NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 1.2021.

Identifying individuals with hereditary syndromes allows for timely cancer surveillance, opportunities for risk reduction, and syndrome-specific management. Establishing criteria for hereditary cancer risk assessment allows for the identification of individuals who are carriers of pathogenic genetic variants. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provides recommendations for the assessment and management of patients at risk for or diagnosed with high-risk colorectal cancer syndromes. The NCCN Genetic/Familial High-Risk Assessment: Colorectal panel meets annually to evaluate and update their recommendations based on their clinical expertise and new scientific data. These NCCN Guidelines Insights focus on familial adenomatous polyposis (FAP)/attenuated familial adenomatous polyposis (AFAP) syndrome and considerations for management of duodenal neoplasia.

Prospective multicentre randomised, double-blind, equivalence study comparing clonidine and midazolam as intravenous sedative agents in critically ill children: the SLEEPS (Safety profiLe, Efficacy and Equivalence in Paediatric intensive care Sedation) study.

BACKGROUND: Children in paediatric intensive care units (PICUs) require analgesia and sedation but both undersedation and oversedation can be harmful. OBJECTIVE: Evaluation of intravenous (i.v.) clonidine as an alternative to i.v. midazolam. DESIGN: Multicentre, double-blind, randomised equivalence trial. SETTING: Ten UK PICUs. PARTICIPANTS: Children (30 days to 15 years inclusive) weighing ≤ 50 kg, expected to require ventilation on PICU for > 12 hours. INTERVENTIONS: Clonidine (3 µg/kg loading then 0-3 µg/kg/hour) versus midazolam (200 µg/kg loading then 0-200 µg/kg/hour). Maintenance infusion rates adjusted according to behavioural assessment (COMFORT score). Both groups also received morphine. MAIN OUTCOME MEASURES: Primary end point Adequate sedation defined by COMFORT score of 17-26 for ≥ 80% of the time with a ± 0.15 margin of equivalence. Secondary end points Percentage of time spent adequately sedated, increase in sedation/analgesia, recovery after sedation, side effects and safety data. RESULTS: The study planned to recruit 1000 children. In total, 129 children were randomised, of whom 120 (93%) contributed data for the primary outcome. The proportion of children who were adequately sedated for ≥ 80% of the time was 21 of 61 (34.4%) - clonidine, and 18 of 59 (30.5%) - midazolam. The difference in proportions for clonidine-midazolam was 0.04 [95% confidence interval (CI) -0.13 to 0.21], and, with the 95% CI including values outside the range of equivalence (-0.15 to 0.15), equivalence was not demonstrated; however, the study was underpowered. Non-inferiority of clonidine to midazolam was established, with the only values outside the equivalence range favouring clonidine. Times to reach maximum sedation and analgesia were comparable hazard ratios: 0.99 (95% CI 0.53 to 1.82) and 1.18 (95% CI 0.49 to 2.86), respectively. Percentage time spent adequately sedated was similar [medians clonidine 73.8% vs. midazolam 72.8%: difference in medians 0.66 (95% CI -5.25 to 7.24)]. Treatment failure was 12 of 64 (18.8%) on clonidine and 7 of 61 (11.5%) on midazolam [risk ratio (RR) 1.63, 95% CI 0.69 to 3.88]. Proportions with withdrawal symptoms [28/60 (46.7%) vs. 30/58 (52.6%)] were similar (RR 0.89, 95% CI 0.62 to 1.28), but a greater proportion required clinical intervention in those receiving midazolam [11/60 (18.3%) vs. 16/58 (27.6%) (RR 0.66, 95% CI 0.34 to 1.31)]. Post treatment, one child on clonidine experienced mild rebound hypertension, not requiring intervention. A higher incidence of inotropic support during the first 12 hours was required for those on clonidine [clonidine 5/45 (11.1%) vs. midazolam 3/52 (5.8%)] (RR 1.93 95% CI 0.49 to 7.61). CONCLUSIONS: Clonidine is an alternative to midazolam. Our trial-based economic evaluation suggests that clonidine is likely to be a cost-effective sedative agent in the PICU in comparison with midazolam (probability of cost-effectiveness exceeds 50%). Rebound hypertension did not appear to be a significant problem with clonidine but, owing to its effects on heart rate, specific cardiovascular attention needs to be taken during the loading and early infusion phase. Neither drug in combination with morphine provided ideal sedation, suggesting that in unparalysed patients a third background agent is necessary. The disappointing recruitment rates reflect a reluctance of parents to provide consent when established on a sedation regimen, and reluctance of clinicians to allow sedation to be studied in unstable critically ill children. Future studies will require less exacting protocols allowing enhanced recruitment. TRIAL REGISTRATION: Current Controlled Trials ISRCTN02639863. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 71. See the NIHR Journals Library website for further project information.

Changing conversations: teaching safety and quality in residency training.

Improving patient safety and quality in health care is one of medicine's most pressing challenges. Residency training programs have a unique opportunity to meet this challenge by training physicians in the science and methods of patient safety and quality improvement (QI).With support from the Health Resources and Services Administration, the authors developed an innovative, longitudinal, experiential curriculum in patient safety and QI for internal medicine residents at the University of Virginia. This two-year curriculum teaches the critical concepts and skills of patient safety and QI: systems thinking and human factors analysis, root cause analysis (RCA), and process mapping. Residents apply these skills in a series of QI and patient safety projects. The constructivist educational model creates a learning environment that actively engages residents in improving the quality and safety of their medical practice.Between 2003 and 2005, 38 residents completed RCAs of adverse events. The RCAs identified causes and proposed useful interventions that have produced important care improvements. Qualitative analysis demonstrates that the curriculum shifted residents' thinking about patient safety to a systems-based approach. Residents completed 237 outcome assessments during three years. Results indicate that seminars met predefined learning objectives and were interactive and enjoyable. Residents strongly believe they gained important skills in all domains.The challenge to improve quality and safety in health care requires physicians to learn new knowledge and skills. Graduate medical education can equip new physicians with the skills necessary to lead the movement to safer and better quality of care for all patients.This article is part of a theme issue of Academic Medicine on the Title VII health professions training programs.

Faculty development for the 21st century: lessons from the Society of General Internal Medicine-Hartford Collaborative Centers for the Care of Older Adults.

In this review of a recent set of faculty development initiatives to promote geriatrics teaching by general internists, nontraditional strategies to promote sustained change were identified, included enrolling a limited number of "star" faculty, creating ongoing working relationships between faculty, and developing projects for clinical or education program improvement. External funding, although limited, garnered administration support and was associated with changes in individual career trajectories. Activities to enfranchise top leadership were felt essential to sustain change. Traditional faculty development programs for clinician educators are periodic, seminar-based interventions to enhance teaching and clinical skills. In 2003/04 the Collaborative Centers for Research and Education in the Care of Older Adults were funded by the John A. Hartford Foundation and administered by the Society of General Internal Medicine. Ten academic medical centers received individual grants of $91,000, with required cost sharing, to develop collaborations between general internists and geriatricians to create sustained change in geriatrics clinical teaching and learning. Through written and structured telephone surveys, activities designed to foster sustainability at funded sites were identified, and the activities and perceived effects of funding at the 10 funded sites were compared with those of the 11 highest-ranking unfunded sites. The experience of the Collaborative Centers supports the conclusion that modest, targeted funding can provide the credibility and legitimacy crucial for clinician educators to allocate time and energy in new directions. Key success factors likely include high intensity and duration, integration into career trajectories, integration into clinical programs, and activities to enfranchise institutional leadership.