Analytic lymph node number establishes staging accuracy by occult tumor burden in colorectal cancer.

BACKGROUND AND OBJECTIVES: Recurrence in lymph node-negative (pN0) colorectal cancer suggests the presence of undetected occult metastases. Occult tumor burden in nodes estimated by GUCY2C RT-qPCR predicts risk of disease recurrence. This study explored the impact of the number of nodes analyzed by RT-qPCR (analytic) on the prognostic utility of occult tumor burden. METHODS: Lymph nodes (range: 2-159) from 282 prospectively enrolled pN0 colorectal cancer patients, followed for a median of 24 months (range: 2-63), were analyzed by GUCY2C RT-qPCR. Prognostic risk categorization defined using occult tumor burden was the primary outcome measure. Association of prognostic variables and risk category were defined by multivariable polytomous and semi-parametric polytomous logistic regression. RESULTS: Occult tumor burden stratified this pN0 cohort into categories of low (60%; recurrence rate (RR) = 2.3% [95% CI 0.1-4.5%]), intermediate (31%; RR = 33.3% [23.7-44.1%]), and high (9%; RR = 68.0% [46.5-85.1%], P \u3c 0.001) risk of recurrence. Beyond race and T stage, the number of analytic nodes was an independent marker of risk category (P \u3c 0.001). When \u3e12 nodes were analyzed, occult tumor burden almost completely resolved prognostic risk classification of pN0 patients. CONCLUSIONS: The prognostic utility of occult tumor burden assessed by GUCY2C RT-qPCR is dependent on the number of analytic lymph nodes

Cost-effectiveness of alternative methods of surgical repair of inguinal hernia

Objectives: To assess the relative cost-effectiveness of laparoscopic methods of inguinal hernia repair compared with open flat mesh and open non-mesh repair. Methods: Data on the effectiveness of these alternatives came from three systematic reviews comparing: (i) laparoscopic methods with open flat mesh or non-mesh methods; (ii) open flat mesh with open non-mesh repair; and (iii) methods that used synthetic mesh to repair the hernia defect with those that did not. Data on costs were obtained from the authors of economic evaluations previously conducted alongside trials included in the reviews. A Markov model was used to model cost-effectiveness for a five-year period after the initial operation. The outcomes of the model were presented using a balance sheet approach and as cost per hernia recurrence avoided and cost per extra day at usual activities. Results: Open flat mesh was the most cost-effective method of preventing recurrences. Laparoscopic repair provided a shorter period of convalescence and less long-term pain compared with open flat mesh but was more costly. The mean incremental cost per additional day back at usual activities compared with open flat mesh was €38 and €80 for totally extraperitoneal and transabdominal preperitoneal repair, respectively. Conclusions: Laparoscopic repair is not cost-effective compared with open flat mesh repair in terms of cost per recurrence avoided. Decisions about the use of laparoscopic repair depend on whether the benefits (reduced pain and earlier return to usual activities) outweigh the extra costs and intraoperative risks. On the evidence presented here, these extra costs are unlikely to be offset by the short-term benefits of laparoscopic repair.Luke Vale, Adrian Grant, Kirsty McCormack, Neil W. Scott and the EU Hernia Trialists Collaboratio

Transparency ethics in practice: Revisiting financial conflicts of interest disclosure forms in clinical practice guidelines

Background Authors of clinical practice guidelines (CPGs) disclose financial conflicts of interest (FCOIs) to promote transparency ethics. Typically, they do so on standard declaration forms containing generic open-ended questions on FCOIs. Yet, the literature is scant on the format and effect of alternative disclosure forms. Does supplementing a standard form with subsequent detailed disclosure forms tailored to the context of the CPG improve the yield or accuracy of FCOIs declarations? Methods For an international CPG in gastroenterology on the endoscopic surveillance for colorectal neoplasia in inflammatory bowel disease, we compared the use of a standard FCOIs disclosure form with a contextual FCOIs disclosure form that detailed commercial relations related to the CPG topic. This included manufacturers of endoscopes, endoscopy equipment and accessories. Participants completed the generic form early, and the supplementary contextual form six months later. We then compared the FCOI disclosures obtained. Findings 26 participants provided FCOIs disclosures using both disclosure forms. We found discrepancies regarding (1) the disclosure of FCOIs (presence/absence), and (2) the listing of financial entities. While the number of participants who disclosed a FCOI remained the same (30.8%) using the two forms, disclosures were not from the same individuals: two additional participants disclosed a FCOI, whereas two participants withdrew previous disclosures. Among those who reported a FCOI in either form, we noted inconsistencies in disclosures for 70% of the participants. This included changes in FCOIs disclosure status or modifications of "their commercial relations". Discussion Accurate reporting of FCOIs advances the transparency and ethical integrity of CPGs. Our experience suggests that a contextual FCOIs disclosure form tailored to content of the CPG with narrow, detailed questions provides supplementary, more complete FCOIs declarations than generic forms alone. The finding raises challenges on how forms are best written and formatted, optimally timed, and more effectively processed with sensitivity to professional behaviour, so as to heighten transparency

Association of GUCY2C expression in lymph nodes with time to recurrence and disease-free survival in pN0 colorectal cancer.

CONTEXT: The established relationship between lymph node metastasis and prognosis in colorectal cancer suggests that recurrence in 25% of patients with lymph nodes free of tumor cells by histopathology (pN0) reflects the presence of occult metastases. Guanylyl cyclase 2C (GUCY2C) is a marker expressed by colorectal tumors that could reveal occult metastases in lymph nodes and better estimate recurrence risk. OBJECTIVE: To examine the association of occult lymph node metastases detected by quantifying GUCY2C messenger RNA, using the reverse transcriptase-polymerase chain reaction, with recurrence and survival in patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 257 patients with pN0 colorectal cancer enrolled between March 2002 and June 2007 at 9 US and Canadian centers (7 academic medical centers and 2 community hospitals) provided 2570 fresh lymph nodes measuring 5 mm or larger for histopathology and GUCY2C messenger RNA analysis. Patients were followed up for a median of 24 months (range, 2-63 months) for disease recurrence or death. MAIN OUTCOME MEASURES: Time to recurrence (primary outcome) and disease-free survival (secondary outcome) relative to expression of GUCY2C in lymph nodes. RESULTS: Thirty-two patients (12.5%) had lymph nodes negative for GUCY2C (pN0 [mol-]), and all but 2 remained free of disease during follow-up (recurrence rate, 6.3%; 95% confidence interval [CI], 0.8%-20.8%). Conversely, 225 patients (87.5%) had lymph nodes positive for GUCY2C (pN0 [mol+]), and 47 developed recurrent disease (20.9%; 95% CI, 15.8%-26.8%) (P = .006). Multivariate analyses revealed that GUCY2C in lymph nodes was an independent marker of prognosis. Patients who were pN0 (mol+) exhibited earlier time to recurrence (adjusted hazard ratio, 4.66; 95% CI, 1.11-19.57; P = .04) and reduced disease-free survival (adjusted hazard ratio, 3.27; 95% CI, 1.15-9.29; P = .03). CONCLUSION: Expression of GUCY2C in histologically negative lymph nodes appears to be independently associated with time to recurrence and disease-free survival in patients with pN0 colorectal cancer

Breaking down the language of racism:a computerised linguistic analysis of racist groups’ self-defining online statements

The Internet represents a powerful tool for racist groups to build a sense of group consciousness and promote their cause. In the current study, we examined the language used by racist (n = 87), anti-racist (n = 50), and nonactivist (n = 1379) groups when describing their self-defining beliefs online. We used computerized linguistic analysis software to measure psychological indicators and antecedents of group consciousness and to examine the persuasive techniques used in online group communication. Racist and anti-racist groups were similar on some linguistic indicators of group consciousness (e.g., use of words reflecting perceived injustice), but differed on others (e.g., use of words reflecting group identification). Linguistic indicators of antecedents of group consciousness (moral foundations and focus on religion) differed across groups, with racist groups focused more on purity, respect for authority, and religion, and less on fairness than anti-racist groups. Racist groups also used less cognitively complex language than nonactivist groups (but similar levels to anti-racist groups). Our results contribute to understanding how racist groups promote their self-defining beliefs online, and identify several key factors that should be considered when designing policies to reduce racist groups' growth and impact

Antimicrobial Drugs and Community–acquired Clostridium difficile–associated Disease, UK

In a population-based case-control study of community-acquired Clostridium difficile–associated disease (CDAD), we matched 1,233 cases to 12,330 controls. CDAD risk increased 3-fold with use of any antimicrobial agent and 6-fold with use of fluoroquinolones. Prior use of antimicrobial agent did not affect risk for CDAD after 6 months

Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs

Background: Misoprostol is effective for ulcers associated with the use of nonsteroidal antiinflammatory drugs (NSAIDs) but is often poorly tolerated because of diarrhea and abdominal pain. We compared the efficacy of omeprazole and misoprostol in healing and preventing ulcers associated with NSAIDs. Methods: in a double-blind study, we randomly assigned 935 patients who required continuous NSAID therapy and who had ulcers or more than 10 erosions in the stomach or duodenum (or both) to receive 20 mg or 40 mg of omeprazole orally in the morning or 200 microg of misoprostol orally four times daily. Patients were treated for four weeks or, in the absence of healing, eight weeks. Treatment success was defined as the absence of ulcers and the presence of fewer than five erosions at each site and not more than mild dyspepsia. We then randomly reassigned 732 patients in whom treatment was successful to maintenance therapy with 20 mg of omeprazole daily, 200 microg of misoprostol twice daily, or placebo for six months. Results: at eight weeks, treatment was successful in 76 percent of the patients given 20 mg of omeprazole (233 of 308), 75 percent of those given 40 mg of omeprazole (237 of 315), and 71 percent of those given misoprostol (212 of 298). The rates of gastric-ulcer healing were significantly higher with 20 mg of omeprazole (but not 40 mg of omeprazole) than with misoprostol. Healing rates among patients with duodenal ulcers were higher with either dose of omeprazole than with misoprostol, whereas healing rates among patients with erosions alone were higher with misoprostol. More patients remained in remission during maintenance treatment with omeprazole (61 percent) than with misoprostol (48 percent, P=0.001) and with either drug than with placebo (27 percent, P<0.001). There were more adverse events during the healing phase in the misoprostol group than in the groups given 20 mg and 40 mg of omeprazole (59 percent, 48 percent, and 46 percent, respectively). Conclusions: the overall rates of successful treatment of ulcers, erosions, and symptoms associated with NSAIDs were similar for the two doses of omeprazole and misoprostol. Maintenance therapy with omeprazole was associated with a lower rate of relapse than misoprostol. Omeprazole was better tolerated than misoprostol

ПОВЫШЕНИЕ ИЗНОСОСТОЙКОСТИ И РЕСУРСА РАБОТЫ МНОГОДИСКОВЫХ ТОРМОЗНЫХ МЕХАНИЗМОВ ТРАКТОРА «БЕЛАРУС» ЛАЗЕРНЫМ ТЕРМОУПРОЧНЕНИЕМ БЫСТРОИЗНАШИВАЮЩИХСЯ ДЕТАЛЕЙ

Problems concerning wear resistance improvement of «Belarus» tractor brake mechanism parts are considered in the paper. Properties of ВЧ-50-pig iron are investigated as a result of laser thermal hardening by various technological methods.Рассмотрены вопросы повышения износостойкости деталей тормозных механизмов трактора «Беларус». Исследованы свойства чугуна ВЧ-50 в результате лазерного термоупрочнения различными технологическими методами

A review of the gastrointestinal safety data—a gastroenterologist’s perspective

Although NSAIDs have a well-established place for certain indications in the management of OA and RA, they are associated with significant gastrointestinal (GI) toxicity. The risk of NSAID-related upper GI events, such as dyspepsia or peptic ulcer and complications such as perforation or bleeding, is well characterized. Non-selective NSAIDs increase the risk of peptic ulcer disease ∼5-fold, and that of upper GI bleeding 4-fold, whereas selective cyclo-oxygenase-2 (COX) inhibitors are associated with a significantly lower GI toxicity than non-selective agents. There is evidence that, while the incidence of NSAID-related upper GI complications has decreased in recent years, that of lower GI complications is increasing. Observational studies and analyses from studies, primarily designed to investigate upper GI events, suggest that lower GI complications are relatively common in NSAID users and that COX-2 selective inhibitors are associated with a lower risk of these events. Such events have been poorly characterized, but are associated with significant mortality; indeed, they may have even more serious consequences than the better characterized upper GI events. There is thus a strong case for evaluating the impact of such complications in prospective outcome studies. To facilitate such studies a new endpoint, Clinically Significant Upper or Lower GI Events, has been introduced that captures both upper and lower GI events