Optimal timing for anticoagulation resumption after polypectomy is unclear. We explored the association between timing of anticoagulation resumption and occurrence of delayed post-polypectomy bleeding (PPB) and thromboembolic (TE) events. We performed a post-hoc analysis of patients in an earlier study whose anticoagulants were interrupted for polypectomy. We compared rates of clinically important delayed PPB and TE events in relationship to timing of anticoagulant resumption. Late resumption was defined as > 2 days after polypectomy. Among 437 patients, 351 had early and 86 late resumption. Compared to early resumers, late resumers had greater polypectomy complexity. PPB rate was higher (but not significantly) in the late versus early resumers (2.3% vs. 0.9%, 1.47% greater, 95% CI [− 2.58 to 5.52], p = 0.26). TE events were more frequent in late versus early resumers [0% vs. 1.2% at 30 days, 0% vs. 2.3%, 95% CI 0.3–8, (p = 0.04) at 90 days]. On multivariate analysis, timing of restarting anticoagulation was not a significant predictor of PPB (OR 0.97, 95% CI 0.61–1.44, p = 0.897). Significant predictors were number of polyps ≥ 1 cm (OR 4.14, 95% CI 1.27–13.66, p = 0.014) and use of fulguration (OR 11.43, 95% CI 1.35–80.80, p = 0.014). Physicians delayed anticoagulation resumption more commonly after complex polypectomies. The timing of restarting anticoagulation was not a significant risk factor for PPB and late resumers had significantly higher rates of TE events within 90 days. Considering the potentially catastrophic consequences of TE events and the generally benign outcome of PPBs, clinicians should be cautious about delaying resumption of anticoagulation after polypectomy.

The optimal time for resuming anticoagulation therapy after polypectomy is not clear. We explored the association between timing of resumption of anticoagulation after polypectomy and occurrence of delayed post-polypectomy bleeding (PPB) and thromboembolic (TE) events. For patients in a clinical trial on prophylactic hemoclipping for PPB prevention, we performed a post-hoc analysis of those whose anticoagulants (warfarin or direct acting oral anticoagulants) were stopped prior to colonoscopy. We compared rates of clinically important delayed PPB (rectal bleeding resulting in either repeat colonoscopy, hemodynamic instability, drop of hemoglobin ≥ 2g/dL, or blood transfusion) within 30 days after colonoscopy for patients whose anticoagulation was resumed within 2 days or after 2 days. TE events included pulmonary embolism, deep vein thrombosis, and cerebrovascular events. We studied 437 patients whose anticoagulants were stopped prior to colonoscopic polypectomy (329 on warfarin, 108 on DOACs); anticoagulation was resumed within 2 days in 351 (80.3%), and after 2 days in 86 (19.7%). There were no differences between the groups in baseline characteristics including HAS-BLED or CHA2DS2-VASc scores. However, those whose anticoagulation was held >2 days had greater polypectomy complexity (i.e. removal of more polyps, more polyps ≥1cm in size, more right-sided polyps) and more use of hot snare, piecemeal technique, lift with polypectomy, and fulguration (Table 1). The rate of PPB was lower for those who resumed anticoagulation within 2 days compared to those resuming after 2 days (0.9% vs 2.3%, p=.26) but the difference did not reach statistical significance. Patients who resumed their anticoagulation within 2 days had no TE events at either 30 days or 90 days post-colonoscopy. In contrast, among patients who resumed anticoagulation more than 2 days post-colonoscopy, 1 of 86 (1.2%) experienced a TE event by 30 days, and 2 of 86 (2.3%, p=0.04) experienced TE events by 90 days. No patients died within 90 days of colonoscopy. For patients with anticoagulants stopped prior to colonoscopic polypectomy, physicians in our study delayed anticoagulation resumption longer for patients who had complex polypectomies. The rate of PPB for patients whose anticoagulation was resumed within 2 days after polypectomy did not differ significantly from that for patients whose anticoagulation was resumed >2 days later, although the PPB rate was numerically higher in the latter group. However, the latter group also had a significantly higher rate of TE events. Considering the potentially catastrophic consequences of TE events and the generally benign outcome of PPBs, clinicians should be cautious about delaying resumption of anticoagulation after polypectomy. Ideally, this important issue will be evaluated in future prospective trials.

Background:Aims of this study were to assess the prevalence of and risk factors for sexual dysfunction (SD) in male veterans with inflammatory bowel disease (IBD).Methods:We collected IBD history, quality of life (QOL), and sexual function surveys.Results:One hundred seventy-one men enrolled, mean age 50 years, 85% had SD, 92% had erectile dysfunction (ED). More severe ED (P = 0.0001), decreased sexual desire (P = 0.004), and decreased satisfaction (P = 0.001) were associated with poorer QOL. Biologic use was associated with increased SD; hypertension with a decrease in sexual desire.Conclusions:SD and ED are highly prevalent and associated with poorer QOL.

the tumor DNA damage responses (DDR) to temporally exert both anti-and pro-tumorigenic activity in developing tumors.Using human CRC xenografts and Azoxymethane (AOM)/ Dextran sodium sulfate (DSS) murine model of colon carcinogenesis, we found that at the onset of tumorigenesis, PMNs induced tumor cell death and suppressed tumor growth, however surprisingly, once established, tumor development was enhanced by the PMN presence.Mechanistically, PMNs via specific microRNA activity induced replicative stress and inhibited double-strand breaks (DSB) repair by homologous recombination (HR) to initially suppress tumor growth.However, persistent HR inhibition by PMNs and accumulation of DSBs led to upregulation of NHEJ transcriptional profile and activity.The PMNenhanced survival and growth of established tumors was confirmed to be due to NHEJ upregulation.PARP1 inhibition by Olaparib (induces synthetic lethality in the absence of HR) at the onset of tumorigenesis, significantly reduced tumor growth and increased tumor cell apoptosis.In contrast, Olaparib treatment of progressive tumors with highly active NHEJ had no effect on tumor growth.Directed NHEJ inhibition similarly reduced tumor growth and increased tumor cell death in PMN intact but not in PMN-depleted tumors.Collectively, our data define a novel phasic function of PMNs in the tumor microenvironment with important therapeutic implications.

BACKGROUND & AIMS:The efficacy of prophylactic placement of hemoclips to prevent delayed bleeding after removal of large colonic polyps has not been established. We conducted a randomized equivalence study to determine whether prophylactic placement of hemoclips affects incidence of delayed post-polypectomy bleeding (PPB). METHODS:During elective colonoscopy performed at 4 Veterans Affairs Medical Centers, 1098 patients who had polyps ≥1 cm removed were randomly assigned to groups that received prophylactic hemoclips (n = 547) or no hemoclips (n = 551), from September 2011 through September 2018. Data on PPB (rectal bleeding resulting in hemoglobin decreases ≥2 g/dL, hemodynamic instability, colonoscopy, angiography, or surgery) within 30 days of colonoscopy (called delayed PPB) were collected during telephone interviews or hospital visits 7 and 30 days after colonoscopy. The primary outcome was the incidence of important post-polypectomy bleeding. RESULTS:Twelve patients in the hemoclip group (2.3%) and 15 patients in the no hemoclip group (2.9%) had important delayed PPB. There were no deaths, and no patients in either group required angiography or surgery. In intention-to-treat analysis, two 1-sided test's lower and upper confidence interval limits were -2.07 and 1.01, indicating that the data approached but did not meet equivalence criteria. On multiple logistic regression analysis, significant predictors of PPB included use of warfarin with bridging, thienopyridines, polyp size, and polyp location, but hemoclip placement did not associate with important delayed PPB. CONCLUSIONS:In a randomized trial, we found that prophylactic placement of hemoclips after removal of large colon polyps does not affect the proportion of important delayed PPB events, compared with no hemoclip placement. These findings call into question the widespread, expensive practice of routinely placing prophylactic hemoclips after polypectomy. ClinicalTrials.gov ID: NCT01647581.

The most common complication of colonic polypectomy is post-polypectomy bleeding (PPB), which can occur immediately or can be delayed for hours to weeks after the procedure. To prevent delayed PPB, it has become a common clinical practice for colonoscopists to place hemoclips “prophylactically” (i.e. in the absence of immediate PPB), particularly after the removal of large polyps. Very few published data support this expensive practice, however, and there are no clear guidelines on when or how to perform prophylactic hemoclipping. We hypothesized that the prophylactic placement of hemoclips after the removal of large polyps does not influence the rate of important delayed PPB, and we have explored that hypothesis in a prospective, randomized equivalency trial.

AbstractThis paper presents latest thinking from the Institute and Faculty of Actuaries’ Model Risk Working Party and follows on from their Phase I work, Model Risk: Daring to Open the Black Box. This is a more practical paper and presents the contributors’ experiences of model risk gained from a wide range of financial and non-financial organisations with suggestions for good practice and proven methods to reduce model risk. After a recap of the Phase I work, examples of model risk communication are given covering communication: to the Board; to the regulator; and to external stakeholders. We present a practical framework for model risk management and quantification with examples of the key actors, processes and cultural challenge. Lessons learned are then presented from other industries that make extensive use of models and include the weather forecasting, software and aerospace industries. Finally, a series of case studies in practical model risk management and mitigation are presented from the contributors’ own experiences covering primarily financial services.

ABSTRACTMost businesses have assets financed by capital providers. The cost of capital is a measure of the returns required by those capital providers. Its main use is to set a target for the profits, which must be achieved on the firm's assets in order to satisfy equity and bond holders.This paper describes the classical theory of the cost of capital, and then applies it to the special case of banking and insurance firms. We develop implications for product pricing, performance measurement and capital structure optimisation.

ABSTRACTIn recent years there has been a trend towards market consistent valuation in those institutions for which actuaries have responsibilities. The larger United Kingdom with-profits insurance companies are now preparing realistic balance sheets, both for internal purposes and also at the request of the Financial Services Authority. International accounting standards have been moving to a fair value approach. Pension fund accounting under FRS 17 has also moved in this direction.In this paper we examine the reasons for the adoption of market consistent valuation and discuss some of the commercial implications and corporate valuation. We consider the methods and assumptions which can be used to develop market consistent valuations of cash flows typically encountered in the liabilities of financial institutions, together with some of the problems inherent in the calibration of models used for the valuation of these cash flows. The volatility assumption is crucial to the valuation of options and guarantees, and we discuss the relationship between historical and implied volatility.While most insurance companies initially adopted formulae to value their with-profits guarantees, several offices are now using a Monte Carlo simulation approach for their realistic balance sheets. The Monte Carlo approach enables allowance to be made for management discretion in bonus and investment policy, as well as policyholder actions. However, in many cases it is possible to develop analytical formulae for cash flows approximating those payable under insurance contracts.The valuation formulae have implications for the hedging of embedded guarantees. The authors discuss the construction of hedges for financial risks in with-profits funds, the separate perspectives of policyholders and shareholders, possible funds in which to hold hedging instruments, limitations of capital market hedging tools and the effect of taxation on hedge effectiveness.

Three children with congenital constriction band syndrome affecting their upper extremities demonstrated clinical and electrophysiologic signs of a complete ulnar nerve palsy. Two of the children were diagnosed immediately postpartum with the subtle findings of an intrinsic minus posture of their hand and inability to actively extend their fingers at the proximal interphalangeal joints. One child had at least 5.5 months of intrauterine compression of the ulnar nerve detected by ultrasound examination at 18 weeks. Despite early release of the constriction bands, at 3 months in 2 children and at 6 months in 1 child, the ulnar nerve palsies persisted for a mean follow-up period of 7 years. If clinical examination of an infant with constriction band syndrome is indicative of a complete ulnar nerve palsy, the constriction band should be released as early as possible. If surgical exploration reveals significant compression of the ulnar nerve, consideration should be given to excising the involved segment of nerve with immediate primary nerve repair or nerve grafting because even early release of the constriction band does not seem to result in neurologic improvement in long-term follow-up studies. (J Hand Surg 2001;26A:467-473. Copyright © 2001 by the American Society for Surgery of the Hand.)

Mathematical modeling of how physical factors alter gastric emptying is limited by lack of precise measures of the forces exerted on gastric contents. We have produced agar gel beads (diameter 1.27 cm) with a range of fracture strengths (0.15-0.90 N) and assessed their breakdown by measuring their half-residence time (RT(1/2)) using magnetic resonance imaging. Beads were ingested either with a high (HV)- or low (LV)-viscosity liquid nutrient meal. With the LV meal, RT(1/2) was similar for bead strengths ranging from 0.15 to 0.65 N but increased from 22 +/- 2 min (bead strength <0.65 N) to 65 +/- 12 min for bead strengths >0.65 N. With the HV meal, emptying of the harder beads was accelerated. The sense of fullness after ingesting the LV meal correlated linearly (correlation coefficient = 0.99) with gastric volume and was independently increased by the harder beads, which were associated with an increased antral diameter. We conclude that the maximum force exerted by the gastric antrum is close to 0.65 N and that gastric sieving is impaired by HV meals.