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Living donor liver transplantation (LDLT) emerged in the 1980s as a viable alternative to scarce cadaveric organs for pediatric patients. However, pediatric waitlist mortality remains high. Long-term outcomes of living and deceased donor liver transplantation (DDLT) are inconsistently described in the literature. Our aim was to systematically review the safety and efficacy of LDLT after 1 year of transplantation among pediatric patients with all causes of liver failure. We searched the MEDLINE, Medline-in-Process, MEDLINE Epub Ahead of Print, Embase + Embase Classic (OvidSP), and Cochrane (Wiley) from February 1, 1947 to February 26, 2020, without language restrictions. The primary outcomes were patient and graft survival beyond 1 year following transplantation. A meta-analysis of unadjusted and adjusted odds and hazard ratios was performed using a random-effects model. A total of 24 studies with 3677 patients who underwent LDLT and 9098 patients who underwent DDLT were included for analysis. In patients with chronic or combined chronic liver failure and acute liver failure (ALF), 1-year (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.53-0.88), 3-year (OR, 0.73; 95% CI, 0.61-0.89), 5-year (OR, 0.71; 95% CI, 0.57-0.89), and 10-year (OR, 0.42; 95% CI, 0.18-1.00) patient and 1-year (OR, 0.50; 95% CI, 0.35-0.70), 3-year (OR, 0.55; 95% CI, 0.37-0.83), 5-year (OR, 0.5; 95% CI, 0.32-0.76), and 10-year (OR, 0.26; 95% CI, 0.14-0.49) graft survival were consistently better in LDLT recipients compared with those in DDLT recipients. In patients with ALF, no difference was seen between the 2 groups except for 5-year patient survival (OR, 0.60; 95% CI, 0.38-0.95), which favored LDLT. Sensitivity analysis by era showed improved survival in the most recent cohort of patients, consistent with the well-described learning curve for the LDLT technique. LDLT provides superior patient and graft survival outcomes relative to DDLT in pediatric patients with chronic liver failure and ALF. More resources may be needed to develop infrastructures and health care systems to support living liver donation.

Background This study aims to: 1) Determine the prevalence of preoperative anemia in arthroplasty; 2) Assess whether preoperative anemia is associated with inferior outcomes; and 3) Ascertain whether optimization in a dedicated blood management program (BMP) is associated with improved outcomes. Methods All primary arthroplasties performed at an academic, tertiary-care, arthroplasty center between 2012 and 2017 were reviewed. Hemoglobin level obtained in the preoperative assessment clinic was recorded. Patients with anemia were then considered for further review in BMP. Outcomes included improvement in hemoglobin level post-BMP; length of stay; perioperative transfusion; 90-day readmission, complication, and reoperation rates. The effect of preoperative anemia and the effect of treatment at the BMP on outcomes were evaluated through multivariable regression analysis controlling for relevant covariates. Results 17% of patients (932/5384) were found to have anemia; 115/357 patients who attended the BMP were no longer anemic. Thus, at time of operation, 15% of patients (817/5384) had anemia. Anemic patients were 4.09 times more likely (95% CI: 2.64-6.35) to require a transfusion; 1.42 times more likely (95% CI: 0.99-2.03) to sustain complications and had 19% longer (95% CI: 13%-26%) length of stay. Those who attended the BMP were less likely to receive a transfusion (OR = 0.32, 95% CI: 0.16-0.66), suffer from postoperative complications (OR = 0.30, 95% CI: 0.14-0.63), or require readmission compared with anemic patients not seen in the BMP (OR = 0.25, 95% CI: 0.09-0.71). Conclusions The prevalence of anemia in this arthroplasty cohort was 15%. Preoperative, timely, optimization of anemia should be strongly considered as it is likely to reduce “anemia-associated burden” after arthroplasty.

BACKGROUND We aim to describe the occurrence of red blood cell transfusion and associated predictive factors and outcomes among patients referred for palliative care. STUDY DESIGN AND METHODS This retrospective cohort study used linked health administrative data of adults referred for palliative care at an academic hospital from 2014 to 2018. Multivariable regression models were employed to evaluate patient characteristics associated with transfusion and the relationship between transfusion status and location of death. Survival analyses were performed using log-rank tests and Cox proportional hazards modeling. RESULTS Of 6980 evaluated patients, 885 (12.7%) were transfused following palliative care consultation. Covariate factors associated with transfusion included younger age, higher performance status, lower baseline hemoglobin, and a diagnosis of hematologic malignancy (OR = 2.97, 95% CI 2.20-4.01) or solid organ tumor (OR = 1.37, 95% CI 1.10-1.71) vs. noncancer diagnosis. Median survival from palliative care consultation was 19 (IQR 5-75) days; 83 (32-305) days in those transfused and 15 (4-57) days in the nontransfused group (p

Purpose There has been an alarming increase in colorectal cancer (CRC) incidence among young adults aged Methods A population-based case–control study was conducted in Ontario, Canada during 2018–2019. EO-CRC cases aged 20–49 years (n = 175) were identified from the Ontario Cancer Registry; sex- and age group-matched controls (n = 253) were recruited through random digit dialing. Data on potential a priori risk factors were collected using a web-based self-reported questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression. Results Family history of CRC in a first- or second-degree relative (OR 2.37; 95% CI 1.47–3.84), longer sedentary time (≥ 10 vs. Conclusion Modifiable factors, particularly sedentary behavior and unhealthy diet including sugary drink consumption, may be associated with EO-CRC risk. Our findings, if replicated, may help inform prevention strategies targeted at younger persons.

Objective The objective of this work was to carry out a meta-analysis of RCTs comparing intraoperative RBC transfusion strategies to determine their impact on postoperative morbidity, mortality, and blood product use. Summary of background data RBC transfusions are common in surgery and associated with widespread variability despite adjustment for casemix. Evidence-based recommendations guiding RBC transfusion in the operative setting are limited. Methods The search strategy was adapted from a previous Cochrane Review. Electronic databases were searched from January 2016 to February 2021. Included studies from the previous Cochrane Review were considered for eligibility from before 2016. RCTs comparing intraoperative transfusion strategies were considered for inclusion. Co-primary outcomes were 30-day mortality and morbidity. Secondary outcomes included intraoperative and perioperative RBC transfusion. Meta-analysis was carried out using random-effects models. Results Fourteen trials (8641 patients) were included. One cardiac surgery trial accounted for 56% of patients. There was no difference in 30-day mortality [relative risk (RR) 0.96, 95% confidence interval (CI) 0.71-1.29] and pooled postoperative morbidity among the studied outcomes when comparing restrictive and liberal protocols. Two trials reported worse composite outcomes with restrictive triggers. Intraoperative (RR 0.53, 95% CI 0.43-0.64) and perioperative (RR 0.70, 95% CI 0.62-0.79) blood transfusions were significantly lower in the restrictive group compared to the liberal group. Conclusions Intraoperative restrictive transfusion strategies decreased perioperative transfusions without added postoperative morbidity and mortality in 12/14 trials. Two trials reported worse outcomes. Given trial design and generalizability limitations, uncertainty remains regarding the safety of broad application of restrictive transfusion triggers in the operating room. Trials specifically designed to address intraoperative transfusions are urgently needed.

Background and study aims We aimed to estimate the rate of hospital admissions for perforation and for post-polypectomy bleeding, after outpatient colonoscopy following a first positive fecal occult blood test screen through the population-based ColonCancerCheck program in Ontario, Canada. Patients and methods We identified all individuals aged 50 to 74 years with a first positive CCC gFOBT screening result from 2008 to 2017 who underwent outpatient colonoscopy ≤ 6 months later and who did not receive a diagnosis of CRC ≤ 24 months later. We identified inpatient hospital admissions for colonic perforation ≤ 7 days after and for post-polypectomy bleeding ≤ 14 days following colonoscopy. Results Among 121,626 individuals who underwent colonoscopy, the rate of perforation was 0.6 per 1000 from 2008 to 2012 and 0.4 per 1000 from 2013 to 2017. The rate was elevated among those aged 70 to 74 years; those with comorbidities; when colonoscopy was performed by endoscopists other than gastroenterologists or endoscopists with low prior year volume; and when polypectomy was performed during colonoscopy. The rate of bleeding was 4.3 per 1000 and was elevated among those aged 70 to 74 years, those with comorbidity, and with complex polypectomy. Both outcomes were more common among those aged 70 to 74 years, those with a 5-year cumulative Charlson score ≥ 1, those with prior hospitalization for ischemic heart disease, and those with endoscopists whose prior year colonoscopy volume was in the three lower quartiles. Conclusions Colonic perforation and post-polypectomy bleeding, among participants of population-based colorectal screening programs who test positive in the absence of colorectal cancer, are infrequent but serious complications, which increase with participant age and comorbidity, and with endoscopist characteristics.

Background The impact of post-transplant red blood cell transfusion (RBCT) and their potential immunomodulatory effects on kidney transplant recipients are unclear. We examined the risks for adverse graft outcomes associated with post-kidney transplant RBCT. Methods We conducted a retrospective cohort study of all adult kidney transplant recipients at The Ottawa Hospital from 2002 to 2018. The exposure of interest was receipt of a RBCT after transplant categorized as 1, 2, 3-5 and >5 RBC. Outcomes of interest were rejection and death-censored graft loss (DCGL). Cox proportional hazards models were used to calculate hazard ratios (HR) with RBCT as a time-varying, cumulative exposure. Results Among 1,258 kidney transplant recipients, 468 (37.2%) received 2,373 a total of RBCT, 197 (15.7%) had rejection and 114 (9.1%) DCGL. For the receipt of 1, 2, 3-5 and >5 RBCT, compared to individuals never transfused, the adjusted HRs (95% CI) for rejection were 2.47 (1.62 to 3.77), 1.27 (0.77 to 2.11), 1.74 (1.00 to 3.05) and 2.23 (1.13 to 4.40) respectively; DCGL 2.32 (1.02 to 5.27), 3.03 (1.62 to 5.64), 7.50 (4.19 to 13.43) and 14.63 (8.32 to 25.72) respectively. Considering a time lag for a RBCT to be considered an exposure prior to an outcome to limit reverse causation, RBCT was not associated with rejection; the HRs for DCGL attenuated but remained similar. RBCT was also associated with a negative control outcome, demonstrating possible unmeasured confounding. Conclusion RBCT after kidney transplant is not associated with rejection, but may carry an increased risk for DCGL.

Background The cost-effectiveness of colorectal screening has been modeled; however, the cost of health care following the diagnosis of colorectal cancer has not been described stratified by history of colorectal evaluative procedures. Methods We identified persons with first diagnosis of colorectal cancer between 2015 and 2017 from the Ontario Cancer Registry, and categorized them by history of colorectal evaluative procedures during Period 1 (the 10 years before the 6-month prediagnostic interval) with or without procedures during Period 2 (the 6 month prediagnostic interval), versus only during Period 2, versus none. We extracted overall health care cost 1 year following diagnosis from population-wide administrative databases. Results Among cases diagnosed at 52 to 74 years, overall health care cost among those with no colorectal evaluative procedures on or before the date of diagnosis is $71,039.65 (SD $51,825.18), compared to $48,406.15 (SD $38,843.64) among those who received colorectal evaluative procedures during Period 1, with or without procedures during Period 2. Among the population aged 20 to 74 years at diagnosis, cases with ≥1 screening colonoscopies for hereditary CRC syndrome, the mean overall initial cost was between $32,300.32 (SD) and $33,084.67 (SD $39,905.77), and those with ≥1 screening colonoscopies because of a first-degree relative with CRC, was between $36,344.71 (SD $35,539.85) and $45,456.41 (SD $49,818.59). Conclusions Overall health care cost is lower among cases who received colorectal evaluative procedures during Period 1, with or without procedures during Period 2, and among those with screening colonoscopy for hereditary CRC syndromes or affected first-degree relatives.

Background & Aims: Routine screening for colorectal cancer typically is recommended until age 74 years. Although it has been proposed that a screening stop age could be determined based on sex and comorbidity, less is known about the impact of screening history. We investigated the effects of screening history on the selection of an optimal age to stop screening. Methods: We used the Microsimulation Screening Analysis–Colon model to estimate the harms and benefits of screening with biennial fecal immunochemical tests by sex, comorbidity status, and screening history. The optimal screening stop age was determined based on the incremental number needed for 1 additional life-year per 1000 screened individuals compared with the threshold provided by stopping screening at 76 years in the average-health population with a perfect screening history (attended all required screening, diagnostic, and follow-up tests) to biennial fecal immunochemical testing from age 50 years. Results: For persons age 76 years, 157 women and 108 men with a perfect screening history would need to be screened to gain 1 life-year per 1000 screened individuals. Previously unscreened women with no comorbid conditions and no history of screening could undergo an initial screening through 90 years, whereas unscreened men could undergo initial screening through 88 years, before this balance is reached. As screening adherence improved or as comorbidities increased, the optimal age to stop screening decreased to a point that, regardless of sex, individuals with severe comorbidities and a perfect screening history should stop screening at age 66 years or younger. Conclusions: Based on the harm–benefit balance, the optimal stop age for colorectal cancer screening ranges from 66 years for unhealthy individuals with a perfect screening history to 90 years for healthy individuals without prior screening. These findings can be used to assist patients and clinicians in making decisions about screening participation.

Importance The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive.Objective To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19.Design, Setting, and Participants The ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021.Interventions The immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916).Main Outcomes and Measures The primary ordinal end point was organ support–free days (days alive and free of intensive care unit–based organ support) up to day 21 (range, −1 to 21 days; patients who died were assigned –1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support–free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support–free days; cardiovascular support–free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events.Results Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support–free days was 0 (IQR, –1 to 16) in the convalescent plasma group and 3 (IQR, –1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (OR Conclusions and Relevance Among critically ill adults with confirmed COVID-19, treatment with 2 units of high-titer, ABO-compatible convalescent plasma had a low likelihood of providing improvement in the number of organ support–free days.Trial Registration ClinicalTrials.gov Identifier: NCT02735707

Tranexamic acid (TXA) reduces red blood cell transfusion in various orthopedic surgeries, yet the degree of practice variation in its use among anesthesiologists and surgeons has not been described. To target future knowledge transfer and implementation strategies, and to better understand determinants of variability in prophylactic TXA use, our primary objective was to evaluate the influence of surgical team members on the variability of prophylactic TXA administration. This was a retrospective cohort study of all adult patients undergoing primary total hip arthroplasty (THA), hip fracture surgery, and spine fusion ± vertebrectomy at two Canadian hospitals between January 2014 and December 2016. We used Canadian Classification of Health Interventions procedure codes within the Discharge Abstract Database which we linked to the Ottawa Data Warehouse. We described the percentage of patients that received TXA by individual surgery, the specifics of TXA dosing, and estimated the effect of anesthesiologists and surgeons on prophylactic TXA using multivariable mixed-effects logistic regression analyses. In the 3,900 patients studied, TXA was most commonly used in primary THA (85%; n = 1,344/1,582), with lower use in hip fracture (23%; n = 342/1,506) and spine fusion surgery (23%; n = 186/812). The median [interquartile range] total TXA dose was 1,000 [1,000–1,000] mg, given as a bolus in 92% of cases. Anesthesiologists and surgeons added significant variability to the odds of receiving TXA in hip fracture surgery and spine fusion, but not primary THA. Most of the variability in TXA use was attributed to patient and other factors. We confirmed the routine use of TXA in primary THA, while observing lower utilization with more variability in hip fracture and spine fusion surgery. Further study is warranted to understand variations in use and the barriers to TXA implementation in a broader population of orthopedic surgical patients at high risk for transfusion.

Perioperative bleeding is a major indication for red blood cell (RBC) transfusion, yet transfusion data in many major noncardiac surgeries are lacking and do not reflect recent blood conservation efforts. We aim to describe transfusion practices in noncardiac surgeries at high risk for RBC transfusion. We completed a retrospective cohort study to evaluate adult patients undergoing major noncardiac surgery at 5 Canadian hospitals between January 2014 and December 2016. We used Canadian Classification of Health Interventions procedure codes within the Discharge Abstract Database, which we linked to transfusion and laboratory databases. We studied all patients undergoing a major noncardiac surgery at ≥5% risk of perioperative RBC transfusion. For each surgery, we characterized the percentage of patients exposed to an RBC transfusion, the mean/median number of RBC units transfused, and platelet and plasma exposure. We identified 85 noncardiac surgeries with an RBC transfusion rate ≥5%, representing 25,607 patient admissions. The baseline RBC transfusion rate was 16%, ranging from 5% to 49% among individual surgeries. Of those transfused, the median (Q1, Q3) number of RBCs transfused was 2 U (1, 3 U); 39% received 1 U RBC, 36% received 2 U RBC, and 8% were transfused ≥5 U RBC. Platelet and plasma transfusions were overall low. In the era of blood conservation, we described transfusion practices in major noncardiac surgeries at high risk for RBC transfusion, which has implications for patient consent, preoperative surgical planning, and blood bank inventory management.

Peak demand analysis is common in industries such as the energy sector, but can also be applied to the field of transfusion to characterize the nature and timing of peak days in hospital blood utilization. This information can be used to forecast future peak days or to inform hospital emergency preparedness plans. The aims of this study are to characterize peak days in red blood cell (RBC) utilization over the past 10 years at our hospital, and to compare RBC peaks with peaks in platelet, plasma, and cryoprecipitate utilization. This was a retrospective cohort study of RBC, platelet, plasma, and cryoprecipitate transfusions in the inpatient and emergency department setting between May 2009 and April 2019 at a large academic hospital, containing regional trauma and cardiovascular surgery centers. For each blood product, a peak in utilization was defined as a day with a ≥50% increase in the number of units transfused compared to the previous 90-day average. Descriptive and inferential analyses were performed to characterize peak days. There were on average 20,501 RBCs transfused per year and 56 RBCs transfused per day over the 10-year period. A total of 134 peaks in RBC utilization occurred over the study period, with an average of 14 peaks per year. RBC peak days required on average 69% more RBC units compared to nonpeak days (P.0001). 77% of RBC peaks were caused either solely or in part by surgical bleeding, 34% were caused entirely or in part by trauma, and other causes were infrequent. RBC peaks occurred most often on Fridays and least often on weekends (P.0001). While there were 134 RBC peaks over the study period, there was a larger number of platelet (n = 292), plasma (n = 467), and cryoprecipitate peaks (n = 579). RBC peak days often coincided with plasma peak days, but less frequently with platelet and cryoprecipitate peaks. More studies are needed to determine whether analysis of peak usage will be of value to hospital blood banks for emergency planning and blood inventory management.

Background and aims Colonoscopy following positive fecal occult blood screening may detect non-malignant polyps deemed to require major large bowel resection. We aimed to estimate the major inpatient morbidity and mortality associated with major resection of non-malignant polyps detected at colonoscopy following positive guaiac fecal occult blood screening in Ontario's population-based colorectal screening program. Methods We identified those without a diagnosis of colorectal cancer in the Ontario Cancer Registry ≤24 months following the date of colonoscopy prompted by positive fecal occult blood screening between 2008 and 2017, who underwent a major large bowel resection ≤24 months after the colonoscopy, with a diagnosis code for non-malignant polyp, in the absence of a code for any other large bowel diagnosis. We extracted records of major inpatient complications and readmissions ≤30 days following resection. We computed mortality within 90 days following resection. Results For those undergoing colonoscopy ≤6 months following positive guaiac fecal occult blood screening, 420/127,872 (0.03%) underwent major large bowel resection for a non-malignant polyp. In 50/420 (11.9%), the resection included one or more rectosigmoid or rectal polyps, with or without a colonic polyp. There were one or more major inpatient complications or readmissions within 30 days in 117/420 (27.9%). Death occurred within 90 days in 6/420 (1.4%). Conclusions Serious inpatient complications and readmissions following major large bowel resection for non-malignant colorectal polyps are common, but mortality ≤90 days following resection is low. These outcomes should be considered as unintended adverse consequences of population-based colorectal screening programs.

Background and aims In 2008, Ontario initiated a population-based colorectal screening program using guaiac fecal occult blood testing. This work was undertaken to fill a major gap in knowledge by estimating serious post-operative complications and mortality following major large bowel resection of colorectal cancer detected by a population-based screening program. Methods We identified persons with a first positive fecal occult blood result between 2008 and 2016, at the age of 50–74 years, who underwent a colonoscopy within 6 months, and proceeded to major large bowel resection for colon cancer within 6 months or rectosigmoid/rectal cancer within 12 months, and identified an unscreened cohort of resected cases diagnosed during the same years at the age of 50–74 years. We identified serious postoperative complications and readmissions ≤30 days following resection, and postoperative mortality ≤30 days, and between 31 and 90 days among the screen-detected and the unscreened cohorts. Results Serious post-operative complications or readmissions within 30 days were observed among 1476/4999 (29.5%) cases in the screen-detected cohort, and among 3060/8848 (34.6%) unscreened cases. Mortality within 30 days was 43/4999 (0.9%) among the screen-detected cohort, and 208/8848 (2.4%) among the unscreened cohort. Among 30 day survivors, mortality between 31 and 90 days was 28/4956 (0.6%) and 111/8640 (1.3%), respectively. Conclusion Serious post-operative complications, readmissions, and mortality may be more common following major large bowel resection for colorectal cancer between the ages of 50 and 74 among unscreened compared to screen-detected cases.

Background: Patients with immune thrombocytopenia are at risk of bleeding during surgery, and intravenous immunoglobulin is commonly used to increase the platelet count. We aimed to establish whether perioperative eltrombopag was non-inferior to intravenous immunoglobulin. Methods: We did a randomised, open-label trial in eight academic hospitals in Canada. Patients were aged at least 18 years, with primary or secondary immune thrombocytopenia and platelet counts less than 100 × 109 cells per L before major surgery or less than 50 × 109 cells per L before minor surgery. Previous intravenous immunoglobulin within 2 weeks or thrombopoietin receptor agonists within 4 weeks before randomisation were not permitted. Patients were randomly assigned to receive oral daily eltrombopag 50 mg from 21 days preoperatively to postoperative day 7 or intravenous immunoglobulin 1 g/kg or 2 g/kg 7 days before surgery. Eltrombopag dose adjustments were allowed weekly based on platelet counts. The randomisation sequence was generated by a computerised random number generator, concealed and stratified by centre and surgery type (major or minor). The central study statistician was masked to treatment allocation. The primary outcome was achievement of perioperative platelet count targets (90 × 109 cells per L before major surgery or 45 × 109 cells per L before minor surgery) without rescue treatment. We did intention-to-treat and per-protocol analyses using an absolute non-inferiority margin of –10%. This trial is registered with ClinicalTrials.gov, NCT01621204. Findings: Between June 5, 2013, and March 7, 2019, 92 patients with immune thrombocytopenia were screened, of whom 74 (80%) were randomly assigned: 38 to eltrombopag and 36 to intravenous immunoglobulin. Median follow-up was 50 days (IQR 49–55). By intention-to-treat analysis, perioperative platelet targets were achieved for 30 (79%) of 38 patients assigned to eltrombopag and 22 (61%) of 36 patients assigned to intravenous immunoglobulin (absolute risk difference 17·8%, one-sided lower limit of the 95% CI 0·4%; pnon-inferiority=0·005). In the per-protocol analysis, perioperative platelet targets were achieved for 29 (78%) of 37 patients in the eltrombopag group and 20 (63%) of 32 in the intravenous immunoglobulin group (absolute risk difference 15·9%, one-sided lower limit of the 95% CI –2·1%; pnon-inferiority=0·009). Two serious adverse events occurred in the eltrombopag group: one treatment-related pulmonary embolism and one vertigo. Five serious adverse events occurred in the intravenous immunoglobulin group (atrial fibrillation, pancreatitis, vulvar pain, chest tube malfunction and conversion to open splenectomy); all were related to complications of surgery. No treatment-related deaths occurred. Interpretation: Eltrombopag is an effective alternative to intravenous immunoglobulin for perioperative treatment of immune thrombocytopenia. However, treatment with eltrombopag might increase risk of thrombosis. The decision to choose one treatment over the other will depend on patient preference, resource limitations, cost, and individual risk profiles. Funding: GlaxoSmithKline and Novartis.

Background & Aims Physicians' own screening practices might affect screening in their patients. We conducted a population-based study to evaluate whether family physicians who underwent colorectal cancer testing were more likely to have patients who underwent colorectal cancer testing. Methods We collected demographic and health care information on residents of Ontario, Canada from administrative databases; the sample was restricted to individuals at average risk of colorectal cancer who were 52–74 years old as of April 21, 2016. We obtained a list of all registered physicians in the province; physicians (n = 11,434) were matched with nonphysicians (n = 45,736) on age, sex, and residential location. Uptake of colorectal tests was defined by a record of a fecal occult blood test in the past 2 years, flexible sigmoidoscopy in the past 5 years, or colonoscopy in the past 10 years. Patients were assigned to family physicians based on billing claim frequency, and then the association between colorectal testing in family physicians and their patients was examined using a modified Poisson regression model. Results Uptake of colorectal tests by physicians and nonphysicians (median age 60 years; 71% men) was 67.9% (95% confidence interval [CI], 67.0%–68.7%) and 66.6% (95% CI, 66.2%–67.1%), respectively. Physicians were less likely than nonphysicians to undergo fecal occult blood testing and were more likely to undergo colonoscopy; prevalence ratios were 0.44 (95% CI, 0.42–0.47) and 1.24 (95% CI, 1.22–1.26), respectively. Uptake of colorectal tests by family physicians was associated with greater uptake by their patients (adjusted prevalence ratio, 1.10; 95% CI, 1.08–1.12). Conclusions Approximately one-third of physicians and nonphysicians are overdue for colorectal cancer screening. Patients are more likely to be tested if their family physician has been tested. There is an opportunity for physicians to increase their participation in colorectal cancer screening, which could, in turn, motivate their patients to undergo screening.

It was highlighted that the original article [1] contained some mistakes in some of the authors’ affiliations. This Correction article shows the correct affiliations. The original article has been updated.

Tranexamic acid (TXA) reduces perioperative blood loss and transfusion requirement following cardiac surgery. Nevertheless, TXA remains underutilized because of concerns regarding development of adverse events. We conducted a systematic review to determine which patients are commonly excluded from TXA cardiac surgery clinical trials to determine if there are patient groups lacking safety data on TXA. The databases Medline, EMBASE, and the Cochrane Central Register of Controlled Trials were searched until September 2017. Eligible studies were randomized-controlled trials (RCTs) administering systemic TXA perioperatively to patients undergoing any cardiac surgery. Our primary outcome was the exclusion criteria for each RCT, and the secondary endpoint was TXA safety. A descriptive synthesis was performed to analyze the exclusion criteria. TXA safety was assessed with meta-analysis. Seventy eligible RCTs were included. The most common reasons for excluding patients from TXA cardiac surgery trials were major hepatic, renal, or cardiac comorbidities (76% of studies). Meta-analysis showed that TXA did not increase the risk of adverse events compared with placebo or no intervention (risk ratio, 0.97; 95% confidence interval, 0.88 to 1.07), including thrombosis and seizure. We found that systemic TXA is safe to use in cardiac surgery. Certain patient groups are frequently excluded from TXA cardiac surgery trials, and may consequently have limited efficacy and safety data on TXA. Further research in these patient groups may be needed; nevertheless, for many patient populations there are sufficient data to inform evidence-based guidelines for TXA use in cardiac surgery. PROSPERO (CRD42017060971); registered 4 April, 2017.

A 34-year-old woman presented to the emergency department with a 1-day history of heavy menstrual bleeding. She described needing to use thick pads or diapers that required changing hourly because of the heavy flow of blood. One month previously, she had had sudden onset pelvic pain resulting from

Background The BETTER (Building on Existing Tools to Improve Chronic Disease Prevention and Screening in Primary Care) intervention was designed to integrate the approach to chronic disease prevention and screening in primary care and demonstrated effective in a previous randomized trial. Methods We tested the effectiveness of the BETTER HEALTH intervention, a public health adaptation of BETTER, at improving participation in chronic disease prevention and screening actions for residents of low-income neighbourhoods in a cluster randomized trial, with ten low-income neighbourhoods in Durham Region Ontario randomized to immediate intervention vs. wait-list. The unit of analysis was the individual, and eligible participants were adults age 40–64 years residing in the neighbourhoods. Public health nurses trained as “prevention practitioners” held one prevention-focused visit with each participant. They provided participants with a tailored prevention prescription and supported them to set health-related goals. The primary outcome was a composite index: the number of evidence-based actions achieved at six months as a proportion of those for which participants were eligible at baseline. Results Of 126 participants (60 in immediate arm; 66 in wait-list arm), 125 were included in analyses (1 participant withdrew consent). In both arms, participants were eligible for a mean of 8.6 actions at baseline. At follow-up, participants in the immediate intervention arm met 64.5% of actions for which they were eligible versus 42.1% in the wait-list arm (rate ratio 1.53 [95% confidence interval 1.22–1.84]). Conclusion Public health nurses using the BETTER HEALTH intervention led to a higher proportion of identified evidence-based prevention and screening actions achieved at six months for people living with socioeconomic disadvantage. Trial registration NCT03052959, registered February 10, 2017.

The efficacy of convalescent plasma for COVID-19 is unclear. While most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content may influence patient outcomes.We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 days of respiratory symptom onset. Patients were allocated 2:1 to 500 mL of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 days. The effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression.The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. 940 patients were randomized and 921 patients were included in the intent-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) in the convalescent plasma arm and 86/307 (28.0%) in the standard of care arm; relative risk (RR) 1.16 (95% confidence interval (CI) 0.94-1.43; p=0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% vs. 26.4%; RR=1.27, 95% CI 1.02-1.57, p=0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standard log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (OR=0.74; 0.57-0.95 and OR=0.66; 0.50-0.87, respectively), while IgG against the full transmembrane Spike protein increased it (OR=1.53, 95% CI 1.14-2.05).Convalescent plasma did not reduce the risk of intubation or death at 30 days among hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavourable antibody profiles may be associated with worse clinical outcomes compared to standard care.Trial registrationCONvalescent Plasma for Hospitalized Adults With COVID-19 Respiratory Illness (CONCOR-1); NCT04348656; https://www.clinicaltrials.gov/ct2/show/NCT04348656

Eltrombopag has been shown to be noninferior to intravenous immunoglobulin (IVIG) for improving perioperative platelet counts in patients with immune thrombocytopenia (ITP) in a randomized trial; thus, cost is an important factor for treatment and policy decisions. We used patient-level data from the trial to conduct a cost-effectiveness analysis comparing perioperative eltrombopag 50 mg daily starting dose, with IVIG 1 or 2 g/kg (according to local practice) from a Canadian public health care payer’s perspective over the observation period, from preoperative day 21 to postoperative day 28. Resource utilization data were obtained from the trial data (eltrombopag, n = 38; IVIG, n = 36), and unit costs were collected from the Ontario Schedule of Benefits, Ontario Drug Formulary, and secondary sources. All costs were adjusted to 2020 Canadian dollars. We calculated the incremental cost per patient for all patients randomized. Uncertainty was addressed using nonparametric bootstrapping. The use of perioperative eltrombopag for patients with ITP resulted in a cost-saving of $413 Canadian per patient. Compared with IVIG, the probability of eltrombopag being cost effective was 70% even with no willingness to pay. In a sensitivity analysis based on IVIG dose, we found that with the higher dose of IVIG (2 g/kg), eltrombopag saved $2,714 per patient, whereas with the lower dose of IVIG (1 g/kg), eltrombopag had a higher mean cost of $562 per patient. In summary, based on data from the randomized trial that demonstrated noninferiority, the use of eltrombopag for the management of ITP in the perioperative setting was less costly than IVIG.

The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset (NCT04348656). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm—relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94–1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02–1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57–0.95 and OR = 0.66, 95% CI 0.50–0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14–2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care., A randomized trial in patients hospitalized with COVID-19 showed no benefit and potentially increased harm associated with the use of convalescent plasma, with subgroup analyses suggesting that the antibody profile in donor plasma is critical in determining clinical outcomes.

Background Convalescent plasma has been used for numerous viral diseases including influenza, severe acute respiratory syndrome, Middle East respiratory syndrome and Ebola virus; however, evidence to support its use is weak. SARS-CoV-2 is a novel coronavirus responsible for the 2019 global pandemic of COVID-19 community acquired pneumonia. We have undertaken a randomized controlled trial to assess the efficacy and safety of COVID-19 convalescent plasma (CCP) in patients with SARS-CoV-2 infection. Methods CONCOR-1 is an open-label, multicentre, randomized trial. Inclusion criteria include the following: patients > 16 years, admitted to hospital with COVID-19 infection, receiving supplemental oxygen for respiratory complications of COVID-19, and availability of blood group compatible CCP. Exclusion criteria are : onset of respiratory symptoms more than 12 days prior to randomization, intubated or imminent plan for intubation, and previous severe reactions to plasma. Consenting patients are randomized 2:1 to receive either approximately 500 mL of CCP or standard of care. CCP is collected from donors who have recovered from COVID-19 and who have detectable anti-SARS-CoV-2 antibodies quantified serologically. The primary outcome is intubation or death at day 30. Secondary outcomes include ventilator-free days, length of stay in intensive care or hospital, transfusion reactions, serious adverse events, and reduction in SARS-CoV-2 viral load. Exploratory analyses include patients who received CCP containing high titre antibodies. A sample size of 1200 patients gives 80% power to detect a 25% relative risk reduction assuming a 30% baseline risk of intubation or death at 30 days (two-sided test; α = 0.05). An interim analysis and sample size re-estimation will be done by an unblinded independent biostatistician after primary outcome data are available for 50% of the target recruitment (n = 600). Discussion This trial will determine whether CCP will reduce intubation or death non-intubated adults with COVID-19. The trial will also provide information on the role of and thresholds for SARS-CoV-2 antibody titres and neutralization assays for donor qualification. Trial registration Clinicaltrials.govNCT04348656. Registered on 16 April 2020.

BackgroundPersons suspected or confirmed with familial colorectal cancer syndrome are recommended to have biennial colonoscopy from late adolescence or early adulthood. Persons without a syndrome but with one or more affected first-degree relatives are recommended to begin colonoscopy 10 years before the age at diagnosis of the youngest affected relative, and every 5 to 10 years. Ontario introduced colonoscopy billing codes for these two indications in 2011.MethodsWe identified persons in Ontario under 50 years of age, without a prior history of colorectal cancer or inflammatory bowel disease, with one or more of these billing claims between 2013 and 2017. We described the index colonoscopy, and subsequent colonoscopy up-to-date status. We computed average annual rates of colorectal and other cancer diagnoses, and displayed mean cumulative function plots, stratified by billing code, age and sex.ResultsBilling claims for ‘familial syndrome’ high-risk screening colonoscopy were identified among 14,846 persons; the average annual rate of CRC diagnoses was 38.6 per 100,000 among males and 22.2 among females. Colonoscopy up-to-date status fell to 50% within 7 years. Billing claims for ‘first-degree relative’ screening colonoscopy was identified among 49,505 persons; average annual rates of CRC diagnoses were 16.3 among males and 13.5 per 100,000 among females, respectively.ConclusionColorectal cancer was more frequent following billing claims for high-risk screening colonoscopy for familial syndromes, as were noncolorectal malignancies potentially associated with these syndromes. This billing claim for familial colorectal cancer syndrome colonoscopy appears to identify a group at elevated short-term risk for cancer.

Introduction Variation in endoscopist performance contributes to poor-quality colonoscopy. Audit and feedback (A/F) can be used to improve physician performance, particularly among lower performing physicians. In this large pragmatic randomized controlled trial, we compared A/F to improve endoscopists' colonoscopy performance to usual practice. Methods Endoscopists practicing in Ontario, Canada, in 2014 were randomly assigned in October 2015 (index date) to receive (intervention group, n = 417) or not receive (control group, n = 416) an A/F report generated centrally using health administrative data. Colonoscopy performance was measured in both groups over two 12-month periods: prereport and postreport (relative to the index date). The primary outcome was polypectomy rate (PR). Secondary outcomes were cecal intubation rate, bowel preparation, and premature repeat after normal colonoscopy. A post hoc analysis used adenoma detection rate as the outcome. Outcomes were compared between groups for all endoscopists and for lower performing endoscopists using Poisson regression analyses under a difference-in-difference framework. Results Among all endoscopists, PR did not significantly improve from prereport to postreport periods for those receiving the intervention (relative rate [RR], intervention vs control: 1.07 vs 1.05, P = 0.09). Among lower performing endoscopists, PR improved significantly (RR, intervention vs control 1.34 vs 1.11, P = 0.02) in the intervention group compared with controls. In this subgroup, adenoma detection rate also improved but not significantly (RR, intervention vs control 1.12 vs 1.04, P = 0.12). There was no significant improvement in secondary outcomes between the intervention and control groups. Discussion A/F reports for colonoscopy improve performance in lower performing endoscopists (ClinicalTrials.gov: NCT02595775).

OBJECTIVES The objective of this work was to carry out a systematic review of clinical practice guidelines (CPGs) pertaining to intraoperative red blood cell (RBC) transfusions, in terms of indications, decision-making, and supporting evidence base. SUMMARY OF BACKGROUND DATA RBC transfusions are common during surgery and there is evidence of wide variability in practice. METHODS Major electronic databases (MEDLINE, EMBASE, and CINAHL), guideline clearinghouses and Google Scholar were systematically searched from inception to January 2019 for CPGs pertaining to indications for intraoperative RBC transfusion. Eligible guidelines were retrieved and their quality assessed using AGREE II. Relevant recommendations were abstracted and synthesized to allow for a comparison between guidelines. RESULTS Ten guidelines published between 1992 and 2018 provided indications for intraoperative transfusions. No guideline addressed intraoperative transfusion decision-making as its primary focus. Six guidelines provided criteria for transfusion based on hemoglobin (range 6.0-10.0 g/dL) or hematocrit (

It is essential to quantify the impacts of the COVID-19 pandemic on cancer screening, including for vulnerable sub-populations, to inform the development of evidence-based, targeted pandemic recovery strategies. We undertook a population-based retrospective observational study in Ontario, Canada to assess the impact of the pandemic on organized cancer screening and diagnostic services, and assess whether patterns of cancer screening service use and diagnostic delay differ across population sub-groups during the pandemic. Provincial health databases were used to identify age-eligible individuals who participated in one or more of Ontario's breast, cervical, colorectal, and lung cancer screening programs from January 1, 2019-December 31, 2020. Ontario's screening programs delivered 951,000 (-41%) fewer screening tests in 2020 than in 2019 and volumes for most programs remained more than 20% below historical levels by the end of 2020. A smaller percentage of cervical screening participants were older (50-59 and 60-69 years) during the pandemic when compared with 2019. Individuals in the oldest age groups and in lower-income neighborhoods were significantly more likely to experience diagnostic delay following an abnormal breast, cervical, or colorectal cancer screening test during the pandemic, and individuals with a high probability of living on a First Nation reserve were significantly more likely to experience diagnostic delay following an abnormal fecal test. Ongoing monitoring and management of backlogs must continue. Further evaluation is required to identify populations for whom access to cancer screening and diagnostic care has been disproportionately impacted and quantify impacts of these service disruptions on cancer incidence, stage, and mortality. This information is critical to pandemic recovery efforts that are aimed at achieving equitable and timely access to cancer screening-related care.

Background Cancer is a leading cause of death, and although screening can reduce cancer morbidity and mortality, participation in screening remains suboptimal. Objective This systematic review and meta-analysis aims to evaluate the effectiveness of social media and mobile health (mHealth) interventions for cancer screening. Methods We searched for randomized controlled trials and quasi-experimental studies of social media and mHealth interventions promoting cancer screening (breast, cervical, colorectal, lung, and prostate cancers) in adults in MEDLINE, Embase, PsycINFO, Scopus, CINAHL, Cochrane Central Register of Controlled Trials, and Communication & Mass Media Complete from January 1, 2000, to July 17, 2020. Two independent reviewers screened the titles, abstracts, and full-text articles and completed the risk of bias assessments. We pooled odds ratios for screening participation using the Mantel-Haenszel method in a random-effects model. Results We screened 18,008 records identifying 39 studies (35 mHealth and 4 social media). The types of interventions included peer support (n=1), education or awareness (n=6), reminders (n=13), or mixed (n=19). The overall pooled odds ratio was 1.49 (95% CI 1.31-1.70), with similar effect sizes across cancer types. Conclusions Screening programs should consider mHealth interventions because of their promising role in promoting cancer screening participation. Given the limited number of studies identified, further research is needed for social media interventions. Trial Registration PROSPERO International Prospective Register of Systematic Reviews CRD42019139615; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=139615 International Registered Report Identifier (IRRID) RR2-10.1136/bmjopen-2019-035411

The aim of this study was to develop a risk prediction model for high risk adenomas (HRAs) detected at screening colonoscopy based on readily available participant information. The cohort consisted of 3035 participants aged 50 to 74 years with no history of cancer who underwent a primary screening colonoscopy at a centralized colon cancer screening centre between 2008 and 2016. A multivariable logistic regression model was created using CRC risk factors identified from prior research. Model covariates were collected from a baseline questionnaire and included participant demographics (age and sex), lifestyle parameters (body mass index, alcohol, smoking, and vitamin D supplement use) and medical history (family history of CRC and diabetes). Mean participant age was 58.8 years, and 54.7% were male. 249 participants with HRAs were identified (8.2%). An adjusted c-statistic of 0.67 was calculated, and a specificity and negative predictive value of 97.2% (95% CI: 96.5–97.8) and 92.5% (95% CI: 92.2–92.8) for the detection of HRAs, respectively, were achieved using 20% predicted probability as a high-risk threshold. However, only a sensitivity of 12.1% (95% CI: 8.3–16.8) was achieved. Our model has moderate predictive ability, with strengths in being able to rule out those with an absence of HRAs on screening colonoscopy. Maximizing screening efficiency through improved risk prediction can enhance resource allocation. Ultimately, this model has the potential to improve patient care by reducing unnecessary colonoscopies, limiting this invasive procedure to those most likely to have significant findings.

When used during surgery, antifibrinolytic hemostatic agents such as lysine analogues are effective at reducing blood loss and the need for transfusions. Despite proven efficacy, use of hemostatic agents remains low during some surgeries. Our objective was to explore surgeon opinions about, and use of lysine analogues in, oncologic surgeries at a large tertiary care academic institution. We administered a survey to surgeons who perform high-transfusion-risk oncologic surgeries at a large academic hospital in Ottawa, Ontario. Design and distribution of the survey followed a modified Dillman method. To ensure that the survey questionnaire was relevant, clear, and concise, we performed informant interviews, cognitive interviews, and pilot-testing. The final survey consisted of 19 questions divided into 3 sections: respondent demographics, use of hemostatic agents, and potential clinical trial opinions. Of 28 surgeons, 24 (86%) participated. When asked to indicate the frequency of lysine analogue use, &ldquo, never&rdquo, accounted for 46% of the responses, and &ldquo, rarely&rdquo, (, unfamiliar with benefits&rdquo, and &ldquo, prefer alternatives.&rdquo, Fifteen surgeons (63%) felt that a trial was needed to demonstrate the efficacy and safety of lysine analogues in their cancer field. Our survey found that lysine analogues are infrequently used during oncologic surgeries at our institution. Many surgeons are unfamiliar with the benefits and side effects of lysine analogues and, alternatively, use topical hemostatic agents. Our results demonstrate that future trials exploring the efficacy and safety of lysine analogues in oncologic surgery are needed.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited.Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19.Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020.Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108).Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%).Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively.Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions.Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.

IntroductionThe patient experience is a critical dimension of colonoscopy quality. Sedative and analgesic drugs are commonly used to improve the patient experience of colonoscopy, with predominant regimens being deep sedation, typically achieved with propofol, and moderate sedation, typically achieved with an opioid and a benzodiazepine. However, non-pharmacological interventions exist that may be used to improve patient experience. Furthermore, by identifying non-pharmacological interventions to increase the quality of patient experience under moderate sedation, jurisdictions facing rising use of deep sedation for colonoscopy and its significant associated costs may be better able to encourage patients and clinicians to adopt moderate sedation. Advancing either of these aims requires synthesising the evidence and raising awareness around these non-pharmacological interventions to improve the patient experience of colonoscopy.Methods and analysisA systematic review will be conducted that searches multiple electronic databases from inception until 2020 to identify randomised controlled trials evaluating what, if any, non-pharmacological interventions are effective compared with placebo or usual care for improving the patient experience of routine colonoscopy under moderate or no sedation. Two reviewers will independently perform a three-stage screening process and extract all study data using piloted forms. Study quality will be assessed using the Cochrane Risk of Bias Tool V.2.0. Where multiple studies evaluate a single intervention, evidence will be quantitatively synthesised using pairwise meta-analysis, otherwise narrative syntheses will be undertaken.Ethics and disseminationThis is a review of existing literature not requiring ethics approval. The review findings will be included in future efforts to develop an implementation strategy to reduce the use of deep sedation for routine colonoscopy. They will also be published in a peer-reviewed journal, presented at conferences and contribute to a doctoral thesis.PROSPERO registration numberCRD42020173906.

Background An increased risk of complications, including death, has been associated with stored red blood cell (RBC) units in observational studies but not in randomized trials. We aimed to evaluate for volume-dependent effects attributable to length of RBC storage in a secondary analysis of the Age of Blood Evaluation (ABLE) trial. Study design and methods In the 2510 critically ill adults from the ABLE trial randomized to receive RBC units stored not more than 7 days or the oldest compatible RBC units, we estimated the hazard ratio (HR) for death by intensive care unit (ICU) and hospital discharge and by days 28, 90, and 180, within subgroups defined by the number of RBC units received. Extended Cox proportional hazards regression was used to model the HR. Results A volume-dependent effect of storage age on survival was present for death by 90 and 180 days, but not earlier endpoints. The HR for death by 90 days was 0.55 (95% confidence interval [CI], 0.11-0.98, fresh vs standard) after transfusion of 6 RBC units but 1.45 (95% CI, 1.06-1.98) after transfusion of 1 RBC unit. Conclusion In this exploratory analysis, volume-dependent effects related to RBC storage were documented in the ABLE trial. The harms associated with small volumes of fresh RBC units and large volumes of older RBC units should be further explored.

Background High-risk human papillomavirus (HPV) has been identified in the pathogenesis of anal cancer. The purpose of this study was to assess the prevalence of abnormal anal cytology and HPV in women aged ≥40 years who have a history of high-grade cervical squamous intraepithelial lesion (SIL) or cancer and to estimate the prevalence of anal intraepithelial neoplasia (AIN) using cytology as the primary screening modality. Methods Women who had a history of high-grade cervical SIL or cancer and were ≥40 years of age were included in this prospective study. Anal cytology with HPV-DNA testing was performed. All patients with abnormal anal cytology were referred for high-resolution anoscopy (HRA), and abnormal lesions were biopsied and treated if pathologically confirmed. Abnormal anal cytology correlated with HPV status, HRA findings, and clinical and demographic characteristics. Results A total of 317 women completed the study. Of these, 96 (30.3%) had abnormal anal cytology (high-grade SIL, 12.5%; low-grade SIL, 19.8%; atypical squamous cells, cannot exclude high-grade SIL, 6.3%; atypical squamous cells of undetermined significance, 61.5%) and 101 (31.9%) were HPV-DNA-positive. There was a significant association between abnormal cytology results and the presence of high-risk HPV. Of the 96 patients with abnormal cytology, 30 (31.3%) had biopsy-proven AIN on HRA, representing 9.5% of the total patient cohort; of these, 10 (33.3%) had low-grade AIN and 20 (66.7%) had high-grade AIN. Older age and smoking were significant risk factors for abnormal anal cytology. Conclusion Women aged ≥40 years with a history of high-grade cervical SIL or cancer have a high rate of AIN. Screening for anal cancer may therefore be considered in this patient population. The optimal screening approach should be addressed in future studies.

Anemia is common in critically ill patients with traumatic brain injury, and often requires red blood cell transfusion. Studies suggest that prolonged storage causes lesions of the red blood cells, including a decreased ability to carry oxygen. Considering the susceptibility of the brain to hypoxemia, victims of traumatic brain injury may thus be more vulnerable to exposure to older red blood cells. Our study aimed to ascertain whether the administration of fresh red blood cells (seven days or less) results in a better neurologic outcome compared with standard red blood cells in critically ill patients with traumatic brain injury requiring transfusion. The Age of Blood Evaluation in traumatic brain injury (ABLE-tbi) study was a nested study within the ABLE study (ISRCTN44878718). Our primary outcome was the extended Glasgow Outcome Scale (GOSe) at six months. In the ABLE study, 217 subjects suffered a traumatic brain injury: 110 in the fresh group, and 107 in the standard group. In the fresh group, 68 (73.1%) of the patients had an unfavourable neurologic outcome (GOSe ≤ 4) compared with 60 (64.5%) in the standard group (P = 0.21). Using a sliding dichotomy approach, we observed no overall effect of fresh red blood cells on neurologic outcome (odds ratio [OR], 1.34; 95% confidence interval [CI], 0.72 to 2.50; P = 0.35) but observed differences across prognostic bands with a decreased odds of unfavourable outcome in patients with the best prognosis at baseline (OR, 0.33; 95% CI, 0.11 to 0.96; P = 0.04) but an increased odds in those with intermediate and worst baseline prognosis (OR, 5.88; 95% CI,1.66 to 20.81; P = 0.006; and OR, 1.67; 95% CI, 0.53 to 5.30; P = 0.38, respectively). Overall, transfusion of fresh red blood cells was not associated with a better neurologic outcome at six months in critically ill patients with traumatic brain injury. Nevertheless, we cannot exclude a differential effect according to the patient baseline prognosis. ABLE study (ISRCTN44878718); registered 22 August, 2008.

Anemia is a frequently diagnosed condition that may be a symptom of or complication of many illnesses affecting patients of all demographics. Anemia can lead to both worsened clinical outcomes and reduced quality of life. Patient-reported outcome measures (PROMs) are methodological tools used to capture the impact of disease on patient well-being. Use of PROMs in medical research is becoming more common as it is increasingly recognized that disease outcomes of interest to researchers and clinicians are not always consistent with patients' greatest concerns related to their diseases. We conducted a scoping review to characterize the studies that have evaluated patient-centered outcomes using PROMs in patients undergoing treatment for anemia. We conducted a search of Medline (Ovid), EMBASE (Ovid), PsychINFO, and CINAHL databases for studies published until January 2017 that investigated an intervention to treat anemia in any patient population and used at least 1 PROM to evaluate patient-centered outcomes. A descriptive synthesis was performed to characterize the PROMs used and to evaluate the quality of patient-centered outcome (PCO) reporting. Of the 3224 studies identified in the initial search, 130 met all eligibility criteria. We found that the population most frequently studied was oncology patients (46.2% of studies). The therapy for anemia evaluated in the most studies was erythropoietin-stimulating agents (77.7% of studies). The most commonly used PROM was the Functional Assessment of Cancer Therapy/Functional Assessment of Chronic Illness Therapy tool (46.9%), and the majority of studies used only 1 PROM tool (53.1%). We found significant variability in the quality of PCO reporting across all included studies. Improved methodologic rigor in the assessment of PCOs in anemia management is needed in future studies.

Background Surveys are a common tool used to gather information about practices across many medical specialties. The quality of survey reporting impacts the strength of any conclusions. Thorough and accurate reporting of survey-based research is critical for evaluation of the validity, reliability, and generalizability of the results. The objective of this study was to appraise the quality of recently reported surveys in transfusion medicine (TM). Study design and methods A systematic review of the literature was performed to identify studies evaluating clinical practices in TM that used a questionnaire as the research tool and were published between January 2001 and November 2017. Manuscripts that met eligible criteria were appraised using a modified Survey Reporting Guideline questionnaire. Results The search identified 1632 references, from which 54 abstracts met eligibility criteria for analysis. Only seven (13%) manuscripts reported reliability and validity of the survey tool, 26 (48%) provided a description of the survey population and sample frame, and 11 (20%) indicated the representativeness of the underlying population. Additional reporting limitations included 31 (57%) manuscripts reporting the response rate calculation, two (4%) the analysis of nonresponse error, nine (17%) the method description for handling of missing data, 11 (20%) the analysis of responder and nonresponder characteristics, and 23 (43%) explicitly discussed the generalizability of the results. Conclusion Our findings document quality deficiencies in the reporting of research conducted using surveys in TM. Validated guidelines for the reporting of survey-based clinical research should be developed and applied to improve the quality of survey reporting in TM.

BACKGROUND Blood transfusion is common in the resuscitation of patients with traumatic injury. However, the clinical impact of the length of storage of transfused blood is unclear in this population. STUDY DESIGN AND METHODS We undertook a prespecified nested analysis of 372 trauma victims of the 2510 critically ill patients from 64 centers treated as part of the Age of Blood Evaluation (ABLE) randomized controlled trial. Patients were randomized according to their trauma status to receive either a transfusion of fresh blood stored not more than 7 days or standard-issue blood. Our primary outcome was 90-day all-cause mortality. RESULTS Overall, 186 trauma patients received fresh blood and 186 received standard-issue blood. Adherence to transfusion protocol was 94% (915/971) for all fresh blood transfused and 100% (753/753) for all standard-issue blood transfused. Mean ± SD blood storage duration was 5.6 ± 3.8 days in the fresh group and 22.7 ± 8.4 days in the standard-issue group (p

Create practice guidelines for the appropriate use of red blood cell transfusions in hepatectomy.Hepatectomy is associated with a high prevalence of transfusions. A transfusion can be life-saving, but can be associated with important adverse effects. Given the prevalence, the potential for benefit and harm, and the difficulty in conducting clinical trials, transfusion in hepatectomy is well-suited for a study of appropriateness.Using the RAND/UCLA appropriateness method, an international, multidisciplinary expert panel in hepatobiliary surgery, anesthesia, transfusion medicine, and critical care rated a series of 468 perioperative scenarios for transfusion appropriateness. Scenarios were rated individually, and again during an inperson group moderated session. Median scores and level of agreement were calculated to classify each scenario as appropriate, inappropriate, or uncertain.Approximately, 47.4% of scenarios were rated as appropriate for transfusion, 28.2% were inappropriate, and 24.4% were uncertain. The key recommendations for intraoperative transfusion were (i) it is never inappropriate to transfuse for significant bleeding or ST segment changes; (ii) it is never inappropriate to transfuse for an intraoperative hemoglobin ≤75 g/L; and (iii) in the absence of significant bleeding or ST changes, transfusion for hemoglobin of ≥95 g/L is inappropriate, and transfusion for hemoglobin of ≥85 g/L requires strong justification. The key recommendations for postoperative transfusions were: (i) in a stable, asymptomatic patient, an appropriate transfusion trigger is 70 g/L (without coronary artery disease) or 80 g/L (with coronary artery disease) and (ii) it is appropriate to transfuse any patient for a hemoglobin of ≤75 g/L either immediately post-operative, or with a significant decrease from the previous day (15 g/L).Based on best available evidence and expert opinion, criteria for appropriate perioperative red blood cell transfusions in hepatectomy were determined.

Background In 2018, the Canadian Association of Gastroenterology (CAG) published an extensive systematic review and guideline on screening in persons with a family history (FHx) of nonhereditary colorectal cancer (CRC) and adenoma. While CAG’s recommendations were evidence-based, some recommendations lacked precision (e.g. ranges for some start ages & intervals) and screening cessation age was not addressed, leading to implementation challenges for practitioners and CRC screening programs. Aims To review and update the evidence since the 2018 guideline and to formulate implementable recommendations in the Ontario context that are aligned with the CAG guideline. Methods ColonCancerCheck (Ontario’s organized CRC screening program) conducted a modified version of the literature search used by CAG (Jan 2017 - Sept 2019). A 19-member expert panel with Canadian and international representatives from endoscopy, primary care, epidemiology, organized CRC screening programs, Ontario’s cancer system and the general public refined the recommendations of the CAG guideline for the purposes of implementation in an organized CRC screening program using a modified Delphi process. This iterative process involved a series of webinars and anonymous survey rounds where the panel reviewed evidence materials and provided online feedback to develop, refine & achieve consensus on screening recommendations in persons with a FHx of CRC/adenoma. Consensus was achieved if ≥75% of members agreed or strongly agreed with the statement. Results Six new systematic reviews and 2 new guidelines were identified. New evidence included data on the absolute risk (10 year & lifetime risk) of CRC by type of FHx, as well as the performance of fecal immunochemical testing (FIT) and barriers to CRC screening in persons with a FHx of CRC. The expert panel participated in 3 webinars and 4 online surveys to arrive at consensus. Panel recommendations and level of consensus will be reported for the 6 statements (Table). Conclusions Building from the CAG guideline, we derived evidence-based and implementable recommendations for screening persons with a FHx of CRC or adenoma. Funding Agencies Ontario Health (Cancer Care Ontario)

Background Development of intraoperative techniques and blood management strategies in liver resection, and the multidisciplinary nature of perioperative transfusion decision making, creates an opportunity for practice variation. The aim of this study was to describe the current practices in perioperative blood management and explore differences between surgeons and anesthesiologists. Study design and methods A Web-based survey was developed, piloted, and circulated to Canadian liver surgeons and anesthesiologists. The survey focused on management of preoperative anemia, blood conservation strategies, estimation of blood loss, and transfusion decision making in a multidisciplinary setting. Results A total of 198 physicians received the survey, with 117 responding (59%). Most responding surgeons (67%) perform more than 20 liver resections per year, while most responding anesthesiologists (90%) take part in fewer than 20. Anesthesiologists most commonly stated that preoperative anemia is managed by someone else (38%), while surgeons most commonly reported "no specific treatment" (45%). The most common intraoperative blood conservation technique used is administration of antifibrinolytics (63% used them at least occasionally). The most important factor for anesthesiologists when deciding on an intraoperative transfusion was hemoglobin value (47%); for surgeons, it was patient hemodynamics (33%). Compared to when they started their career, 60% of respondents felt that they were less likely to transfuse a patient now. Conclusion The results of our survey provide insights into current transfusion practice and decision making in liver resection, including a comparison between anesthesiologist and surgeon transfusion behavior. Management of preoperative anemia, increased use of intraoperative blood conservation techniques, and improved communication between providers were identified as targets for quality improvement.

Pathogen inactivation of platelet concentrates reduces the risk for blood-borne infections. However, its effect on platelet function and hemostatic efficacy of transfusion is unclear. We conducted a randomized noninferiority trial comparing the efficacy of pathogen-inactivated platelets using riboflavin and UV B illumination technology (intervention) compared with standard plasma-stored platelets (control) for the prevention of bleeding in patients with hematologic malignancies and thrombocytopenia. The primary outcome parameter was the proportion of transfusion-treatment periods in which the patient had grade 2 or higher bleeding, as defined by World Health Organization criteria. Between November 2010 and April 2016, 469 unique patients were randomized to 567 transfusion-treatment periods (283 in the control arm, 284 in the intervention arm). There was a 3% absolute difference in grade 2 or higher bleeding in the intention-to-treat analysis: 51% of the transfusion-treatment periods in the control arm and 54% in the intervention arm (95% confidence interval [CI], -6 to 11; P=.012 for noninferiority). However, in the per-protocol analysis, the difference in grade 2 or higher bleeding was 8%: 44% in the control arm and 52% in the intervention arm (95% CI22 to 18; P=.19 for noninferiority). Transfusion increment parameters were similar to 50% lower in the intervention arm. There was no difference in the proportion of patients developing HLA class I alloantibodies. In conclusion, the noninferiority criterion for pathogen-inactivated platelets was met in the intention-to-treat analysis. This finding was not demonstrated in the per-protocol analysis. This trial was registered at The Netherlands National Trial Registry as # NTR2106 and at www. clinicaltrials. gov as # NCT02783313.

Although promising for colorectal cancer screening, hemoglobin (Hb) stability remains a concern with fecal immunochemical tests. This study implemented a novel, standardized method to compare Hb stability across various fecal immunochemical tests. The method can be used to inform decisions when selecting a kit for use in colorectal cancer screening. In so doing, this work addressed a critical need for standardization in this field.- To compare the stability of Hb across 5 different immunochemical kits and one guaiac kit.- The stability of Hb was analyzed in collection devices inoculated with Hb-spiked feces and (1) stored at various temperatures (frozen, refrigerated, ambient, and elevated) for more than 60 days; (2) after undergoing 3 controlled, freeze-thaw cycles; and (3) after being transported by courier or postal services in uncontrolled temperature conditions from 3 locations in Ontario, Canada, to a central testing center.- The stability of Hb varied with time and temperature and by kit. Lower Hb recoveries occurred with increasing temperature and increasing time from sample collection to testing. Refrigeration provided the best stability, although results varied across kits (eg, from 4.2 days to60 days before a prespecified threshold [70% probability of the test results remaining positive] was reached). Freeze-thaw stability varied across kits and cycles (Hb recoveries: NS Plus [Alfresa Pharma, Chuo-ku, Osaka, Japan], 91.7% to 95.4%; OC Diana [Eiken Chemical, Taito-ku, Tokyo, Japan], 57.6% to 74.9%). Agreement regarding Hb levels before and after transportation varied across kits (from 57% to 100%).- Important differences in Hb stability were found across the included fecal immunochemical tests. These findings should inform practice-based and population-based colorectal cancer screening.

Background Receipt of a red blood cell transfusion (RBCT) post-kidney transplantation may alter immunity which could predispose to subsequent infection. Methods We carried out a single-center, retrospective cohort study of 1,258 adult kidney transplant recipients from 2002 to 2018 (mean age 52, 64% male). The receipt of RBCT post-transplant (468 participants transfused, total 2,373 RBCT) was analyzed as a time-varying, cumulative exposure. Adjusted cox proportional hazards models were used to calculate hazard ratios (HR) for outcomes of bacterial or viral (BK or CMV) infection. Results Over a median follow-up of 3.8 years, bacterial infection occurred in 34% of participants at a median of 409 days post-transplant and viral infection occurred in 25% at a median of 154 days post-transplant. Transfusion was associated with a step-wise higher risk of bacterial infection (HR 1.35, 95%CI 0.95–1.91; HR 1.29, 95%CI 0.92–1.82; HR 2.63, 95%CI 1.94–3.56; HR 3.38, 95%CI 2.30–4.95, for 1, 2, 3–5 and >5 RBCT respectively), but not viral infection. These findings were consistent in multiple additional analyses, including accounting for reverse causality. Conclusion Blood transfusion after kidney transplant is associated with a higher risk for bacterial infection, emphasizing the need to use transfusions judiciously in this population already at risk for infections.