PURPOSE: We investigated the safety and efficacy of peroneal electrical transcutaneous neuromodulation using the URIS neuromodulation system in a home-based setting in comparison with standard treatment using solifenacin in treatment-naïve female patients with overactive bladder. MATERIALS AND METHODS: A total of 120 patients were screened, of whom 77 were randomized in a 2:1 ratio to 12 weeks of treatment with daily peroneal electrical transcutaneous neuromodulation or solifenacin 5 mg. The primary endpoint was safety; efficacy assessments included proportion of responders, defined as subjects with ≥50% reduction in bladder diary-derived variables; Overactive Bladder-Validated 8-question Screener, and European Quality of Life-5 Dimensions questionnaire; and treatment satisfaction after 12 weeks of therapy. RESULTS: Seventy-one out of 77 randomized patients completed the study. In the peroneal electrical transcutaneous neuromodulation group 6/51 (12%) patients reported a treatment-related adverse event vs 12/25 (48%) in the solifenacin group (P < .001). No clinically significant changes were observed in any other safety endpoint. The proportions of responders in the peroneal electrical transcutaneous neuromodulation group vs the solifenacin group were 87% vs 74% with respect to Patient Perception of Intensity of Urgency Scale grade 3 urgency episodes, 87% vs 75% with respect to grade 3+4 urgency episodes, and 90% vs 94% with respect to urgency incontinence episodes. In post hoc analyses we observed significant improvement over time in multiple efficacy variables in both treatment arms. CONCLUSIONS: Peroneal electrical transcutaneous neuromodulation is a safe and effective method for overactive bladder treatment associated with a significantly lower incidence of treatment-related adverse events compared to solifenacin and a considerably better benefit-risk profile.
- MeSH
- antagonisté muskarinových receptorů MeSH
- hyperaktivní močový měchýř * farmakoterapie MeSH
- kvalita života MeSH
- lidé MeSH
- prospektivní studie MeSH
- solifenacin sukcinát * terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- Klíčová slova
- peruánská kůra,
- MeSH
- Anopheles fyziologie metabolismus účinky léků MeSH
- antimalarika MeSH
- chinin * farmakologie terapeutické užití MeSH
- DDT farmakologie škodlivé účinky MeSH
- insekticidy * škodlivé účinky MeSH
- lidé MeSH
- malárie * dějiny etiologie mortalita prevence a kontrola MeSH
- mokřady MeSH
- Plasmodium růst a vývoj MeSH
- rezistence k insekticidům MeSH
- Check Tag
- lidé MeSH
BACKGROUND: Malaria in the first trimester of pregnancy is associated with adverse pregnancy outcomes. Artemisinin-based combination therapies (ACTs) are a highly effective, first-line treatment for uncomplicated Plasmodium falciparum malaria, except in the first trimester of pregnancy, when quinine with clindamycin is recommended due to concerns about the potential embryotoxicity of artemisinins. We compared adverse pregnancy outcomes after artemisinin-based treatment (ABT) versus non-ABTs in the first trimester of pregnancy. METHODS: For this systematic review and individual patient data (IPD) meta-analysis, we searched MEDLINE, Embase, and the Malaria in Pregnancy Library for prospective cohort studies published between Nov 1, 2015, and Dec 21, 2021, containing data on outcomes of pregnancies exposed to ABT and non-ABT in the first trimester. The results of this search were added to those of a previous systematic review that included publications published up until November, 2015. We included pregnancies enrolled before the pregnancy outcome was known. We excluded pregnancies with missing estimated gestational age or exposure information, multiple gestation pregnancies, and if the fetus was confirmed to be unviable before antimalarial treatment. The primary endpoint was adverse pregnancy outcome, defined as a composite of either miscarriage, stillbirth, or major congenital anomalies. A one-stage IPD meta-analysis was done by use of shared-frailty Cox models. This study is registered with PROSPERO, number CRD42015032371. FINDINGS: We identified seven eligible studies that included 12 cohorts. All 12 cohorts contributed IPD, including 34 178 pregnancies, 737 with confirmed first-trimester exposure to ABTs and 1076 with confirmed first-trimester exposure to non-ABTs. Adverse pregnancy outcomes occurred in 42 (5·7%) of 736 ABT-exposed pregnancies compared with 96 (8·9%) of 1074 non-ABT-exposed pregnancies in the first trimester (adjusted hazard ratio [aHR] 0·71, 95% CI 0·49-1·03). Similar results were seen for the individual components of miscarriage (aHR=0·74, 0·47-1·17), stillbirth (aHR=0·71, 0·32-1·57), and major congenital anomalies (aHR=0·60, 0·13-2·87). The risk of adverse pregnancy outcomes was lower with artemether-lumefantrine than with oral quinine in the first trimester of pregnancy (25 [4·8%] of 524 vs 84 [9·2%] of 915; aHR 0·58, 0·36-0·92). INTERPRETATION: We found no evidence of embryotoxicity or teratogenicity based on the risk of miscarriage, stillbirth, or major congenital anomalies associated with ABT during the first trimester of pregnancy. Given that treatment with artemether-lumefantrine was associated with fewer adverse pregnancy outcomes than quinine, and because of the known superior tolerability and antimalarial effectiveness of ACTs, artemether-lumefantrine should be considered the preferred treatment for uncomplicated P falciparum malaria in the first trimester. If artemether-lumefantrine is unavailable, other ACTs (except artesunate-sulfadoxine-pyrimethamine) should be preferred to quinine. Continued active pharmacovigilance is warranted. FUNDING: Medicines for Malaria Venture, WHO, and the Worldwide Antimalarial Resistance Network funded by the Bill & Melinda Gates Foundation.
- MeSH
- antimalarika * škodlivé účinky MeSH
- artemether terapeutické užití MeSH
- chinin škodlivé účinky MeSH
- ethanolaminy terapeutické užití MeSH
- fixní kombinace léků MeSH
- kombinace léků artemether a lumefantrin terapeutické užití MeSH
- lidé MeSH
- malárie * farmakoterapie MeSH
- narození mrtvého plodu epidemiologie MeSH
- prospektivní studie MeSH
- první trimestr těhotenství MeSH
- samovolný potrat * MeSH
- těhotenství MeSH
- tropická malárie * farmakoterapie MeSH
- výsledek těhotenství MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- systematický přehled MeSH
CONTEXT: The choice of the most efficacious drug for patients with idiopathic overactive bladder (IOAB) remains challenging. OBJECTIVE: The aim of this network meta-analysis was to determine the most efficacious oral antimuscarinic or β-adrenoceptor agonist accounting for adverse events for the management of IOAB. EVIDENCE ACQUISITION: A comprehensive electronic search was done in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Ovid for studies in any language in February 2021 considering the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. We included all randomized controlled trials assessing oral antimuscarinics or β-adrenoceptor agonists for the treatment of IOAB. We determined the effect of specific bothersome symptoms separately. EVIDENCE SYNTHESIS: Fifty-four articles were included in our analysis. The most efficacious agents considering the evaluated outcomes were oxybutynin 15 mg/d in reducing incontinence episodes, imidafenacin 0.5 mg/d together with solifenacin 10 and 5 mg/d in reducing micturition episodes, fesoterodine 4 and 8 mg/d as well as solifenacin 10 mg/d in reducing urgency episodes, imidafenacin 0.5 mg/d and solifenacin 10 mg/d in reducing urgency urinary incontinence episodes, and solifenacin 10 mg/d, vibegron 50 mg/d, and fesoterodine 8 mg/d in improving the voided volume. Gastrointestinal problems, especially due to antimuscarinic agents, were the most prevalent adverse events. CONCLUSIONS: Taken together, there is only minimal difference between the efficacy of oral antimuscarinics and that of β-adrenoceptor agonists. Although finding the best medication for all is impossible, finding the best treatment for every individual patient can be done by considering the efficacy of a medicine for the most bothersome symptom(s) in balance with drug-specific adverse events. PATIENT SUMMARY: This study aimed to find the most efficient oral medication to treat overactive bladder, taking into consideration the adverse events. Based on our study, there is a minimal difference in the efficacy between the two major drug classes used to treat overactive bladder. Gastrointestinal problems were the most common adverse events in medical treatment of overactive bladder. Selection of the best treatment is possible through shared decision-making between the doctor and the patient based on the patient's most bothersome symptom. We provide a framework for physicians to facilitate shared decision-making with each individual patient.
- MeSH
- adrenergní receptory terapeutické užití MeSH
- antagonisté muskarinových receptorů terapeutické užití MeSH
- benzhydrylové sloučeniny MeSH
- hyperaktivní močový měchýř * diagnóza farmakoterapie MeSH
- inkontinence moči * farmakoterapie MeSH
- lidé MeSH
- síťová metaanalýza MeSH
- solifenacin sukcinát škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- systematický přehled MeSH
V článku je podán obecný přehled anticholinergik, jejich vlastnosti a možné nežádoucí účinky. Hlavním cílem je porovnání vedlejších účinků spasmolytik v léčbě syndromu OAB a odhalení možných úskalí terapie.
The article presents a general overview of anticholinergic drugs, their properties, and possible adverse effects. The main goal is to compare the side effects of spasmolytic drugs in treating overactive bladder syndrome and to identify possible pitfalls of treatment.
- Klíčová slova
- darifenacin, fesoterodin, oxybutynin, propiverin,
- MeSH
- antagonisté muskarinových receptorů farmakologie škodlivé účinky terapeutické užití MeSH
- cholinergní antagonisté farmakologie škodlivé účinky terapeutické užití MeSH
- hyperaktivní močový měchýř * farmakoterapie MeSH
- lékové interakce MeSH
- lidé MeSH
- nežádoucí účinky léčiv MeSH
- parasympatolytika farmakologie škodlivé účinky terapeutické užití MeSH
- solifenacin sukcinát terapeutické užití MeSH
- tolterodin tartarát terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Cíl: Cílem práce bylo zjistit význam "warning time" při hodnocení efektivity léčby syndromu hyperaktivního močového měchýře. Materiál a metoda: V databázi PubMed byly vyhledány všechny relevantní klinické studie hodnotící warning time při medikamentózní terapii hyperaktivního močového měchýře. Výsledky: Byly nalezeny čtyři klinické studie hodnotící celkem tři preparáty pro léčbu hyperaktivního močového měchýře. Ve všech studiích bylo zjištěno prodloužení hodnoty "warning time" u studijního preparátu oproti placebu, z toho ve třech statisticky významně. Ve všech studiích byla použita jiná metodika stanovení hodnoty "warning time". Závěr: Medikamentózní léčba hyperaktivního močového měchýře vede k významnému prodloužení "warning time". K posouzení významu tohoto parametru bude nutno standardizovat metodiku stanovení a provést více prospektivních kontrolovaných klinických studií.
Aim: The aim of this study was to determine the significance of warning time for the evaluation of treatment efficacy of overactive bladder syndrome. Methods: The PubMed database was searched for all relevant clinical studies evaluating warning time for the medicamentous treatment of overactive bladder. Results: Four clinical studies evaluating three different drugs for the treatment of overactive bladder were found. The value of warning time increased in active arms compared to placebo in all studies, in three of them significantly. Various methods of evaluating warning time were used in the studies. Conclusions: Medicamentous treatment of overactive bladder leads to the significant increase of warning time. More clinical studies with a standardized method of evaluation must be performed to determine a role of warning time in the assessment of overactive bladder treatment.
- Klíčová slova
- Warning time, Darifenacin, OXYBUTININ,
- MeSH
- benzofurany aplikace a dávkování terapeutické užití MeSH
- cholinergní antagonisté aplikace a dávkování terapeutické užití MeSH
- hodnocení léčiv MeSH
- hyperaktivní močový měchýř * farmakoterapie patologie MeSH
- inkontinence moči farmakoterapie patologie MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- solifenacin sukcinát aplikace a dávkování terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
At present, Alzheimer's disease (AD) and related dementias cannot be cured. Therefore, scientists all over the world are trying to find a new approach to prolong an active life of patients with initial dementia. Both pharmacological and non-pharmacological pathways are investigated to improve the key symptom of the disease, memory loss. In this respect, influencing the neuromodulator acetylcholine via muscarinic receptors, such as cevimeline, might be one of the therapeutic alternatives. The purpose of this study is to explore the potential of cevimeline on the cognitive functions of AD patients. The methodology is based on a systematic literature review of available studies found in Web of Science, PubMed, Springer, and Scopus on the research topic. The findings indicate that cevimeline has shown an improvement in experimentally induced cognitive deficits in animal models. Furthermore, it has demonstrated to positively influence tau pathology and reduce the levels of amyloid-β (Aβ) peptide in the cerebral spinal fluid of Alzheimer's patients. Although this drug has not been approved by the FDA for its use among AD patients and there is a lack of clinical studies confirming and extending this finding, cevimeline might represent a breakthrough in the treatment of AD.
- MeSH
- agonisté muskarinových receptorů farmakologie MeSH
- chinuklidiny farmakologie MeSH
- kognitivní poruchy farmakoterapie MeSH
- léčivé přípravky aplikace a dávkování MeSH
- lidé MeSH
- neurodegenerativní nemoci farmakoterapie MeSH
- neurofarmakologie * MeSH
- thiofeny farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
3-Quinuclidinyl benzilate (BZ) ranks among incapacitating military warfare agents. It acts as a competitive inhibitor on muscarinic receptors leading to non-lethal mental impairment. The present study aimed to investigate toxicokinetics of BZ in rats. Moreover, BZ can be exploited to produce a pharmacological model of Alzheimer's disease; thus, this paper focuses mainly on the BZ distribution to the brain. Wistar rats were administered i.p. with BZ (2 and 10 mg/kg). The BZ concentration was determined using LC-MS/MS in plasma, urine, bile, brain, kidney and liver. The sample preparation was based on a solid phase extraction (liquids) or protein precipitation (organ homogenates). The plasma concentration peaked at 3 min (204.5 ± 55.4 and 2185.5 ± 465.4 ng/ml). The maximal concentration in the brain was reached several minutes later. Plasma elimination half-life was 67.9 ± 3.4 in the 2 mg/kg group and 96.6 ± 27.9 in the 10 mg/kg group. BZ concentrations remained steady in the brain, with slow elimination (t1/2 506.9 ± 359.5 min). Agent BZ is excreted mainly via the urine. Steady BZ concentration in the brain could explain the previously published duration of the significant impairment in passive avoidance tasks in rats after an injection of BZ.
- MeSH
- antagonisté muskarinových receptorů krev metabolismus toxicita moč MeSH
- chinuklidinylbenzilát krev metabolismus toxicita moč MeSH
- krysa rodu rattus MeSH
- metabolom MeSH
- moč MeSH
- mozek metabolismus MeSH
- potkani Wistar MeSH
- toxikokinetika MeSH
- žluč metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- studie IMPACT, umeclidinium/vilanterol,
- MeSH
- analýza přežití MeSH
- benzylalkoholy terapeutické užití MeSH
- bronchodilatancia * terapeutické užití MeSH
- chinuklidiny terapeutické užití MeSH
- chronická obstrukční plicní nemoc * farmakoterapie mortalita MeSH
- fixní kombinace léků MeSH
- flutikason terapeutické užití MeSH
- glukokortikoidy terapeutické užití MeSH
- lidé MeSH
- randomizované kontrolované studie jako téma MeSH
- Check Tag
- lidé MeSH
