Real-life effectiveness of dupilumab in chronic rhinosinusitis with nasal polyps. Results from eight Hungarian centres with 12-month follow-up.

BACKGROUND: Research on the immune mechanism behind chronic rhinosinusitis (CRS) has revealed various new endotypes, leading to targeted therapies, especially for severe uncontrolled CRS. Biologics are novel therapeutic strategies providing targeted treatment for the difficult-to-treat recalcitrant CRSwNP patients. Dupilumab is a fully human-derived monoclonal antibody that binds to IL4Rα, inhibiting the signalling of both IL-4 and IL-13. In Hungary, it is approved for the treatment of uncontrolled CRSwNP according to criteria based on the EPOS2020 and the Hungarian guidelines. METHODOLOGY: This study aimed to collect and evaluate real-world therapeutic data of CRSwNP patients treated with dupilumab. One hundred thirty-five patients from eight different referral centres have been enrolled in this study, who received dupilumab since 2020. All subjects were adult patients (over 18 years) with uncontrolled CRSwNP. Baseline data collection included demographics, medical history, previous surgeries, related comorbidities, total endoscopic nasal polyp score (NPS), SNOT22, nasal congestion parameters measured with visual analogue scale (VAS) and nasal obstruction evaluation scale (NOSE), loss of smell score (LSS) and eosinophil count. 300 mg dupilumab was administered subcutaneously every second week. Follow up visits were performed after 6 and 12 months. RESULTS: After 6 and 12 months of treatment significant improvement was detected in all clinical parameters. Safety was proved, no severe side effects occurred, and no rescue treatment was necessary. CONCLUSIONS: Our real-life findings show that continuous dupilumab treatment is effective and safe in daily clinical practice in CRSwNP and other type 2 comorbidities such as bronchial asthma and NERD.

Multidisciplinary management of acute cholecystitis during the COVID-19 pandemic.

The coronavirus disease 2019 pandemic had a major impact on most medical services. Our aim was to assess the outcome of acute cholecystitis during the nationwide lockdown period. All patients admitted to our emergency department for AC were analysed. Patient characteristics, performance status, AC severity, treatment modality and outcome of AC were assessed during the lockdown period (Period II: 1 April 2020-30 November 2021) and compared to a historical control period (Period I: 1 May 2017-31 December 2018). AC admissions increased by 72.8% in Period II. Patients were younger (70 vs. 74 years, p = 0.017) and greater in number in the CCI 1 group (20.4% vs. 11.2%, p = 0.043) in Period II. The unplanned readmission rate (6.3 vs. 0%, p = 0.004) and the gallbladder perforation (GP) rate was higher (18.0 vs. 7.3%, p = 0.006) in Period II. Percutaneous transhepatic gallbladder drainage (PTGBD) was more frequent (24.1 vs. 12.8%, p = 0.012) in Period II. In addition to a drop in patient age and CCI, a significant rise in the prevalence of acute cholecystitis, GP and unplanned readmissions was observed during the nationwide lockdown due to the COVID-19 pandemic. PTGBD was more frequent during this period, whereas successful conservative treatment was less frequent.

Use of glucose-lowering drugs in Hungary between 2008 and 2017: the increasing use of novel glucose-lowering drug groups.

AIMS: To analyse glucose-lowering drug utilization, focusing on the novel glucose-lowering drug groups dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors, and the financial burden they entail. METHODS: Crude reimbursed national drug utilization and expenditure data for the entire population of Hungary were obtained from the National Health Insurance Fund for the study period: 2008 to 2017. Data were analysed using the WHO's Anatomical Therapeutic Chemical Classification/defined daily dose system and were expressed in defined daily dose per 1000 inhabitants per day. RESULTS: Total glucose-lowering drug consumption in Hungary showed an 18% increase over the study period, reaching 74.7 defined daily doses per 1000 inhabitants per day, while novel glucose-lowering drug use increased to 11.7 defined daily doses per 1000 inhabitants per day (16% of total glucose-lowering drug use) by 2017. Dipeptidyl-peptidase 4 inhibitor consumption grew to 7.4 defined daily doses per 1000 inhabitants per day by 2017. The most widely used dipeptidyl-peptidase 4 inhibitor was sitagliptin. Glucagon-like peptide-1 receptor agonists were used the least, but by 2017 rose to 1.5 defined daily doses per 1000 inhabitants per day, led by liraglutide. Sodium-glucose co-transporter-2 inhibitors appeared in the utilization data in 2014 and their consumption, mainly empagliflozin, reached 2.8 defined daily doses per 1000 inhabitants per day by 2017. The total expenditure on glucose-lowering drugs increased 94% between 2008 and 2017, and the total cost of novel glucose-lowering drug utilization comprised 44% of the total glucose-lowering drug expenditure in 2017. CONCLUSIONS: Both the use of and the financial burden posed by novel glucose-lowering drugs in Hungary increased steadily between 2008 and 2017. This increase is expected to continue.

Hungarian hospital antibiotic consumption at the regional level, 1996-2005.

BACKGROUND: Regional variations in antibiotic consumption in outpatients have been reported previously, but nothing is as yet known about the regional distribution of antibiotic consumption in the hospital sector in Hungary. This study was designed to explore regional variations and investigate determinants of antibiotic consumption in hospital care in Hungary. MATERIALS AND METHODS: Regional distribution-based antibiotic sales data were obtained for a 10-year period (1996-2005) for the 20 Hungarian counties. Systemic antibacterial use (Anatomical Therapeutic Chemical code: J01) was expressed as the number of defined daily doses (DDD) per 100 patient-days. The multiple linear regression model was applied to investigate the determinants of regional differences in hospital antibiotic consumption. Independent variables related to health care access, utilization of hospital resources, doctors' workload, type of hospital care provided, and patient's characteristics and infections were considered as possible determinants, and data on these variables were obtained for 2 years (2004, 2005). We also tested the association between hospital and ambulatory care antibiotic consumption in Hungarian regions using the Pearson correlation test. RESULTS: For each year during the 1996-2005 study period, there were large and stable variations in total hospital antibiotic consumption (e.g., min-max(1996): 16.0-28.2; min-max(2005): 15.2-32.2 DDD per 100 patient-days) depending on the region. In the two developed models (Model 1 and Model 2), the number of reported infections accounted for 53% of the observed regional variations in hospital antibiotic consumption (Model 1), and the number of reported infections together with the case-mix index were responsible for 61% (Model 2) . Total antibiotic consumption in hospitals showed a positive correlation (R = 0.71, p = 0.002) with total antibiotic consumption in ambulatory care. CONCLUSION: The case-mix index and the number of reported infections explained some of the observed regional variations. However, the moderate value of the models in explaining these regional variations suggest that determinants which could not be explored in this preliminary study may also contribute to regional differences. Future studies should aim at collecting data for each individual hospital as well as data on possible determinants for hospital antibiotic consumption.

Results of a local antibiotic management program on antibiotic use in a tertiary intensive care unit in Hungary.

BACKGROUND: Massive antibiotic use in intensive care units (ICU) is associated with increased microbial resistance. Therefore avoiding unneccesary antibiotic usage is essential. To achieve a more considered antibiotic prescribing practice, a new antibiotic policy was implemented at our ICU. In this paper, we evaluated the impact of this intervention, and described the aetiology and incidence of blood stream infections and selected antibiotic-resistant pathogens. MATERIALS AND METHODS: In November 2002, a local antibiotic management program (LAMP) was implemented. This included a new infectious diseases specialist consultation service and restricted authorisation to prescribe antibiotics. The effect on ward-level antibiotic use was examined by segmented regression analysis. Patient, ICU and microbiology data were also recorded and compared before and after policy implementation. RESULTS: The patient populations and the subsequent mortality rate were comparable before and after the implementation of the policy. Total antibiotic consumption was markedly reduced from 162.9 to 101.3 defined daily dose (DDD) per 100 patients, and per day (DDD per 100 patient-days). This was mainly accounted for a reduction in the use of quinolones, aminoglycosides, glycopeptides, metronidazol, carbepenems and third generation cephalosporins. CONCLUSION: This study has confirmed that establishing a targeted LAMP, based on close co-operation between intensive care physicians and infectious disease specialists together with a restricted prescribing authority, can reduce the use of antibiotics.

An 8-year evaluation of antibiotic consumption and antibiotic resistance among Streptococcus pneumoniae from in- and out-patients in Szeged, Hungary.

At the beginning of the 1990s, the prevalence of penicillin resistance of Streptococcus pneumoniae strains in Hungary was found to be extremely high (up to 58% non-susceptible) in some studies, while in other publications the percentage of penicillin highly resistant strains was 0-2%. To see whether this was due to differences in methodology or the composition of the patient population studied, a retrospective evaluation was carried out of the penicillin, amoxicillin, ceftriaxone and macrolide resistance of all S. pneumoniae strains isolated from in- and outpatients in our laboratory between 1998 and 2005. Of the 2670 S. pneumoniae isolates only 5.58% was found to exhibit high-level resistance to penicillin, while resistance to amoxicillin, ceftriaxone and erythromycin was 2.62%, 1.12% and 42.06%, respectively. During this period 6 (3.8%) of 155 S. pneumoniae strains isolated from invasive samples displayed high-level resistance to penicillin. Earlier surveillance data on penicillin resistance of S. pneumoniae may have been biased by the age groups affected by the infection, by whether the strain was isolated from an out-patient or an in-patient, and by whether the isolates were obtained from invasive samples. Our 8-year study using the NCCLS/CLSI methodology consequently revealed a low prevalence of high-level resistance to penicillin in S. pneumoniae strains obtained both from adults and children.

The first steps towards fluoroquinolone resistance in Hungarian pneumococci.

The incidence of fluoroquinolone resistance among Hungarian routine laboratory Streptococcus pneumoniae isolates, collected in 2000-2002, in common with other European countries, was very low; only 5/304 strains (1.64%) were resistant to ciprofloxacin (MIC = 4 microg/ml), and the other fluoroquinolones showed full efficacy. However, we could identify the Lys-137-Asp amino acid change, caused by a point mutation in the QRDR of the parC gene, in five strains. Additionally, we observed a definite shift in the minimum inhibitory concentrations (MICs) of all fluoroquinolones towards higher values throughout the study period. These two findings, coupled with the increasing consumption figures of fluoroquinolones, suggest that pneumococcal resistance looks poised to develop in Hungary.