• MeSH
• balneologie klasifikace   MeSH
• bolest chemicky indukované   klasifikace   MeSH
• kineziologie aplikovaná metody   MeSH
• lidé MeSH
• nádory * klasifikace   komplikace   rehabilitace   MeSH
• nežádoucí účinky léčiv klasifikace   terapie   MeSH
• rehabilitace * metody   MeSH
• terapie škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND: Results of this double-blind, phase 2 trial showed patients with metastatic castration-resistant prostate cancer given olaparib plus abiraterone versus placebo plus abiraterone had significantly improved progression-free survival. Here, we present an exploratory analysis of pain and health-related quality of life (HRQOL). METHODS: This double-blind, randomised, placebo-controlled, phase 2 trial was conducted across 41 urological oncology sites in 11 countries in Europe and North America. Eligible patients were aged 18 years or older, had metastatic castration-resistant prostate cancer, and had previously received docetaxel and up to one additional line of previous chemotherapy. Metastatic castration-resistant prostate cancer was defined as increasing prostate-specific antigen (PSA) concentration or other signs of disease progression despite androgen-deprivation therapy and serum testosterone concentrations at castrate levels (≤50 ng/dL), and with at least one metastatic lesion on bone scan, CT, or MRI. Eligible patients were randomly assigned (1:1) to receive oral olaparib (300 mg twice per day) plus oral abiraterone (1000 mg once a day) and oral prednisone or prednisolone (5 mg twice a day) or placebo plus abiraterone (1000 mg once a day) and prednisone or prednisolone (5 mg twice a day). Randomisation was done without stratification and by use of an interactive voice or web response system. A randomised treatment kit ID number was assigned sequentially to each patient as they became eligible. The primary endpoint (radiographic progression-free survival) has previously been reported. HRQOL was a prespecified exploratory patient-reported outcome. Patients were asked to complete the Brief Pain Inventory-Short Form (BPI-SF), single-item worst bone pain, Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire, and EuroQol-5 five-dimension five level (EQ-5D-5L) assessment at baseline, at weeks 4, 8, and 12, then every 12 weeks until treatment discontinuation. Prespecified outcomes were change from baseline in BPI-SF worst pain, single-item worst bone pain and FACT-P Total Outcome Index (TOI) scale scores, time to deterioration in BPI-SF worst pain and worst bone pain, and assessment of the EQ-5D-5L pain and discomfort domain. All analyses were exploratory and done in the full analysis set (all randomly assigned patients, including patients who were randomly assigned but did not subsequently go on to receive study treatment), with the exception of mean baseline and total change from baseline analyses, for which we used the population who had a valid baseline and at least one post-baseline assessment. This trial is registered with Clinicaltrials.gov, NCT01972217, and is no longer recruiting patients. FINDINGS: Between Nov 25, 2014, and July 14, 2015, 171 patients were assessed for eligibility. 29 patients were excluded, and 142 were enrolled and randomly assigned to receive olaparib and abiraterone (n=71) or placebo and abiraterone (n=71). Data cutoff was Sept 22, 2017. Median follow-up was 15·9 months (IQR 8·1-25·5) in the olaparib plus abiraterone group and 24·5 months (8·1-27·6) in the placebo plus abiraterone group. Questionnaire compliance was generally high (43-100%). Least-squares mean changes from baseline in BPI-SF worst pain, single-item worst bone pain, and FACT-P TOI remained stable across all visits for patients in both treatment groups. Adjusted mean change in FACT-P TOI from baseline across all visits was -0·10 (95% CI -2·50 to 2·71) in the olaparib plus abiraterone group and -1·20 (-4·15 to 1·74) in the placebo plus abiraterone group (difference 1·30, 95% CI -2·70 to 5·30; p=0·52). Time to deterioration in pain was similar in both groups (BPI-SF worst pain HR 0·90 [95% CI 0·62-1·32], p=0·30; worst bone pain HR 0·85 [0·59-1·22], p=0·18). Improvement rates in the pain and discomfort domain of the EQ-5D-5L were similar in both groups from baseline to week 48, beyond which a higher proportion of patients in the olaparib plus abiraterone arm reported an improvement compared to the placebo plus abiraterone group. INTERPRETATION: In these prespecified exploratory analyses, there was no significant difference in pain or HRQOL when olaparib was added to abiraterone. In this phase 2 trial, a statistically significant radiographic progression-free survival benefit was observed with the olaparib plus abiraterone combination. These results suggest that the improved survival benefits observed when combining olaparib with abiraterone does not result in different HRQOL compared with placebo plus abiraterone. Phase 3 studies are required to validate these results. FUNDING: AstraZeneca and Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA.

• MeSH
• androgeny MeSH
• androsteny MeSH
• antagonisté androgenů terapeutické užití   MeSH
• bolest chemicky indukované   MeSH
• docetaxel škodlivé účinky   MeSH
• dvojitá slepá metoda MeSH
• ftalaziny MeSH
• hodnocení výsledků péče pacientem MeSH
• kvalita života MeSH
• lidé MeSH
• nádory prostaty rezistentní na kastraci * patologie   MeSH
• piperaziny MeSH
• prednisolon MeSH
• prednison MeSH
• prostatický specifický antigen * terapeutické užití   MeSH
• protokoly antitumorózní kombinované chemoterapie škodlivé účinky   MeSH
• testosteron MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

• MeSH
• bolest chemicky indukované   MeSH
• bortezomib škodlivé účinky   terapeutické užití   MeSH
• dexamethason škodlivé účinky   terapeutické užití   MeSH
• hydraziny škodlivé účinky   terapeutické užití   MeSH
• lidé MeSH
• mnohočetný myelom farmakoterapie   MeSH
• nemoci periferního nervového systému chemicky indukované   MeSH
• protokoly antitumorózní kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• senioři MeSH
• triazoly škodlivé účinky   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• klinické zkoušky, fáze III MeSH

Osteoartróza (OA) je chronické degenerativní onemocnění kloubů, které nejčastěji postihuje osoby starší 40 let. U pacientů může způsobit značná omezení hybnosti, bolest, diskomfort a celkové snížení kvality života. Jde o značně heterogenní onemocnění s komplexními patofyziologickými mechanismy a jeho příčiny nejsou zatím zcela jasné. Dosud se nepodařilo vytvořit takový animální model OA, který by postihoval všechny aspekty onemocnění u člověka. Z toho důvodu patří OA k patologickým stavům, pro něž bylo v minulosti definováno velké množství různých typů animálních modelů. V tomto přehledném článku je představena systematická klasifikace jednotlivých modelů a u nejpoužívanějších z nich jsou uvedeny jejich hlavní výhody a nevýhody. Za nedílnou součást většiny uvedených modelů lze považovat vznik, rozvoj, transmisi a percepci bolesti. Možnosti jejího hodnocení jsou proto důležitou kapitolou používání modelů OA. Text rovněž zmiňuje u několika modelů důležitost posouzení újmy pro pokusná zvířata. To dosud není u článků tohoto typu běžné.

Osteoarthritis (OA) is a chronic degenerative disease of joints. This disease most commonly affects people over the age of forty. It is a debilitating illness causing pain and immense discomfort to the affected individual. OA is a heterogenic disease with very complex pathophysiological mecha- nisms and the causes of OA are still unknown. There is currently no animal model of this disease that reflects all aspects of OA in man. Therefore, OA belongs to pathological conditions, for them many models of different types have been created. In this review article, the animal models are classified systematically, and their main advantages and disadvantages are listed for the most common ones. An important part of the described models is the onset, development, transmission and perception of pain and the possibilities of its measurement. The text also mentions the aspect of harm to the animals, which is not yet common in articles of this type.

• MeSH
• bolest chemicky indukované   chirurgie   patofyziologie   MeSH
• laboratorní zvířata MeSH
• modely nemocí na zvířatech MeSH
• modely u zvířat MeSH
• osteoartróza * klasifikace   patofyziologie   patologie   MeSH
• Publikační typ
• práce podpořená grantem MeSH

INTRODUCTION: Statin intolerance (SI) occurs in patients with dyslipidemia treated with statins. Statin-associated symptoms have been reported, but the overall patient experience is poorly understood. No instruments are available to collect this patient experience. Our aim is to develop a patient survey to define SI from the patient's perspective, inform clinical practice, and identify potential patient characteristics and barriers associated with discontinuing treatment when statin-related difficulties are encountered. METHODS: We conducted qualitative concept elicitation interviews with 65 patients across 12 European study sites. A semi-structured qualitative interview guide was developed based on literature review and clinician interviews. Concept elicitation interviews with patients were used to describe the patient experience and develop the conceptual framework for the survey. RESULTS: Symptoms experienced by patients included muscle and non-muscle-related pain and discomfort; other muscle-related symptoms; gastrointestinal, cardiovascular, cold-like, fatigue-related, and sensory and systems symptoms; mood changes; and cognitive and memory problems. Impacts included limitations on general physical functioning; physical activities; social functioning; emotional impacts; sleep disturbances; decreased productivity; and increased healthcare use. Conceptual framework elements to support survey goals include demographic and clinical characteristics, health information and beliefs, statin side-effect history, symptom severity, and impact severity. CONCLUSIONS: Symptoms and impacts described by patients showed a wider range of symptoms and impacts than usually discussed clinically. The patient survey is designed to capture information from patients who experience difficulties with statin therapy and may be useful in identifying patients who are at higher risk for giving up or discontinuing their treatment. FUNDING: Amgen Inc.

• MeSH
• anticholesteremika škodlivé účinky   terapeutické užití   MeSH
• bolest chemicky indukované   MeSH
• dospělí MeSH
• dyslipidemie farmakoterapie   epidemiologie   MeSH
• kvalitativní výzkum MeSH
• lidé středního věku MeSH
• lidé MeSH
• průzkumy a dotazníky MeSH
• senioři MeSH
• spokojenost pacientů statistika a číselné údaje   MeSH
• statiny škodlivé účinky   terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH

• MeSH
• bolest * chemicky indukované   komplikace   MeSH
• klinické lékařství MeSH
• lékařská onkologie MeSH
• lidé MeSH
• protokoly protinádorové léčby MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

• MeSH
• analgetika aplikace a dávkování   farmakologie   MeSH
• bolest chemicky indukované   etiologie   farmakoterapie   klasifikace   komplikace   MeSH
• lidé MeSH
• management bolesti klasifikace   metody   MeSH
• nádorová bolest * chemicky indukované   etiologie   farmakoterapie   klasifikace   komplikace   terapie   MeSH
• opioidní analgetika aplikace a dávkování   farmakologie   MeSH
• průlomová bolest farmakoterapie   MeSH
• průzkumy a dotazníky MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• novinové články MeSH

Here we studied whether descending control of mechanical nociception by glutamate in the central nucleus of the amygdala (CeA) of healthy control animals is induced by amygdaloid NMDA receptors and relayed through the midbrain periaqueductal gray (PAG). Mechanical nociception in the hind paws was assessed in rats with chronic guide cannulae for glutamate administration in the right CeA and for inducing local anesthesia in the PAG. In a separate electrophysiological study, ON-like PAG neurons giving an excitatory response to noxious pinch of the tail were recorded in anesthetized rats following glutamate administration into the CeA. A high dose of glutamate (100 microg) in the CeA induced mechanical antinociception in the contra- but not ipsilateral hind limb. Antinociception was prevented by an NMDA receptor antagonist in the CeA or local anesthesia of the PAG. Discharge rate of ON-like PAG neurons was increased by a high dose of glutamate (100 microg) in the CeA and this increase was prevented by an NMDA receptor antagonist in the CeA. The results indicate that amygdaloid NMDA receptors in the CeA may induce contralaterally mechanical antinociception through a circuitry relaying in the PAG. Activation of ON-like PAG neurons is associated with the descending antinociceptive effect. Mechanisms and causality of this association still remain to be studied.

• MeSH
• antagonisté excitačních aminokyselin farmakologie   terapeutické užití   MeSH
• bolest chemicky indukované   patofyziologie   prevence a kontrola   MeSH
• centrální jádro amygdaly účinky léků   fyziologie   MeSH
• krysa rodu rattus MeSH
• kyselina glutamová toxicita   MeSH
• měření bolesti účinky léků   metody   MeSH
• nervová síť účinky léků   fyziologie   MeSH
• potkani Wistar MeSH
• substantia grisea centralis účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Endothelin-1 (ET-1) and Nerve Growth Factor (NGF) are proteins, released from cancer-ridden tissues, which cause spontaneous pain and hypersensitivity to noxious stimuli. Here we examined the electrophysiological and behavioral effects of these two agents for evidence of their interactions. Individual small-medium cultured DRG sensory neurons responded to both ET-1 (50 nM, n=6) and NGF (100 ng/ml, n=4), with increased numbers of action potentials and decreased slow K(+) currents; pre-exposure to ET-1 potentiated NGF´s actions, but not vice versa. Behaviorally, single intraplantar (i.pl.) injection of low doses of ET-1 (20 pmol) or NGF (100 ng), did not increase hindpaw tactile or thermal sensitivity, but their simultaneous injections sensitized the paw to both modalities. Daily i.pl. injections of low ET-1 doses in male rats caused tactile sensitization after 21 days, and enabled further tactile and thermal sensitization from low dose NGF, in ipsilateral and contralateral hindpaws. Single injections of 100 ng NGF, without changing the paw's tactile sensitivity by itself, acutely sensitized the ipsilateral paw to subsequent injections of low ET-1. The sensitization from repeated low ET-1 dosing and the cross-sensitization between NGF and ET-1 were both significantly greater in female than in male rats. These findings reveal a synergistic interaction between cutaneously administered low doses of NGF and ET-1, which could contribute to cancer-related pain.

• MeSH
• bolest chemicky indukované   metabolismus   MeSH
• endotelin-1 aplikace a dávkování   metabolismus   toxicita   MeSH
• fyzikální stimulace škodlivé účinky   MeSH
• hmat účinky léků   fyziologie   MeSH
• injekce subkutánní MeSH
• krysa rodu rattus MeSH
• měření bolesti metody   MeSH
• nervový růstový faktor aplikace a dávkování   metabolismus   toxicita   MeSH
• potkani Sprague-Dawley MeSH
• vazba proteinů fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Podání intramuskulární injekce benzathin benzylpenicilinu (benzathin PNC G) je spojeno s bolestivostí či dyskomfortem, které mohou vést k non-adherenci v léčbě. Toto riziko může být výraznější u dětí a adolescentů a je tedy nezbytné bolest minimalizovat, zejména při nedostupnosti léčivých přípravků (LP) obsahujících vedle benzathin PNC G další složku zmírňující bolestivost. Předkládaný text popisuje na základě publikované literatury dva postupy, které mohou bolest snížit, a to i u pediatrické populace. Jednak smísení dvou dostupných monokomponentních LP obsahujících benzathin a prokain PNC G, a jednak použití roztoku lidokainu pro rekonstituci injekčního prášku benzathin PNC G. Doklady uvádějící oba postupy nenaznačují snížení bezpečnosti ani požadované sérové koncentrace PNC G. Na závěr je zmíněna i naše klinická zkušenost.

Administration of the intramuscular injection of benzathine benzylpenicillin (benzathine PNC G) is associated with pain or discomfort, which could lead to non-adherence to the therapy. This risk may be even greater in children and adolescents, therefore, it is desirable to minimize the pain, especially when medications containing benzathine PNC G alongside with other ingredients relieving pain are not registered and commercially unavailable. This paper reviews evidence of published literature, describing two alternatives which could be also employed in paediatric practice to alleviate the pain. Firstly, the procedure of mixing two available medicinal products containing benzathine and procaine PNC G, secondly, the use of a lidocaine solution for reconstitution of benzathine PNC G powder for injection. Reported evidence suggests both options are safe and does not lead to decrease in PNC G serum concentrations. Finally, a case study is described demonstrating our clinical experience.

• MeSH
• benzathin-penicilin G * aplikace a dávkování   farmakologie   MeSH
• bolest farmakoterapie   chemicky indukované   MeSH
• dítě MeSH
• injekce intramuskulární škodlivé účinky   MeSH
• lidé MeSH
• lidokain aplikace a dávkování   MeSH
• prokain penicilin G aplikace a dávkování   farmakologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• přehledy MeSH