The Efficacy of Real-time Computer-aided Detection of Colonic Neoplasia in Community Practice: A Pragmatic Randomized Controlled Trial.

BACKGROUND & AIMS: The use of computer-aided detection (CADe) has increased the adenoma detection rates (ADRs) during colorectal cancer (CRC) screening/surveillance in randomized controlled trials (RCTs) but has not shown benefit in real-world implementation studies. We performed a single-center pragmatic RCT to evaluate the impact of real-time CADe on ADRs in colonoscopy performed by community gastroenterologists. METHODS: We enrolled 1100 patients undergoing colonoscopy for CRC screening, surveillance, positive fecal-immunohistochemical tests, and diagnostic indications at one community-based center from September 2022 to March 2023. Patients were randomly assigned (1:1) to traditional colonoscopy or real-time CADe. Blinded pathologists analyzed histopathologic findings. The primary outcome was ADR (the percentage of patients with at least 1 histologically proven adenoma or carcinoma). Secondary outcomes were adenomas detected per colonoscopy (APC), sessile-serrated lesion detection rate, and non-neoplastic resection rate. RESULTS: The median age was 55.5 years (interquartile range, 50-62 years), 61% were female, 72.7% were of Hispanic ethnicity, and 9.1% had inadequate bowel preparation. The ADR for the CADe group was significantly higher than the traditional colonoscopy group (42.5% vs 34.4%; P = .005). The mean APC was significantly higher in the CADe group compared with the traditional colonoscopy group (0.89 ± 1.46 vs 0.60 ± 1.12; P < .001). The improvement in adenoma detection was driven by increased detection of <5 mm adenomas. CADe had a higher sessile-serrated lesion detection rate than traditional colonoscopy (4.7% vs 2.0%; P = .01). The improvement in ADR with CADe was significantly higher in the first half of the study (47.2% vs 33.7%; P = .002) compared with the second half (38.7% vs 34.9%; P = .33). CONCLUSIONS: In a single-center pragmatic RCT, real-time CADe modestly improved ADR and APC in average-detector community endoscopists. (ClinicalTrials.gov number, NCT05963724).

External validation and clinical utility of a prediction model for 6-month mortality in patients undergoing hemodialysis for end-stage kidney disease.

BACKGROUND: End-stage kidney disease is associated with poor prognosis. Health care professionals must be prepared to address end-of-life issues and identify those at high risk for dying. A 6-month mortality prediction model for patients on dialysis derived in the United States is used but has not been externally validated. AIM: We aimed to assess the external validity and clinical utility in an independent cohort in Canada. DESIGN: We examined the performance of the published 6-month mortality prediction model, using discrimination, calibration, and decision curve analyses. SETTING/PARTICIPANTS: Data were derived from a cohort of 374 prevalent dialysis patients in two regions of British Columbia, Canada, which included serum albumin, age, peripheral vascular disease, dementia, and answers to the "the surprise question" ("Would I be surprised if this patient died within the next year?"). RESULTS: The observed mortality in the validation cohort was 11.5% at 6 months. The prediction model had reasonable discrimination (c-stat = 0.70) but poor calibration (calibration-in-the-large = -0.53 (95% confidence interval: -0.88, -0.18); calibration slope = 0.57 (95% confidence interval: 0.31, 0.83)) in our data. Decision curve analysis showed the model only has added value in guiding clinical decision in a small range of threshold probabilities: 8%-20%. CONCLUSION: Despite reasonable discrimination, the prediction model has poor calibration in this external study cohort; thus, it may have limited clinical utility in settings outside of where it was derived. Decision curve analysis clarifies limitations in clinical utility not apparent by receiver operating characteristic curve analysis. This study highlights the importance of external validation of prediction models prior to routine use in clinical practice.

Effect of age on discrimination learning, reversal learning, and cognitive bias in family dogs.

Several studies on age-related cognitive decline in dogs involve laboratory dogs and prolonged training. We developed two spatial tasks that required a single 1-h session. We tested 107 medium-large sized dogs: "young" (N=41, aged 2.5-6.5 years) and "old" (N=66, aged 8-14.5 years). Our results indicated that, in a discrimination learning task and in a reversal learning task, young dogs learned significantly faster than the old dogs, indicating that these two tasks could successfully be used to investigate differences in spatial learning between young and old dogs. We also provide two novel findings. First, in the reversal learning, the dogs trained based on the location of stimuli learned faster than the dogs trained based on stimulus characteristics. Most old dogs did not learn the task within our cut-off of 50 trials. Training based on an object's location is therefore more appropriate for reversal learning tasks. Second, the contrast between the response to the positive and negative stimuli was narrower in old dogs, compared to young dogs, during the reversal learning task, as well as the cognitive bias test. This measure favors comparability between tasks and between studies. Following the cognitive bias test, we could not find any indication of differences in the positive and negative expectations between young and old dogs. Taken together, these findings do not support the hypothesis that old dogs have more negative expectations than young dogs and the use of the cognitive bias test in older dogs requires further investigation.

Balancing the Needs of Acute and Maintenance Dialysis Patients during the COVID-19 Pandemic: A Proposed Ethical Framework for Dialysis Allocation.

The COVID-19 pandemic continues to strain health care systems and drive shortages in medical supplies and equipment around the world. Resource allocation in times of scarcity requires transparent, ethical frameworks to optimize decision making and reduce health care worker and patient distress. The complexity of allocating dialysis resources for both patients receiving acute and maintenance dialysis has not previously been addressed. Using a rapid, collaborative, and iterative process, BC Renal, a provincial network in Canada, engaged patients, doctors, ethicists, administrators, and nurses to develop a framework for addressing system capacity, communication challenges, and allocation decisions. The guiding ethical principles that underpin this framework are (1) maximizing benefits, (2) treating people fairly, (3) prioritizing the worst-off individuals, and (4) procedural justice. Algorithms to support resource allocation and triage of patients were tested using simulations, and the final framework was reviewed and endorsed by members of the provincial nephrology community. The unique aspects of this allocation framework are the consideration of two diverse patient groups who require dialysis (acute and maintenance), and the application of two allocation criteria (urgency and prognosis) to each group in a sequential matrix. We acknowledge the context of the Canadian health care system, and a universal payer in which this framework was developed. The intention is to promote fair decision making and to maintain an equitable reallocation of limited resources for a complex problem during a pandemic.

Combining classifiers to predict gene function in Arabidopsis thaliana using large-scale gene expression measurements.

BACKGROUND: Arabidopsis thaliana is the model species of current plant genomic research with a genome size of 125 Mb and approximately 28,000 genes. The function of half of these genes is currently unknown. The purpose of this study is to infer gene function in Arabidopsis using machine-learning algorithms applied to large-scale gene expression data sets, with the goal of identifying genes that are potentially involved in plant response to abiotic stress. RESULTS: Using in house and publicly available data, we assembled a large set of gene expression measurements for A. thaliana. Using those genes of known function, we first evaluated and compared the ability of basic machine-learning algorithms to predict which genes respond to stress. Predictive accuracy was measured using ROC50 and precision curves derived through cross validation. To improve accuracy, we developed a method for combining these classifiers using a weighted-voting scheme. The combined classifier was then trained on genes of known function and applied to genes of unknown function, identifying genes that potentially respond to stress. Visual evidence corroborating the predictions was obtained using electronic Northern analysis. Three of the predicted genes were chosen for biological validation. Gene knockout experiments confirmed that all three are involved in a variety of stress responses. The biological analysis of one of these genes (At1g16850) is presented here, where it is shown to be necessary for the normal response to temperature and NaCl. CONCLUSION: Supervised learning methods applied to large-scale gene expression measurements can be used to predict gene function. However, the ability of basic learning methods to predict stress response varies widely and depends heavily on how much dimensionality reduction is used. Our method of combining classifiers can improve the accuracy of such predictions - in this case, predictions of genes involved in stress response in plants - and it effectively chooses the appropriate amount of dimensionality reduction automatically. The method provides a useful means of identifying genes in A. thaliana that potentially respond to stress, and we expect it would be useful in other organisms and for other gene functions.

Maximum conservative management: a worthwhile treatment for elderly patients with renal failure who choose not to undergo dialysis.

This paper has been compiled from a presentation given by the first author to the "Palliative and End of Life Care in Chronic Kidney Disease: The Evidence" meeting held in London in October 2006. It summarizes some of what is known about the topic as well as the authors' research and experience in the field.

A Survey of Canadian Nephrologists Assessing Prognostication in End-Stage Renal Disease.

BACKGROUND: Patients with end-stage renal disease (ESRD) frequently have a relatively poor prognosis with complex care needs that depend on prognosis. While many means of assessing prognosis are available, little is known about how Canadian nephrologists predict prognosis, whether they routinely share prognostic information with their patients, and how this information guides management. OBJECTIVE: To guide improvements in the management of patients with ESRD, we aimed to better understand how Canadian nephrologists consider prognosis during routine care. DESIGN AND METHODS: A web-based multiple choice survey was designed, and administered to adult nephrologists in Canada through the e-mail list of the Canadian Society of Nephrology. The survey asked the respondents about their routine practice of estimating survival and the perceived importance of prognostic practices and tools in patients with ESRD. Descriptive statistics were used in analyzing the responses. RESULTS: Less than half of the respondents indicated they always or often make an explicit attempt to estimate and/or discuss survival with ESRD patients not on dialysis, and 25% reported they do so always or often with patients on dialysis. Survival estimation is most frequently based on clinical gestalt. Respondents endorse a wide range of issues that may be influenced by prognosis, including advance care planning, transplant referral, choice of dialysis access, medication management, and consideration of conservative care. LIMITATIONS: This is a Canadian sample of self-reported behavior, which was not validated, and may be less generalizable to non-Canadian health care jurisdictions. CONCLUSIONS: In conclusion, prognostication of patients with ESRD is an important issue for nephrologists and impacts management in fairly sophisticated ways. Information sharing on prognosis may be suboptimal.

CONTEXTE: En règle générale, le pronostic des patients atteints d'insuffisance rénale terminale (IRT) est plutôt sombre et implique des besoins complexes en matière de soins. Bien qu'il existe diverses approches, on en sait peu sur la façon dont les néphrologues canadiens s'y prennent réellement pour établir le pronostic de leurs patients, et on ignore, premièrement, si l'information pronostique est systématiquement communiquée au patient et deuxièmement, comment cette information oriente la prise en charge du patient. OBJECTIFS DE L'ÉTUDE: Nous avons voulu mieux comprendre la manière dont les néphrologues canadiens tiennent compte du pronostic dans les soins aux patients afin d'éclairer les avancées dans la prise en charge des patients atteints d'IRT. CONCEPTION DE L'ÉTUDE ET MÉTHODOLOGIE: On a envoyé par courriel, un sondage Web à choix multiples à des néphrologues canadiens figurant sur la liste d'envoi de la Société canadienne de néphrologie. Le sondage interrogeait les répondants sur leur pratique habituelle d'évaluation de la durée de survie et sur leur perception de l'importance des outils et des pratiques pronostiques chez les patients atteints d'IRT. On a effectué une analyse statistique descriptive des réponses reçues. RÉSULTATS: Moins de la moitié des répondants a indiqué faire systématiquement ou souvent une tentative claire d'estimer la durée de survie ou d'en discuter avec le patient atteints d'IRT non dialysé, alors que seulement 25% le font dans le cas d'un patients dialysé. L'estimation de la durée de survie est le plus fréquemment basée sur une gestalt clinique. Les répondants rapportent un large éventail de questions pouvant être influencé par le pronostic, notamment la planification préalable des soins, la consultation en vue d'une transplantation, le choix de l'accès pour la dialyse, la gestion de la médication et la prise en considération d'un traitement conservateur. LIMITES DE L'ÉTUDE: Il s'agit d'un échantillon canadien non validé dont le comportement est autodéclaré et par conséquent, il pourrait ne pas correspondre à des systèmes de soins de santé à l'extérieur du Canada. CONCLUSIONS: L'établissement d'un pronostic chez les patients atteints d'IRT est un enjeu majeur dans la pratique des néphrologues canadiens et entraîne des répercussions relativement pointues sur la prise en charge du patient. La transmission de renseignements pronostiques pourrait ne pas être optimale.

Complete Genome Sequence of Bacillus thuringiensis Bacteriophage Smudge.

Smudge, a bacteriophage enriched from soil using Bacillus thuringiensis DSM-350 as the host, had its complete genome sequenced. Smudge is a myovirus with a genome consisting of 292 genes and was identified as belonging to the C1 cluster of Bacillus phages.

Urea clearance in dysfunctional catheters is improved by reversing the line position despite increased access recirculation.

BACKGROUND: Problematic or dysfunctional hemodialysis (HD) catheters are routinely reversed to achieve adequate blood flow for dialysis delivery. The purpose of the study is to determine the effect of varying blood pump speed (Qb) on access recirculation (AR), and urea clearance (K) in dysfunctional catheters in the normal and reversed positions. METHODS: Nineteen HD patients with tunneled cuffed catheters (5 functional and 14 dysfunctional catheters) were included; dysfunctional catheters are defined as the inability to attain a Qb of 300 mL/min or greater on 2 consecutive HD runs. AR and K measurements were obtained systematically for each catheter in the normal and reversed positions at increasing Qbs. K was measured using the ionic dialysance technique. RESULTS: In functional catheters, AR in the normal position was 0% and increased to 15% +/- 13% when reversed. Dysfunctional catheters had a greater AR of 25% +/- 16% when reversed. In functional catheters, there was no evidence of an increase in AR with increasing Qb irrespective of position. Similarly, there was no relationship between increasing AR and greater Qbs (r 2 = 0.10) in dysfunctional catheters. In dysfunctional catheters, when reversed, mean K increased from 128 +/- 10 mL/min at a Qb of 200 mL/min to 157 +/- 38 mL/min at maximal Qb (P < 0.05). CONCLUSION: We show that at increasing Qbs, K is improved in both functional and dysfunctional catheters. Data from the study are used to describe a nomogram to determine minimum Qb for a dysfunctional catheter in reversed position to maximize K.

Is maximum conservative management an equivalent treatment option to dialysis for elderly patients with significant comorbid disease?

BACKGROUND AND OBJECTIVES: There is ongoing growth of elderly populations with ESRD in Western Europe and North America. In our center, we offer an alternative care pathway of 'maximum conservative management' (MCM) to patients who elect not to start dialysis, often because of a heavy burden of comorbid illness and advanced age. The objective of our study was to compare clinical outcomes for patients who had ESRD and chose either MCM or renal replacement therapy (RRT). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is an observational study of a single-center cohort in the United Kingdom that evaluating 202 elderly (> or =70 yr) patients who had ESRD and had chosen either MCM (n = 29) or RRT (n = 173). We report survival, hospitalization rates, and location of death for this cohort. Survival was measured from a standardized 'threshold' estimated GFR of 10.8 ml/min per 1.73 m(2). RESULTS: Median survival, including the first 90 d, was 37.8 mo (range 0 to 106 mo) for RRT patients and 13.9 mo (range 2 to 44) for MCM patients (P < 0.01). RRT patients had higher rates of hospitalization (0.069 [95% confidence interval (CI) 0.068 to 0.070]) versus 0.043 [95% CI 0.040 to 0.047] hospital days/patient-days survived) compared with MCM patients. MCM patients were significantly more likely to die at home or in a hospice (odds ratio 4.15; 95% CI 1.67 to 10.25). A survey of the literature describing elderly ESRD outcomes is also presented. CONCLUSIONS: Dialysis prolongs survival for elderly patients who have ESRD with significant comorbidity by approximately 2 yr; however, patients who choose MCM can survive a substantial length of time, achieving similar numbers of hospital-free days to patients who choose hemodialysis.