Léčebné postupy zaměřené na játra, např. resekce nebo jaterní arteriální infuze, se u nemocných s jaterními metastázami karcinomu žaludku příliš neuplatňují z důvodů přítomnosti extrahepatického postižení ve většině těchto případů. Publikované zkušenosti na toto téma jsou vzácné. Provedli jsme souhrnnou analýzu publikovaných případů použití jaterní arteriální infuze u nemocných s jaterními metastázami při karcinomu žaludku. Metodika. Sdělení týkající se jaterní arteriální infuze byly vyhledány pomocí databáze MEDLINE. Celkem 47 sdělení o 192 pacientech bylo zahrnuto v souhrnné analýze. Přežití bylo analyzováno Kaplan-Meierovou metodou. Univariantní analýza byla provedena pomocí log-rank testu, multivariantní analýza byla provedena pomocí Coxovy regrese. Výsledky. Úplná odpověď byla popsána u 19 % a částečná odpověď u 45 % nemocných. V univariatní analýze bylo přežití delší u nemocných s objektivní odpovědí, u nemocných popsaných ve sděleních o 1 či 2 případech, u mužů, u pacientů s H1 nebo H2 metastázami a u nemocných, u kterých byla provedena resekce jater. Objektivní odpověď, stadium metastáz, použití antracyklinů v jaterní arteriální infuzi a počet pacientů popsaných ve sdělení byly nezávislými ukazateli přežití v multivariantní analýze. Závěr. Jaterní arteriální infuze může být účinnou léčbou ve vzácných případech izolovaného metastatického postižení jater při karcinomu žaludku. Prognóza je významně lepší u nemocných, u kterých bylo dosaženo objektivní odpovědi, nemocných s H1 nebo H2 metastázami a nemocných léčených antracykliny. Delší přežití nemocných ve sděleních popisujících 1 nebo 2 případy svědčí pro selektivní publikaci pozitivních výsledků, která je nejzávažnějším omezením provedené analýzy.

Liver-directed therapeutic approaches, e.g. resection or hepatic arterial infusion (HAI), have not been widely used in patients with gastric cancer liver metastases because of frequent presence of extrahepatic disease, and the published experience is scanty. We performed a pooled analysis of reports of HAI in gastric cancer liver metastases. Methods. Reports on HAI in gastric cancer liver metastases were identified though searching the MEDLINE database. A total of 47 reports of 192 patients were included in the pooled analysis. The survival was analyzed by the Kaplan-Meier method. Univariate analysis was performed by the log-rank test, and multivariable analysis was performed by the Cox regression method. Results. Complete response was reported in 19 % and partial response in 45 % of the patients. The median survival of all patients was 14 months. On univariate analysis, survival was significantly longer in patients with objective response, those reported in papers describing 1 or 2 cases, in males, patients with H1 or H2 metastases, and in patients treated by liver resection. On multivariable analysis, objective response, metastasis stage, HAI of anthracyclines and number of patients per report were independent indicators of survival. Conclusions. HAI may be effective in the rare patient with isolated gastric cancer liver metastases. The prognosis is significantly better in patients who attained an objective response, H1 or H2 metastases, and in patients treated with anthracyclines. Longer survival of patients reported in papers describing 1 or 2 cases is explained by a publication bias that represents the most serious limitation of the present analysis.

• MeSH
• chemoembolizace MeSH
• financování organizované MeSH
• intraarteriální infuze MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádory jater etiologie   terapie   MeSH
• nádory žaludku diagnóza   enzymologie   MeSH
• protinádorové látky aplikace a dávkování   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Recently, concerns regarding the safety of red yeast rice (RYR) have been raised after the publication of some case reports claiming toxicity. Since the previous meta-analyses on the effects of RYR were mainly focused on its efficacy to improve lipid profile and other cardiovascular parameters, we carried out a meta-analysis on safety data derived from the available randomized controlled clinical trials (RCTs). Primary outcomes were musculoskeletal disorders (MuD). Secondary outcomes were non-musculoskeletal adverse events (Non-MuD) and serious adverse events (SAE). Subgroups analyses were carried out considering the intervention (RYR alone or in association with other nutraceutical compounds), monacolin K administered daily dose (≤3, 3.1-5 or >5 mg/day), follow-up (>12 or ≤12 weeks), with statin therapy or statin-intolerance and type of control treatment (placebo or statin treatment). Data were pooled from 53 RCTs comprising 112 treatment arms, which included 8535 subjects, with 4437 in the RYR arm and 4303 in the control one. Monacolin K administration was not associated with increased risk of MuD (odds ratio (OR) = 0.94, 95% confidence interval (CI) 0.53,1.65). Moreover, we showed reduced risk of Non-MuD (OR = 0.59, 95%CI 0.50, 0.69) and SAE (OR = 0.54, 95%CI 0.46, 0.64) vs. control. Subgroups analyses confirmed the high tolerability profile of RYR. Furthermore, increasing daily doses of monacolin K were negatively associated with increasing risk of Non-MuD (slope: -0.10; 95%CI: -0.17, -0.03; two-tailed p < 0.01). Based on our data, RYR use as lipid-lowering dietary supplement seems to be overall tolerable and safe in a large kind of moderately hypercolesterolaemic subjects.

• MeSH
• biologické přípravky škodlivé účinky   MeSH
• lidé MeSH
• muskuloskeletální nemoci MeSH
• potravní doplňky škodlivé účinky   MeSH
• randomizované kontrolované studie jako téma MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH

OBJECTIVES: Epidemiological studies of underground miners have provided clear evidence that inhalation of radon decay products causes lung cancer. Moreover, these studies have served as a quantitative basis for estimation of radon-associated excess lung cancer risk. However, questions remain regarding the effects of exposure to the low levels of radon decay products typically encountered in contemporary occupational and environmental settings on the risk of lung cancer and other diseases, and on the modifiers of these associations. These issues are of central importance for estimation of risks associated with residential and occupational radon exposures. METHODS: The Pooled Uranium Miner Analysis (PUMA) assembles information on cohorts of uranium miners in North America and Europe. Data available include individual annual estimates of exposure to radon decay products, demographic and employment history information on each worker and information on vital status, date of death and cause of death. Some, but not all, cohorts also have individual information on cigarette smoking, external gamma radiation exposure and non-radiological occupational exposures. RESULTS: The PUMA study represents the largest study of uranium miners conducted to date, encompassing 124 507 miners, 4.51 million person-years at risk and 54 462 deaths, including 7825 deaths due to lung cancer. Planned research topics include analyses of associations between radon exposure and mortality due to lung cancer, cancers other than lung, non-malignant disease, modifiers of these associations and characterisation of overall relative mortality excesses and lifetime risks. CONCLUSION: PUMA provides opportunities to evaluate new research questions and to conduct analyses to assess potential health risks associated with uranium mining that have greater statistical power than can be achieved with any single cohort.

• MeSH
• hodnocení rizik MeSH
• horníci * MeSH
• kohortové studie MeSH
• kouření cigaret epidemiologie   MeSH
• lidé MeSH
• nádory plic epidemiologie   mortalita   MeSH
• nádory vyvolané zářením epidemiologie   mortalita   MeSH
• nemoci z povolání epidemiologie   MeSH
• pracovní expozice škodlivé účinky   MeSH
• radon škodlivé účinky   MeSH
• uran * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Geografické názvy
• Evropa MeSH
• Severní Amerika MeSH

• MeSH
• metaanalýza jako téma * MeSH
• statistika jako téma MeSH
• Publikační typ
• metaanalýza MeSH
• příručky MeSH

• Konspekt
• Statistika
• NLK Obory
• statistika, zdravotnická statistika

The pooled incidences of treatment-emergent adverse events (TEAEs) were examined by indication using the integrated clinical database of Merz-sponsored, placebo-controlled, or repeat-dose studies of incobotulinumtoxinA in adults with cervical dystonia, blepharospasm, limb spasticity, sialorrhea, or essential tremor of the upper limb. Overall incidences of TEAEs, serious TEAEs, TEAEs leading to discontinuation, fatal TEAEs, TEAEs of special interest (TEAESIs; indicating possible toxin spread), and treatment-related (TR) events were determined for incobotulinumtoxinA and placebo after a single injection and for repeated dose cycles of incobotulinumtoxinA. The most frequent events after a single dose of incobotulinumtoxinA are summarized. After a single cycle, incidences of overall TEAEs were similar between incobotulinumtoxinA and the placebo in most indications, although between-indication differences were observed. Few TEAEs led to incobotulinumtoxinA discontinuation; there were no fatal TEAEs with incobotulinumtoxinA. In general, repeated cycles did not increase the incidence of any event. The most frequent TR-TEAEs were indication-dependent, including dysphagia for indications affecting the head or neck. The TR-TEAESIs across all indications were most commonly muscular weakness, dysphagia and dry mouth. Overall, the results of this pooled analysis support and extend the favorable safety and tolerability profile of incobotulinumtoxinA for the treatment of adult neurological disorders established by individual clinical studies.

• MeSH
• botulotoxiny typu A * škodlivé účinky   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• lidé MeSH
• nemoci nervového systému * farmakoterapie   MeSH
• nervosvalové látky * škodlivé účinky   MeSH
• poruchy polykání * farmakoterapie   MeSH
• tortikolis * farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: In women with severe aortic stenosis, there are limited data regarding outcome differences following transcatheter (TAVR) vs surgical aortic valve replacement (SAVR). OBJECTIVES: The authors sought to examine outcomes of TAVR vs SAVR in a patient-level pooled analysis of women in the RHEIA and PARTNER 3 trials. METHODS: Patients in both trials were randomly allocated to a balloon-expandable SAPIEN 3/Ultra valve or to surgical bioprostheses. Individual patient data of female participants in the 2 trials were pooled. The primary endpoint was all-cause mortality, all stroke, or rehospitalization at 1 year. RESULTS: A total of 376 women were randomized to TAVR and 336 to SAVR. The mean age was ∼73 years, and the mean Society of Thoracic Surgeons (STS) score was 2.1%. Kaplan-Meier estimates of event rates at 1 year with TAVR vs SAVR were 8.5% vs 16.8% for the composite of all-cause mortality, all stroke, or rehospitalization (absolute difference -8.2%; 95% CI: -13.1% to -3.3%; P < 0.001), 1.1% vs 2.1% (P = 0.27) for all-cause mortality, 2.7% vs 3.9% (P = 0.35) for all stroke, and 5.4% vs 11.9% (P = 0.002) for rehospitalization. The composite endpoint of all-cause death or stroke was similar between the 2 treatment groups: 3.5% vs 5.4% (absolute difference -1.9%; 95% CI: -5.0% to 1.1%; P = 0.21). CONCLUSIONS: Among women with symptomatic severe aortic stenosis, TAVR led to a reduction in the rate of the combined endpoint of all-cause mortality, stroke, or rehospitalization at 1-year follow-up, largely due to a significant reduction in the rate of rehospitalization.

• MeSH
• aortální chlopeň * chirurgie   patofyziologie   diagnostické zobrazování   MeSH
• aortální stenóza * mortalita   chirurgie   patofyziologie   diagnostické zobrazování   MeSH
• bioprotézy MeSH
• časové faktory MeSH
• cévní mozková příhoda mortalita   etiologie   terapie   MeSH
• chirurgická náhrada chlopně * škodlivé účinky   mortalita   přístrojové vybavení   MeSH
• hodnocení rizik MeSH
• lidé MeSH
• protézy - design MeSH
• randomizované kontrolované studie jako téma MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sexuální faktory MeSH
• srdeční chlopně umělé MeSH
• stupeň závažnosti nemoci MeSH
• transkatetrální implantace aortální chlopně * škodlivé účinky   mortalita   přístrojové vybavení   MeSH
• výsledek terapie MeSH
• znovupřijetí pacienta MeSH
• Check Tag
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

BACKGROUND: The increasing incidence of oropharyngeal cancer in many developed countries has been attributed to human papillomavirus type 16 (HPV16) infections. Recently, HPV16 E6 serology has been identified as a promising early marker for oropharyngeal cancer. Therefore, characterization of HPV16 E6 seropositivity among individuals without cancer is warranted. METHODS: A total of 4,666 controls were pooled from several studies of cancer and HPV seropositivity, all tested within the same laboratory. HPV16 E6 seropositive controls were classified as having (i) moderate [mean fluorescent intensity (MFI) ≥ 484 and <1,000] or (ii) high seroreactivity (MFI ≥ 1,000). Associations of moderate and high HPV16 E6 seroreactivity with (i) demographic risk factors; and seropositivity for (ii) other HPV16 proteins (E1, E2, E4, E7, and L1), and (iii) E6 proteins from non-HPV16 types (HPV6, 11, 18, 31, 33, 45, and 52) were evaluated. RESULTS: Thirty-two (0.7%) HPV16 E6 seropositive controls were identified; 17 (0.4%) with moderate and 15 (0.3%) with high seroreactivity. High HPV16 E6 seroreactivity was associated with former smoking [odds ratio (OR), 5.5; 95% confidence interval (CI), 1.2-51.8], and seropositivity against HPV16 L1 (OR, 4.8; 95% CI, 1.3-15.4); E2 (OR, 7.7; 95% CI, 1.4-29.1); multiple HPV16 proteins (OR, 25.3; 95% CI, 2.6-119.6 for three HPV16 proteins beside E6) and HPV33 E6 (OR, 17.7; 95% CI, 1.9-81.8). No associations were observed with moderate HPV16 E6 seroreactivity. CONCLUSIONS: High HPV16 E6 seroreactivity is rare among individuals without diagnosed cancer and was not explained by demographic factors. IMPACT: Some HPV16 E6 seropositive individuals without diagnosed HPV-driven cancer, especially those with seropositivity against other HPV16 proteins, may harbor a biologically relevant HPV16 infection.

• MeSH
• dospělí MeSH
• ELISA MeSH
• infekce papilomavirem imunologie   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidský papilomavirus 16 imunologie   MeSH
• mladý dospělý MeSH
• nádory orofaryngu imunologie   virologie   MeSH
• onkogenní proteiny virové imunologie   MeSH
• protilátky virové krev   MeSH
• represorové proteiny imunologie   MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• spinocelulární karcinom imunologie   virologie   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Intramural MeSH

BACKGROUND: The Pooled Uranium Miners Analysis (PUMA) study draws together information from cohorts of uranium miners from Canada, the Czech Republic, France, Germany and the USA. METHODS: Vital status and cause of death were ascertained and compared with expectations based upon national mortality rates by computing standardized mortality ratios (SMRs) overall and by categories of time since first hire, calendar period of first employment and duration of employment as a miner. RESULTS: There were 51 787 deaths observed among 118 329 male miners [SMR = 1.05; 95% confidence interval (CI): 1.04, 1.06]. The SMR was elevated for all cancers (n = 16 633, SMR = 1.23; 95% CI: 1.21, 1.25), due primarily to excess mortality from cancers of the lung (n = 7756, SMR = 1.90; 95% CI: 1.86, 1.94), liver and gallbladder (n = 549, SMR = 1.15; 95% CI: 1.06, 1.25), larynx (n = 229, SMR = 1.10; 95% CI: 0.97, 1.26), stomach (n = 1058, SMR = 1.08; 95% CI: 1.02, 1.15) and pleura (n = 39, SMR = 1.06; 95% CI: 0.75, 1.44). Lung-cancer SMRs increased with duration of employment, decreased with calendar period and persisted with time since first hire. Among non-malignant causes, the SMR was elevated for external causes (n = 3362, SMR = 1.41; 95% CI: 1.36, 1.46) and respiratory diseases (n = 4508, SMR = 1.32; 95% CI: 1.28, 1.36), most notably silicosis (n = 814, SMR = 13.56; 95% CI: 12.64, 14.52), but not chronic obstructive pulmonary disease (n = 1729, SMR = 0.98; 95% CI: 0.93, 1.02). CONCLUSIONS: Whereas there are important obstacles to the ability to detect adverse effects of occupational exposures via SMR analyses, PUMA provides evidence of excess mortality among uranium miners due to a range of categories of cause of death. The persistent elevation of SMRs with time since first hire as a uranium miner underscores the importance of long-term follow-up of these workers.

• MeSH
• kohortové studie MeSH
• lidé MeSH
• nádory plic * MeSH
• nemoci z povolání * MeSH
• pracovní expozice * škodlivé účinky   MeSH
• radon * MeSH
• uran * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Geografické názvy
• Evropa MeSH
• Francie MeSH
• Kanada MeSH
• Německo MeSH
• Severní Amerika MeSH

Although numerous clinical trials have demonstrated the efficacy and tolerability of erythropoiesis-stimulating agents (ESAs) in patients with chemotherapy-induced anemia (CIA), results of some recent trials and one meta-analysis have suggested that ESAs may negatively impact survival and/or disease control in patients with cancer. METHODS: To assess the benefits and risks of ESAs in CIA, we conducted a pooled analysis of individual patient-level data from all randomized, double-blind, placebo-controlled trials in 2,122 patients with CIA receiving darbepoetin alfa (DA; n = 1,200) or placebo (n = 912). RESULTS: DA did not increase mortality (hazard ratio = 0.97; 95% CI, 0.85 to 1.1) and had no effect on progression-free survival (hazard ratio = 0.93; 95% CI, 0.84 to 1.04) and disease progression (hazard ratio = 0.92; 95% CI, 0.82 to 1.03), but, as expected, increased the risk for thromboembolic events (hazard ratio = 1.57; 95% CI, 1.10 to 2.26). Overall and progression-free survival were not affected by baseline hemoglobin and seemed better in patients who achieved hemoglobin more than 12 or more than 13 g/dL. Transfusions and rates of hemoglobin increase (> 1 g/dL in 14 days; > 2 g/dL in 28 days) owing to transfusions were associated with an increased risk for death and disease progression in both treatment groups; in the absence of transfusions, rates of hemoglobin increase did not appear to increase the risk for adverse outcomes. Compared with placebo, DA significantly reduced the risk of receiving one or more transfusion. CONCLUSION: There seemed to be no association between DA and risk of death or disease progression in this meta-analysis of individual patient data from DA studies conducted in CIA, the approved indication for ESAs in oncology.

• MeSH
• anemie etiologie   farmakoterapie   metabolismus   MeSH
• autologní krevní transfuze MeSH
• erythropoetin analogy a deriváty   terapeutické užití   MeSH
• farmakoterapie MeSH
• financování organizované MeSH
• hemoglobiny metabolismus   MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• metaanalýza jako téma MeSH
• nežádoucí účinky léčiv MeSH
• přežití bez známek nemoci MeSH
• protinádorové látky škodlivé účinky   MeSH
• randomizované kontrolované studie jako téma MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

: We conducted a pooled analysis of two phase III trials, RV-MM-EMN-441 and EMN01, to compare maintenance with lenalidomide-prednisone vs. lenalidomide in newly diagnosed transplant-eligible and -ineligible myeloma patients. Primary endpoints were progression-free survival, progression-free survival 2 and overall survival with both regimens. A secondary aim was to evaluate the impact of duration of maintenance on overall survival and on outcome after relapse. A total of 625 patients (lenalidomide-prednisone arm, n = 315; lenalidomide arm, n = 310) were analyzed. The median follow-up was 58 months. Median progression-free survival (25 vs. 19 months; p = 0.08), progression-free survival 2 (56 vs. 49 months; p = 0.9) and overall survival (73 months vs. NR; p = 0.08) were not significantly different between the two arms. Toxicity profiles of lenalidomide-prednisone and lenalidomide were similar, with the exception of neutropenia that was higher in the lenalidomide arm (grade ≥ 3: 9% vs. 19%, p < 0.001), without an increase in the rate of infections. Overall survival (median NR vs. 49 months, p < 0.001), progression-free survival from relapse (median 35 vs. 24 months, p = 0.004) and overall survival from relapse (median not reached vs. 41 months, p = 0.002) were significantly longer in patients continuing maintenance for ≥2 years. We showed that the addition of prednisone at 25 or 50 mg every other day (eod) to lenalidomide maintenance did not induce any significant advantage.

• Publikační typ
• časopisecké články MeSH