The objective of this study was to assess recent data on the prevalence of chronic pain as part of chronic diseases; the prevalence of chronic pain as a chronic condition in its own right; the costs attributed to chronic pain; and the European Union (EU) policies to addressing chronic pain. Recent literature was reviewed for data on the prevalence and cost implications of chronic pain in the EU. Following on from an earlier systematic review, 8 databases were searched for prevalence and 10 for cost information from 2009 to 2011 and relevant EU organizations were contacted. Ten cost and 29 prevalence studies were included from the 142 full papers screened. The general adult population reported an average chronic pain prevalence of 27%, which was similar to those for common chronic conditions. Fibromyalgia had the highest unemployment rate (6%; Rivera et al., Clin Exp Rheumatol. 2009;27[Suppl 56]:S39-S45) claims for incapacity benefit (up to 29.9%; Sicras-Mainar et al., Arthritis Res Ther. 2009;11:R54), and greatest number of days of absence from work (Rivera et al., Clin Exp Rheumatol. 2009;27[Suppl 56]:S39-S45). Chronic pain is common and the total population cost is high. Despite its high impact, chronic pain as a condition seems to have had little specific policy response. However, there does appear to be sufficient evidence to at least make addressing chronic pain a high priority alongside other chronic diseases as well as to conduct more research, particularly regarding cost.
Background The interim analysis of the multicentre New EPOC trial in patients with resectable colorectal liver metastasis showed a significant reduction in progression-free survival in patients allocated to cetuximab plus chemotherapy compared with those given chemotherapy alone. The focus of the present analysis was to assess the effect on overall survival.Methods New EPOC was a multicentre, open-label, randomised, controlled, phase 3 trial. Adult patients (aged ≥18 years) with KRAS wild-type (codons 12, 13, and 61) resectable or suboptimally resectable colorectal liver metastases and a WHO performance status of 0-2 were randomly assigned (1:1) to receive chemotherapy with or without cetuximab before and after liver resection. Randomisation was done centrally with minimisation factors of surgical centre, poor prognosis cancer, and previous adjuvant treatment with oxaliplatin. Chemotherapy consisted of oxaliplatin 85 mg/m² administered intravenously over 2 h, l-folinic acid (175 mg flat dose administered intravenously over 2 h) or d,l-folinic acid (350 mg flat dose administered intravenously over 2 h), and fluorouracil bolus 400 mg/m² administered intravenously over 5 min, followed by a 46 h infusion of fluorouracil 2400 mg/m² repeated every 2 weeks (regimen one), or oxaliplatin 130 mg/m² administered intravenously over 2 h and oral capecitabine 1000 mg/m² twice daily on days 1-14 repeated every 3 weeks (regimen two). Patients who had received adjuvant oxaliplatin could receive irinotecan 180 mg/m² intravenously over 30 min with fluorouracil instead of oxaliplatin (regimen three). Cetuximab was given intravenously, 500 mg/m² every 2 weeks with regimen one and three or a loading dose of 400 mg/m² followed by a weekly infusion of 250 mg/m² with regimen two. The primary endpoint of progression-free survival was published previously. Secondary endpoints were overall survival, preoperative response, pathological resection status, and safety. Trial recruitment was halted prematurely on the advice of the Trial Steering Committee on Nov 1, 2012. All analyses (except safety) were done on the intention-totreat population. Safety analyses included all randomly assigned patients. This trial is registered with ISRCTN, number 22944367.
The 8q24 region harbors multiple risk variants for distinct cancers, including >8 for prostate cancer. In this study, we conducted fine mapping of the 8q24 risk region (127.8-128.8Mb) in search of novel associations with common and rare variation in 4853 prostate cancer case patients and 4678 control subjects of African ancestry. All statistical tests were two-sided. We identified three independent associations at P values of less than 5.00×10(-8), all of which were replicated in studies from Ghana and Uganda (combined sample = 5869 case patients, 5615 control subjects; rs114798100: risk allele frequency [RAF] = 0.04, per-allele odds ratio [OR] = 2.31, 95% confidence interval [CI] = 2.04 to 2.61, P = 2.38×10(-40); rs72725879: RAF = 0.33, OR = 1.37, 95% CI = 1.30 to 1.45, P = 3.04×10(-27); and rs111906932: RAF = 0.03, OR = 1.79, 95% CI = 1.53 to 2.08, P = 1.39×10(-13)). Risk variants rs114798100 and rs111906923 are only found in men of African ancestry, with rs111906923 representing a novel association signal. The three variants are located within or near a number of prostate cancer-associated long noncoding RNAs (lncRNAs), including PRNCR1, PCAT1, and PCAT2. These findings highlight ancestry-specific risk variation and implicate prostate-specific lncRNAs at the 8q24 prostate cancer susceptibility region.
There is strong evidence of a correlation between pain severity and QoL. There is some evidence that treatment in chronic pain patients can reduce pain and simultaneously improve QoL. Prevention and treatment of chronic pain may be of significant help in reaching the aim to increase the healthy lifespan.
Prostate cancer is the most common non-skin cancer in males, with a ∼1.5-2-fold higher incidence in African American men when compared with whites. Epidemiologic evidence supports a large heritable contribution to prostate cancer, with over 100 susceptibility loci identified to date that can explain ∼33% of the familial risk. To explore the contribution of both rare and common variation in coding regions to prostate cancer risk, we sequenced the exomes of 2165 prostate cancer cases and 2034 controls of African ancestry at a mean coverage of 10.1×. We identified 395 220 coding variants down to 0.05% frequency [57% non-synonymous (NS), 42% synonymous and 1% gain or loss of stop codon or splice site variant] in 16 751 genes with the strongest associations observed in SPARCL1 on 4q22.1 (rs13051, Ala49Asp, OR = 0.78, P = 1.8 × 10(-6)) and PTPRR on 12q15 (rs73341069, Val239Ile, OR = 1.62, P = 2.5 × 10(-5)). In gene-level testing, the two most significant genes were C1orf100 (P = 2.2 × 10(-4)) and GORAB (P = 2.3 × 10(-4)). We did not observe exome-wide significant associations (after correcting for multiple hypothesis testing) in single variant or gene-level testing in the overall case-control or case-case analyses of disease aggressiveness. In this first whole-exome sequencing study of prostate cancer, our findings do not provide strong support for the hypothesis that NS coding variants down to 0.5-1.0% frequency have large effects on prostate cancer risk in men of African ancestry. Higher-coverage sequencing efforts in larger samples will be needed to study rarer variants with smaller effect sizes associated with prostate cancer risk.
Tirofiban was more effective than usual care for STEMI and NSTE ACS patients receiving planned PCI, and NSTE ACS patients receiving medical management. Tirofiban and abciximab were equally effective. Comparisons of tirofiban and eptifibatide were inconclusive.
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