Crisis Standards of Care Guidelines for the COVID-19 Pandemic: Fresno Resource Allocation Guide (FRAG).

The coronavirus disease 2019 (COVID-19) pandemic has forced healthcare providers and policymakers to look candidly at the possibility that critical care resources, such as ventilators, medical staff, extracorporeal membrane oxygenation (ECMO), bilevel positive airway pressure (BiPAP) machines, and high-flow oxygen, may become scarce or depleted if the virus continues to move throughout the United States unabated. With hospitalizations and ICU occupancy rates rapidly increasing all over the US, we must face the uncomfortable truth that a triage system, much like on the battlefields of war, will need to be implemented. Ethical concerns abound, but the process for addressing limited resources must continue to be explored. Multiple frameworks have previously been developed to address the use of limited medical resources during catastrophic public health emergencies. Many crisis care guidelines and protocols address the maximizing of surge capabilities and allocation of resource use (specifically, ventilators). While overwhelming scenarios unfolded in Europe and then on the East Coast of the United States in March of 2020, our hospital system in central California was obligated to consider previously unimaginable scenarios. In an effort to pro-actively address these, an expert group, consisting of intensivists (adult and pediatric), trauma surgery, palliative care, and ethicists was organized to develop guidelines for resource allocation to be utilized for our medical system in the event of a public health emergency. As part of this process, existing guidelines and consensus documents were reviewed. A novel system for ventilator allocation was developed, termed the Fresno Resource Allocation Guide (FRAG). As the pandemic continued to surge into 2021, we began to look at other resources, such as oxygen delivery systems other than ventilators, as well as healthcare team members. This resource allocation guide takes into account a depletion in critical care supplies for adults and children. It employs ethical principles and evidence-based tools for critical care.

Incorporating Quality Assurance in Pharmaceutical Compounding-related Courses in the PharmD Curricula.

The art and the skill set of compounding fulfill the important need of tailor-made pharmaceuticals for use by both institutions and individual  patients. Over the last 20 years, there have been more than 200 adverse events involving compounded products; infections, poisonings, contaminations, and dosing inaccuracies have been problematic. The probability of a correlation between the lack of institutional training and number of serious events could be significant. This survey was an endeavor at fundamental cause analysis and proactive management in relation to the PharmD Curricula as a means of error prevention. A questionnaire was sent to the pharmacy school faculty (department chairs, dean/assistant deans, and pharmaceutical science faculty) across the country. The survey responses were received from 78 participants. The questionnaire evaluated the respondent's overall knowledge and approach toward the subject in their curriculum. The survey results show 38.9% faculty agree that their college's curricula lacks sufficient training in microbiological testing, and 16.7% faculty agree their college does not provide sufficient training in nonsterile and sterile compounding (as per United States Pharmacopeia Chapters <795> and <797>). A majority of faculty agree on the implementation of quality assurance in compounding courses (as per United States Pharmacopeia Chapter  <1163>) as either an elective (62.5%) or mandatory class (43.3%), and most of the participants (85.1%) think there is a need to teach quality assurance as continuing education to practicing pharmacists. The survey data suggest a general desire for enhancement of compounding course curriculum, which could reduce the number of adverse events related to compounding. The data also suggests a necessity for the implementation of continuing education programs for practicing pharmacists and academic faculty across the country.

Comprehensive Quality Assessment in Clinical Ethics.

Scholars and professional organizations in bioethics describe various approaches to "quality assessment" in clinical ethics. Although much of this work represents significant contributions to the literature, it is not clear that there is a robust and shared understanding of what constitutes "quality" in clinical ethics, what activities should be measured when tracking clinical ethics work, and what metrics should be used when measuring those activities. Further, even the most robust quality assessment efforts to date are idiosyncratic, in that they represent evaluation of single activities or domains of clinical ethics activities, or a range of activities at a single hospital or healthcare system. Countering this trend, iin this article we propose a framework for moving beyond our current ways of understanding clinical ethics quality, toward comprehensive quality assessment. We first describe a way to conceptualize quality assessment as a process of measuring disparate, isolated work activities; then, we describe quality assessment in terms of tracking interconnected work activities holistically, across different levels of assessment. We conclude by inviting future efforts in quality improvement to adopt a comprehensive approach to quality assessment into their improvement practices, and offer recommendations for how the field might move in this direction.

Efficacy and safety results from a phase 1b/2, multicenter, open-label study of oprozomib and dexamethasone in patients with relapsed and/or refractory multiple myeloma.

Oprozomib is an oral proteasome inhibitor with activity in multiple myeloma (MM). Our phase 1b/2 study examined the safety and efficacy of oprozomib with dexamethasone in patients with relapsed and refractory MM. Oprozomib was administered with a 5/14 or 2/7 schedule with dexamethasone. Phase 1b primary objectives were to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of oprozomib; phase 2 primary objectives were to determine overall response rate (ORR) and safety/tolerability of the RP2D. Between July 2, 2013, and August 29, 2016, data were available on 65 enrolled patients (5/14 schedule, n = 19; 2/7 schedule, n = 46). In phase 1b, MTD was 180 mg (5/14 schedule) and not reached (2/7 schedule); RP2D was 300 mg (2/7 schedule). In phases 1b and 2, ORR across dosing cohorts (210-330 mg) for the 2/7 schedule was 58.7% overall and 46.4% for bortezomib-refractory patients (n = 28). All patients reported ≥1 treatment-emergent adverse event (AE); the most common AEs were gastrointestinal. Grade ≥3 AEs occurred in 78.9% and 82.6% of patients on the 5/14 and 2/7 schedules, respectively. The oprozomib and dexamethasone combination has encouraging activity and could be an important MM therapy if gastrointestinal tolerability is improved.

Accuracy of visual prediction of pathology of colorectal polyps: how accurate are we?

BACKGROUND: Small and diminutive polyps seen at colonoscopy could be left unresected because of a balance of risks between perceived low malignant potential and complications of removing the polyp. This relies on a high accuracy in prediction of the pathology of the polyp. This study was undertaken to determine if experienced endoscopists could determine the histological types of polyps found at colonoscopy. METHODS: We performed a prospective study at Christchurch Hospital from December 2010 to December 2012. Gastroenterologists and surgeons were asked to fill out a questionnaire at time of colonic polypectomy, predicting pathology of polyp excised. Data were collected on indication for colonoscopy, location, size of polyp and use of narrow band imaging. Predictive accuracy was then calculated. RESULTS: A total of 527 polyps were excised from 258 patients. Ninety-one per cent were less than 1 cm. Predictive accuracy of hyperplastic polyps was 47%. Of the 53% wrong predictions, 82% were adenomas. Predictive accuracy of adenoma was 42%, with 66% of incorrect predictions being hyperplastic polyps. Accuracy was lowest in the right colon, with only 25% of predicted hyperplastic polyps actually being hyperplastic. A patient's age, sex, polyp size and site did not affect prediction accuracy. Overall accuracy of visual prediction of pathology of all colorectal polyps was 45%. Narrow band imaging was used too infrequently to determine how useful it was. CONCLUSION: Pathology of colorectal polyps cannot be accurately predicted visually alone. All polyps visualized at colonoscopy should be excised for ex vivo histology, regardless of size, location or predicted pathology.

Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer.

PURPOSE: XL184 (cabozantinib) is a potent inhibitor of MET, vascular endothelial growth factor receptor 2 (VEGFR2), and RET, with robust antiangiogenic, antitumor, and anti-invasive effects in preclinical models. Early observations of clinical benefit in a phase I study of cabozantinib, which included patients with medullary thyroid cancer (MTC), led to expansion of an MTC-enriched cohort, which is the focus of this article. PATIENTS AND METHODS: A phase I dose-escalation study of oral cabozantinib was conducted in patients with advanced solid tumors. Primary end points included evaluation of safety, pharmacokinetics, and maximum-tolerated dose (MTD) determination. Additional end points included RECIST (Response Evaluation Criteria in Solid Tumors) response, pharmacodynamics, RET mutational status, and biomarker analyses. RESULTS: Eighty-five patients were enrolled, including 37 with MTC. The MTD was 175 mg daily. Dose-limiting toxicities were grade 3 palmar plantar erythrodysesthesia (PPE), mucositis, and AST, ALT, and lipase elevations and grade 2 mucositis that resulted in dose interruption and reduction. Ten (29%) of 35 patients with MTC with measurable disease had a confirmed partial response. Overall, 18 patients experienced tumor shrinkage of 30% or more, including 17 (49%) of 35 patients with MTC with measurable disease. Additionally, 15 (41%) of 37 patients with MTC had stable disease (SD) for at least 6 months, resulting in SD for 6 months or longer or confirmed partial response in 68% of patients with MTC. CONCLUSION: Cabozantinib has an acceptable safety profile and is active in MTC. Cabozantinib may provide clinical benefit by simultaneously targeting multiple pathways of importance in MTC, including MET, VEGFR2, and RET. A global phase III pivotal study in MTC is ongoing (ClinicalTrials.gov number NCT00215605).

Platelet-leucocyte aggregates form in the mesenteric vasculature in patients with ulcerative colitis.

BACKGROUND AND AIMS: Inflammation and thrombosis are closely related processes, which may play a role in the pathogenesis, as well as complications, of inflammatory bowel disease (IBD). Platelet activation and platelet-leucocyte aggregation are increased and platelet aggregation is known to occur in the mesenteric vasculature in IBD. The aims of this study were to test the hypotheses that platelet-leucocyte aggregation, platelet activation and neutrophil activation occur in the mesenteric vessels of patients with ulcerative colitis (UC). PATIENTS AND METHODS: Platelet-leucocyte aggregates (PLAs), platelet activation (P-selectin expression) and neutrophil activation (L-selectin expression, which decreases on neutrophil activation) were assessed flow cytometrically in mesenteric arterial, and venous blood sampled in eight patients with UC and eight controls with colonic carcinoma undergoing intestinal resections. RESULTS: In the patients with UC, the number of PLAs in the mesenteric vein exceeded that in the artery, the median rise being 38% (P=0.02). In UC, arterial PLA numbers were 0.17 (0.02-0.32) (median, range) x 10(9)/l versus venous 0.26 (0.09-1.6) x 10(9)/l (P=0.02). The median percentage increase was 45%. Mesenteric PLA formation did not occur in patients with colonic carcinoma [arterial 0.06 (0.03-0.49) x 10(9)/l vs. venous 0.05 (0.02-0.35) x 10(9)/l; P=0.55]. The median percentage change was +45% for UC patients and -5% for controls. No arteriovenous gradient was observed in P-selectin expression, but L-selectin expression (arbitrary units), increased in the mesenteric vasculature of the UC patients [arterial 839 (503-995), venous 879 (477-1035); P=0.03] and fell in those with colonic carcinoma [arterial 900 (660-959), venous 850 (546-957); P=0.04]. The median percentage change was +4% for UC and -7% for controls. CONCLUSION: The finding of increased numbers of PLAs in the venous mesenteric circulation supports the hypothesis that activated vascular endothelium stimulates PLA formation in UC.

Stents or open operation for palliation of colorectal cancer: a retrospective, cohort study of perioperative outcome and long-term survival.

PURPOSE: Expandable, metallic stents provide a new modality of palliation for patients with noncurable metastatic colorectal adenocarcinoma. This study was designed to compare the use of expandable metallic stents as a palliative measure to traditional open surgical management, with particular reference to length of stay, and survival. METHODS: Patients admitted between 1997 and 2002 with left-sided (splenic flexure and distal), colorectal adenocarcinoma and nonresectable metastatic disease (Stage 4) were treated with expandable metal stents or open surgery (resection, bypass, or stoma). The group of patients having stents inserted were compared with regard to perioperative outcome and survival to those having open surgical procedures. RESULTS: Twenty-two of 25 patients had colonic stents successfully inserted and 19 patients underwent open surgery. The two groups were comparable: stent: median age, 66 (range, 37-88) years; 13 males; and open operation: median age, 68 (range, 51-85) years; 12 males. The tumors were primary in 22 stents procedures and 18 open operations. The site of obstruction was: splenic flexure, 2 stent vs. 0 open operation; descending colon, 2 stent vs. 2 open operation; sigmoid colon, 12 stent vs. 6 open operation; rectum, 9 stent vs. 11 open operation. The American Society of Anesthesiologists (ASA) class was: ASA 1, 0 stent vs. 0 open operation; ASA 2, 6 stent vs. 9 open operation; ASA 3, 15 stent vs. 7 open operation; ASA 4, 4 stent vs. 3 open operation. The open operations were laparotomy only (n = 2), bypass (n = 1), stoma (n = 7), resection with anastomosis (n = 4), resection without anastomosis (n = 5). The complications after open operation were urinary (n = 2), stroke (n = 1), cardiac (n = 2), respiratory (n = 2), deep vein thrombosis (n = 1), anastomotic leak (n = 1). There were no stent-related complications. The mean length of stay was significantly shorter in the stent group (4 vs. 10.4 days; P < 0.0001). There was no difference in survival between the two groups (median survival: stent group, 7.5 months; open operation, 3.9 months; log-rank P value = 0.2156). CONCLUSIONS: Patients treated with stents are discharged earlier than after open surgery. Stents do not affect survival. Expandable metal stents provide an acceptable alternative and may be better than traditional open surgical techniques.

Abdominoperineal resection or low Hartmann's procedure.

AIM: To compare patients having low Hartmann's resection (LHP) with abdominoperineal resection (APR) by investigating postoperative complications. METHODS: Retrospective comparative analysis of preoperative state and postoperative course for patients having surgery from 1 January 1997 to 1 July 2001, by the surgeons of the Colorectal Unit, Christchurch Hospital, Christchurch, New Zealand. RESULTS: Over a 54-month period 65 patients underwent either LHP or APR (29 LHP, 36 APR). The median age/sex (male:female) of patients for LHP was 76 years (51-90 years) (14:15), for APR 72 years (31-93 years) (19:17). The indication for surgery was predominantly cancer (LHP 89.6%, APR 94.4%). There was a high rate of preoperative comorbidities: LHP 75.9% (cardiac 62.1%, pulmonary 17.2%), APR 75% (cardiac 50%, pulmonary 15.9%). Preoperative chemoradiation was used in 10.3% of patients having LHP and 30.6% with APR. There was no difference in postoperative non-septic complications. There was a significant difference in the types of septic complications (P = 0.018), with a higher rate of pelvic abscesses after LHP (5). Perineal wound infection occurred in five patients having APR (14.3%). The median time to heal a perineal wound was 1 month (0.5-7 months). The median length of stay was 13 days for LHP (5-33 days) and 11 days for APR (6-19 days) (P = 0.0266). CONCLUSION: This non-randomized, retrospective, cohort study shows a surprisingly high rate of pelvic abscesses after LHP compared with APR. Perineal wound healing was a problem after APR, but less of a management problem than the septic complications after LHP. Both LHP and APR might be associated with significant morbidity. A high pelvic abscess rate following LHP is associated with a high likelihood of further surgical intervention and a prolonged length of stay.

Parastomal hernia following minimally invasive stoma formation.

BACKGROUND: Minimally invasive intestinal stoma formation using a laparoscopic approach or through a trephine, is widely described in published literature. The incidence of parastomal hernia (PH) following a stoma formed without formal laparotomy is not well reported. The present review aims to assess the current data available on minimally invasive stoma formation, with particular reference to the incidence of PH. METHODS: A literature search using the Pubmed Medline database was performed, locating English language articles on minimally invasive stoma formation from 1970 to 2002. The manuscripts were searched manually for further references. RESULTS: The number of published studies describing laparoscopic stoma formation is small (263 stomas) and the follow-up studied were short (none longer than 1 year). The incidence of PH was 0-6.7%. The incidence following a trephine stoma was 6.7-12%, and the number of patients was small (118) and the follow up short (up to 12 months). CONCLUSIONS: The incidence of PH following minimally invasive stoma formation using a trephine or a laparoscopic technique remains unclear. Studies published to date are generally small and the follow up is short. A prospective randomized trial comparing minimally invasive stoma formation with stoma formation with laparotomy, is required.