Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study: a double-blind, randomised, placebo-controlled trial.

BACKGROUND: Lynch syndrome is associated with an increased risk of colorectal cancer and with a broader spectrum of cancers, especially endometrial cancer. In 2011, our group reported long-term cancer outcomes (mean follow-up 55·7 months [SD 31·4]) for participants with Lynch syndrome enrolled into a randomised trial of daily aspirin versus placebo. This report completes the planned 10-year follow-up to allow a longer-term assessment of the effect of taking regular aspirin in this high-risk population. METHODS: In the double-blind, randomised CAPP2 trial, 861 patients from 43 international centres worldwide (707 [82%] from Europe, 112 [13%] from Australasia, 38 [4%] from Africa, and four [<1%] from The Americas) with Lynch syndrome were randomly assigned to receive 600 mg aspirin daily or placebo. Cancer outcomes were monitored for at least 10 years from recruitment with English, Finnish, and Welsh participants being monitored for up to 20 years. The primary endpoint was development of colorectal cancer. Analysis was by intention to treat and per protocol. The trial is registered with the ISRCTN registry, number ISRCTN59521990. FINDINGS: Between January, 1999, and March, 2005, 937 eligible patients with Lynch syndrome, mean age 45 years, commenced treatment, of whom 861 agreed to be randomly assigned to the aspirin group or placebo; 427 (50%) participants received aspirin and 434 (50%) placebo. Participants were followed for a mean of 10 years approximating 8500 person-years. 40 (9%) of 427 participants who received aspirin developed colorectal cancer compared with 58 (13%) of 434 who received placebo. Intention-to-treat Cox proportional hazards analysis revealed a significantly reduced hazard ratio (HR) of 0·65 (95% CI 0·43-0·97; p=0·035) for aspirin versus placebo. Negative binomial regression to account for multiple primary events gave an incidence rate ratio of 0·58 (0·39-0·87; p=0·0085). Per-protocol analyses restricted to 509 who achieved 2 years' intervention gave an HR of 0·56 (0·34-0·91; p=0·019) and an incidence rate ratio of 0·50 (0·31-0·82; p=0·0057). Non-colorectal Lynch syndrome cancers were reported in 36 participants who received aspirin and 36 participants who received placebo. Intention-to-treat and per-protocol analyses showed no effect. For all Lynch syndrome cancers combined, the intention-to-treat analysis did not reach significance but per-protocol analysis showed significantly reduced overall risk for the aspirin group (HR=0·63, 0·43-0·92; p=0·018). Adverse events during the intervention phase between aspirin and placebo groups were similar, and no significant difference in compliance between intervention groups was observed for participants with complete intervention phase data; details reported previously. INTERPRETATION: The case for prevention of colorectal cancer with aspirin in Lynch syndrome is supported by our results. FUNDING: Cancer Research UK, European Union, MRC, NIHR, Bayer Pharma AG, Barbour Foundation.

Routine Disinfection of Mobile Communication Devices in the Postanesthesia Care Unit.

PURPOSE: Explore the effect of routine disinfection of mobile communication devices (MCDs) in postanesthesia care unit (PACU). DESIGN: Experimental, repeated measures design. METHODS: At a 247-bed, 20-bed PACU hospital, Mid-Atlantic region, United States, mean baseline bacterial adenosine triphosphate (ATP) counts of six MCDs were established with 3M Clean-Trace Luminometer. MCDs were routinely disinfected with CaviWipes for 10 days, every 12 hours. Mean bacterial ATP counts on six MCDs were repeated at day 11 and month 36. FINDINGS: For six MCDs, baseline ATP counts identified Failure for cleanliness. Postroutine disinfection bacterial ATP counts identified Caution and Passing; 36-month bacterial ATP counts identified sustained Passing for cleanliness. CONCLUSIONS: Routine disinfection of MCDs in the PACU defined by time and method, obtains, and sustains Passing level of cleanliness. Staff nurses identified trigger, researched practice, changed practice, and implemented quality improvement follow-up.

Cecal microbiota of feedlot cattle fed a four-species Bacillus supplement.

As commercial fed cattle consume large amounts of concentrate feedstuffs, hindgut health can be challenged. The objective of this study was to evaluate the effects of a commercially available Bacillus feed additive on cattle health outcomes and cecal microbiota of fed cattle at the time of harvest. Commercial cattle from a single feedlot were identified for characterization of cecal microbial communities using 16S ribosomal ribonucleic acid gene sequencing. All cattle were fed a common corn-based finishing diet. Control cattle (CON) were administered no treatment while treated cattle (TRT) were supplemented daily with 0.050 g of MicroSaf 4C 40 (2 billion colony forming units of Bacillus spp.; Phileo by Lesaffre, Milwaukee, WI). Immediately after harvest and evisceration, the cecal contents of cattle were sampled. After DNA extraction, amplification, and sequencing, reads from CON samples (N = 12) and TRT samples (N = 12) were assigned taxonomy using the SILVA 138 database. Total morbidity, first treatment of atypical interstitial pneumonia, and early shipments for harvest were decreased among TRT cattle compared to CON cattle (P ≤ 0.021). On average, cecal microbiota from TRT cattle had greater alpha diversity than microbiota from CON cattle as measured by Shannon diversity, Pielou's evenness, and feature richness (P < 0.010). Additionally, TRT microbial communities were different (P = 0.001) and less variable (P < 0.001) than CON microbial communities when evaluated by unweighted UniFrac distances. By relative abundance across all samples, the most prevalent phyla were Firmicutes (55.40%, SD = 15.97) and Bacteroidetes (28.17%, SD = 17.74) followed by Proteobacteria (6.75%, SD = 10.98), Spirochaetes (4.54%, SD = 4.85), and Euryarchaeota (1.77%, SD = 3.00). Spirochaetes relative abundance in TRT communities was greater than that in CON communities and was differentially abundant between treatments by ANCOM testing (W = 11); Monoglobaceae was the only family-level taxon identified as differentially abundant (W = 59; greater mean relative abundance in TRT group by 2.12 percentage points). Half (N = 6) of the CON samples clustered away from all other samples based on principal coordinates and represented cecal dysbiosis among CON cattle. The results of this study indicated that administering a four-species blend of Bacillus positively supported the cecal microbial communities of finishing cattle. Further research is needed to explore potential mechanisms of action of Bacillus DFM products in feedlot cattle.

Microbes in the rumen break down fiber and complex nutrients into energy that cattle can absorb. Rumen microbes are becoming well studied, but the microbes of the hindgut­specifically of the cecum and large intestine­are less well-studied. As feedlot cattle eat large amounts of grain, maintaining health and balance of microbes in the hindgut is important. Overconsumption of a meal causes a greater proportion of digestion to occur in the hindgut, causing greater acid production that damages the gastrointestinal lining. If dietary microbial supplements support a more diverse microbial population, the challenges caused by greater hindgut digestion could be mitigated. To test this, cecal microbes were characterized after feedlot cattle were fed a conventional diet, with or without a supplement of Bacillus bacteria. Cecal samples from cattle that were fed Bacillus had greater microbial diversity. Approximately half of the cecal samples from cattle that were not fed Bacillus had disrupted microbial balance. Based on taxonomic assignment, bacteria observed in these disrupted samples indicated greater energy density of digesta and increased methane production. Supplementing feedlot cattle with Bacillus could improve hindgut microbial diversity.

Cancer Prevention with Resistant Starch in Lynch Syndrome Patients in the CAPP2-Randomized Placebo Controlled Trial: Planned 10-Year Follow-up.

ABSTRACT: The CAPP2 trial investigated the long-term effects of aspirin and resistant starch on cancer incidence in patients with Lynch syndrome (LS). Participants with LS were randomized double-blind to 30 g resistant starch (RS) daily or placebo for up to 4 years. We present long-term cancer outcomes based on the planned 10-year follow-up from recruitment, supplemented by National Cancer Registry data to 20 years in England, Wales, and Finland. Overall, 463 participants received RS and 455 participants received placebo. After up to 20 years follow-up, there was no difference in colorectal cancer incidence (n = 52 diagnosed with colorectal cancer among those randomized to RS against n = 53 on placebo) but fewer participants had non-colorectal LS cancers in those randomized to RS (n = 27) compared with placebo (n = 48); intention-to-treat (ITT) analysis [HR, 0.54; 95% confidence interval (CI), 0.33-0.86; P = 0.010]. In ITT analysis, allowing for multiple primary cancer diagnoses among participants by calculating incidence rate ratios (IRR) confirmed the protective effect of RS against non-colorectal cancer LS cancers (IRR, 0.52; 95% CI, 0.32-0.84; P = 0.0075). These effects are particularly pronounced for cancers of the upper GI tract; 5 diagnoses in those on RS versus 21 diagnoses on placebo. The reduction in non-colorectal cancer LS cancers was detectable in the first 10 years and continued in the next decade. For colorectal cancer, ITT analysis showed no effect of RS on colorectal cancer risk (HR, 0.92; 95% CI, 0.62-1.34; P = 0.63). There was no interaction between aspirin and RS treatments. In conclusion, 30 g daily RS appears to have a substantial protective effect against non-colorectal cancer cancers for patients with LS. PREVENTION RELEVANCE: Regular bowel screening and aspirin reduce colorectal cancer among patients with LS but extracolonic cancers are difficult to detect and manage. This study suggests that RS reduces morbidity associated with extracolonic cancers. See related Spotlight, p. 557.

Black cosmetologists promote diabetes awareness and screening among African American women.

PURPOSE: his study evaluated several factors that were thought to contribute to African American women's disproportionate incidence and sequelae of diabetes. METHODS: African American women (1055) living in San Diego County completed surveys about diabetes-related beliefs, screening behaviors, knowledge, and attitudes. Participants' ages ranged from 20 to 94 years, and 33.7% of the women reported completing college. RESULTS: Most of the women (59%) perceived diabetes to be a serious health threat to African American women. Thirty-two percent of the total sample and 37% of the high-risk group reported having been screened for diabetes within the past year. Nearly 37% reported never having been screened for diabetes, and 31% of those at above-average risk of developing diabetes could not recall ever having been screened. Women had a limited knowledge of the symptoms of diabetes, ways to decrease the risk factors and the sequelae of diabetes. Higher-risk women showed greater diabetes knowledge. CONCLUSIONS: Most participants reported that diabetes was a significant threat to their health but lacked sufficient knowledge to protect themselves from the disease. A focused, aggressive education campaign could yield better health outcomes.