Favipiravir does not improve viral clearance in mild to moderate COVID-19 - A systematic review and meta-analysis of randomized controlled trials.

Purpose: Favipiravir has been used in the therapy of COVID-19, including patients with mild to moderate symptoms in certain countries. The aim of our systematic review and meta-analysis was to investigate its efficacy and safety in mild-to-moderate COVID-19 infections. Methods: The PubMed, Embase, Web of Science, and Cochrane databases were systematically reviewed for articles reporting the results of randomized controlled trials published until January 6, 2023, resulting in the identification of 20 eligible studies. Results: There were no significant differences in viral clearance time (HR = 1.20, p = 0.09) compared to those without favipiravir therapy. However, in the subgroup analyses, favipiravir treatment significantly increased viral clearance by 59 % (HR = 1.59, p < 0.01) and 42 % (HR = 1.42, p < 0.01], I2 = 20 %) compared to the comparator group in patients with moderate severity of COVID-19 and in the inpatient care setting, respectively. Favipiravir had no beneficial effects in the case of patients with mild symptoms and treated in ambulatory care. Conclusions: The use of favipiravir is questionable in the treatment of outpatients with COVID-19 with mild symptoms. Moderate beneficial effects in the case of patients with moderate symptoms and inpatients should be treated with care due to the limitations of the analysed trials.

Functional Assessment of Long-Term Microvascular Cardiac Allograft Vasculopathy.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is a leading cause of death and retransplantation following heart transplantation (HTX). Surveillance angiography performed yearly is indicated for the early detection of the disease, but it remains of limited sensitivity. METHODS: We performed bolus thermodilution-based coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) and fractional flow reserve (FFR) measurements in HTX patients undergoing yearly surveillance coronary angiography without overt CAV. RESULTS: In total, 27 HTX patients were included who had 52 CFR, IMR, and FFR measurements at a mean of 43 months after HTX. Only five measurements were performed in the first year. CFR decreased significantly by 0.13 every year (p = 0.04) and IMR tended to increase by 0.98 every year (p = 0.051), whereas FFR did not change (p = 0.161) and remained well above 0.80 over time. After one year, CFR decreased significantly (p = 0.022) and IMR increased significantly (p = 0.015), whereas FFR remained unchanged (p = 0.72). CONCLUSIONS: The functional status of the epicardial coronary arteries of transplanted hearts did not deteriorate over time. On the contrary, a significant decrease in CFR was noted. In view of the increasing IMR, this is caused by the deterioration of the function of microvasculature. CFR and IMR measurements may provide an early opportunity to diagnose CAV.

Benefits and Harms of Edible Vegetable Oils and Fats Fortified with Vitamins A and D as a Public Health Intervention in the General Population: A Systematic Review of Interventions.

This systematic review aims to assess whether edible vegetable oils and fats fortified with vitamin A and/or D are effective and safe in improving vitamin intake and ameliorating deficiency states in the general population. In November 2022, we systematically searched MEDLINE, Cochrane CENTRAL, Scopus, Global Index Medicus, ClinicalTrials.gov, and WHO ICTRP (International Clinical Trials Registry Platform) for randomized controlled trials (RCT) and non-randomized studies of interventions (NRSI) investigating the fortification of edible vegetable oils and fats with either vitamin A or vitamin D or both as compared to the same vegetable oils and/or fats without vitamin A and D fortification or no interventions, in the general population, without age restriction. We assessed the methodological quality of included RCTs using Cochrane's risk of bias tool 2.0 and of NRSIs using ROBINS-I tool. We performed random-effects meta-analysis and assessed certainty of evidence using GRADE. We included eight studies. Available evidence showed no significant effect of fortification with vitamin A on serum retinol levels (RCTs: MD 0.35 µmol/L, 95% CI -0.43 to 1.12; two trials; 514 participants; low-certainty evidence; CCTs: MD 0.31 µmol/L, 95% CI -0.18 to 0.80; two trials; 205 participants; very low-certainty evidence) and on subclinical vitamin A deficiency. Low-certainty evidence showed no effect of vitamin D fortification on serum 25-hydroxy vitamin D concentration (MD 6.59 nmol/L, 95% CI -6.89 to 20.07; one trial; 62 participants). In conclusion, vitamin A-fortified vegetable oils and fats may result in little to no difference in serum retinol levels in general populations. The dose of vitamin A used in the trials may be safe but may not be sufficient to reduce subclinical vitamin A deficiency. Further, the evidence suggests that vitamin D fortification results in little to no difference in serum 25-hydroxy vitamin D concentration. Several aspects of providing fortified oils and fats to the general population as a public health intervention should be further investigated, including optimal fortification dose, effects on vitamin D deficiency and its clinical symptoms and potential adverse effects.

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.

[One-year persistence of renin-angiotensin-aldosterone system inhibitors fixed drug combinations in hypertensive patients]. / Renin-angiotenzin-aldoszteron-rendszer-gátlók fix gyógyszer-kombinációinak egyéves perzisztenciája hypertoniás betegekben.

INTRODUCTION: Various fixed combinations of antihypertensive agents are highlighted in European and Hungarian hypertension guidelines. A renin-angiotensin-aldosterone system antagonist (RAAS inhibitor) in combination with calcium channel blockers (CCBs) or diuretics are recommended as the first step in antihypertensive therapy. OBJECTIVES: The aim of the authors was to compare the one-year persistence of RAAS inhibitor fixed-dose combinations (FDCs) in hypertension. METHOD: The authors have analyzed the prescription database of the National Health Insurance Fund and selected patients who first filled prescriptions for any RAAS inhibitor FDC between October 1, 2012, and September 30, 2013, and who did not redeem prescriptions for similar preparations in the year preceding the selection period. Apparatus of survival analysis was used, where "survival" was the time to abandon the medication. RESULTS: A total of 443 149 patients met the selection criteria. The one-year persistence of angiotensin-converting enzyme inhibitor (ACE inhibitor)/CCB FDCs was 44.59%, while that of angiotensin II receptor inhibitor (ARB)/thiazide diuretic (HCT) FDCs was 42.52%. This was followed by ACE inhibitor/indapamide FDCs at 37.27%, ARB/CCB FDCs at 29.04%, and ACE inhibitors/HCT FDCs at 27.47%. Compared to ACE inhibitor/indapamide FDCs (reference), the risk of discontinuing ACE inhibitor/CCBs was 31 percentage points lower (HR = 0.69, 95% CI 0.6855-0.6996, p<0.0001), and the risk of discontinuing ARB/HCT FDCs was 18 percentage points lower (HR = 0.82, 95% CI 0.8096-0.8267, p<0.0001). However, the risk of discontinuing ACE inhibitor/HCT FDCs was 17 percentage points higher (HR = 1.17, 95% CI 1.1562-1.1825, p<0.0001), and the risk of discontinuing ARB/CCB FDCs was 20 percentage points higher (HR = 1.20, 95% CI 1.17316-1.2239, p<0.0001). The average medication adherence time limited to 360 days was 239.9 days for ACE inhibitor/CCB FDCs, 214.8 days for ARB/HCT FDCs, 193.8 days for ACE inhibitor/indapamide FDCs, 178.8 days for ARB/CCB FDCs, and 177.6 days for ACE inhibitor/HCT FDCs. CONCLUSIONS: The authors have demonstrated that the one-year persistence of RAAS inhibitor FDCs varies significantly in hypertensive patients. ACE inhibitor/CCB FDCs were found to be the most advantageous. Orv Hetil. 2023; 164(34): 1337-1341.

External validation of the GRACE risk score in patients with myocardial infarction in Hungary.

Background: Literature confirms that the Global Registry of Acute Coronary Events (GRACE) risk score provides a better risk evaluation than clinical judgment in patients with acute myocardial infarction. We aimed to externally validate the GRACE risk score in unselected patients with myocardial infarction in Hungary. Methods: Data from the comprehensive Hungarian Myocardial Infarction Registry (HUMIR), a national registry that collects data on consecutive acute myocardial infarction (AMI) patients, were used. Hospitals registered 102,939 infarction events in the HUMIR between January 1, 2014, and December 31, 2020. The data required to calculate GRACE risk score were available for 75,199 events. We studied the 6-months, 1-year, and 3-year outcomes. We calculated widely used metrics to characterise calibration (calibration curve, calibration intercept and slope, Eavg, Emax, and E90) and discrimination (c-score, equivalent to AUC, and Somer's Dxy). Results: The risk of low-risk patients was underestimated, and the risk of high-risk patients was overestimated. However, the deviation was small, especially for the three-year survival (E90 was 0.15, 0.22, and 0.08). Discrimination was good, with an AUC of approximately 0.8, and was very similar in all the periods. Conclusions: These data confirmed the usefulness of GRACE risk score in selecting high-risk patients with myocardial infarction in the Hungarian population.

[Determining factors of survival in patients with severe coronavirus infection admitted to intensive care unit in the third and fourth waves of COVID-19 pandemic]. / A kórházi túlélést meghatározó tényezok a COVID­19-járvány 3. és 4. hulláma idején súlyos koronavírus-fertozéssel intenzív osztályra felvett betegekben.

INTRODUCTION: During COVID-19 pandemic, a high mortality rate (20-60%) of patients admitted to intensive care unit has been observed. Identification of risk factors can support the understanding of disease pathophysiology and the recognition of vulnerable patients, prognostication and selection of appropriate treatment. OBJECTIVE: Beyond characterisation of a local, critically ill COVID-19 population, analysis of the associations between demographic/clinical data and patient survival were investigated. METHOD: Retrospective, observational study has been performed by recording demographic, clinical data and outcome parameters on patients with severe respiratory insufficiency caused by COVID-19. RESULTS: 88 patients were enrolled. Median age was 65 years and 53% of patients were male, median BMI was 29 kg/m2. Noninvasive ventilation was used in 81%, endotracheal intubation in 45%, prone positioning in 59% of all cases. Vasopressor treatment was introduced in 44%, secondary bacterial infection was detected in 36% of all cases. Hospital survival rate was 41%. Risk factors for survival and the effect of evolving treatment protocols were analyzed with multivariable regression model. A better survival chance was associated to younger age, lower APACE II score and non-diabetic status. Effect of the treatment protocol was found to be significant (OR = 0.18 [95% CI: 0.04-0.76], p = 0.01976) after controlling for APACHE II, BMI, sex, two comorbidities and two pharmaceutical agents (tocilizumab, remdesivir). CONCLUSION: Survival rate was favourable if patients were younger, with lower APACHE II score and if non-diabetic. Low initial survival rate (15%) significantly improved (49%) in association with the protocol changes. We would like to facilitate Hungarian centres to publish their data and initiate a nationwide database to improve the management of severe COVID disease. Orv Hetil. 2023; 164(17): 651-658.

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.

The Use of Extreme Value Statistics to Characterize Blood Glucose Curves and Patient Level Risk Assessment of Patients With Type I Diabetes.

OBJECTIVE: Characterizing blood glucose curves and providing precise patient level risk assessment of hyperglycemia using extreme value statistics and comparing these assessments with traditional indicators of glycemic variability which are not designed to specifically capture the risk of hyperglycemia. RESEARCH DESIGN AND METHODS: One year return level (blood glucose level exceeded exactly once every year on average) and probability of exceeding and expected time spent above certain thresholds (600 and 400 mg/dL) per year were calculated. As a comparison, traditional metrics for glycemic variability were determined too. The effect of body mass index on extremes was also investigated using non-stationary models. Metrics were calculated on a dataset containing 170.8 patient-years of measurements of 226 patients. RESULTS: Nine high-risk patients were identified with the novel metrics: their estimated time spent above 600 mg/dL per year were above 2 hours. These patients were at moderate risk according to the traditional metrics. Higher body mass index was associated with more extreme glucose levels. CONCLUSIONS: Through these estimates it is possible to assess each patient's individual clinical risk of hyperglycemia even beyond the observed blood glucose levels and detection limits. Additionally, it allows the assessment of the impact of clinical characteristics and treatments on blood glucose control in a novel, mathematically well-founded and potentially clinically more useful way than the already existing indicators.

The metabolic effect of Momordica charantia cannot be determined based on the available clinical evidence: a systematic review and meta-analysis of randomized clinical trials.

Several studies have shown that Momordica charantia L. (Cucurbitaceae, bitter melon) has beneficial effects on metabolic syndrome (MetS) parameters and exerts antidiabetic, anti-hyperlipidemic, and anti-obesity activities. Since the findings of these studies are contradictory, the goal of this systematic review and meta-analysis was to assess the efficacy of bitter melon in the treatment of metabolic syndrome, with special emphasis on the anti-diabetic effect. Embase, Cochrane, PubMed, and Web of Science databases were searched for randomized controlled human trials (RCTs). The meta-analysis was reported according to the PRISMA statement. The primary outcomes of the review are body weight, BMI, fasting blood glucose, glycated hemoglobin A1c, systolic blood pressure, diastolic blood pressure, serum triglyceride, HDL, LDL, and total cholesterol levels. Nine studies were included in the meta-analysis with 414 patients in total and 4-16 weeks of follow-up. In case of the meta-analysis of change scores, no significant effect could be observed for bitter melon treatment over placebo on fasting blood glucose level (MD = -0.03; 95% CI: -0.38 to 0.31; I2 = 34%), HbA1c level (MD = -0.12; 95% CI: -0.35 to 0.11; I2 = 56%), HDL (MD = -0.04; 95% CI: -0.17 to 0.09; I2 = 66%), LDL (MD = -0.10; 95% CI: -0.28 to 0.08; I2 = 37%), total cholesterol (MD = -0.04; 95% CI: -0.17 to 0.09; I2 = 66%,), body weight (MD = -1.00; 95% CI: -2.59-0.59; I2 = 97%), BMI (MD = -0.42; 95% CI: -0.99-0.14; I2 = 95%), systolic blood pressure (MD = 1.01; 95% CI: -1.07-3.09; I2 = 0%) and diastolic blood pressure levels (MD = 0.24; 95% CI: -1.04-1.53; I2 = 0%). Momordica treatment was not associated with a notable change in ALT, AST, and creatinine levels compared to the placebo, which supports the safety of this plant. However, the power was overall low and the meta-analyzed studies were also too short to reliably detect long-term metabolic effects. This highlights the need for additional research into this plant in carefully planned clinical trials of longer duration.

Ankle Brachial Index is a strong predictor of mortality in hypertensive patients: results of a five-year follow-up study.

BACKGROUND: In the hypertensive population, the peripheral arterial disease (PAD) is considered one of the target organ damages. Ankle Brachial Index (ABI) measurement represents the widely accepted clinical method that may objectively detect the presence of PAD. The study aimed to assess how PAD revealed by ABI predicts mortality in patients with hypertension. METHODS: In the follow-up time (5 years period) of the Hungarian ERV Study, a large scale, multicenter observational study, recruiting hypertensive subjects between 50-75 years, the association of PAD with the survival time was analysed. Several multivariate, interval-censored survival models were developed to assess this association. RESULTS: Among the 21892 enrolled hypertensive patients, the prevalence of PAD (ABI≤0.9) was 14.4%. The crude death rate was 5.44% (1190 cases) over the available observational period. In multivariate models male sex, myocardial infarction in patients' history, diabetes, renal failure, PAD and cardiovascular risk (SCORE risk) were significantly associated with mortality. Lower ABI showed a continuous, close to linear association with worse survival. PAD was predictive for mortality risk in all SCORE patient groups. CONCLUSIONS: Low ABI is a strong predictor of mortality in hypertensive patients between the age 50-75, even after adjustment for several potential confounders. The association is linear, with no apparent cut-off, suggesting that ABI should be handled as a continuous variable. The detection of PAD in hypertensives may contribute to the determination of total cardiovascular risk in hypertensive population.

Real-Time Monitoring of the Effectiveness of Six COVID-19 Vaccines against Laboratory-Confirmed COVID-19 in Hungary in 2021 Using the Screening Method.

Several studies have reported the waning effectiveness of COVID-19 vaccines. This study aims to demonstrate the applicability of the screening method for estimating vaccine effectiveness (VE) in a pandemic. We report VE in Hungary, estimated with the screening method, in 2021, covering a period of Alpha and the Delta variant, including the booster dose roll-out. Hungary is in a unique position to use six different vaccines in the same population. All vaccines provided a high level of protection initially, which declined over time. While the picture is different in each age group, the waning of immunity is apparent for all vaccines, especially in the younger age groups and the Sinopharm, Sputnik-V, and AstraZeneca vaccines, which performed similarly. This is clearly reversed by booster doses, more prominent for those three vaccines, where the decline in protection is more evident. Overall, two vaccines, Pfizer/BioNTech and Moderna, tend to produce the best results in all age groups, even with waning immunity considered. Using the screening method in future pandemic waves is worthwhile, especially in countries struggling with a lack of resources or when there is a need to deliver VE results within a short timeframe due to urgent decision-making.

Evaluation of Isolation Area, Myocardial Injury and Left Atrial Function Following High-Power Short-Duration Radiofrequency or Second-Generation Cryoballoon Ablation for Atrial Fibrillation.

This randomized study aims to compare the left atrial (LA) lesion size, function, and tissue damage following pulmonary vein isolation (PVI) by high-power short-duration (HPSD) radiofrequency (RF) and second-generation cryoballoon (CB2) ablation. We enrolled 40 patients with paroxysmal atrial fibrillation who underwent PVI by HPSD RF (n = 21) or CB2 (n = 19). Every patient underwent LA CT angiography and transthoracic echocardiography (TTE) to assess the LA anatomy and function. Biomarker levels (hs-cTnT, hs-CRP, LDH) were compared pre- and post-procedurally. Pre- and post-ablation high-density mapping (HDM) was performed. The isolation area was defined under 0.2 mV bipolar voltage (low voltage area, LVA). We calculated the post-PVI LVA/LA surface ratio using LA CT-HDM merge images. At 3-month follow-up, TTE was performed to assess the changes in LA function. Post-ablation hs-cTnT level was significantly higher in the RF group (RF: 1249 ± 469 ng/L, CB2: 995 ± 280 ng/L, p = 0.024). Post-PVI hs-CRP (RF: 9.53 ± 10.30 mg/L, CB2: 12.36 ± 5.76 mg/L, p = 0.034) and LDH levels (RF: 349.9 ± 65.6 U/L, CB2: 451.6 ± 91.3 U/L, p < 0.001) were significantly higher following CB2 ablation. Post-PVI LVA/LA surface ratios were 8.37 ± 6.42% in the RF group and 13.58 ± 8.92% in the CB2 group (p = 0.022). LA function did not change significantly after the PVI procedure. Our data indicate that second-generation cryoballoon ablation produces a significantly larger LA lesion size compared to "point-by-point" HPSD radiofrequency. Both techniques preserve LA function. The myocardial component of tissue loss appears to be higher using HPSD radiofrequency ablation, with less collateral damage.

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.

Prognostic Value of Measuring Fractional Flow Reserve After Percutaneous Coronary Intervention in Patients With Complex Coronary Artery Disease: Insights From the FAME 3 Trial.

BACKGROUND: We evaluate the prognostic value of measuring fractional flow reserve (FFR) after percutaneous coronary intervention (post-PCI FFR) and intravascular imaging in patients undergoing PCI for 3-vessel coronary artery disease in the FAME 3 trial (Fractional Flow Reserve versus Angiography for Multivessel Evaluation). METHODS: The FAME 3 trial is a multicenter, international, randomized study comparing FFR-guided PCI with coronary artery bypass grafting in patients with multivessel coronary artery disease. PCI was not noninferior with respect to the primary end point of death, myocardial infarction, stroke, or repeat revascularization at 1 year. Post-PCI FFR data were acquired on a patient and vessel-related basis. Intravascular imaging guidance was tracked. The primary end point is a comparison of target vessel failure (TVF) defined as a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization at 1 year based on post-PCI FFR values. Cox regression with robust SEs was used for analysis. RESULTS: Of the 757 patients randomized to PCI, 461 (61%) had post-PCI FFR measurement and 11.1% had intravascular imaging performed. The median post-PCI FFR was 0.89 [IQR' 0.85-0.94]. On a vessel-level, post-PCI FFR was found to be a significant predictor of TVF univariately (hazard ratio=0.67 [95% CI' 0.48-0.93] for 0.1 unit increase, P=0.0165). On a patient-level, the single lowest post-PCI FFR value was also found to be a significant predictor of TVF univariately (hazard ratio=0.65 [95% CI' 0.48-0.89] for 0.1 unit increase, P=0.0074). Post-PCI FFR was an independent predictor of TVF in multivariable analysis adjusted for key clinical parameters. Outcomes were similar between patients who had intravascular imaging guidance and those who did not. CONCLUSIONS: Post-PCI FFR measurement was a significant predictor of TVF on a vessel and patient level and an independent predictor of outcomes in a population with complex 3-vessel coronary artery disease eligible for coronary artery bypass grafting. The limited use of intravascular imaging did not affect outcomes. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02100722.

Severity of depressive but not anxiety symptoms impacts glucose metabolism among patients with type 2 diabetes in primary care.

Background: Data from primary care regarding the prevalence of symptoms of depression and anxiety, and their effect on glycemic control among people with diabetes is lacking in Hungary. The recently introduced Patient Health Record (PHR) requires family doctors to screen for depressive symptoms. Objectives: We aimed to investigate the prevalence of depressive and anxiety symptoms among patients with type 2 diabetes in the general practice, and the relationship between these affective disorders and glycated hemoglobin (HbA1c) level. Methods: We included 338 consecutive patients with type 2 diabetes from six primary care practices in this cross-sectional study. A self-administered questionnaire (patient history, anthropometric, socioeconomic, laboratory parameters), the Beck Depression Inventory (BDI) and the Hamilton Anxiety Scale (HAM-A) were used. Results: The mean age of the sample was 64.0 ± 11.5 (years ± SD), 61% of participants were female. The prevalence of depressive symptoms was 21%, mainly moderate/severe symptoms (13%). Anxiety symptoms were more common (35%). We found significant univariate association between the depressive symptoms and HbA1c (p = 0.001), suicide attempt (p < 0.001), anxiety (p < 0.001), micro- and macrovascular complication (p = 0.028 and p < 0.001), education (p = 0.001) and place of residence (p = 0.002). In multivariate analysis, however, only BDI score had significant (p = 0.03191) association with glycemic control. Conclusion: Among primary care patients with type 2 diabetes, the prevalence of depressive symptoms was less frequent than anxiety symptoms. More severe depressive symptoms were associated with worse glycemic control.

Sex-related differences in the management and outcomes of patients hospitalized with ST-elevation myocardial infarction: a comparison within four European myocardial infarction registries.

Aims: Data on how differences in risk factors, treatments, and outcomes differ between sexes in European countries are scarce. We aimed to study sex-related differences regarding baseline characteristics, in-hospital managements, and mortality of ST-elevation myocardial infarction (STEMI) patients in different European countries. Methods and results: Patients over the age of 18 with STEMI who were treated in hospitals in 2014-17 and registered in one of the national myocardial infarction registers in Estonia (n = 5817), Hungary (n = 30 787), Norway (n = 33 054), and Sweden (n = 49 533) were included. Cardiovascular risk factors, hospital treatment, and recommendation of discharge medications were obtained from the infarction registries. The primary outcome was mortality, in-hospital, after 30 days and after 1 year. Logistic and cox regression models were used to study the associations of sex and outcomes in the respective countries. Women were older than men (70-78 and 62-68 years, respectively) and received coronary angiography, percutaneous coronary intervention, left ventricular ejection fraction assessment, and evidence-based drugs to a lesser extent than men, in all countries. The crude mortality in-hospital rates (10.9-15.9 and 6.5-8.9%, respectively) at 30 days (13.0-19.9 and 8.2-10.9%, respectively) and at 1 year (20.3-28.1 and 12.4-17.2%, respectively) after hospitalization were higher in women than in men. In all countries, the sex-specific differences in mortality were attenuated in the adjusted analysis for 1-year mortality. Conclusion: Despite improved awareness of the sex-specific inequalities on managing patients with acute myocardial infarction in Europe, country-level data from this study show that women still receive less guideline-recommended management.

Health outcomes associated with micronutrient-fortified complementary foods in infants and young children aged 6-23 months: a systematic review and meta-analysis.

BACKGROUND: Appropriate feeding of infants and young children is essential for healthy growth and the prevention of stunting, wasting, and overweight. We aimed to assess the beneficial versus harmful effects of providing fortified complementary foods to children in the complementary feeding period. METHODS: In this systematic review and meta-analysis, we searched the databases Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, Global Index Medicus, Web of Science, ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform from inception to March 9, 2021. We included randomised controlled trials and controlled clinical trials done in infants and children aged 6-23 months with no identified health problems. Consumption of foods fortified centrally (ie, during industrial processing) with one micronutrient or a combination of vitamins, minerals, or both was compared with the same complementary foods, but without micronutrient fortification. Two review authors independently screened studies for eligibility, extracted data, assessed risk of bias, and rated the certainty of the evidence. The main outcomes were growth (measured by Z scores for weight for age, weight for height or length, and height or length for age, or other growth measures), stunting, wasting, nutrient adequacy or excess, anaemia, haemoglobin concentration, iron status, serum zinc concentration, and serum retinol concentration. We used a random-effects meta-analysis for combining data. This study is registered with PROSPERO, CRD42021245876. FINDINGS: We included 16 studies with 6423 participants, 13 of which were done in malaria-endemic areas. Overall, 12 studies were included in the quantitative syntheses. We identified five further ongoing studies. There was no difference between participants who received fortified complementary foods and those who received non-fortified complementary foods in weight-for-age Z scores (mean difference -0·01, 95% CI -0·07 to 0·06; five trials; 1206 participants; moderate-certainty evidence), weight-for-height or length Z scores (-0·05, -0·19 to 0·10; four trials; 1109 participants; moderate-certainty evidence), and height or length-for-age Z scores (-0·01, -0·21 to 0·20; four trials; 811 participants; low-certainty evidence); stunting and wasting were not assessed in any study as outcomes. Moderate-certainty evidence from six trials with 1209 patients showed that providing fortified complementary foods to children aged 6-23 months reduced the risk of anaemia (risk ratio 0·57, 95% CI 0·39 to 0·82). Those who received fortified complementary foods compared with those who did not had higher haemoglobin concentrations (mean difference 3·44 g/L, 95% CI 1·33 to 5·55; 11 trials; 2175 participants; moderate-certainty evidence) and ferritin concentration (0·43 µg/L on log scale, 0·14 to 0·72; six trials; 903 participants; low-certainty evidence). The intervention led to no effects on serum zinc concentration (-0·13 g/dL, -0·82 to 0·56; two trials; 333 participants; low-certainty evidence) and serum retinol concentration (0·03 µmol/L, -0·02 to 0·08; five trials; 475 participants; moderate-certainty evidence). INTERPRETATION: Fortified complementary foods are effective strategies to prevent anaemia in infants and young children aged 6-23 months in malaria-endemic regions. Effects of complementary food fortification should be further investigated in low-income and middle-income countries, but should also be assessed in high-income countries, and in regions where malaria is not endemic. FUNDING: WHO.

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.