Despite currently used intravesical therapies in non-muscle-invasive bladder cancer (NMIBC), the rate of intravesical recurrence remains very high. We aimed to evaluate the effectiveness of adding nonintravesical interventions to standard intravesical therapies to prevent intravesical recurrence. In April 2024, 3 databases were queried for prospective studies evaluating nonintravesical interventions in addition to standard intravesical therapies for NMIBC (CRD42024490988). The primary outcome was intravesical recurrence-free survival (iRFS). Standard pairwise meta-analyses were performed using hazard ratios (HR) and 95% confidence intervals (95% CI) with a random-effects model. We identified 18 eligible studies (14 RCTs and 4 prospective trials) comprising 4,593 NMIBC patients, which investigated pharmacological interventions (eg, selenium, vitamins, Lactobacillus casei, celecoxib, metformin, mistletoe lectin) and lifestyle modifications (diet). The addition of Lactobacillus casei significantly improved iRFS (HR: 0.50; 95% CI: 0.34-0.73; P < .001). A high western diet pattern significantly worsened iRFS (HR:1.48, 95%CI:1.06-2.06, P = .03). The other nonintravesical interventions were not associated with iRFS. Our comprehensive review of the published literature highlights the need for further research into the efficacy of nonvesical interventions for NMIBC. While Lactobacillus was shown to improve iRFS in 2 RCTs, additional high-quality randomized studies are required to evaluate the effectiveness of other interventions.
- MeSH
- aplikace intravezikální MeSH
- celekoxib aplikace a dávkování terapeutické užití MeSH
- Lactobacillus casei MeSH
- lidé MeSH
- lokální recidiva nádoru * prevence a kontrola MeSH
- metformin terapeutické užití aplikace a dávkování MeSH
- nádory močového měchýře * patologie farmakoterapie MeSH
- probiotika aplikace a dávkování terapeutické užití MeSH
- randomizované kontrolované studie jako téma MeSH
- selen aplikace a dávkování terapeutické užití MeSH
- vitaminy aplikace a dávkování terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
- systematický přehled MeSH
Neurozánět hraje důležitou roli v patogenezi epilepsie, a proto je nutné objasnit vliv klasických antiepileptik i adjuvantních látek (např. srdečního glykosidu digoxinu, který již dříve vykazoval jasný antikonvulzivní potenciál) na dráhu cyklooxygenázy a neuron-specifické enolázy v podmínkách chronické epileptogeneze. Cílem článku bylo objasnit vliv digoxinu, natrium-valproátu a celekoxibu samostatně, ale i kombinace digoxinu s natrium-valproátem na obsah cyklooxygenázy 1. a 2. typu, prostaglandinů E2, F2α, I2, tromboxanu B2, 8-isoprostanu a neuron-specifické enolázy v mozku myší na modelu pentylenetetrazolem podnícených záchvatů. Bylo zjištěno, že pouze kombinace natriumvalproátu s digoxinem poskytuje úplný ochranný účinek (absence záchvatů) a vykazuje nejzřetelnější vliv na markery neurozánětu a poškození neuronů ve srovnání s monoterapií každým z těchto léčiv a celekoxibem, který se ukázal jako neúčinné antikonvulzivum. Získané výsledky naznačují, že digoxin je slibným adjuvantním lékem ke klasickým antiepileptikům (především natrium-valproátu) v léčbě epilepsie.
Neuroinflammation plays an important role in the pathogenesis of epilepsy, so it is necessary to clarify the influence of standard antiepileptic drugs as well as adjuvant agents (e.g., cardiac glycoside digoxin, which previously showed a clear anticonvulsant potential) on cyclooxygenase pathway and neuron-specific enolase under the conditions of chronic epileptogenesis. The aim of the article is to determine the effect of digoxin, sodium valproate, and celecoxib per se, as well as the combination of digoxin with sodium valproate on the content of cyclooxygenase 1 and 2 types, prostaglandins E2, F2α, I2, thromboxane B2, 8-isoprostane and neuron-specific enolase in the brain of mice in the pentylenetetrazole-induced kindling model. It was found that only the combination of sodium valproate with digoxin provides a complete protective effect (absence of seizures) and shows the clearest influence on neuroinflammation markers and neuronal damage than monotherapy with each of these drugs and celecoxib, which appeared to be an ineffective anticonvulsant. The obtained results indicate that digoxin is a promising adjuvant drug to classical antiepileptic drugs (mostly sodium valproate) in epilepsy treatment.c
- MeSH
- antikonvulziva * farmakologie terapeutické užití MeSH
- celekoxib aplikace a dávkování farmakologie terapeutické užití MeSH
- cyklooxygenasy účinky léků MeSH
- digoxin aplikace a dávkování terapeutické užití MeSH
- epilepsie chemicky indukované farmakoterapie MeSH
- fosfopyruváthydratasa terapeutické užití MeSH
- kombinovaná farmakoterapie MeSH
- kyselina valproová aplikace a dávkování farmakologie terapeutické užití MeSH
- modely u zvířat MeSH
- neurozánětlivé nemoci * patologie MeSH
- pentylentetrazol farmakologie terapeutické užití MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
OBJECTIVE: The objective of this study was to investigate whether diacerein has comparable efficacy with celecoxib in pain reduction for treatment in symptomatic knee OA patients. METHODS: This randomized double-blind multicentre non-inferiority trial evaluated diacerein vs celecoxib treatment in patients with Kellgren-Lawrence grade 2-3 and pain scoring ≥4 (10-cm VAS). Patients were randomized to 6 months of treatment with diacerein 50 mg (n = 187) once daily for 1 month and twice daily thereafter, or celecoxib 200 mg (n = 193) once daily. The primary outcome was the change in WOMAC pain score (0-50 cm) at 6 months, and the secondary outcomes were WOMAC sub-scores, VAS pain score, and the OMERACT-OARSI responder rate. RESULTS: In the per protocol population, the adjusted mean change from baseline in the WOMAC pain score was -11.1 ( 0.9) with diacerein (n = 140) and -11.8 (0.9) with celecoxib (n = 148). The intergroup difference was 0.7 (95% CI: -1.8, 3.2; P = 0.597), meeting the non-inferiority margin. Supportive analysis of the intention-to-treat population gave similar results. Other outcomes showed no significant difference between treatment groups. The incidence of treatment-related adverse events was low and balanced between groups, but a greater incidence of diarrhoea occurred with diacerein (10.2% vs 3.7%). Diarrhoea was considered mild-to-moderate in all but one case with complete resolution. CONCLUSIONS: Diacerein was non-inferior to celecoxib in reducing knee OA pain and improving physical function. Diacerein also demonstrated a good safety profile. TRIAL REGISTRATION: A multicentre study on the effect of DIacerein on Structure and Symptoms vs Celecoxib in Osteoarthritis is a National Institutes of Health (NCT02688400) and European Clinical Trial Database (2015-002933-23) registered phase III (Canada) or IV (Europe) study.
- MeSH
- anthrachinony terapeutické užití MeSH
- antiflogistika nesteroidní terapeutické užití MeSH
- artralgie farmakoterapie MeSH
- artróza kolenních kloubů farmakoterapie MeSH
- celekoxib terapeutické užití MeSH
- dvojitá slepá metoda MeSH
- lidé středního věku MeSH
- lidé MeSH
- měření bolesti MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- hodnocení ekvivalence MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
OBJECTIVES: Chondroitin sulfate 800 mg/day (CS) pharmaceutical-grade in the management of symptomatic knee osteoarthritis consistent with the European Medicines Agency guideline. METHODS: A prospective, randomised, 6-month, 3-arm, double-blind, double-dummy, placebo and celecoxib (200 mg/day)-controlled trial assessing changes in pain on a Visual Analogue Scale (VAS) and in the Lequesne Index (LI) as coprimary endpoints. Minimal-Clinically Important Improvement (MCII), Patient-Acceptable Symptoms State (PASS) were used as secondary endpoints. RESULTS: 604 patients (knee osteoarthritis) diagnosed according to American College of Rheumalogy (ACR) criteria, recruited in five European countries and followed for 182 days. CS and celecoxib showed a greater significant reduction in pain and LI than placebo. In the intention-to-treat (ITT) population, pain reduction in VAS at day 182 in the CS group (-42.6 mm) and in celecoxib group (-39.5 mm) was significantly greater than the placebo group (-33.3 mm) (p=0.001 for CS and p=0.009 for celecoxib), while no difference observed between CS and celecoxib. Similar trend for the LI, as reduction in this metric in the CS group (-4.7) and celecoxib group (-4.6) was significantly greater than the placebo group (-3.7) (p=0.023 for CS and p=0.015 for celecoxib), no difference was observed between CS and celecoxib. Both secondary endpoints (MCII and PASS) at day 182 improved significantly in the CS and celecoxib groups. All treatments demonstrated excellent safety profiles. CONCLUSION: A 800 mg/day pharmaceutical-grade CS is superior to placebo and similar to celecoxib in reducing pain and improving function over 6 months in symptomatic knee osteoarthritis (OA) patients. This formulation of CS should be considered a first-line treatment in the medical management of knee OA.
- MeSH
- artróza kolenních kloubů farmakoterapie patofyziologie MeSH
- celekoxib terapeutické užití MeSH
- chondroitinsulfáty terapeutické užití MeSH
- dvojitá slepá metoda MeSH
- inhibitory cyklooxygenasy 2 terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- měření bolesti MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
