Prague wastewater treatment plant was intensified during 1994--1997 by construction of new regeneration tank and four new secondary settling tanks. Nevertheless, more stringent effluent limits and operational problems gave rise to necessity for further intensification and optimisation of plant performance. This paper describes principal operational problems of the plant and shows solutions and achieved results that have lead to plant performance stabilisation. The following items are discussed: low nitrification capacity, nitrification bioaugmentation, activated sludge bulking, insufficient sludge disposal capacity, chemical precipitation of raw wastewater, simultaneous precipitation, sludge chlorination, installation of denitrification zones, sludge rising in secondary settling tanks due to denitrification, dosage of cationic polymeric organic flocculant to secondary settling tanks, thermophilic operation of digestors, surplus activated sludge pre-thickening, mathematical modelling.

• MeSH
• biodegradace MeSH
• bioreaktory MeSH
• chlor chemie   MeSH
• čištění vody přístrojové vybavení   metody   MeSH
• dusík chemie   MeSH
• kationty MeSH
• kyslík metabolismus   MeSH
• odpad tekutý - odstraňování přístrojové vybavení   metody   MeSH
• odpadní vody MeSH
• počítačová simulace MeSH
• pohyb vody MeSH
• průmyslový odpad MeSH
• teoretické modely MeSH
• vzduch MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• chlor MeSH
• dusík MeSH
• kationty MeSH
• kyslík MeSH
• odpadní vody MeSH
• průmyslový odpad MeSH

The management of type 2 diabetes (T2D) often necessitates treatment intensification, and sometimes simplification to achieve glycaemic targets and mitigate complications. This expert opinion paper evaluates the use and positioning of the fixed-ratio combinations (FRCs) of basal insulin (BI) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in optimising T2D management. On the basis of the evidence presented and discussions, these FRCs offer a promising approach for both treatment intensification and simplification in people with suboptimal glucose control despite receiving various therapies. In treatment intensification, FRCs provide a synergistic effect by addressing multiple pathophysiological defects contributing to hyperglycaemia. These FRCs effectively control both fasting and postprandial glucose (PPG) excursions, offering significantly improved glycaemic control with a lower hypoglycaemia risk and weight neutrality compared to traditional or complex insulin regimens. Moreover, the reduced injection frequency (once daily) and flexibility in the dosing schedule (with any major meal of the day) help mitigate patient resistance to insulin initiation or titration. This further reduces treatment burden, facilitating treatment adherence and enhancing patient convenience. These key benefits of FRCs over complex insulin regimens play a crucial role in long-term glycaemic management and overall treatment outcomes. Hence, the timely use of FRCs in the treatment algorithm for people with T2D represents a valuable strategy for optimising glycaemic control, addressing treatment barriers and enhancing patient-reported outcomes.

• Klíčová slova
• Clinical criteria, Fixed-ratio combination, Intensification, Simplification, Type 2 diabetes,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

INTRODUCTION: Multiple daily injection insulin regimen (MDI) represents the most intensive insulin regimen used in the management of people with type 2 diabetes (PwT2D). Its efficacy regarding glycaemic control is counterbalanced by the increased risk of hypoglycaemia, frequently observed tendency to weight gain and necessity for frequent glucose monitoring. Recent introduction of novel antidiabetic medications with pleiotropic effects reaching far beyond the reduction of glycaemia (HbA1c), such as the glucagon-like peptide 1 receptor agonist (GLP-1 RA), has significantly widened the therapeutic options available for management of T2D. Consequently, there is currently a substantial number of PwT2D for whom the MDI regimen was initiated at a time when no other options were available. Yet, in present times, these individuals could benefit from simplified insulin regimens ideally taking advantage of the beneficial effects of the novel classes of antidiabetic medications. iGlarLixi (Suliqua®) is a once-daily fixed-ratio combination of basal insulin analogue glargine 100 U/ml and a GLP-1 RA lixisenatide. METHODS: Insulin therapy DE-intensificAtion with iglarLixi (IDEAL) is a six-centre, open-label, parallel-group, active comparator, phase IV randomised controlled trial with a 24-week active treatment period examining the efficacy and safety of MDI regimen de-intensification with once-daily administration of iGlarLixi versus MDI regimen continuation in PwT2D on a backgroud therapy with metformin ± sodium-glucose cotransporter 2 inhibitor. PLANNED OUTCOMES: The primary objective is to compare the effects of MDI therapy de-intensification with iGlarLixi versus MDI regimen continuation regarding glycaemic control (HbA1c). Secondary objectives include detailed evaluation of the effects of MDI regimen de-intensification with iGlarLixi on glycaemic control using standardised continuous glucose monitoring (CGM) metrics and self-monitoring of plasma glucose. Furthermore, body weight and body composition analysis, quality of life and safety profile are evaluated. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT04945070.

• Klíčová slova
• Complex insulin therapy simplification, Fixed-ratio combination of GLP-1 receptor agonist and basal insulin (FRC), Insulin glargine/lixisenatide (iGlarLixi), Insulin therapy de-intensification, Intensified insulin therapy (IIT), Multiple daily injections insulin regimen (MDI), Type 2 diabetes (T2D),
• Publikační typ
• časopisecké články MeSH

BACKGROUND: High-dose therapy with autologous stem cell transplantation (HDT-ASCT) and maintenance treatment with novel agents are the best options for patients with newly diagnosed multiple myeloma, increasing the rate of complete response (CR) and prolonging progression-free survival (PFS) and overall survival (OS). Indeed, the achievement of a CR is a predictor of long-term survival among transplant-eligible patients. However, it is unclear whether patients reaching a CR after induction treatment could receive less intense consolidation or avoid maintenance therapy. PATIENTS AND METHODS: We analyzed CR patients treated in 2 phase III trials, GIMEMA-RV-MM-PI-209 and RV-MM-EMN-441, to compare HDT-ASCT with an R-Alk (lenalidomide, alkylator) regimen as consolidation, and lenalidomide (R) maintenance with no maintenance. The primary endpoints were PFS, second PFS (PFS2), and OS from consolidation and maintenance (_m). RESULTS: Overall, the data from 166 patients in CR were analyzed, 95 in the HDT-ASCT group and 71 in the R-Alk group. The CR patients who received HDT-ASCT had a better PFS (hazard ratio [HR], 0.55; P = .01), PFS2 (HR, 0.46; P = .02), and OS (HR, 0.42; P = .03) compared with patients randomized to R-Alk. The survival benefit with HDT-ASCT was confirmed among all the subgroups, according to age, International Staging System (ISS stage, cytogenetic profile, and receipt of maintenance therapy. CR patients who received lenalidomide maintenance had a better PFS_m (4 years: 54% vs. 19%; HR, 0.43; P = .02) compared with those who received no maintenance. However, no difference was observed in terms of PFS2_m (4 years: 72% vs. 58%; HR, 0.83; P = .67) and OS_m (4 years: 79% vs. 72%; HR, 0.82; P = .73) with maintenance therapy. CONCLUSION: Even in CR patients, outcomes were improved by an intensified approach with HDT-ASCT consolidation and lenalidomide-based maintenance therapy.

• Klíčová slova
• ASCT, CR, Lenalidomide, MM, Treatment intensification,
• MeSH
• adjuvantní chemoterapie MeSH
• alkylační protinádorové látky aplikace a dávkování   škodlivé účinky   MeSH
• autologní transplantace MeSH
• časové faktory MeSH
• doba přežití bez progrese choroby MeSH
• klinické zkoušky, fáze III jako téma MeSH
• konsolidační chemoterapie MeSH
• lenalidomid aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom diagnóza   mortalita   terapie   MeSH
• multicentrické studie jako téma MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• randomizované kontrolované studie jako téma MeSH
• reziduální nádor MeSH
• rizikové faktory MeSH
• transplantace kmenových buněk * škodlivé účinky   mortalita   MeSH
• udržovací chemoterapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• alkylační protinádorové látky MeSH
• lenalidomid MeSH

BACKGROUND: Successful conversion from insulin therapy to glucagon-like peptide 1 receptor agonist (GLP-1RA) with basal insulin in well-controlled patients has already been demonstrated. However, the data concerning individuals with poor glycaemic control are scarce. The aim of this work was to assess the success rate of insulin therapy to liraglutide transition in poorly controlled diabetes in a real-world clinical setting and to define predictors of success. We are the first to present the method of a fasting test as a way to identify the patients at higher risk of failure after treatment de-intensification. METHODS: The retrospective observational study analyzed data of 62 poorly controlled obese diabetic patients on high-dose insulin therapy, who were subjected to a 72 h fasting test during hospitalization and subsequently switched to liraglutide ± basal insulin therapy. During the fasting, all antidiabetic treatment was discontinued. Patients were classified as responders if they remained on GLP-1RA treatment after 12 months. Non-responders restarted the basal-bolus insulin (BBI) regimen. Development of glycated hemoglobin (HbA1c) and body weight in both groups, alongside with parameters associated with the higher risk of return to the BBI regimen, were analyzed. RESULTS: A total of 71% of patients were switched successfully (=responders). Responders had more significant improvement in HbA1c (-6.4 ± 19.7 vs. -3.4 ± 22.9 mmol/mol) and weight loss (-4.6 ± 7.1 vs. -2.5 ± 4.0). Statistically significant difference between groups was found in initial HbA1c (75.6 ± 17.9 vs. 90.5 ± 23.6; p = 0.04), total daily dose of insulin (67.6 ± 36.4 vs. 90.8 ± 32.4; p = 0.02), and mean glycaemia during the fasting test (6.9 ± 1.7 vs. 8.6 ± 2.2 mmol/L; p < 0.01). CONCLUSIONS: This study confirms that therapy de-intensification in poorly controlled patients with a BBI regimen is possible. Higher baseline HbA1c, total daily insulin dose, and mean glucose during fasting test are negative predictive factors of successful therapy de-escalation.

• Klíčová slova
• bolus-basal insulin therapy, fasting test, glucagon-like peptide 1 analogues, liraglutide, therapy de-intensification, type 2 diabetes,
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• časopisecké články MeSH

CONTEXT: Several recent randomised trials have evaluated the role of combination systemic treatment using androgen deprivation therapy (ADT) plus chemotherapy or an androgen receptor signaling inhibitor (ARSI) in patients with high-risk and/or unfavourable nonmetastatic prostate cancer (nmPC). OBJECTIVE: To assess the outcomes associated with adding combination systemic treatment to primary definitive local therapy in patients with high-risk and/or unfavourable nmPC. EVIDENCE ACQUISITION: We queried the PubMed, Web of Science, and Scopus databases and conference abstracts to identify prospective randomised trials examining the value of adding chemotherapy or an ARSI to ADT and primary local therapy with curative intent for nmPC. The primary endpoints were overall survival (OS), cancer-specific survival (CSS), metastasis-free survival (MFS), and failure-free survival (FFS). Secondary endpoints included adverse events (AEs) and pathologic outcomes. EVIDENCE SYNTHESIS: We identified 15 randomised studies, of which nine evaluated chemohormonal and six investigated ARSI-based treatment strategies. In both radical prostatectomy (RP) and radiation therapy (RT) settings, addition of docetaxel to ADT was associated with significantly better CSS (pooled hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.49-0.95; p = 0.025), MFS (pooled HR 0.82, 95% CI 0.71-0.95; p = 0.008), and FFS (pooled HR 0.70, 95% CI 0.62-0.79; p < 0.001); the difference did not meet the conventional level of statistical significance for OS (pooled HR 0.86, 95% CI 0.73-1.01; p = 0.072). For patients treated with RT alone, docetaxel-based combination treatment did not meet the significance threshold set for OS (p = 0.3), CSS (p = 0.072), or MFS (p = 0.079), but the difference for FFS was statistically significant (pooled HR 0.72, 95% CI 0.63-0.84; p < 0.001). On network meta-analyses including RT studies, ARSI + ADT outperformed docetaxel + ADT for survival endpoints and had a more favourable AE profile. CONCLUSIONS: Intensification of systemic therapy with docetaxel or an ARSI in addition to ADT improves oncologic endpoints in high-risk and/or unfavourable nmPC treated with local definitive therapy. The highest efficacy was achieved with ARSI + ADT, specifically in patients treated with RT. PATIENT SUMMARY: Our findings highlight that selected patients with high-risk nonmetastatic prostate cancer benefit from intensification of systemic therapy beyond hormonal treatment.

• Klíčová slova
• Abiraterone, Chemotherapy, Docetaxel, Enzalutamide, Prostate cancer, Radiation therapy, Radical prostatectomy,
• MeSH
• antagonisté androgenů škodlivé účinky   MeSH
• docetaxel terapeutické užití   MeSH
• lidé MeSH
• nádory prostaty * farmakoterapie   patologie   MeSH
• prospektivní studie MeSH
• protinádorové látky * terapeutické užití   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• systematický přehled MeSH
• Názvy látek
• antagonisté androgenů MeSH
• docetaxel MeSH
• protinádorové látky * MeSH

INTRODUCTION: The aim of this study was to evaluate the long-term cost-effectiveness of the insulin degludec/liraglutide combination (IDegLira) versus basal insulin intensification strategies for patients with type 2 diabetes mellitus (T2DM) not optimally controlled on basal insulin in the Czech Republic. METHODS: Cost-effectiveness was evaluated using the QuintilesIMS Health CORE Diabetes model, an interactive internet-based model that simulates clinical outcomes and costs for cohorts of patients with diabetes. The analysis was conducted from the perspective of the Czech Republic public payer. Sensitivity analyses were conducted to explore the sensitivity of the model to plausible variations in key parameters. RESULTS: The use of IDegLira was associated with an improvement in the quality-adjusted life expectancy of 0.31 quality-adjusted life-years (QALYs), at an additional cost of Czech Koruna (CZK) 107,829 over a patient's lifetime compared with basal-bolus therapy, generating an incremental cost-effectiveness ratio (ICER) of CZK 345,052 per QALY gained. In a scenario analysis, IDegLira was associated with an ICER of CZK 693,763 per QALY gained compared to basal insulin + glucagon-like peptide-1 receptor agonist (GLP-1 RA). The ICERs are below the generally accepted willingness-to-pay threshold (CZK 1,100,000/QALY gained at the time of this analysis). CONCLUSIONS: Results from this evaluation suggest that IDegLira is a cost-effective treatment option compared with basal-bolus therapy and basal insulin + GLP-1 RA for patients with T2DM in the Czech Republic whose diabetes is not optimally controlled with basal insulin. FUNDING: Novo Nordisk.

• Klíčová slova
• Cost-effectiveness, Fixed-ratio combination therapy, IDegLira, QALY, Type 2 diabetes,
• Publikační typ
• časopisecké články MeSH

The knowledge on the performance enhancement of nitrogen and organic matter in the expanded constructed wetlands (CWs) with various new designs, configurations, and technology combinations are still not sufficiently summarized. A comprehensive review is accordingly necessary for better understanding of this state-of-the-art-technology for optimum design and new ideas. Considering that the prevailing redox conditions in CWs have a strong effect on removal mechanisms and highly depend on wetland designs and operations, this paper reviews different operation strategies (recirculation, aeration, tidal operation, flow direction reciprocation, and earthworm integration), innovative designs, and configurations (circular-flow corridor wetlands, towery hybrid CWs, baffled subsurface CWs) for the intensifications of the performance. Some new combinations of CWs with technologies in other field for wastewater treatment, such as microbial fuel cell, are also discussed. To improve biofilm development, the selection and utilization of some specific substrates are summarized. Finally, we review the advances in electron donor supply to enhance low C/N wastewater treatment and in thermal insulation against low temperature to maintain CWs running in the cold areas. This paper aims to provide and inspire some new ideas in the development of intensified CWs mainly for the removal of nitrogen and organic matter. The stability and sustainability of these technologies should be further qualified.

• Klíčová slova
• Constructed wetlands, Operation strategy, Performance enhancement, Wastewater treatment,
• MeSH
• dusík chemie   MeSH
• mokřady * MeSH
• odpad tekutý - odstraňování metody   MeSH
• odpadní voda analýza   MeSH
• organické látky chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• dusík MeSH
• odpadní voda MeSH
• organické látky MeSH

BACKGROUND: Investigation remains incomplete regarding potential variations in the effect of androgen receptor pathway inhibitors, including apalutamide, based on baseline tumor burden in patients with metastatic castration-sensitive prostate cancer (mCSPC). METHODS: The authors analyzed individual participant-level data from 1052 patients with mCSPC who were randomized in the TITAN trial (apalutamide vs. placebo, both with androgen-deprivation therapy). Outcomes included radiographic progression-free survival (PFS), second PFS (PFS2), and overall survival (OS). Multivariable Cox proportional hazards regression models, with and without restricted cubic splines, were used to determine the association between apalutamide benefit and bone metastasis count or visceral metastasis. Subgroup treatment effects were quantified based on inverse probability of treatment weighting-adjusted hazard ratios (HRs). RESULTS: Analysis using restricted cubic splines indicated that apalutamide provided less benefit for PFS2 and OS in patients with fewer bone metastases. The authors also found evidence of a heterogeneous effect of apalutamide on PFS2 and OS between patients with two or less bone metastases and those with three or more bone metastases. In patients who had two or less bone metastases, there was no evidence of a benefit from apalutamide for radiographic PFS (HR, 0.65; 95% confidence interval [CI], 0.35-1.22), PFS2 (HR, 1.18; 95% CI, 0.66-2.12), or OS (HR, 1.05; 95% CI, 0.60-1.83). No evidence of an association was noted between visceral metastasis and apalutamide benefit. CONCLUSIONS: The addition of apalutamide to androgen-deprivation therapy may provide less benefit in patients with mCSPC who have fewer bone metastases. Counting baseline bone metastases may help identify optimal candidates for apalutamide treatment of mCSPC. CLINICAL TRIALS REGISTRATION: NCT02489318 PLAIN LANGUAGE SUMMARY: In an analysis of individual participant data from a trial (the TITAN trial) in patients with metastatic (spreading) castration-sensitive prostate cancer, treatment intensification based on the addition new drugs to standard androgen-deprivation therapy (ADT) was analyzed and compared with the effects in patients who received only standard ADT. Compared with ADT alone, the survival benefit of adding the new drug apalutamide to standard ADT varied according to the number of bone metastases, but no association was observed between the spread of cancer to soft tissues and organs and a survival benefit from adding apalutamide. The results indicate that counting the number of bone metastases may help identify which patients with metastatic castration-sensitive prostate cancer are optimal candidates for treatment intensification with the addition of apalutamide to standard ADT.

• Klíčová slova
• apalutamide, castration‐sensitive prostate cancer, heterogeneity in treatment effect, prostate cancer,
• MeSH
• antagonisté androgenních receptorů * terapeutické užití   MeSH
• antagonisté androgenů terapeutické užití   MeSH
• doba přežití bez progrese choroby MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádory kostí * sekundární   farmakoterapie   MeSH
• nádory prostaty rezistentní na kastraci * farmakoterapie   patologie   mortalita   MeSH
• senioři MeSH
• thiohydantoiny * terapeutické užití   aplikace a dávkování   MeSH
• tumor burden * účinky léků   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antagonisté androgenních receptorů * MeSH
• antagonisté androgenů MeSH
• apalutamide MeSH Prohlížeč
• thiohydantoiny * MeSH