Development of an Integrated Platform Using Multidisciplinary Real-World Data to Facilitate Biomarker Discovery for Medical Products

© 2019 The Authors. Clinical and Translational Science published by Wiley Periodicals Inc. on behalf of the American Society of Clinical Pharmacology & Therapeutics. This article has been contributed to by US Government employees and their work is in the public domain in the USA. Translational multidisciplinary research is important for the Center for Devices and Radiological Health\u27s efforts for utilizing real-world data (RWD) to enhance predictive evaluation of medical device performance in patient subpopulations. As part of our efforts for developing new RWD-based evidentiary approaches, including in silico discovery of device-related risk predictors and biomarkers, this study aims to characterize the sex/race-related trends in hip replacement outcomes and identify corresponding candidate single nucleotide polymorphisms (SNPs). Adverse outcomes were assessed by deriving RWD from a retrospective analysis of hip replacement hospital discharge data from the National Inpatient Sample (NIS). Candidate SNPs were explored using pre-existing data from the Personalized Medicine Research Project (PMRP). High-Performance Integrated Virtual Environment was used for analyzing and visualizing putative associations between SNPs and adverse outcomes. Ingenuity Pathway Analysis (IPA) was used for exploring plausibility of the sex-related candidate SNPs and characterizing gene networks associated with the variants of interest. The NIS-based epidemiologic evidence showed that periprosthetic osteolysis (PO) was most prevalent among white men. The PMRP-based genetic evidence associated the PO-related male predominance with rs7121 (odds ratio = 4.89; 95% confidence interval = 1.41−17.05) and other candidate SNPs. SNP-based IPA analysis of the expected gene expression alterations and corresponding signaling pathways suggested possible role of sex-related metabolic factors in development of PO, which was substantiated by ad hoc epidemiologic analysis identifying the sex-related differences in metabolic comorbidities in men vs. women with hip replacement-related PO. Thus, our in silico study illustrates RWD-based evidentiary approaches that may facilitate cost/time-efficient discovery of biomarkers for informing use of medical products

Patients with Crohn's disease have longer post-operative in-hospital stay than patients with colon cancer but no difference in complications' rate

BACKGROUNDRight hemicolectomy or ileocecal resection are used to treat benign conditions like Crohn's disease (CD) and malignant ones like colon cancer (CC).AIMTo investigate differences in pre- and peri-operative factors and their impact on post-operative outcome in patients with CC and CD.METHODSThis is a sub-group analysis of the European Society of Coloproctology's prospective, multi-centre snapshot audit. Adult patients with CC and CD undergoing right hemicolectomy or ileocecal resection were included. Primary outcome measure was 30-d post-operative complications. Secondary outcome measures were post-operative length of stay (LOS) at and readmission.RESULTSThree hundred and seventy-five patients with CD and 2,515 patients with CC were included. Patients with CD were younger (median = 37 years for CD and 71 years for CC (P < 0.01), had lower American Society of Anesthesiology score (ASA) grade (P < 0.01) and less comorbidity (P < 0.01), but were more likely to be current smokers (P < 0.01). Patients with CD were more frequently operated on by colorectal surgeons (P < 0.01) and frequently underwent ileocecal resection (P < 0.01) with higher rate of de-functioning/primary stoma construction (P < 0.01). Thirty-day post-operative mortality occurred exclusively in the CC group (66/2515, 2.3%). In multivariate analyses, the risk of post-operative complications was similar in the two groups (OR 0.80, 95%CI: 0.54-1.17; P = 0.25). Patients with CD had a significantly longer LOS (Geometric mean 0.87, 95%CI: 0.79-0.95; P < 0.01). There was no difference in re-admission rates. The audit did not collect data on post-operative enhanced recovery protocols that are implemented in the different participating centers.CONCLUSIONPatients with CD were younger, with lower ASA grade, less comorbidity, operated on by experienced surgeons and underwent less radical resection but had a longer LOS than patients with CC although complication's rate was not different between the two groups

Association of mechanical bowel preparation with oral antibiotics and anastomotic leak following left sided colorectal resection: an international, multi-centre, prospective audit.

This is the peer reviewed version of the following article: , (2018), Association of mechanical bowel preparation with oral antibiotics and anastomotic leak following left sided colorectal resection: an international, multi‐centre, prospective audit. Colorectal Dis, 20: 15-32. doi:10.1111/codi.14362, which has been published in final form at https://doi.org/10.1111/codi.14362. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsINTRODUCTION: The optimal bowel preparation strategy to minimise the risk of anastomotic leak is yet to be determined. This study aimed to determine whether oral antibiotics combined with mechanical bowel preparation (MBP+Abx) was associated with a reduced risk of anastomotic leak when compared to mechanical bowel preparation alone (MBP) or no bowel preparation (NBP). METHODS: A pre-planned analysis of the European Society of Coloproctology (ESCP) 2017 Left Sided Colorectal Resection audit was performed. Patients undergoing elective left sided colonic or rectal resection with primary anastomosis between 1 January 2017 and 15 March 2017 by any operative approach were included. The primary outcome measure was anastomotic leak. RESULTS: Of 3676 patients across 343 centres in 47 countries, 618 (16.8%) received MBP+ABx, 1945 MBP (52.9%) and 1099 patients NBP (29.9%). Patients undergoing MBP+ABx had the lowest overall rate of anastomotic leak (6.1%, 9.2%, 8.7% respectively) in unadjusted analysis. After case-mix adjustment using a mixed-effects multivariable regression model, MBP+Abx was associated with a lower risk of anastomotic leak (OR 0.52, 0.30-0.92, P = 0.02) but MBP was not (OR 0.92, 0.63-1.36, P = 0.69) compared to NBP. CONCLUSION: This non-randomised study adds 'real-world', contemporaneous, and prospective evidence of the beneficial effects of combined mechanical bowel preparation and oral antibiotics in the prevention of anastomotic leak following left sided colorectal resection across diverse settings. We have also demonstrated limited uptake of this strategy in current international colorectal practice

An international assessment of the adoption of enhanced recovery after surgery (ERAS®) principles across colorectal units in 2019–2020

Aim: The Enhanced Recovery After Surgery (ERAS®) Society guidelines aim to standardize perioperative care in colorectal surgery via 25 principles. We aimed to assess the variation in uptake of these principles across an international network of colorectal units. Method: An online survey was circulated amongst European Society of Coloproctology members in 2019–2020. For each ERAS principle, respondents were asked to score how frequently the principle was implemented in their hospital, from 1 (‘rarely’) to 4 (‘always’). Respondents were also asked to recall whether practice had changed since 2017. Subgroup analyses based on hospital characteristics were conducted. Results: Of hospitals approached, 58% responded to the survey (195/335), with 296 individual responses (multiple responses were received from some hospitals). The majority were European (163/195, 83.6%). Overall, respondents indicated they ‘most often’ or ‘always’ adhered to most individual ERAS principles (18/25, 72%). Variability in the uptake of principles was reported, with universal uptake of some principles (e.g., prophylactic antibiotics; early mobilization) and inconsistency from ‘rarely’ to ‘always’ in others (e.g., no nasogastric intubation; no preoperative fasting and carbohydrate drinks). In alignment with 2018 ERAS guideline updates, adherence to principles for prehabilitation, managing anaemia and postoperative nutrition appears to have increased since 2017. Conclusions: Uptake of ERAS principles varied across hospitals, and not all 25 principles were equally adhered to. Whilst some principles exhibited a high level of acceptance, others had a wide variability in uptake indicative of controversy or barriers to uptake. Further research into specific principles is required to improve ERAS implementation

An international assessment of the adoption of enhanced recovery after surgery (ERAS®) principles across colorectal units in 2019–2020

AimThe Enhanced Recovery After Surgery (ERAS®) Society guidelines aim to standardize perioperative care in colorectal surgery via 25 principles. We aimed to assess the variation in uptake of these principles across an international network of colorectal units.MethodAn online survey was circulated amongst European Society of Coloproctology members in 2019–2020. For each ERAS principle, respondents were asked to score how frequently the principle was implemented in their hospital, from 1 (‘rarely’) to 4 (‘always’). Respondents were also asked to recall whether practice had changed since 2017. Subgroup analyses based on hospital characteristics were conducted.ResultsOf hospitals approached, 58% responded to the survey (195/335), with 296 individual responses (multiple responses were received from some hospitals). The majority were European (163/195, 83.6%). Overall, respondents indicated they ‘most often’ or ‘always’ adhered to most individual ERAS principles (18/25, 72%). Variability in the uptake of principles was reported, with universal uptake of some principles (e.g., prophylactic antibiotics; early mobilization) and inconsistency from ‘rarely’ to ‘always’ in others (e.g., no nasogastric intubation; no preoperative fasting and carbohydrate drinks). In alignment with 2018 ERAS guideline updates, adherence to principles for prehabilitation, managing anaemia and postoperative nutrition appears to have increased since 2017.ConclusionsUptake of ERAS principles varied across hospitals, and not all 25 principles were equally adhered to. Whilst some principles exhibited a high level of acceptance, others had a wide variability in uptake indicative of controversy or barriers to uptake. Further research into specific principles is required to improve ERAS implementation.AimThe Enhanced Recovery After Surgery (ERAS®) Society guidelines aim to standardize perioperative care in colorectal surgery via 25 principles. We aimed to assess the variation in uptake of these principles across an international network of colorectal units.MethodAn online survey was circulated amongst European Society of Coloproctology members in 2019–2020. For each ERAS principle, respondents were asked to score how frequently the principle was implemented in their hospital, from 1 (‘rarely’) to 4 (‘always’). Respondents were also asked to recall whether practice had changed since 2017. Subgroup analyses based on hospital characteristics were conducted.ResultsOf hospitals approached, 58% responded to the survey (195/335), with 296 individual responses (multiple responses were received from some hospitals). The majority were European (163/195, 83.6%). Overall, respondents indicated they ‘most often’ or ‘always’ adhered to most individual ERAS principles (18/25, 72%). Variability in the uptake of principles was reported, with universal uptake of some principles (e.g., prophylactic antibiotics; early mobilization) and inconsistency from ‘rarely’ to ‘always’ in others (e.g., no nasogastric intubation; no preoperative fasting and carbohydrate drinks). In alignment with 2018 ERAS guideline updates, adherence to principles for prehabilitation, managing anaemia and postoperative nutrition appears to have increased since 2017.ConclusionsUptake of ERAS principles varied across hospitals, and not all 25 principles were equally adhered to. Whilst some principles exhibited a high level of acceptance, others had a wide variability in uptake indicative of controversy or barriers to uptake. Further research into specific principles is required to improve ERAS implementation.A

Safety of primary anastomosis following emergency left sided colorectal resection: an international, multi-centre prospective audit.

This is the peer reviewed version of the following article: group, T. E. S. o. C. c. (2018). "Safety of primary anastomosis following emergency left sided colorectal resection: an international, multi-centre prospective audit." Colorectal Disease 20(S6): 47-57., which has been published in final form at https://doi.org/10.1111/codi.1437. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsINTRODUCTION: Some evidence suggests that primary anastomosis following left sided colorectal resection in the emergency setting may be safe in selected patients, and confer favourable outcomes to permanent enterostomy. The aim of this study was to compare the major postoperative complication rate in patients undergoing end stoma vs primary anastomosis following emergency left sided colorectal resection. METHODS: A pre-planned analysis of the European Society of Coloproctology 2017 audit. Adult patients (> 16 years) who underwent emergency (unplanned, within 24 h of hospital admission) left sided colonic or rectal resection were included. The primary endpoint was the 30-day major complication rate (Clavien-Dindo grade 3 to 5). RESULTS: From 591 patients, 455 (77%) received an end stoma, 103 a primary anastomosis (17%) and 33 primary anastomosis with defunctioning stoma (6%). In multivariable models, anastomosis was associated with a similar major complication rate to end stoma (adjusted odds ratio for end stoma 1.52, 95%CI 0.83-2.79, P = 0.173). Although a defunctioning stoma was not associated with reduced anastomotic leak (12% defunctioned [4/33] vs 13% not defunctioned [13/97], adjusted odds ratio 2.19, 95%CI 0.43-11.02, P = 0.343), it was associated with less severe complications (75% [3/4] with defunctioning stoma, 86.7% anastomosis only [13/15]), a lower mortality rate (0% [0/4] vs 20% [3/15]), and fewer reoperations (50% [2/4] vs 73% [11/15]) when a leak did occur. CONCLUSIONS: Primary anastomosis in selected patients appears safe after left sided emergency colorectal resection. A defunctioning stoma might mitigate against risk of subsequent complications

The impact of conversion on the risk of major complication following laparoscopic colonic surgery: an international, multicentre prospective audit.

This is the peer reviewed version of the following article: The and E. S. o. C. c. groups (2018). "The impact of conversion on the risk of major complication following laparoscopic colonic surgery: an international, multicentre prospective audit." Colorectal Disease 20(S6): 69-89., which has been published in final form at https://doi.org/10.1111/codi.14371. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.BACKGROUND: Laparoscopy has now been implemented as a standard of care for elective colonic resection around the world. During the adoption period, studies showed that conversion may be detrimental to patients, with poorer outcomes than both laparoscopic completed or planned open surgery. The primary aim of this study was to determine whether laparoscopic conversion was associated with a higher major complication rate than planned open surgery in contemporary, international practice. METHODS: Combined analysis of the European Society of Coloproctology 2017 and 2015 audits. Patients were included if they underwent elective resection of a colonic segment from the caecum to the rectosigmoid junction with primary anastomosis. The primary outcome measure was the 30-day major complication rate, defined as Clavien-Dindo grade III-V. RESULTS: Of 3980 patients, 64% (2561/3980) underwent laparoscopic surgery and a laparoscopic conversion rate of 14% (359/2561). The major complication rate was highest after open surgery (laparoscopic 7.4%, converted 9.7%, open 11.6%, P < 0.001). After case mix adjustment in a multilevel model, only planned open (and not laparoscopic converted) surgery was associated with increased major complications in comparison to laparoscopic surgery (OR 1.64, 1.27-2.11, P < 0.001). CONCLUSIONS: Appropriate laparoscopic conversion should not be considered a treatment failure in modern practice. Conversion does not appear to place patients at increased risk of complications vs planned open surgery, supporting broadening of selection criteria for attempted laparoscopy in elective colonic resection