Using Metamodeling to Identify the Optimal Strategy for Colorectal Cancer Screening

ObjectivesMetamodeling can address computational challenges within decision-analytic modeling studies evaluating many strategies. This article illustrates the value of metamodeling for evaluating colorectal cancer screening strategies while accounting for colonoscopy capacity constraints.MethodsIn a traditional approach, the best screening strategy was identified from a limited subset of strategies evaluated with the validated Adenoma and Serrated pathway to Colorectal CAncer model. In a metamodeling approach, metamodels were fitted to this limited subset to evaluate all potentially plausible strategies and determine the best overall screening strategy. Approaches were compared based on the best screening strategy in life-years gained compared with no screening. Metamodel runtime and accuracy was assessed.ResultsThe metamodeling approach evaluated >40 000 strategies in <1 minute with high accuracy after 1 adaptive sampling step (mean absolute error: 0.0002 life-years) using 300 samples in total (generation time: 8 days). Findings indicated that health outcomes could be improved without requiring additional colonoscopy capacity. Obtaining similar insights using the traditional approach could require at least 1000 samples (generation time: 28 days). Suggested benefits from screening at ages <40 years require adequate validation of the underlying Adenoma and Serrated pathway to Colorectal CAncer model before making policy recommendations.ConclusionsMetamodeling allows rapid assessment of a vast set of strategies, which may lead to identification of more favorable strategies compared to a traditional approach. Nevertheless, metamodel validation and identifying extrapolation beyond the support of the original decision-analytic model are critical to the interpretation of results. The screening strategies identified with metamodeling support ongoing discussions on decreasing the starting age of colorectal cancer screening.     

Efficacy of different irrigation technique in simulated curved root canals

The aim of this study was to assess the influence of the canal curvature on the efficacy of sonically, ultrasonically, and laser-activated irrigation in removing a biofilm-mimicking hydrogel (BMH) from simulated canal irregularities. Transparent resin blocks containing a curved root canal (40° or 60°) were used as test models. A 4-mm groove at 1 mm from the apex was filled with BMH. Five different irrigation procedures were performed (n=20): needle irrigation (NI), EndoActivator (EA), Eddy, ultrasonically activated irrigation (UAI) (Irrisafe), and laser-activated irrigation (LAI) using a pulsed erbium laser (PIPS approach). All protocols were executed for 3×20s. Images of the groove were taken before and after irrigation, and the percentage BMH removal was calculated using image analysis software. In the 40° canal curvature model, the highest BMH removal was observed for UAI (99.9%), yielding a significantly better removal than that of EA (57.2%) and NI (53.8%), but not of LAI (96.8%) and Eddy (99.4%). In the 60° canal curvature model, UAI removed 99.5%, which resulted in significantly greater hydrogel removal than all other groups (P < 0.05). The difference between LAI (82.5%) and Eddy (78.1%) was not statistically significant, but both were more effective than EA (13.5%) and NI (7.3%). Canal curvature negatively affects the cleaning efficacy of different irrigation methods. The effect was most pronounced for the sonic techniques, while this was not the case for UAI. This could be ascribed to the prebent ultrasonic tip. Despite the position of the laser tip at the orifice level, fluid streaming during LAI resulted in substantial BMH removal beyond the curve.

     

What Are the Frequency,Related Mortality,and Factors Associated with Bone Cement Implantation Syndrome in Arthroplasty Surgery?

BackgroundBone cement implantation syndrome (BCIS) is characterized by hypoxia, hypotension, and the loss of consciousness during cemented arthroplasty; it may result in death. Its incidence has only been explored for hemiarthroplasty and THA after fracture or cancer. To our knowledge, there are no studies that comprehensively explore and compare the incidence of BCIS in other arthroplasty procedures.Questions/purposes(1) To report the incidence of BCIS in TKA, unicondylar knee arthroplasty, hip hemiarthroplasty, THA, shoulder arthroplasty, TKA, and revision THA and TKA; (2) to determine whether severe BCIS is associated with an increased risk of death within 30 days of surgery; and (3) to identify factors associated with the development of severe BCIS.MethodsAll patients undergoing cemented arthroplasty for any reason (TKA [11% cemented, 766 of 7293], unicondylar knee arthroplasty [100% cemented, 562 procedures], hip hemiarthroplasty for femur fractures [100% cemented, 969 procedures], THA [8% cemented, 683 of 8447], shoulder arthroplasty [84% cemented, 185 of 219], and revision arthroplasty of the hip and knee [36% cemented, 240 of 660]) between January 2008 and August 2019 were considered for inclusion in the current retrospective observational study. Fixation choice was dependent on surgeon preference (THA and TKA), prosthesis design (shoulder arthroplasty), or bone quality (revision arthroplasty). The following procedures were excluded because of insufficient data: < 1% (1 of 766) of TKAs, 1% (4 of 562) of unicondylar knee arthroplasties, 6% (54 of 969) of hip hemiarthroplasties, 1% (6 of 683) of THAs, 6% (12 of 185) of shoulder arthroplasties, and 14% (34 of 240) of revision procedures. This resulted in a final inclusion of 3294 procedures (765 TKAs [23%], 558 unicondylar knee arthroplasties [17%], 915 hip hemiarthroplasties [28%], 677 THA [21%], 173 shoulder arthroplasties [5%], and 206 revision arthroplasties [6%]), of which 28% (930 of 3294) had an emergent indication for surgery. Of the patients, 68% (2240 of 3294) were females, with a mean age of 75 ± 11 years. All anesthetic records were extracted from our hospital’s database, and the severity of BCIS was retrospectively scored (Grade 0 [no BCIS], Grade 1 [O₂% < 94% or fall in systolic blood pressure of 20% to 40%], Grade 2 [O₂% < 88% or fall in systolic blood pressure of > 40%], and Grade 3 [cardiovascular collapse requiring CPR]). Procedures were dichotomized into no or moderate BCIS (Grades 0 and 1) and severe BCIS (Grades 2 and 3). The adjusted 30-day mortality of patients with severe BCIS was assessed with a multivariate Cox regression analysis. A multivariate logistic regression analysis was performed to identify factors associated with the development of severe BCIS.ResultsBCIS occurred in 26% (845 of 3294) of arthoplasty procedures. The incidence was 31% (282 of 915) in hip hemiarthroplasty, 28% (210 of 765) in TKA, 24% (165 of 677) in THA, 23% (47 of 206) in revision arthroplasty, 20% (113 of 558) in unicondylar knee arthroplasty, and 16% (28 of 173) in shoulder arthroplasty. Patients with severe BCIS were more likely (hazard ratio 3.46 [95% confidence interval 2.07 to 5.77]; p < 0.001) to die within 30 days of the index procedure than were patients with less severe or no BCIS. Factors independently associated with the development of severe BCIS were age older than 75 years (odds ratio 1.57 [95% CI 1.09 to 2.27]; p = 0.02), American Society of Anesthesiologists Class III or IV (OR 1.58 [95% CI 1.09 to 2.30]; p = 0.02), and renal impairment (OR 3.32 [95% CI 1.45 to 7.46]; p = 0.004).ConclusionBCIS is common during cemented arthroplasty; severe BCIS is uncommon, but it is associated with an increased risk of death within 30 days of surgery. Medically complex patients undergoing hip hemiarthroplasty may be at particular risk. Patients at high risk for severe BCIS (renal impairment, ASA III/IV, and age older than 75 years) should be identified and preventive measures such as medullary lavage before cementation, femoral venting, and avoidance of excessive pressurization of implants should be taken to reduce the likelihood and consequences of BCIS. Because of the increased risk of periprosthetic fractures in uncemented hip stems, factors associated with the development of BCIS should be weighed against the risk factors for sustaining periprosthetic fractures (poor bone quality, female sex) to balance the risks of fixation method against those of BCIS for each patient.Level of EvidenceLevel III, therapeutic study.     

The Impact of Pre-exposure Prophylaxis on Sexual Well-Being Among Men Who Have Sex with Men

Archives of Sexual Behavior - Pre-exposure prophylaxis (PrEP) is a promising strategy to reduce HIV incidence among men who have sex with men (MSM). How and when PrEP is used could in part be...     

Reimbursement models to tackle market failures for antimicrobials: Approaches taken in France,Germany, Sweden,the United Kingdom,and the United States

IntroductionThe pipeline of new antibacterials remains limited. Reasons include low research investments, limited commercial prospects, and scientific challenges. To complement existing initiatives such as research grants, governments are exploring policy options for providing new market incentives to drug developers.Materials and methodsReimbursement interventions for antibacterials in France, Germany, Sweden, US, and UK were reviewed and analysed by the authors.ResultsIn France, Germany, and the US, implemented interventions centre on providing exceptions in cost-containment mechanisms to allow higher prices for certain antibacterials. In the US, also, certain antibacterials are granted additional years of protection from generic competition (exclusivity) and faster regulatory review. The UK is piloting a model that will negotiate contracts with manufacturers to pay a fixed annual fee for ongoing supply of as many units as needed. Sweden is piloting a model that will offer manufacturers of selected antibacterials contracts that would guarantee a minimum annual revenue. A similar model of guaranteed minimal annual revenues is under consideration in the US (PASTEUR Act).ConclusionsThe UK and Sweden are piloting entirely novel procurement and reimbursement models. Existing interventions in the US, France, and Germany represent important, but relatively minor interventions. More countries should explore the use of novel models and international coordination will be important for ‘pull’ incentives to be effective. If adopted, the PASTEUR legislation in the US would constitute a significant ‘pull’ incentive.     

Glutathione S-transferases and cancer (Review)

Cytosolic glutathione S-transferases are a family of enzymes involved in the metabolism of drugs, toxins, carcinogens and also of anticancer drugs. Recent studies have indicated that glutathione S-transferases (GSTs) may play an important role in the resistance of cells to toxins and carcinogens but also to anticancer drugs. This report reviews the current literature concerning the role of glutathione S-transferases in anticancer drug resistance. Moreover, the significance of GST pi in carcinogenesis and its role as prognostic factor is discussed.     

Surgical treatment of ulcerative colitis and familial adenomatous polyposis: recent developments]

Reconstructive surgery for ulcerative colitis and familial adenomatous polyposis nowadays usually takes the form of an ileoanal pouch, involving making a reservoir of the terminal portion of the ileum which subsequently is anastomosed to the anal canal. This method results in definite cure in many cases, but is associated with a morbidity of 15-30% and fails in 10%. A new surgical treatment includes complete removal of the affected large bowel mucosa, guaranteeing oroanal intestinal continuity, limiting complications and providing good function of the reservoir or of the new rectum. In creation of an ileoneorectal anastomosis, complete removal of the affected mucous membrane is followed by preparing a functional 'neorectum' by means of pedicle grafting of ileal mucous membrane on to the uncovered muscular wall of the rectum. This operation gave good results in a small-scale clinical trial.     

Perioperative circulatory side effects of topical 5% phenylephrine for mydriasis

PURPOSE: To study the systemic effects of topically applied 5% phenylephrine. To investigate intraoperative injection of epinephrine in the anterior chamber as an alternative. METHOD: 75 patients undergoing cataract surgery were randomized into three groups. In group 1, the pupil was dilated using topically 5% phenylephrine and 1% cyclopentolate, the patients blocked the lacrimal drainage system themselves by digital compression. Group 2 received the same drops, digital compression was performed by one of the investigators. In Group 3, no preoperative phenylephrine was used--instead, epinephrine 1:25,000 was injected in the anterior chamber at the beginning of surgery. Retrobulbar anesthesia was performed in a short narcosis with ketamine and propofol. RESULTS: Mean preoperative blood pressure values were higher than the day before. They fell during narcosis, to increase significantly after the injection of the local anesthetics. At the beginning of surgery they were back to prenarcotic values. Intraoperative blood pressure remained stable. Preoperative day values were found two hours postop. There was no significant difference in the circulatory behavior between the three groups. For mydriasis, intraoperative intracameral epinephrine was not as effective as preoperative phenylephrine. CONCLUSION: In normotonic or medically treated arterial hypertensive patients, preoperative mydriasis using 5% phenylephrine is safe--proceeding the way described above. Compression of the lacrimal drainage system can be performed by the patients effectively. Intraoperative intracameral epinephrine does not replace preoperative phenylephrine.