Comparing methods to predict baseline mortality for excess mortality calculations.

BACKGROUND: The World Health Organization (WHO)'s excess mortality estimates presented in May 2022 stirred controversy, due in part to the high estimate provided for Germany, which was later attributed to the spline model used. This paper aims to reproduce the problem using synthetic datasets, thus allowing the investigation of its sensitivity to parameters, both of the mortality curve and of the used method, thereby shedding light on the conditions that gave rise to this error and identifying possible remedies. METHODS: A negative binomial model was used accounting for long-term change, seasonality, flu seasons, and heat waves. Simulated mortality curves from this model were then analysed using simple methods (mean, linear trend), the WHO method, and the method of Acosta and Irizarry. RESULTS: The performance of the WHO's method with its original parametrization was indeed very poor, however it can be profoundly improved by a better choice of parameters. The Acosta-Irizarry method outperformed the WHO method despite being also based on splines, but it was also dependent on its parameters. Linear extrapolation could produce very good results, but was highly dependent on the choice of the starting year, while the average was the worst in almost all cases. CONCLUSIONS: Splines are not inherently unsuitable for predicting baseline mortality, but caution should be taken. In particular, the results suggest that the key issue is that the splines should not be too flexible to avoid overfitting. Even after having investigated a limited number of scenarios, the results suggest that there is not a single method that outperforms the others in all situations. As the WHO method on the German data illustrates, whatever method is chosen, it remains important to visualize the data, the fit, and the predictions before trusting any result. It will be interesting to see whether further research including other scenarios will come to similar conclusions.

Clinical Implications of Fractional Flow Reserve Measured Immediately After Percutaneous Coronary Intervention.

PURPOSE: The purpose of the present study was to find the independent predictors of Fractional Flow Reserve (FFR) measured immediately after percutaneous coronary intervention with drug-eluting stent implantation (post-PCI FFR) and investigate if applying vessel-specific post-PCI FFR cut-off values to predict target vessel failure (TVF), a composite of cardiac death (CD), non-fatal myocardial infarction (MI) and target vessel revascularization (TVR), or a composite of CD and MI ameliorated its predictive power. METHODS: Consecutive patients with post-PCI FFR measurement at our center between 2009 and 2021 were included in this analysis. RESULTS: A total of 434 patients with 500 vessels were included. Median pre-PCI FFR was 0.72 with no difference between LAD and non-LAD vessels. Median post-PCI FFR was 0.87. LAD location, male gender, smaller stent diameter, and lower pre-PCI FFR proved to be significant predictors of a lower post-PCI FFR. On a vessel-level, post-PCI FFR, stent length, and diabetes mellitus proved to be significant predictors of TVF and the composite of CD and MI. The best post-PCI FFR cut-off to predict TVF or a composite of CD and MI was 0.83 in the LAD and 0.91 in non-LAD vessels. CONCLUSION: LAD location is a predictor of a lower post-PCI FFR. Post-PCI FFR is an independent predictor of TVF as well as of the composite of CD and MI. No uniform target post-PCI FFR value exists; different cut-off values may have to be applied in LAD as opposed to non-LAD vessels.

High Level of Unwarranted Clinical Variation in the Use of Lower Extremity Revascularisation Procedures in Hungary (2013-2017).

OBJECTIVE: Assessment of variations in the use of lower extremity open vascular surgical procedures (LEOPEN) and lower extremity endovascular procedures (LEENDO) across small geographic areas in Hungary from 2013 to 2017. Introduction of a new metric giving a rough estimate of unwarranted clinical variation in revascularisation practice. METHODS: Spatial variation (at local administrative unit level) of referral for LEOPEN and LEENDO was evaluated through a retrospective analysis using healthcare administrative data of all beneficiaries in Hungary. The same assessment was performed for percutaneous coronary intervention in acute myocardial infarction (PCIAMI). The latter was considered a reasonable comparator (similar at risk population, well organised, guideline driven patient pathways, small room for referral discretion). Consequently, the ratio of spatial variations of LEOPEN and LEENDO to PCIAMI (as a reference) are thought to reflect unwarranted clinical variation. RESULTS: A total of 109 882 procedures were identified in the database (LEOPEN, LEENDO, PCIAMI) affecting 85 083 patients. While estimates of spatial variations for LEOPEN and LEENDO turned out to be high (systematic component of variation [SCV] 0.09 and 0.21, respectively), PCIAMI showed a low SCV value of 0.02. Consequently, the ratios of SCVs were SCV/SCVref = 4.67 (LEOPEN) and SCV/SCVref = 10.3 (LEENDO), indicating high levels of unwarranted clinical variation. CONCLUSION: The analysis showed that patients living in different locations of Hungary face very different odds of having lower extremity revascularisation procedures (open or endovascular). This spatial variation is thought to be related mainly to the failure in vascular service organisation. The newly introduced numerical estimate of unwarranted clinical variation may support within, and also between, system comparisons.

RBD-specific antibody responses after two doses of BBIBP-CorV (Sinopharm, Beijing CNBG) vaccine.

BACKGROUND: Limited information is available on the effectiveness of the BBIBP-CorV (Sinopharm, Beijing CNBG) vaccine, especially in the elderly, despite the fact that it is approved in more than 50 countries. METHODS: RBD-specific antibody titres, as a rapidly available and highly predictive surrogate marker, were measured after two doses of the BBIBP-CorV vaccine in 450 subjects. Results were analyzed in a multivariable model accounting for age, sex and time since the administration of the second dose of the vaccine. RESULTS: Sex and time since the second dose had little association with the antibody titres. Age, however, was highly relevant: measurable antibody levels were present in about 90% of individuals below the age of 50, but antibody production after BBIBP-CorV vaccination was strongly reduced with increasing age. A large number of elderly subjects, reaching 25% at 60 years, and up to 50% at ages over 80, were found not to produce any protective antibody. CONCLUSIONS: RBD-specific antibody titre, as a correlate of protection for COVID-19 disease susceptibility, should help to evaluate the effectiveness of the BBIBP-CorV vaccine. Results suggest that proper measures should be undertaken to prevent a potential outbreak of COVID-19 in BBIBP-CorV vaccinated but eventually unprotected elderly individuals.

Real-world effectiveness of IDegLira compared with intensified conventional insulin therapy in adults with type 2 diabetes: a retrospective cohort study.

BACKGROUND: IDegLira is a fixed-ratio combination of insulin degludec and liraglutide with proven efficacy against simpler regimens and non-inferiority against basal-bolus insulin therapy. However, the evaluation of its real-world effectiveness is hindered by technical issues and requires further exploration. Thus we aimed to compare effectiveness of insulin degludec/liraglutide (IDegLira) versus intensified conventional insulin therapy (ICT) for type 2 diabetes in a real-world setting. METHODS: This retrospective cohort study from an outpatient clinic in Hungary included people who initiated IDegLira due to inadequate glycaemic control (HbA1c > 7.0% [53.0 mmol/mol]) with oral and/or injectable antidiabetic drugs. Data were compared with a historical cohort who initiated ICT. Outcomes included HbA1c, body weight, and hypoglycaemia differences over 18 months of follow-up. RESULTS: Data were included from 227 and 72 people who initiated IDegLira and ICT, respectively. Estimated mean difference (MD) in HbA1c at 18 months favoured IDegLira versus ICT (MD 0.60, 95% CI 0.88-0.32 [MD 6.6 mmol/mol, 95% CI 9.6-3.5]). More people reached target HbA1c ≤7.0% (53.0 mmol/mol) with IDegLira than ICT (odds ratio 3.36, 95% CI 1.52-7.42). IDegLira treatment was associated with weight loss compared with gain for ICT (MD 6.7 kg, 95% CI 5.0-8.5). The hazard ratio for hypoglycaemia comparing IDegLira with ICT was 0.18 (95% CI 0.08-0.49). CONCLUSIONS: Treatment with IDegLira over 18 months resulted in greater HbA1c reductions, weight loss versus gain, and a lower rate of hypoglycaemia versus ICT in people with type 2 diabetes.

Spatial analysis of factors impacting lower limb major amputation rates in Hungary: Is geography partially destiny?

Background: Lower limb major amputations represent a substantial public health burden in Hungary, where previous research revealed markedly high rates with significant spatial variations. Therefore, we aimed to assess to what extent healthcare and socio-economic factors in the local environment explain the regional disparity. Patients and methods: In a retrospective cohort analysis, based on the healthcare administrative data of the Hungarian population, lower limb major amputations were identified from 1st of January 2017 to 31st of December 2019. The permanent residence of the amputees on the local administrative level (197 geographic units) was used to identify potential healthcare (outpatient care, revascularisation activity) and socio-economic (educational attainment, local infrastructure and services, income and employment) determinants of amputations. Spatial effects were modelled using the spatial Durbin error regression model. Results: 10,209 patients underwent 11,649 lower limb major amputations in the observational period. In our spatial analysis, outpatient care was not associated with local amputation rates. However, revascularisation activity in a geographic unit entailed an increased rate of amputations, while revascularisations in the neighbouring areas were associated with a lower rate of amputations, resulting in an overall neutral effect (ß=-0.002, 95% CI: -0.05 - 0.04, p=0.96). The local socio-economic environment had a significant direct inverse association with amputations (ß=-7.45, 95% CI: -10.50 - -4.42, p<0.0001) . Our spatial model showed better performance than the traditional statistical modelling (ordinary least squares regression), explaining 37% of the variation in amputations rates. Conclusions: Regional environmental factors explain a substantial portion of spatial disparities in amputation practice. While the socio-economic environment shows a significant inverse relationship with the regional amputation rates, the impact of the local healthcare-related factors (outpatient care, revascularisation activity) is not straightforward. Unravelling the impact of the location on amputation practice requires complex spatial modelling, which may guide efficient healthcare policy decisions.

Different approaches to quantify years of life lost from COVID-19.

The burden of an epidemic is often characterized by death counts, but this can be misleading as it fails to acknowledge the age of the deceased patients. Years of life lost is therefore widely used as a more relevant metric, however, such calculations in the context of COVID-19 are all biased upwards: patients dying from COVID-19 are typically multimorbid, having far worse life expectation than the general population. These questions are quantitatively investigated using a unique Hungarian dataset that contains individual patient level data on comorbidities for all COVID-19 deaths in the country. To account for the comorbidities of the patients, a parametric survival model using 11 important long-term conditions was used to estimate a more realistic years of life lost. As of 12 May, 2021, Hungary reported a total of 27,837 deaths from COVID-19 in patients above 50 years of age. The usual calculation indicates 10.5 years of life lost for each death, which decreases to 9.2 years per death after adjusting for 11 comorbidities. The expected number of years lost implied by the life table, reflecting the mortality of a developed country just before the pandemic is 11.1 years. The years of life lost due to COVID-19 in Hungary is therefore 12% or 1.3 years per death lower when accounting for the comorbidities and is below its expected value, but how this should be interpreted is still a matter of debate. Further research is warranted on how to optimally integrate this information into epidemiologic risk assessments during a pandemic.

Supraventricular tachycardias in neonates and infants: factors associated with fatal or near-fatal outcome.

Prognosis of supraventricular tachycardias in neonates and infants is thought to be excellent with rare fatal outcomes. Nevertheless, initial management can be challenging. The aim of this study was to perform a retrospective analysis in neonates/infants with non-pos-toperative supraventricular tachycardias regarding risk factors for clinical outcome and type of antiarrhythmic drug therapy. The data of 157 patients aged < 1 year who presented between 2000 and 2015 with symptomatic tachycardias were retrospectively reviewed. Pharmacological therapy was successful in 151 patients (96%); 1 patient (1%) required catheter ablation and 5 patients (3%) died (1 death linked to hemodynamical reasons after effective arrhythmia control). Serious complications following acute medical therapy occurred in 4 patients of survivors. Patients with complications or death had a lower bodyweight, more frequent intrauterine tachycardia, transplacental therapy, urgent caesarian section, higher PRISM II score, longer period to control tachycardia, more frequent proarrhythmia, and major adverse event-defined as life-threatening event without a documented new arrhythmia-compared to the group without complications. There was no significant difference between the groups regarding prematurity, structural heart disease, and type of tachycardia. Proarrhythmia occurred in 6 cases and was related to intravenous drug use with class IC antiarrhythmics in 3/6 cases, digoxin in 2/6 cases, and amiodarone in 1/6 cases. ECG signs of impending proarrhythmia without new-onset arrhythmia requiring cessation of therapy were detected in 6 patients.Conclusion: Although rare, non-post-operative supraventricular tachycardia in neonates and infants might be a serious disease. Acute intravenous pharmacological treatment to control tachycardia might pose a risk for fatal or near-fatal outcome. Detection of proarrhythmia related to class IC antiarrhythmics in neonates might be especially difficult and requires alertness. What is Known • Prognosis of supraventricular tachycardias in children are thought to be excellent with fatal outcomes being rare. • Mortality is increased in the very young and in those with structural heart disease. What is New • Complicated outcome of non-post-operative supraventricular tachycardias in neonates is associated with lower bodyweight, age, prenatal tachycardia, higher PRISM II score, longer period to control tachycardia, and proarrhythmia. • Detection of class IC proarrhythmic effect is especially difficult in neonates because of their narrow QRS and warrants alertness.

Lower Limb Amputations and Revascularisation Procedures in the Hungarian Population: A 14 Year Retrospective Cohort Study.

OBJECTIVE: The aim of this study was to assess the long term trends of lower limb amputation and revascularisation in Hungary over 14 years. METHODS: This was a retrospective cohort study that included all patients who underwent lower limb amputation or revascularisation over a 14 year period (2004-2017) in Hungary. Inpatient administrative data claims covering the entire beneficiary population were incorporated. Lower limb amputations (both minor and major) and revascularisation procedures (both open and endovascular) were identified in the claims files. Incidence rates were calculated and time trends were assessed via a generalised additive model. RESULTS: From 2004 to 2017, a total of 121 351 lower limb amputations (61 154 minor; 60 197 major) and 149 355 revascularisation procedures (89 243 open; 60 112 endovascular) were detected in 140 581 patients. The number of minor amputations decreased moderately in the last few years of the study period, while major amputations showed a slight decline (15%) beginning after 2013, which was more marked (22%) following adjustment for age. While the crude incidence of open vascular surgery procedures decreased by 31% (from 74.5/105 to 51.4/105), endovascular procedures showed growth by 79% (from 33.7/105 to 60.4/105) over the whole observation period. CONCLUSION: Observed amputation and revascularisation trends in Hungary are similar to the international experience. The major difference is a more than one decade lag in the starting point of the decline of amputations and in the move towards endovascular procedures. The number of amputations is more than twofold higher and the number of revascularisations is close to half that reported internationally. This comprehensive report of two vascular care performance indicators reveals an east/west vascular health divide in Europe and indicates the need to improve amputation prevention.

Non-nutritive sweeteners for diabetes mellitus.

BACKGROUND: Products sweetened with non-nutritive sweeteners (NNS) are widely available. Many people with type 1 or type 2 diabetes use NNS as a replacement for nutritive sweeteners to control their carbohydrate and energy intake. Health outcomes associated with NNS use in diabetes are unknown. OBJECTIVES: To assess the effects of non-nutritive sweeteners in people with diabetes mellitus. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, Scopus, the WHO ICTRP, and ClinicalTrials.gov. The date of the last search of all databases (except for Scopus) was May 2019. We last searched Scopus in January 2019. We did not apply any language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with a duration of four weeks or more comparing any type of NNS with usual diet, no intervention, placebo, water, a different NNS, or a nutritive sweetener in individuals with type 1 or type 2 diabetes. Trials with concomitant behaviour-changing interventions, such as diet, exercise, or both, were eligible for inclusion, given that the concomitant interventions were the same in the intervention and comparator groups. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts, full texts, and records retrieved from trials registries, assessed the certainty of the evidence, and extracted data. We used a random-effects model to perform meta-analysis, and calculated effect estimates as risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs). We assessed risk of bias using the Cochrane 'Risk of bias' tool and the certainty of evidence using the GRADE approach. MAIN RESULTS: We included nine RCTs that randomised a total of 979 people with type 1 or type 2 diabetes. The intervention duration ranged from 4 to 10 months. We judged none of these trials as at low risk of bias for all 'Risk of bias' domains; most of the included trials did not report the method of randomisation. Three trials compared the effects of a dietary supplement containing NNS with sugar: glycosylated haemoglobin A1c (HbA1c) was 0.4% higher in the NNS group (95% CI -0.5 to 1.2; P = 0.44; 3 trials; 72 participants; very low-certainty evidence). The MD in weight change was -0.1 kg (95% CI -2.7 to 2.6; P = 0.96; 3 trials; 72 participants; very low-certainty evidence). None of the trials with sugar as comparator reported on adverse events. Five trials compared NNS with placebo. The MD for HbA1c was 0%, 95% CI -0.1 to 0.1; P = 0.99; 4 trials; 360 participants; very low-certainty evidence. The 95% prediction interval ranged between -0.3% and 0.3%. The comparison of NNS versus placebo showed a MD in body weight of -0.2 kg, 95% CI -1 to 0.6; P = 0.64; 2 trials; 184 participants; very low-certainty evidence. Three trials reported the numbers of participants experiencing at least one non-serious adverse event: 36/113 participants (31.9%) in the NNS group versus 42/118 participants (35.6%) in the placebo group (RR 0.78, 95% CI 0.39 to 1.56; P = 0.48; 3 trials; 231 participants; very low-certainty evidence). One trial compared NNS with a nutritive low-calorie sweetener (tagatose). HbA1c was 0.3% higher in the NNS group (95% CI 0.1 to 0.4; P = 0.01; 1 trial; 354 participants; very low-certainty evidence). This trial did not report body weight data and adverse events. The included trials did not report data on health-related quality of life, diabetes complications, all-cause mortality, or socioeconomic effects. AUTHORS' CONCLUSIONS: There is inconclusive evidence of very low certainty regarding the effects of NNS consumption compared with either sugar, placebo, or nutritive low-calorie sweetener consumption on clinically relevant benefit or harm for HbA1c, body weight, and adverse events in people with type 1 or type 2 diabetes. Data on health-related quality of life, diabetes complications, all-cause mortality, and socioeconomic effects are lacking.

Potentials, challenges, and limitations of the analysis of administrative data on vascular limb amputations in health care.

Although more and more data on lower limb amputations are becoming available by leveraging the widening access to health care administrative databases, the applicability of these data for public health decisions is still limited. Problems can be traced back to methodological issues, how data are generated and to conceptual issues, namely, how data are interpreted in a multidimensional environment. The present review summarised all of the steps from converting the claims data of administrative databases into the analytical data and reviewed the wide array of sources of potential biases in the analysis of such data. The origins of uncertainty of administrative data analysis include uncontrolled confounding due to a lack of clinical data, the left- and right-censored nature of data collection, the non-standardized diagnosis/procedure-based data extraction methods (i.e., numerator/denominator problems) and additional methodological problems associated with temporal and spatial analyses. The existence of these methodological challenges in the administrative data-based analysis should not deter the analysts from using these data as a powerful tool in the armamentarium of clinical research. However, it must be done with caution and a thorough understanding and respect of the methodological limitations. In addition to this requirement, there is a profound need for pursuing further research on methodology and widening the search for other indicators (structural, process or outcome) that allow a deeper insight how the quality of vascular care may be assessed. Effective research using administrative data is based on strong collaboration in three domains, namely expertise in claims data handling and processing, the clinical field, and statistical analysis. The final interpretations of results and the countermeasures on the level of vascular care ought to be grounded on the integrity of research, open discussions and institutionalized mechanisms of science arbitration and honest brokering.

Regional variation of lower limb major amputations on different geographic scales - a Hungarian nationwide study over 13 years.

Background: The incidence of lower limb major amputations is an important healthcare quality indicator, as it reflects all efforts aimed to prevent limb loss. Analysis of within-country regional variations in incidence may reveal the sources of disparities in care. Materials and methods: Based on the data of the Hungarian healthcare beneficiary population from 2004 to 2016, the incidence of lower limb major amputations and its spatial variations was determined regionally on four levels of geographic resolution. Variability and autocorrelation were quantified on different resolutions. Results: A total of 56,468 lower limb major amputation procedures were identified in 49,528 patients over the observation period. Marked regional variations were detected at all geographic scale levels. In the case of county-level and local administrative level, the systematic component of variation was 0.03 and 0.09, respectively. Only half of the variation at local administrative level was explained by county. Conclusions: Lower limb major amputations show marked regional variations on the different geographic levels of resolution. The more granular the assessment, the higher the regional variation was. Assumingly, this observation is partially a mathematical necessity but may also be related to the different characteristics of care at a given level of spatial aggregation. The decomposition of the variance of amputation rates indicates that the potential explanatory factors contributing to spatial variability are multiple and may be interpreted on different levels of geographic resolution. Addressing the unwarranted variations and resolving the issues that contribute to high lower limb major amputation rates needs further explorative analysis.

[Effect of smoking on survival after myocardial infarction - smoker's paradox in Hungary?] / A dohányzás hatása a szívinfarktus utáni túlélésre ­ dohányzási paradoxon Magyarországon?

INTRODUCTION: The strong, positive relationship between smoking and myocardial infarction was proven in the 1960s and 1970s. The prognostic significance of smoking in the acute phase of the infarction, and later in patients who survive the acute phase is, however, not clear. Numerous international studies focus on the phenomenon called the "smoker's paradox", which means that smokers have a lower mortality rate after suffering myocardial infarction than non-smokers. Although in many cases smoking does not have a positive effect on survival after controlling for confounders, an international consensus has not been reached regarding this issue. AIM: The aim of this paper was to investigate whether the paradox effect exists in the case of Hungarian patients after controlling for the patients' risk profiles. METHOD: The database used for the research was based on the 2014-2016 data of the Hungarian Myocardial Infarction Registry (n = 20 811) supervised by the Gottsegen György National Institute of Cardiology. The present analysis uses multivariate methodology to adjust for confounding: logistic regression is used for the short-term survival and survival analysis - with Cox proportional hazards model and Accelerated Failure Time models - is used for the long-term survival. Age, sex, performing of PCI, type of infarction (ST-elevation or not), creatinine abnormality, need for prehospital reanimation, cardiogenic shock and the presence of several comorbidities and medical history data were controlled for in the multivariate analysis. RESULTS: Both the short term - 30 day - mortality (OR = 1.517, 99% confidence interval: 1.229-1.872) and the long term mortality (HR = 1.395, 99% confidence interval: 1.232-1.579) were worse for smokers than non-smokers after adjusting for the abovementioned factors. CONCLUSION: The "smoker's paradox" cannot be observed in the case of Hungarian patients, moreover smoking in itself is associated with worse prognosis. Orv Hetil. 2018; 159(14): 557-565.

[The significance of ECG recorded at hospitalization in determining the prognosis of patients treated with myocardial infarction]. / A kórházi felvétel idején rögzített EKG jelentosége a szívinfarktus miatt kezelt betegek prognózisának meghatározásában.

INTRODUCTION AND AIM: By using the database of the National Registry of Myocardial Infarction, the authors examine the prognosis of patients treated with acute myocardial infarction, in case of whom there was new or presumably new left bundle branch block (nLBBB) on the ECG recorded at hospitalization. METHOD: We recorded the details of 18 091 patients treated with acute myocardial infarction (AMI) between 1 January 2014 and 30 June 2015 in the National Registry of Myocardial Infarction. In case of 8334 patients, the clinical diagnosis was ST-elevation myocardial infarction (STEMI), whereas in 9757 cases it was non-ST elevation myocardial infarction (NSTEMI). In the STEMI population we examined the clinical characteristics and prognosis of patients with ST-elevation (n = 7937) and nLBBB (n = 397). We used the proportional hazards regression model (Cox-regression) to examine mortality. RESULTS: In the AMI patient population, we found LBBB in 1274 cases (7%). In case of STEMI clinical diagnosis, the patients belonging to the nLBBB subpopulation (n = 397) were older, and the proportion of men and the occurrence of co-morbidities was higher than in case of those who had ST-elevation on their ECG recorded at hospitalization. The mortality rate of the LBBB population was higher than that of the ST-elevation patient population in both the 30-day (25.4% versus 12.4%) and the 1-year period (47.3 versus 19.9%). Percutaneous coronary intervention (PCI) had significantly lower mortality in both populations. In the course of a multifactorial analysis we verified the independent prognostic significance of LBBB: the hazard ratio compared to ST-elevation was 1.33 (95% confidence interval: 1.10-1.62), checked for gender, age, occurrence of PCI, systolic blood pressure, cardiac frequency, serum creatinine difference, and the details of five anamneses/co-morbidities. CONCLUSION: The admission ECG has prognostic significance. Patients with LBBB have poorer prognosis compared to patients with ST-elevation on admission ECG. Orv Hetil. 2018; 159(17): 677-681.

Performance of a new HPV and biomarker assay in the management of hrHPV positive women: Subanalysis of the ongoing multicenter TRACE clinical trial (n > 6,000) to evaluate POU4F3 methylation as a potential biomarker of cervical precancer and cancer.

The ongoing Triage and Risk Assessment of Cervical Precancer by Epigenetic Biomarker (TRACE) prospective, multicenter study aimed to provide a clinical evaluation of the CONFIDENCE™ assay, which comprises a human papillomavirus (HPV) DNA and a human epigenetic biomarker test. Between 2013 and 2015 over 6,000 women aged 18 or older were recruited in Hungary. Liquid-based cytology (LBC), high-risk HPV (hrHPV) DNA detection and single target host gene methylation test of the promoter sequence of the POU4F3 gene by quantitative methylation-specific polymerase chain reaction (PCR) were performed from the same liquid-based cytology sample. The current analysis is focused on the baseline cross-sectional clinical results of 5,384 LBC samples collected from subjects aged 25 years or older. The performance of the CONFIDENCE HPV™ test was found to be comparable to the cobas® HPV test with good agreement. When applying the CONFIDENCE Marker™ test alone in hrHPV positives, it showed significantly higher sensitivity with matching specificity compared to LBC-based triage. For CIN3+ histological endpoint in the age group of 25-65 and 30-65, the methylation test of POU4F3 achieved relative sensitivities of 1.74 (95% CI: 1.25-2.33) and 1.64 (95% CI: 1.08-2.27), respectively, after verification bias adjustment. On the basis of our findings, POU4F3 methylation as a triage test of hrHPV positives appears to be a noteworthy method. We can reasonably assume that its quantitative nature offers the potential for a more objective and discriminative risk assessment tool in the prevention and diagnostics of high-grade cervical intraepithelial neoplasia (CIN) lesions and cervical cancer.

[One year adherence of ramipril versus ramipril/amlodipine fixed dose combination therapy in hypertension]. / A ramipril versus ramipril/amlodipin fix kombináció egyéves perzisztenciája hypertoniás betegekben.

INTRODUCTION: In the treatment of hypertension avoiding adverse cardiovascular complications to achieve target blood pressure is essential. The appropriate drug selection, and if necessary to change to combination therapy, patients adherence is important which may help fixed dose combination. AIM: The aim of the authors was to investigate the one year adherence of the ramipril and ramipril/amlodipine fixed dose combination in hypertensive patients. METHOD: Prescriptions database of the National Health Insurance Fund in Hungary on pharmacy-claims was analysed between October 1, 2012 and September 30, 2013. The authors identified patients who filled prescriptions for ramipril monotherapy and fixed dose combinations of ramipril/amlodipine prescribed for the first time in hypertensive patients who have not received similar drugs in the previous year. To model the adherence, the apparatus of survival analysis was used, where "survival" was the time to abandon the medication. As it was available to month precision, discrete time survival analysis was applied: a generalized linear model was estimated with complementary log-log link function with the kind of drug being the only explanatory variable. RESULTS: 92,546 patients met the inclusion criteria. During the trial period, ramipril therapy or ramipril/amlodipine fixed dose combination was started in 82,251 and 10,295 patients, respectively. One year persistence rate in patients with ramipril was 30% and 54% in patients with ramipril/amlodipine fixed dose combination therapy. Considering only the 360-day study period, the mean duration of persistence was 189.9 days in patients on ramipril and 270.6 days on ramipril/amlodipine fixed dose combination therapy. The hazard of discontinuation was more than twofold higher during treatment with ramipril compared with the use of the ramipril/amlodipine fixed dose combination therapy (HR = 2.11 [95% CI: 2.05-2.17], p<0,001). CONCLUSIONS: There is a significant difference between the one year persistence of ramipril and ramipril/amlodipine fixed dose combination therapy in hypertension. The result demonstrated that ramipril/amlodipine fixed dose combination therapy has a better one year persistence rate. When the next step is necessary to achieve target blood pressure, ramipril/amlodipine fixed dose combination therapy is preferable. Orv Hetil. 2017; 158(42): 1668-1673.

[One year persistence of free and fixed dose combinations of perindopril/amlodipine]. / A perindopril/amlodipin szabad és fix kombinációk egyéves terápiahusége.

INTRODUCTION: In management of hypertension patient adherence is one of the most important factors. In hypertension the cardiovascular risk reduction can be reached only by prolonged and effective pharmacotherapy. AIM: To evaluate the persistence of one-year treatment of free and fixed-dose combination of perindopril/amlodipine in hypertension. METHOD: Information from the National Health Insurance of Hungary prescriptions database on pharmacy claims between October 1, 2012 and September 30, 2013 was analysed. Authors identified patients who filled prescriptions for free and fixed-dose combination of perindopril/amlodipine, prescribed for the first time for hypertension. Patients have not received antihypertensive therapy with similar active substances during the one year before. Apparatus of survival analysis was used, where "survival" was the time to abandon the medication. As it was available to month precision, discrete time survival analysis was applied. RESULTS: 109,248 patients met the inclusion criteria. Combination antihypertensive therapy with perindopril/amlodipine was started with a free or a fixed-dose combination of these agents in 19,365 and 89,883 patients, respectively. One year persistence rate in patients taking perindopril/amlodipine as a free combination was 27.15%, whereas it was 46.89% in those on the fixed-dose combination. Mean duration of persistence was 177.6 days in patients on the perindopril/amlodipine free, whereas 245.7 days on fixed-dose combination. Actual rate of discontinuation was approximately twice higher with the treatment of free, compared with the use of the fixed-dose combination (hazard ratio =1.94 [95% CI: 1.91-1.98], p<0.001). Orv Hetil. 2017; 158(36): 1421-1425.

[Adherence to medication after myocardial infarction and its impact on outcome: a registry-based analysis from the Hungarian Myocardial Infarction Registry]. / Szívinfarktust túlélt betegek terápiahusége a másodlagos megelozés szempontjából fontos gyógyszeres kezelésekhez.

INTRODUCTION AND AIM: The aim was to study the patients' adherence to some evidence-based medication (statins, beta blockers, platelet and RAS inhibitors) after suffering a myocardial infarction, and its impact on the outcome. METHOD: Retrospective observational cohort study was carried out from the data of the Hungarian Myocardial Infarction Registry between January 1, 2013, and December 31, 2014. 14,843 patients were alive at the end of hospital treatment, from them, those who had no myocardial infarction or death until 180 days were followed for one year. The adherence was defined as the proportion of time from the index event to the endpoint (or censoring) covered with prescription fillings. The endpoint was defined as death or reinfarction. Information on filling prescriptions for statins, platelet aggregation inhibitors, beta blockers and ARB/ACEI-inhibitors were obtained. Multivariate regression was used to model adherence and survival time. RESULTS: Good adherence (\>80%) to clopidogrel, statins, beta blockers, aspirin and ARB/ACEI was found in 64.9%, 54.4%, 36.5%, 31.7% and 64.0%, respectively. Patients treated with PCI during the index hospitalization had higher adherence to all medication (all p<0.01), except for beta-blocker (p = 0.484). Multivariate analysis confirmed that adherence to statins, to clopidogrel and ARB/ACEI-inhibitors was associated with 10.1% (p<0.0001), 10.4% (p = 0.0002) and 15.8% (p<0.0001) lower hazard of endpoint respectively for 25% points increase in adherence, controlling for age, sex, performing of PCI, 5 anamnestic data and date of index event. Adherence to aspirin and beta blockers was not significantly associated with the hazard. CONCLUSION: Higher adherence to some evidence-based medications was found to be associated with improved long term prognosis of the patients. Orv Hetil. 2017; 158(27): 1051-1057.

[A családorvosok alvási apnoéval kapcsolatos ismeretei és attitudjei. Megvalósul-e az OSAS szurése a jármuvezetok egészségi alkalmasságának vizsgálata során?] / A családorvosok alvási apnoéval kapcsolatos ismeretei és attitudjei. Megvalósul-e az OSAS szurése a jármuvezetok egészségi alkalmasságának vizsgálata során?

BACKGROUND AND PURPOSE: Obstructive sleep apnea syndrome (OSAS) without treatment can cause serious cardiovascular, cardiorespiratory, neurological and other complications. Family physicians have an important role in recognizing the disease. The aim of the study is to assess the knowledge and attitude of family physicians related to sleep apnea. Whether OSAS screening is realized during the general medical checkup for drivers. METHODS: In the cross-sectional study we used a validated OSAKA questionnaire in mandatory continuous medical education courses, supplemented with four additional questions. RESULTS: 116 family physicians and 103 family medicine residents filled out the questionnaire. Hungarian family physicians, especially male doctors lack the adequate knowledge of sleep apnea. The average score of female physicians was significantly higher than that of males (13.4±1.8 vs. 11.7±2.6, p=0.005). The more specializations the doctor has, the higher the score. Zero or one special examination holders reached 12.5±2.3 points, two special examination holders 12.7±2.2 points. three or four special examination holders reached 14.0±2.1 (p=0.05). Residents' average score was 12.1±2.4 points, which is higher than that of family doctors (p=0.012). Female residents also had higher average points than male residents (12.6±2.0 vs. 11.3±2.7; p=0.008). The size, location and type of the practice or the doctor's age did not show any statistically significant correlation with the number of points achieved. According to our regression analysis, corrected to variables in the model, we found correlation between gender and medical knowledge, but there was no correlation between age, number of specialities, body mass index and the theoretical knowledge of the doctors. In terms of attitude female GPs had higher average scores than male GPs (3.5±0.6 vs. 2.9±0.6, p<0.001). Despite the modification of the 13/1992 regulation only 39% of the practices carried out regularly the required OSAS screening as part of the medical examination for a driving licence. CONCLUSION: Despite the high prevalence and clinical importance of OSAS, GPs often do not recognize sleep apnea and they have difficulty in treating their patients for this problem.