.01). CONCLUSIONS: A majority of patients with IBD complain of urgency. Fecal incontinence is reported by over 50% of patients. Both worsen patients' everyday functioning. A relevant proportion of patients have symptoms consistent with constipation, which is in connection with an abnormal push/strain maneuver in more than 1/3 of them.

ECONOMIC ISSUES IN THERAPEUTIC DRUG MONITORING.

The fact that resources for health care are limited has been found as a rationale for the development of pharmacoeconomics. Pharmacoeconomic analysis identifies, measures and compares the costs and the economic, clinical and humanistic outcomes of diseases, drug therapies and programmes directed to these diseases. As health care expenditures have escalated over the past decades, the number of its applications has increased. Taking into consideration outcome and economic issues and establishing their mutual relationship helps proper resource allocation. In the case of some effective and toxic drugs therapeutic drug monitoring has been proven to allow obtaining the desired clinical effects safely and thus to improve outcome. However, it requires the presence of clinical pharmacology or clinical pharmacy service within a hospital, which in turn is associated with some additional costs. This review sums up the results of pharmacoeconomic studies relevant to the use of therapeutic drug monitoring in case of the medicines for which it has been commonly performed so far.

Costs in inflammatory bowel diseases.

Variables influencing total direct medical costs in inflammatory bowel diseases include country, diagnosis (generally, patients with Crohn's disease generated higher costs compared with patients with ulcerative colitis), and year since diagnosis. In all studies the mean costs were higher than the median costs, which indicates that a relatively small group of the most severely ill patients significantly affect the total cost of treatment of these diseases. A major component of direct medical costs was attributed to hospitalisation, ranging from 49% to 80% of the total. The costs of surgery constituted 40-61% of inpatient costs. Indirect costs in inflammatory bowel diseases, unappreciated and often underestimated (considered by few authors and as a loss of work), are in fact important and may even exceed direct medical costs.

Is the use of esomeprazole in gastroesophageal reflux disease a cost-effective option in Poland?

OBJECTIVES: To compare the cost-effectiveness of therapy of gastroesophageal reflux disease with esomeprazole and other proton pump inhibitors (PPIs) in Poland. MATERIALS & METHODS: Studies comparing esomeprazole with other PPIs in the treatment of erosive esophagitis, non-erosive reflux disease and gastroesophageal reflux disease maintenance therapy were systematically reviewed. 9 randomized clinical trials were selected, meta-analyses were conducted. Cost data derived from Polish Ministry of Health and Pharmacies in Wroclaw. RESULTS: In the treatment of erosive esophagitis esomeprazole was significantly more effective than other PPIs. Both for 4- and 8-week therapy respective incremental cost-effectiveness ratio values were acceptably low. Differences in effectiveness of non-erosive reflux disease therapy were not significant. The replacement of pantoprazole 20 mg with more effective esomeprazole 20 mg in the 6-month maintenance therapy was associated with a substantially high incremental cost-effectiveness ratio.

Economic implications of biological therapy for Crohn's disease.

In the early 90s American authors estimated that if a theoretical new drug was introduced that was capable of changing the natural course of the disease and reducing direct non-drug medical costs (including hospitalisation and surgery) by 20%, despite doubling the overall drugs bill, there would still be a reduction in total direct medical costs of Crohn's disease by 13%. Infliximab proved to be efficacious in reducing and maintaining remission in moderate to severe active Crohn's disease and/or fistulising Crohn's disease. A higher acquisition cost still remains its major limitation. Currently only the use of infliximab in case of treatment for flares seems to be cost-effective. However, this statement may be modified in the near future.

Non-medical costs of colonoscopy.

Colorectal cancer is one of the most common malignancies in Europe and North America. Colonoscopy done every 10 years beginning at age 50 is the preferred method of screening. In Poland and some other countries examinations are offered to subjects free of charge. However, as well as direct medical costs there are direct non-medical costs, which include the cost of transportation and costs related to caregivers' time, and indirect costs, which are costs related to patients' time. These costs essentially augment the total societal costs of colonoscopy.

[Costs and range of health care consumption under general health insurance and sick leaves among patients with inflammatory bowel disease in chosen countries -- a literature review]. / Koszty i zakres korzystania ze swiadczen zdrowotnych w ramach powszechnego ubezpieczenia zdrowotnego oraz czasowa niezdolnosc do pracy u pacjentów z nieswoistymi zapaleniami jelit w wybranych krajach -- przeglad pismiennictwa.

Inflammatory bowel disease (IBD) is considered to be common in the developed countries of Europe and in North America. A chronic nature of the disease, bowel and systemic symptoms debilitating daily functioning, coexisting extraintestinal complications, recurrent, not infrequently severe and unpredictable clinical course significantly lower patients' quality of life. When compared with the general population, IBD patients more often take use of health care services. They also experience more episodes of sick leave, which is associated with a greater number of sick leave days per year.

Enhanced formation of advanced oxidation protein products in IBD.

BACKGROUND: Advanced oxidation protein products (AOPPs) are new protein markers of oxidative stress with pro-inflammatory properties, accumulated in many pathological conditions. The issue of their enhanced formation in IBD has not been addressed yet. METHODS: The concentration of relative AOPPs (rAOPP; concentration of AOPPs divided by albumin level) were measured in 68 subjects with ulcerative colitis (UC), 50 subjects with Crohn's disease (CD) and 45 healthy volunteers, and related to disease phenotype, clinical and biochemical activity, and therapeutic strategy. Diagnostic utility of rAOPP was evaluated by ROC analysis. RESULTS: In comparison with controls (1.367 micromol/g), rAOPP were increased in inactive (1.778 micromol/g, P = 0.053) and active (1.895 micromol/g, P = 0.013) UC and in active (1.847 micromol/g, P = 0.003) CD. In CD, but not UC, rAOPP correlated with disease activity (r = 0.42, P = 0.013). Significant correlations with the inflammatory/malnutrition indices-erythrocyte sedimentation rate (ESR) (r = 0.53), leukocytes (r = 0.33), platelets (r = 0.38), IL-6 (r = 0.36), and transferrin (r = -0.35) were demonstrated in CD. In UC, rAOPP correlated only with ESR (r = 0.35) and IL-6 (r = 0.30). Instead, associations with antioxidant dismutase (r = 0.29) and catalase (r = 0.22) were observed. The diagnostic power of rAOPP in discriminating diseased from non-diseased subjects was less than that of C-reactive protein (CRP). Simultaneous determination of rAOPP and CRP did not significantly improve the power of single CRP determination. CONCLUSIONS: IBD was associated with enhanced formation of AOPP, which differed between C and UC with respect to the relationship between rAOPP and disease activity, inflammatory and antioxidant response. These differences may reflect divergent ways that oxidative stress develops in CD and UC. The diagnostic power of rAOPP was insufficient for its clinical application.