Spiral.imperial.ac.uk



TitleComplications after discharge and delays in adjuvant chemotherapy following colonic resection: a cohort study of linked primary and secondary care dataAuthorsChanpreet S Arhi1 Clinical Research Fellow MRCS Bsc, Elaine M Burns1 Clinical Lecturer FRCS PhD, George Bouras1 Consultant Surgeon FRCS PhD, Paul Aylin2 Professor in Epidemiology and Public Health MBChB FFPH FRCPE, Paul Ziprin1 Consultant Surgeon FRCS, Ara Darzi1 Professor of Surgery OM FRS FRCS FREng FMEdSciAddresses: 1. Imperial College London, Department of Surgery and Cancer, St Mary’s Hospital Campus, Praed Street, W2 1NY 2. Imperial College London, School of Public Health, 3 Dorset Rise, EC4Y 8ENCorresponding author: Chanpreet Arhi, c.arhi@imperial.ac.uk 007949762763All authors have completed the ICMJE uniform disclosure form at coi_disclosure.pdf and declare: the Sowerby Foundation provided funding for the data; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted workWhat does this paper add to the literature?By improving our understanding of the reasons for delays in adjuvant chemotherapy for colon cancer patients, there is the potential to improve patient outcome. This study determines the extent of complications by using both primary and secondary care data, which adjusting for emergency admissions, operative technique and patient demographics. ABSTRACTAim: By understanding the reasons for delays in adjuvant chemotherapy (AC) after colonic resection, there is the potential to improve patient outcome. The aim of this study is to determine the extent and impact of complications post hospital discharge on AC delays.Method: The study cohort included patients who had a colorectal cancer resection in HES, with linkage to primary care data provided by CPRD. Complications during the index hospital stay (from HES) and post discharge (from CPRD) were compared. The risk of late AC treatment (eight weeks or later) following a complication, stoma at index procedure, or emergency admission was described after accounting for age and Charlson score. A Cox hazards model determined the association of these factors on overall survival (OS).Results: 1266 patients underwent AC following colon cancer resection, of which 598 (47.2%) received treatment within eight weeks. Patients receiving late AC had a significantly higher proportion of re-operations (7.0% vs 3.3% p<0.005) and wound infections (5.5% vs 3.7% p=0.042), 96% of the latter only noted in CPRD. In multivariate analysis, the risk of AC delay significantly increased following a complication (1.53 95%CI 1.16-2.03 p=0.003) or a stoma at the index operation. AC delay was associated with worse OS(HR 1.44 95%CI 1.16-1.79,p=0.001), as was an emergency admission(HR 1.59 95%CI 1.21-1.98, p<0.0005). However, the presence of a complication did not independently reduce OS (HR 1.15 95%CI 0.89-1.48,p=0.295).Conclusion: By using only secondary care data, the true extent and impact of complications following colonic resection is underestimated. Abstract word count: 249Article word count: 2999 INTRODUCTIONAdjuvant chemotherapy (AC) following resection for stage III colon cancers has been shown to improve prognosis, with an absolute increase of 7% in overall 5-year survivalADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1200/JCO.2004.09.059","ISSN":"0732183X","PMID":"15067028","abstract":"PURPOSE: Although it is well-established that fluorouracil- (FU-) based adjuvant therapy improves survival for patients with resected high-risk colon cancer, the magnitude of adjuvant therapy benefit across specific subgroups and for individual patients has been uncertain.\\n\\nPATIENTS AND METHODS: Using a pooled data set of 3,302 patients with stage II and III colon cancer from seven randomized trials comparing FU + leucovorin or FU + levamisole to surgery alone, we performed an analysis based on a Cox proportional hazards regression model. Treatment, age, sex, tumor location, T stage, nodal status, and grade were tested for both prognostic and predictive significance. Model derived estimates of 5-year disease-free survival and overall survival (OS) for surgery alone and surgery plus FU-based therapy were calculated for a range of patient subsets.\\n\\nRESULTS: Nodal status, T stage, and grade were the only prognostic factors independently significant for both disease-free survival and OS. Age was significant only for OS. In a multivariate analysis, adjuvant therapy showed a beneficial treatment effect across all subsets. Treatment benefits were consistent across sex, location, age, T-stage, and grade. A significant stage by treatment interaction was present, with treatment benefiting stage III patients to a greater degree than stage II patients.\\n\\nCONCLUSION: Patients with high-risk resected colon cancer obtain benefit from FU-based therapy across subsets of age, sex, location, T stage, nodal status, and grade. Model estimates of survival stratified by T stage, nodal status, grade, and age are available at . This information may improve patients' and physicians' understanding of the potential benefits of adjuvant therapy.","author":[{"dropping-particle":"","family":"Gill","given":"Sharlene","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Loprinzi","given":"Charles L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sargent","given":"Daniel J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Thomé","given":"Stephan D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Alberts","given":"Steven R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Haller","given":"Daniel G.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Benedetti","given":"Jacqueline","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Francini","given":"Guido","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shepherd","given":"Lois E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Seitz","given":"Jean Francois","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Labianca","given":"Roberto","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chen","given":"Wei","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cha","given":"Stephen S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Heldebrant","given":"Michael P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Goldberg","given":"Richard M.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Clinical Oncology","id":"ITEM-1","issue":"10","issued":{"date-parts":[["2004"]]},"page":"1797-1806","title":"Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: Who benefits and by how much?","type":"article-journal","volume":"22"},"uris":[""]}],"mendeley":{"formattedCitation":"¹","plainTextFormattedCitation":"1","previouslyFormattedCitation":"¹"},"properties":{"noteIndex":0},"schema":""}1. Although there are no official guidelines regarding the timing of AC, multiple studies have found a delay beyond eight weeks is associated with a reduction in the benefit of treatmentADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1001/jama.2011.749","ISSN":"1538-3598","PMID":"21642686","abstract":"Adjuvant chemotherapy (AC) improves survival among patients with resected colorectal cancer. However, the optimal timing from surgery to initiation of AC is unknown.","author":[{"dropping-particle":"","family":"Biagi","given":"James J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Raphael","given":"Michael J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mackillop","given":"William J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kong","given":"Weidong","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"King","given":"Will D","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Booth","given":"Christopher M","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"JAMA : the journal of the American Medical Association","id":"ITEM-1","issue":"22","issued":{"date-parts":[["2011"]]},"note":"From Duplicate 1 (Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer: a systematic review and meta-analysis. - Biagi, James J; Raphael, Michael J; Mackillop, William J; Kong, Weidong; King, Will D; Booth, Christopher M)\n\nMeta - analayis regarding timing\nConsiders all colorectal tumours - does not split\nDoes not take into consideration wheter patints completed treatment\n\nNo mention about differenctating according to stage\n\nNo regression analysis in terms of patient demographics or type of operation\nconversion of discrete data waitting time categories into 4 week blocks\n\nUse our data to extrapolate over years and the effect of different regimes\n\n\nmeta-analyis - indicates that relativeOS\ndecreases by 14% for every 4-week delay to initiation of AC.\n\nIncludes theory about why time makes a difference\n\nThis papaer uses the data for predictive modelling","page":"2335-2342","title":"Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer: a systematic review and meta-analysis.","type":"article-journal","volume":"305"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1016/j.ejca.2010.01.020","ISSN":"1879-0852","PMID":"20138505","abstract":"BACKGROUND: In stage III colorectal cancer (CRC), adjuvant chemotherapy (CT) is usually prescribed within two months after curative surgery. Whether or not delaying initiation of CT affects survival is still debated. MATERIAL AND METHODS: We performed a meta-analysis (MA) of all published studies (full papers or abstracts) comparing delayed CT with standard care. Studies were obtained from a PubMed query (keywords: CRC, adjuvant treatment, delay of CT), a review (Chau et al., 2006), cross-checking references and abstracts from the proceedings of ASCO, ASCO GI and WCGI annual meetings. We chose a cutoff delay of 8 weeks. Risk Ratios (RRs) were calculated from the recorded events (deaths, relapses). We used EasyMA software (fixed-effect model). RESULTS: Fourteen studies (including four abstracts) were identified (17,645 patients; 5,952 males, 5,151 females, mean age 70 years). Of these, three could not be statistically analysed and three used another cutoff (4, 5 or 6 weeks), leaving 8 studies for main MA (13,158 patients; 3,932 males, 3,644 females, 5,942 missing data; 5,576 colon cancers, 6,677 rectal, 1,265 missing data). Delaying CT more than 8 weeks was associated to worse Overall Survival (OS) (RR: 1.20; 95% Confidence Interval (CI) 1.15-1.26). In the MA including all studies whatever their cutoff, longer delay was similarly associated to a worse OS but not a worse Relapse-Free Survival (RFS) (five studies). CONCLUSION: Adjuvant chemotherapy should be started within 8 weeks after surgery. Delaying the initiation of adjuvant CT for more than 8 weeks after surgery significantly decreased OS but not RFS. This discrepancy might be due to factors not directly related to cancer (post-operative complications, social status) or to a more accurate appraisal of death.","author":[{"dropping-particle":"","family":"Guetz","given":"Gaetan","non-dropping-particle":"Des","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nicolas","given":"Patrick","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Perret","given":"Gérard-Yves","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Morere","given":"Jean-Fran?ois","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Uzzan","given":"Bernard","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"European journal of cancer (Oxford, England : 1990)","id":"ITEM-2","issue":"6","issued":{"date-parts":[["2010","4"]]},"page":"1049-55","title":"Does delaying adjuvant chemotherapy after curative surgery for colorectal cancer impair survival? A meta-analysis.","type":"article-journal","volume":"46"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.1002/cncr.22316","ISSN":"0008-543X","PMID":"17078055","abstract":"BACKGROUND: An important advance in medical oncology has been the use of adjuvant chemotherapy for lymph node-positive colon cancer. However, to the authors' knowledge, the effect of the interval between surgery and the initiation of chemotherapy on survival has not been investigated. METHODS: The authors analyzed predictors and outcomes of time intervals to treatment after surgery among patients older than 65 years who were diagnosed with stage III colon cancer between 1992 and 1999 using Surveillance, Epidemiology, and End Results (SEER)-Medicare data. Linear and logistic regression analyses were used to model predictors of delay, and Cox proportional hazards models were used to analyze the impact of treatment timing on survival. RESULTS: Among 4382 patients with colon cancer, 1122 patients (26%) began adjuvant chemotherapy within 1 month, 2391 patients (55%) began adjuvant chemotherapy in 1 to 2 months, 454 patients (10%) began adjuvant chemotherapy in 2 to 3 months, and 415 patients (9%) began adjuvant chemotherapy >/=3 months after surgery. Intervals of >/=3 months (delay) were associated with older age, increased comorbid conditions, well/moderately differentiated grade, and being unmarried. Colon cancer-specific mortality was associated with a delay in the initiation of chemotherapy (hazards ratio [HR], 1.48; 95% confidence interval [95% CI], 1.15-1.92), advanced age, increased comorbidity, poorly differentiated tumor grade, the presence of >/=4 positive lymph nodes, and undergoing surgery in a nonteaching hospital. All-cause mortality was associated with intervals >2 months between surgery and chemotherapy (2 to 3 months: HR, 1.41; 95% CI, 1.15-1.74; >/=3 months: HR, 1.62; 95% CI, 1.31-1.99) compared with <1 month. CONCLUSIONS: In the older population that was studied, only 9% of patients initiated adjuvant chemotherapy >3 months after the date of curative surgery. However, delay in initiation was associated with both cancer-specific and all-cause mortality. Determining whether these results were because of chemotherapy timing or other associated factors will require further study.","author":[{"dropping-particle":"","family":"Hershman","given":"Dawn","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hall","given":"Michael J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wang","given":"Xiaoyan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jacobson","given":"Judith S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"McBride","given":"Russell","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Grann","given":"Victor R","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Neugut","given":"Alfred I","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Cancer","id":"ITEM-3","issue":"11","issued":{"date-parts":[["2006","12","1"]]},"page":"2581-8","title":"Timing of adjuvant chemotherapy initiation after surgery for stage III colon cancer.","type":"article-journal","volume":"107"},"uris":[""]}],"mendeley":{"formattedCitation":"^2–4","plainTextFormattedCitation":"2–4","previouslyFormattedCitation":"^2–4"},"properties":{"noteIndex":0},"schema":""}2–4. Recent studies have suggested complications following resection may lead to a delay in adjuvant chemotherapyADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1097/DCR.0b013e3182a857eb","ISSN":"1530-0358","PMID":"24201387","abstract":"OBJECTIVE: The objective of this study was to identify the risk factors for delays in chemotherapy after rectal cancer surgery and evaluate the effects of delayed therapy on long-term outcomes. We also sought to clarify what time frame should be used to define delayed adjuvant chemotherapy.\\n\\nBACKGROUND: Postoperative complications have been found to influence the timing of chemotherapy in patients with colon cancer. Delays in chemotherapy have been shown to be associated with worse overall and disease-free survival in patients with colorectal cancer, although the timing of delay has not been agreed upon in the literature.\\n\\nSTUDY DESIGN: We performed a retrospective review of a prospectively maintained rectal cancer database. Univariate analysis was used to identify risk factors for delayed chemotherapy. Kaplan-Meier curves were generated to compare overall and disease-free survival in patients based on complications and timing of chemotherapy.\\n\\nSETTINGS: This study was performed at the University of Wisconsin Hospital, Madison, Wisconsin, between 1995 and 2012.\\n\\nPATIENTS: Patients with rectal cancer who underwent proctectomy with curative intent were included in this study.\\n\\nOUTCOME MEASURES: Timing of chemotherapy, 30-day complications, and 30-day readmissions were the main outcome measures.\\n\\nRESULTS: Postoperative complications and 30-day readmissions were associated with delays in chemotherapy ≥8 weeks after surgery. Patients who received chemotherapy ≥8 weeks postoperatively were found to have worse local and distant recurrence rates and worse overall survival in comparison with patients who received chemotherapy within 8 weeks of surgery.\\n\\nLIMITATIONS: The limitations of this study include its retrospective nature and that it was performed at a single institution.\\n\\nCONCLUSIONS: We found complications and readmissions to be risk factors for delayed chemotherapy. Patients who received therapy ≥8 weeks postoperatively had worse disease-free and overall survival.","author":[{"dropping-particle":"","family":"Tevis","given":"Sarah E","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kohlnhofer","given":"Brittney M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stringfield","given":"Sarah","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Foley","given":"Eugene F","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Harms","given":"Bruce a","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Heise","given":"Charles P","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kennedy","given":"Gregory D","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Diseases of the colon and rectum","id":"ITEM-1","issued":{"date-parts":[["2013"]]},"note":"This study finds the obvious. Although they have not included data for co-founders - could this make the effect of timing insignificant?\n\nAlso our study could set out excatly when to give chemo and whether it is poinless after a certain amoint of weeks.\n\nWE could investigate which complications lead to delays\n\n\n\nThe median survival in patients who received delayed chemotherapy was 77.5 months (95% CI, 53.1–101.9). A Cox regression analy- sis was performed with the following potential cofounders: timing of chemotherapy, pathologic stage, margin status, neoadjuvant chemotherapy, comorbidity and postopera- tive complications; delays in chemotherapy remained a sig- nificant predictor of survival, local recurrence ,and distant recurrence (Table 3). These data suggest that delays in che- motherapy ≥8 weeks are associated with worse disease-free and overall survivThis study suggests the relationship between timimg of adjuvant therapy and survival has not been established\n\nProctectomy with TME\n\nOnly 355 patients initially - reduced to 136 with postop chemotherapy - - we should have more and also multi-instituional\n\nThese data show that the risk of death was significantly greater for patients with compli- cations who received adjuvant chemotherapy at ≥8 weeks compared with &lt;8 weeks. In patients without complica- tions, a similar trend in worse overall survival at ≥8 weeks was observed, but it lacked statistical significance.\n\ndeay chemo worsened disease free survival","page":"1339-48","title":"Postoperative complications in patients with rectal cancer are associated with delays in chemotherapy that lead to worse disease-free and overall survival.","type":"article-journal","volume":"56"},"uris":[""]}],"mendeley":{"formattedCitation":"⁵","plainTextFormattedCitation":"5","previouslyFormattedCitation":"⁵"},"properties":{"noteIndex":0},"schema":""}5. However these studies have concentrated on hospital data, and have not considered complications post-discharge such as venothromboembolic events or wound infections. These are often managed in primary care and have the potential to delay treatment further. In addition, no study has investigated an association between complications and a delay in adjuvant chemotherapy while confounding for the urgency of admission that led to the resection, co-morbidities and the type of surgical approach. It is unclear whether the impact of a delay in adjuvant chemotherapy on overall survival is maintained after taking into account these factors.The aim of this observational cohort study was to describe the patient factors and complications encountered in primary and secondary care associated with an increased risk of a delay in adjuvant chemotherapy beyond eight weeks and the impact on survival. METHODData sourceData were derived from the Clinical Practice Research Datalink (CPRD), which provides primary care data for 8-10% of the UK populationADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/j.1365-2125.2009.03537.x","ISBN":"1365-2125 (Electronic)\\n0306-5251 (Linking)","ISSN":"03065251","PMID":"20078607","abstract":"To investigate the range of methods used to validate diagnoses in the General Practice Research Database (GPRD), to summarize findings and to assess the quality of these validations.","author":[{"dropping-particle":"","family":"Herrett","given":"Emily","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Thomas","given":"Sara L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schoonen","given":"W. Marieke","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Smeeth","given":"Liam","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hall","given":"Andrew J.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"British Journal of Clinical Pharmacology","id":"ITEM-1","issued":{"date-parts":[["2010"]]},"note":"A publication was considered for initial inclusion when a set of medical codes for a syn- drome, disease diagnosis or death, defined by the investi- gators as a ‘case’, was verified using one of the methods summarized in Table 1. Such methods use data either entirely contained within the database (internal valida- tions) or from outside the database (external validations).\nInclusion\n\nThe aims of the review were to investigate the range of methods used to validate diag- noses in the GPRD,summarize the findings of these studies and assess the quality of reporting of validation methods and results\n\n\n\nmethods used to validate diagnoses in the General Practice Research Database (GPRD),\n\nPubMed and Embase for publications using GPRD data published between 1987 and April 2008\n\nAdditional publications were identified from conference proceedings, back issues of relevant journals, bibliographies of retrieved publications and relevant websites.\n\nThe majority of validations were external, and most\nfrequently were requests to GPs to provide additional information.","page":"4-14","title":"Validation and validity of diagnoses in the General Practice Research Database: A systematic review","type":"article-journal","volume":"69"},"uris":[""]}],"mendeley":{"formattedCitation":"⁶","plainTextFormattedCitation":"6","previouslyFormattedCitation":"⁶"},"properties":{"noteIndex":0},"schema":""}6 and is considered accurate and representative of the whole populationADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1177/2042098611435911","ISSN":"2042-0986","PMID":"25083228","abstract":"Since its inception in the mid-1980s, the General Practice Research Database (GPRD) has undergone many changes but remains the largest validated and most utilised primary care database in the UK. Its use in pharmacoepidemiology stretches back many years with now over 800 original research papers. Administered by the Medicines and Healthcare products Regulatory Agency since 2001, the last 5 years have seen a rebuild of the database processing system enhancing access to the data, and a concomitant push towards broadening the applications of the database. New methodologies including real-world harm-benefit assessment, pharmacogenetic studies and pragmatic randomised controlled trials within the database are being implemented. A substantive and unique linkage program (using a trusted third party) has enabled access to secondary care data and disease-specific registry data as well as socio-economic data and death registration data. The utility of anonymised free text accessed in a safe and appropriate manner is being explored using simple and more complex techniques such as natural language processing.","author":[{"dropping-particle":"","family":"Williams","given":"Tim","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Staa","given":"Tjeerd","non-dropping-particle":"van","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Puri","given":"Shivani","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Eaton","given":"Susan","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Therapeutic advances in drug safety","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2012","4","1"]]},"note":"No real description of publications from linked datasets\n\nNo specific validation work has been conducted on this method (to check for quality) as much of it is based on logical inconsistency of the registration data. \n\nVision GP system provides GPRD data\n\nGPRD can be used to produce a study with direct patient contact\n\nEach parameter generated an earliest date at which it is accepta- ble, and the UTS date was set to the earliest date at which nine of these were acceptable, with the exception of the mortality parameter which was mandatory\n\nIn its current form the UTS date is based on two central concepts: assurance of con- tinuity in data recording, and mortality rate com- pared with an expected range.\n\nA collaboration involving GPRD has recently been undertaken to develop such data quality parameters, initial pilot phase results exploring baseline parameters across the data [Tate et al. 2011].\n\nGPRD has a long history of validation studies which has been recently reviewed [Herret et al. 2010]. This study reviewed 212 publications involving 357 validations classifying them as either internal (manual/algorithmic review of database records or sensitivity analysis) or exter- nal (questionnaires or patient record requests to GPs and comparison with external data sources). Generally a high proportion of cases were con- firmed but for the majority of studies only positive predictive values (PPVs) are obtainable.\n\nThe importance of code selection is an area explored by a GPRD stroke study which stresses the need for trans- parency and an understanding of the context of code selection [Gulliford et al. 2009]. \n\nA smaller review of GPRD validation studies [Khan et al. 2010] came to similar conclusions reporting high PPVs, citing the Morbidity Statistics from General Practice 1991–1992 (MSGP4) as a frequent external comparator, and also noting the use of both Read codes and OXMIS codes (Oxford Medical Information System codes: an early clinical dictionary used by VM system) as a complication of coding.\n\nAll previous monthly databases are retained and at any one time six previous monthly versions are available for access on the online system.","page":"89-99","title":"Recent advances in the utility and use of the General Practice Research Database as an example of a UK Primary Care Data resource.","type":"article-journal","volume":"3"},"uris":[""]}],"mendeley":{"formattedCitation":"⁷","plainTextFormattedCitation":"7","previouslyFormattedCitation":"⁷"},"properties":{"noteIndex":0},"schema":""}7. Internal criteria ensures the anonymized records are of an ‘acceptable’ standardADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.3399/bjgp10X483562","ISSN":"09601643","abstract":"Background: The UK-based General Practice Research Database (GPRD) is a valuable source of longitudinal primary care records and is increasingly used for epidemiological research. Aim: To conduct a systematic review of the literature on accuracy and completeness of diagnostic coding in the GPRD. Design of study: Systematic review. Method: Six electronic databases were searched using search terms relating to the GPRD, in association with terms synonymous with validity, accuracy, concordance, and recording. A positive predictive value was calculated for each diagnosis that considered a comparison with a gold standard. Studies were also considered that compared the GPRD with other databases and national statistics. Results: A total of 49 papers are included in this review. Forty papers conducted validation of a clinical diagnosis in the GPRD. When assessed against a gold standard (validation using GP questionnaire, primary care medical records, or hospital correspondence), most of the diagnoses were accurately recorded in the patient electronic record. Acute conditions were not as well recorded, with positive predictive values lower than 50%. Twelve papers compared prevalence or consultation rates in the GPRD against other primary care databases or national statistics. Generally, there was good agreement between disease prevalence and consultation rates between the GPRD and other datasets; however, rates of diabetes and musculoskeletal conditions were underestimated in the GPRD. Conclusion: Most of the diagnoses coded in the GPRD are well recorded. Researchers using the GPRD may want to consider how well the disease of interest is recorded before planning research, and consider how to optimise the identification of clinical events","author":[{"dropping-particle":"","family":"Khan","given":"Nada F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Harrison","given":"Sian E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rose","given":"Peter W.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"British Journal of General Practice","id":"ITEM-1","issue":"March","issued":{"date-parts":[["2010"]]},"page":"199-206","title":"Validity of diagnostic coding within the General Practice Research Database: A systematic review","type":"article-journal","volume":"60"},"uris":[""]}],"mendeley":{"formattedCitation":"⁸","plainTextFormattedCitation":"8","previouslyFormattedCitation":"⁸"},"properties":{"noteIndex":0},"schema":""}8, and from practices with research quality data. Individual patient records are linked to Hospital Episodes Statistics (HES) and the Office for National Statistics (ONS) cause of mortality, making it is possible to identify the clinical events of interest along the patient pathway. Data was provided under protocol 13_078 with ethics approval from CPRD and ISAC. Patient selectionA patient was deemed to have undergone a resection for colon cancer if a relevant procedure was recorded in the linked HES dataset based on OPCS coding(Appendix A) during the same admission as an ICD-10 diagnosis of colon cancer(Appendix B) between 1st April 2000 and 1st April 2011. From this population the study cohort was selected as those with a HES episode for chemotherapy (Appendix C) within 16 weeks of the resection. A threshold of 16 weeks has previously been used as it is unlikely AC treatment beyond this is for curative intentADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.ejso.2015.09.009","ISSN":"07487983","author":[{"dropping-particle":"","family":"Nachiappan","given":"Subramanian","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Askari","given":"Alan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mamidanna","given":"Ravikrishna","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Munasinghe","given":"Aruna","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Currie","given":"Andrew","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stebbing","given":"Justin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Faiz","given":"Omar","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"European Journal of Surgical Oncology (EJSO)","id":"ITEM-1","issue":"12","issued":{"date-parts":[["2015","12"]]},"page":"1636-1644","publisher":"Elsevier Ltd","title":"The impact of adjuvant chemotherapy timing on overall survival following colorectal cancer resection","type":"article-journal","volume":"41"},"uris":[""]}],"mendeley":{"formattedCitation":"⁹","plainTextFormattedCitation":"9","previouslyFormattedCitation":"⁹"},"properties":{"noteIndex":0},"schema":""}9. Patients were excluded if they were under 18 years of age, had an ICD code indicating metastatic disease(Appendix D) recorded within 28 days of the resection, or an alternative cancer diagnosis within three years before the resection. Defining the start of Adjuvant ChemotherapyPatients in the early AC group included those with their first AC episode within eight weeks of the resection, the remainder forming the late group. Differences between the early and late groups were compared for age (under 60, 60 to 75, over 75), gender, smoking history, Charlson score (zero, one or more), year of procedure (2000 to 2003, 2004 to 2007, 2008 to 2011), surgical access (laparoscopic or open), admission type for resection (emergency or elective), stoma at resection and a complication following a resection. Study variablesCharlson score was calculated from three years of HES data preceding the resectionADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.jclinepi.2004.03.012","ISBN":"0895-4356","ISSN":"08954356","PMID":"15617955","abstract":"The ICD-9-CM adaptation of the Charlson comorbidity score has been a valuable resource for health services researchers. With the transition into ICD-10 coding worldwide, an ICD-10 version of the Deyo adaptation was developed and validated using population-based hospital data from Victoria, Australia. The algorithm was translated from ICD-9-CM into ICD-10-AM (Australian modification) in a multistep process. After a mapping algorithm was used to develop an initial translation, these codes were manually examined by the coding experts and a general physician for face validity. Because the ICD-10 system is country specific, our goal was to keep many of the translated code at the three-digit level for generalizability of the new index. There appears to be little difference in the distribution of the Charlson Index score between the two versions. A strong association between increasing index scores and mortality exists: the area under the ROC curve is 0.865 for the last year using the ICD-9-CM version and remains high, at 0.855, for the ICD-10 version. This work represents the first rigorous adaptation of the Charlson comorbidity index for use with ICD-10 data. In comparison with a well-established ICD-9-CM coding algorithm, it yields closely similar prevalence and prognosis information by comorbidity category. ? 2004 Elsevier Inc. All rights reserved.","author":[{"dropping-particle":"","family":"Sundararajan","given":"Vijaya","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Henderson","given":"Toni","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Perry","given":"Catherine","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Muggivan","given":"Amanda","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Quan","given":"Hude","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ghali","given":"William A.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Clinical Epidemiology","id":"ITEM-1","issue":"12","issued":{"date-parts":[["2004"]]},"page":"1288-1294","title":"New ICD-10 version of the Charlson comorbidity index predicted in-hospital mortality","type":"article-journal","volume":"57"},"uris":[""]}],"mendeley":{"formattedCitation":"¹⁰","plainTextFormattedCitation":"10","previouslyFormattedCitation":"¹⁰"},"properties":{"noteIndex":0},"schema":""}10. A laparoscopic resection was defined by OPCS code (Appendix A) at the time of the resection. Conversion to open was considered as an open procedure rather than laparoscopic. Stoma at index procedure was defined as a Hartmann's procedure or the relevant OPCS code. The rate of stoma reversal (OPCS – G75.3 or H15.4) before the start of chemotherapy, and within 18 months of the original resection was also compared between the two groups. Complications were defined as re-operation (Appendix E), bowel obstruction without operation, wound infection or systemic (acute renal failure, myocardial infarction, cerebrovascular event, pneumonia, venothromboembolic event (VTE)). These complications were searched in HES in the interval between resection and start of AC, while CPRD was used to identify pneumonia, VTE or wound complications following discharge. A patient may have experienced more than one complication. These complications were included as they were considered relevant causes for a delay in adjuvant chemotherapyStatistical analysisChi square test was used to investigate differences in categorical variables between the two AC groups. These variables were included in a binary logistic regression model to determine the risk of a delay in AC. Complications were considered either as present or absent. Clinically relevant two-way interactions were entered individually with the main effects model to determine whether they produced a significant change. All such interactions were then entered together into the model and removed step-wise if found to be non-significant. The only significant interaction included in the model was between the type of admission and surgical access. A Cox proportional hazards model identified whether there was a difference in mortality between the two AC groups, while taking into consideration the aforementioned patient and surgery variables. Survival was calculated from the start of AC to the date of death in ONS. No time dependent factors were found that would have violated the proportional hazards assumption. Smoking history and a delay in AC was the only significant interaction and was included in the full model. Kaplan Meier curves described the difference in survival function between the early and late AC groups. Robust standard errors were constructed that accounted for heteroscedasticity. All analysis was carried out using SPSS (IBM v22), with significance taken at p<0.05.RESULTSIn total 7501 patients had a colon cancer resection between 2000 and 2011. Of these 1266 (16.9%) underwent AC within sixteen weeks. The median time to the first treatment was 8.1 weeks (Interquartile range 6.7 to 10.1). The earliest was at 2.3 weeks (figure 1), with the latest as per the criterion of 16 weeks. 598 patients (47.2%) started their AC within 8 weeks of the resection. Summary statisticsA higher proportion of patients over 75 (59.9%) experienced a delay in treatment compared with those under 60 (50.1%) and aged 60 to 75 (52.0%), although this did not reach significance (p=0.067) (table 1). A significantly higher percentage of patients receiving AC late had a stoma at the time of the resection (65.5% p<0.005). There was no difference found between the two groups in terms of gender, year of resection or Charlson score, surgical access (laparoscopy 46.8% early vs 53.2% late, p=0.871) nor emergency admission (44.6% vs 55.4% respectively, p=0.241). Of the early AC group who had a stoma, one patient underwent a reversal before the start of chemotherapy, while 37.7% underwent a reversal within 18 months. This compares with 5 (4.3% p = 0.351) and 23.3% (p = 0.043). The proportion of patients undergoing an emergency resection decreased with time (2000 to 2003 = 31.9%, 2004 to 2007 = 26.7%, 2008 to 2011 = 26.0% p = 0.153).Complications From CPRD, 59 patients suffered a wound infection managed conservatively, of which 57 (96.6%) were not noted in HES (table 2). All patients who experienced a delay in AC and had a wound infection in CPRD (n = 37) did not have this complication recorded in HES. A further six cases of VTE were in CPRD but not described in HES. There were no cases of pneumonia in CPRD.A significantly higher percentage from the late group underwent a re-operation compared with the early group (3.3% vs 7.0% p=0.005). Although there was no significant difference in the rate of wound infections in the HES data between the two AC groups, this complication was significantly higher in the late AC group (5.5% vs 3.3% p=0.040). Using HES alone, 88 (14.7%) patients from the early adjuvant chemotherapy group compared with 142 (21.3%) in the late group experienced a complication. By also including CPRD data, the number of patients identified increased by 24% for both groups. Regression analysis for delaysThe risk of late AC treatment increased significantly following a complication (OR 1.53 CI 1.16-2.03 p=0.003) (table 3). Patients under 60 were significantly less likely to experience a delay in AC compared with those over 75 (OR 0.65 CI 0.46-0.93, p<0.019) while there was no difference compared with the 60 to 75 age group. Smoking (OR 1.60 CI 1.08-2.35 p=0.018) or a stoma at the index operation (OR 1.79 CI 1.26-2.52 p=0.001) increased the risk of a delay. Gender, the year of resection, laparoscopy or the type of admission did not alter the odds of a delay in AC.Impact on survival A significantly higher proportion of patients in the late AC group had died by the end of ONS coverage (32.9% vs 27.3%). Compared with patients who received AC early, those in the late group were associated with an increase in the risk of death (HR 1.44 CI 1.16 – 1.79 p=0.001), as were smokers (HR 2.26 CI 1.41-3.64). Undergoing a laparoscopic rather than an open resection (HR 0.84 CI 0.56-1.27, p=0.414) or experiencing a complication (HR 1.15 CI 0.89-1.48, p=0.295) did not significantly alter prognosis. However an emergency resection significantly increased the risk of death by 59% (CI 1.28-1.98, p<0.0005) compared with those who underwent an elective procedure. A resection between 2008 to 2011 inclusive was associated with a significant decrease in the risk of death compared with patients treated between 2000 to 2003 (HR 0.64 CI 0.46-0.88 p=0.007).Figure 2 suggests adjuvant chemotherapy within eight weeks was associated with a relative increase in survival by 12.3% at 5 years (65% in the early treatment group vs 73% in the late treatment group).DISCUSSIONSummaryThe aim of this study was to determine the factors associated with a delay in initiating adjuvant chemotherapy following colonic cancer resection, and their impact on long term prognosis. CPRD was shown to include a proportion of wound infections and VTE events that were not noted in HES, suggesting secondary care data is insufficient to describe the extent of complications experienced by patients before AC treatment. Smoking history, stoma at the time of resection and older age were associated with a delay in AC after eight weeks. By definition all the patients in this study survived to receive adjuvant chemotherapy. Therefore, although complications were associated with a delay in adjuvant chemotherapy, they did not independently impact survival. Comparison to previous studiesThis is the first study to use routinely collected national primary and secondary care data to identify a combination of factors that are associated with a delay in adjuvant chemotherapy. CPRD has been validated as being reliable in terms of patient demographics, diagnoses and prescription dataADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/j.1365-2125.2009.03537.x","ISBN":"1365-2125 (Electronic)\\n0306-5251 (Linking)","ISSN":"03065251","PMID":"20078607","abstract":"To investigate the range of methods used to validate diagnoses in the General Practice Research Database (GPRD), to summarize findings and to assess the quality of these validations.","author":[{"dropping-particle":"","family":"Herrett","given":"Emily","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Thomas","given":"Sara L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schoonen","given":"W. Marieke","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Smeeth","given":"Liam","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hall","given":"Andrew J.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"British Journal of Clinical Pharmacology","id":"ITEM-1","issued":{"date-parts":[["2010"]]},"note":"A publication was considered for initial inclusion when a set of medical codes for a syn- drome, disease diagnosis or death, defined by the investi- gators as a ‘case’, was verified using one of the methods summarized in Table 1. Such methods use data either entirely contained within the database (internal valida- tions) or from outside the database (external validations).\nInclusion\n\nThe aims of the review were to investigate the range of methods used to validate diag- noses in the GPRD,summarize the findings of these studies and assess the quality of reporting of validation methods and results\n\n\n\nmethods used to validate diagnoses in the General Practice Research Database (GPRD),\n\nPubMed and Embase for publications using GPRD data published between 1987 and April 2008\n\nAdditional publications were identified from conference proceedings, back issues of relevant journals, bibliographies of retrieved publications and relevant websites.\n\nThe majority of validations were external, and most\nfrequently were requests to GPs to provide additional information.","page":"4-14","title":"Validation and validity of diagnoses in the General Practice Research Database: A systematic review","type":"article-journal","volume":"69"},"uris":[""]}],"mendeley":{"formattedCitation":"⁶","plainTextFormattedCitation":"6","previouslyFormattedCitation":"⁶"},"properties":{"noteIndex":0},"schema":""}6. AC following colonic resection can be considered a marker of the standard of treatmentADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1007/DCR.0b013e3181f2f202","ISSN":"1530-0358","PMID":"21178851","abstract":"PURPOSE: Appropriate use of adjuvant chemotherapy is a widely recognized quality measure of colorectal cancer care. The objective of this study was to test the hypothesis that surgical complications are associated with omission of chemotherapy for colorectal cancer. METHODS: We used the 1998 to 2005 Surveillance, Epidemiology and End Results-Medicare database to study adjuvant chemotherapy use among patients with stage III colorectal cancer who underwent surgical resection. Chemotherapy use was compared between patients with and without complications. Univariate analyses and multiple logistic regression were used to test the association between complications and chemotherapy omission, while adjusting for demographics, comorbidity, and other factors. Associations between complications and time to chemotherapy were also studied. RESULTS: We identified 17,108 eligible patients with stage III colorectal cancer (median age, 75 y; 24% rectal/rectosigmoid). Using a parsimonious list of complication codes, 18% of patients had ≥ 1 complication. Thirteen percent of patients had medical complications and 3.8% of patients had complications requiring reoperation or another procedure. Adjuvant chemotherapy was omitted among 46% of patients with complications, compared with 31% of patients with no complications (P < .0001). Having a complication was independently associated with omission of chemotherapy in multivariable analysis (adjusted OR, 1.76; 95% CI 1.59-1.95). Other factors significantly associated with chemotherapy omission were age, race, marital status, urgent/emergent admission, and type of operation. Risk ratios increase with multiple complications (P < .0001). Complications were also associated with an increased risk of chemotherapy delay (P < .0001). CONCLUSIONS: Surgical complications are independently associated with omission of chemotherapy for stage III colorectal cancer and with a delay in adjuvant chemotherapy. These data suggest that complications of colorectal surgery may affect both short- and long-term cancer outcomes. Thus, the implementation of quality improvement measures that effectively reduce perioperative complications may also provide a long-term cancer survival benefit.","author":[{"dropping-particle":"","family":"Hendren","given":"Samantha","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Birkmeyer","given":"John D","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yin","given":"Huiying","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Banerjee","given":"Mousumi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sonnenday","given":"Christopher","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Morris","given":"Arden M","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Diseases of the colon and rectum","id":"ITEM-1","issue":"12","issued":{"date-parts":[["2010","12"]]},"page":"1587-93","title":"Surgical complications are associated with omission of chemotherapy for stage III colorectal cancer.","type":"article-journal","volume":"53"},"uris":[""]}],"mendeley":{"formattedCitation":"¹¹","plainTextFormattedCitation":"11","previouslyFormattedCitation":"¹¹"},"properties":{"noteIndex":0},"schema":""}11. No study has shown a poorer outcome if the treatment is started ‘too early’, but starting adjuvant chemotherapy after 12 weeks has been shown to produce little beneiftADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1371/journal.pone.0107993","ISSN":"1932-6203","PMID":"25238395","abstract":"BACKGROUND: Delayed chemotherapy is associated with inferior survival in stage III colon and stage II/III rectal cancer patients, but similar studies have not been performed in stage II colon cancer patients. We investigate the association between delayed and incomplete chemotherapy, and the association of delayed chemotherapy with survival in stage II colon cancer patients.\n\nPATIENTS AND METHODS: Patients (age ≥ 66) diagnosed as stage II colon cancer and received chemotherapy from 1992 to 2005 were identified from the linked SEER-Medicare database. The association between delayed and incomplete chemotherapy was assessed using unconditional and conditional logistic regressions. Survival outcomes were assessed using stratified Cox regression based on propensity score matched samples.\n\nRESULTS: 4,209 stage II colon cancer patients were included, of whom 73.0% had chemotherapy initiated timely (≤ 2 months after surgery), 14.7% had chemotherapy initiated with moderate delay (2-3 months), and 12.3% had delayed chemotherapy (≥ 3 months). Delayed chemotherapy was associated with not completing chemotherapy (adjusted odds ratio (OR): 1.33 (95% confidence interval: 1.11, 1.59) for moderately delayed group, adjusted OR: 2.60 (2.09, 3.24) for delayed group). Delayed chemotherapy was associated with worse survival outcomes (hazard ratio (HR): 1.75 (1.29, 2.37) for overall survival; HR: 4.23 (2.19, 8.20) for cancer-specific survival).\n\nCONCLUSION: Although the benefit of chemotherapy is unclear in stage II colon cancer patients, delay in initiation of chemotherapy is associated with an incomplete chemotherapy course and poorer survival, especially cancer-specific survival. Causal inference in the association between delayed initiation of chemotherapy and inferior survival requires further investigation.","author":[{"dropping-particle":"","family":"Xu","given":"Fang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rimm","given":"Alfred A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fu","given":"Pingfu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Krishnamurthi","given":"Smitha S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cooper","given":"Gregory S","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"PloS one","id":"ITEM-1","issue":"9","issued":{"date-parts":[["2014","1"]]},"page":"e107993","title":"The impact of delayed chemotherapy on its completion and survival outcomes in stage II colon cancer patients.","type":"article-journal","volume":"9"},"uris":[""]}],"mendeley":{"formattedCitation":"¹²","plainTextFormattedCitation":"12","previouslyFormattedCitation":"¹²"},"properties":{"noteIndex":0},"schema":""}12. The findings of an improvement of 12.3% survival at 5 years for patients treated within eight weeks is similar to previous studiesADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.ejso.2015.09.009","ISSN":"07487983","author":[{"dropping-particle":"","family":"Nachiappan","given":"Subramanian","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Askari","given":"Alan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mamidanna","given":"Ravikrishna","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Munasinghe","given":"Aruna","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Currie","given":"Andrew","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stebbing","given":"Justin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Faiz","given":"Omar","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"European Journal of Surgical Oncology (EJSO)","id":"ITEM-1","issue":"12","issued":{"date-parts":[["2015","12"]]},"page":"1636-1644","publisher":"Elsevier Ltd","title":"The impact of adjuvant chemotherapy timing on overall survival following colorectal cancer resection","type":"article-journal","volume":"41"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1001/jama.2011.749","ISSN":"1538-3598","PMID":"21642686","abstract":"Adjuvant chemotherapy (AC) improves survival among patients with resected colorectal cancer. However, the optimal timing from surgery to initiation of AC is unknown.","author":[{"dropping-particle":"","family":"Biagi","given":"James J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Raphael","given":"Michael J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mackillop","given":"William J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kong","given":"Weidong","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"King","given":"Will D","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Booth","given":"Christopher M","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"JAMA : the journal of the American Medical Association","id":"ITEM-2","issue":"22","issued":{"date-parts":[["2011"]]},"note":"From Duplicate 1 (Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer: a systematic review and meta-analysis. - Biagi, James J; Raphael, Michael J; Mackillop, William J; Kong, Weidong; King, Will D; Booth, Christopher M)\n\nMeta - analayis regarding timing\nConsiders all colorectal tumours - does not split\nDoes not take into consideration wheter patints completed treatment\n\nNo mention about differenctating according to stage\n\nNo regression analysis in terms of patient demographics or type of operation\nconversion of discrete data waitting time categories into 4 week blocks\n\nUse our data to extrapolate over years and the effect of different regimes\n\n\nmeta-analyis - indicates that relativeOS\ndecreases by 14% for every 4-week delay to initiation of AC.\n\nIncludes theory about why time makes a difference\n\nThis papaer uses the data for predictive modelling","page":"2335-2342","title":"Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer: a systematic review and meta-analysis.","type":"article-journal","volume":"305"},"uris":[""]}],"mendeley":{"formattedCitation":"^2,9","plainTextFormattedCitation":"2,9","previouslyFormattedCitation":"^2,9"},"properties":{"noteIndex":0},"schema":""}2,9. Although it may be expected that complications are associated with a delay in the first episode of adjuvant chemotherapy, we were able to describe in detail complications from both primary and secondary care. For example, in previous studies post-operative hospital stay has been used as a surrogate marker for complications managed conservativelyADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1007/DCR.0b013e3181a51173","ISSN":"1530-0358","PMID":"19581846","abstract":"PURPOSE: This study was designed to evaluate the role of access to care and postsurgical recovery on delays in adjuvant chemotherapy for rectal cancer.\n\nMETHODS: Using data from the linked Surveillance, Epidemiology, and End Results-Medicare database, we analyzed patients with Stage II or III rectal cancer who received adjuvant chemotherapy after curative rectal cancer surgery between 1991 and 2002. Logistic and Cox regressions were performed to assess determinants of adjuvant chemotherapy delays and outcomes in two cohorts: patients with access to medical oncology care because of prior neoadjuvant chemotherapy (Group A) and patients without such access (Group B). Length of postoperative hospital stay served as the main proxy for postsurgical recovery.\n\nRESULTS: A total of 442 and 5,617 patients were included in Groups A and B, respectively. The median interval between surgery and adjuvant chemotherapy was 46 days in Group A and 42 days in Group B. Although 17 percent and 11 percent of patients in Groups A and B, respectively, waited three or more months for adjuvant chemotherapy, median overall survival was worse in this subset than in those who waited less than 3 months (54 vs. 76 months, P < 0.01). Postoperative hospital stay independently predicted for adjuvant chemotherapy delay in both groups. Disparities in delays were seen only in Group B, such that patients who were older or black had greater odds of an adjuvant chemotherapy delay (for both, P < 0.05).\n\nCONCLUSION: Advanced age and black race contribute to adjuvant chemotherapy delays and inferior outcomes, but postoperative recovery is the more important driver.","author":[{"dropping-particle":"","family":"Cheung","given":"Winson Y","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Neville","given":"Bridget A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Earle","given":"Craig C","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Diseases of the colon and rectum","id":"ITEM-1","issue":"6","issued":{"date-parts":[["2009","6"]]},"page":"1054-63; discussion 1064","title":"Etiology of delays in the initiation of adjuvant chemotherapy and their impact on outcomes for Stage II and III rectal cancer.","type":"article-journal","volume":"52"},"uris":[""]}],"mendeley":{"formattedCitation":"¹³","plainTextFormattedCitation":"13","previouslyFormattedCitation":"¹³"},"properties":{"noteIndex":0},"schema":""}13, but data for conservative treatment of bowel obstruction has not previously been published. In our study this was the most common complication (9.6% n=122), and in the majority is likely to represent post-operative ileus. By utilising CPRD, we identified 56 extra patients as having suffered a complication, with the majority being wound infections. 5.3% of all patients underwent a re-operation, with a significantly higher proportion in the delayed AC group (7.0%, n=47). The overall re-operation rate is lower than the 14% reported by van der Geest et al.ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/codi.12288","ISSN":"1463-1318","PMID":"23679338","abstract":"AIM: The study included investigation of factors determining suboptimal adjuvant chemotherapy of patients diagnosed with Stage III colon cancer. METHOD: All 606 patients diagnosed with Stage III colon cancer between 2006 and 2008 in the western part of the Netherlands were included. Patient [gender, age, comorbidity and socio-economic status (SES)], tumour (location, stage and grade) and treatment (emergency surgery, laparoscopic surgery, reoperation, hospital stay and multidisciplinary meeting) factors were examined in logistic regression analyses predicting a complicated postoperative period and omission, delay and discontinuation of adjuvant chemotherapy. RESULTS: Overall, 27% of all patients experienced a complicated postoperative period, which was independently associated with emergency surgery, older age, multiple comorbidity, male gender and poor tumour grade. Of patients who survived this period, 60% received chemotherapy. Chemotherapy was omitted more often in women, the elderly and in patients with Stage IIIB, reoperation, prolonged hospital stay and (borderline) after open surgery. Of patients who received chemotherapy, 86% started within 8 weeks after surgery. Patients with a higher SES, reoperation and prolonged hospital stay had a higher probability of a delayed start. Sixty-seven per cent of patients completed their chemotherapy. For women, elderly patients and patients with prolonged hospital stay a higher probability of discontinuation was noted. CONCLUSION: Age was the most important predictive factor for receiving adjuvant chemotherapy. However, at all ages, complicated postoperative recovery negatively influenced the administration of chemotherapy to Stage III colon cancer patients, as well as a timely start and completion of chemotherapy.","author":[{"dropping-particle":"","family":"Geest","given":"L G M","non-dropping-particle":"van der","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Portielje","given":"J E A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wouters","given":"M W J M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Weijl","given":"N I","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tanis","given":"B C","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tollenaar","given":"R A E M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Struikmans","given":"H","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nortier","given":"J W R","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland","id":"ITEM-1","issue":"10","issued":{"date-parts":[["2013","1"]]},"page":"e582-91","title":"Complicated postoperative recovery increases omission, delay and discontinuation of adjuvant chemotherapy in patients with Stage III colon cancer.","type":"article-journal","volume":"15"},"uris":[""]}],"mendeley":{"formattedCitation":"¹⁴","plainTextFormattedCitation":"14","previouslyFormattedCitation":"¹⁴"},"properties":{"noteIndex":0},"schema":""}14 but similar to the 5.6% reported by Nachiappan et al. This reflects the different data sources: Geest et al. ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/codi.12288","ISSN":"1463-1318","PMID":"23679338","abstract":"AIM: The study included investigation of factors determining suboptimal adjuvant chemotherapy of patients diagnosed with Stage III colon cancer. METHOD: All 606 patients diagnosed with Stage III colon cancer between 2006 and 2008 in the western part of the Netherlands were included. Patient [gender, age, comorbidity and socio-economic status (SES)], tumour (location, stage and grade) and treatment (emergency surgery, laparoscopic surgery, reoperation, hospital stay and multidisciplinary meeting) factors were examined in logistic regression analyses predicting a complicated postoperative period and omission, delay and discontinuation of adjuvant chemotherapy. RESULTS: Overall, 27% of all patients experienced a complicated postoperative period, which was independently associated with emergency surgery, older age, multiple comorbidity, male gender and poor tumour grade. Of patients who survived this period, 60% received chemotherapy. Chemotherapy was omitted more often in women, the elderly and in patients with Stage IIIB, reoperation, prolonged hospital stay and (borderline) after open surgery. Of patients who received chemotherapy, 86% started within 8 weeks after surgery. Patients with a higher SES, reoperation and prolonged hospital stay had a higher probability of a delayed start. Sixty-seven per cent of patients completed their chemotherapy. For women, elderly patients and patients with prolonged hospital stay a higher probability of discontinuation was noted. CONCLUSION: Age was the most important predictive factor for receiving adjuvant chemotherapy. However, at all ages, complicated postoperative recovery negatively influenced the administration of chemotherapy to Stage III colon cancer patients, as well as a timely start and completion of chemotherapy.","author":[{"dropping-particle":"","family":"Geest","given":"L G M","non-dropping-particle":"van der","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Portielje","given":"J E A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wouters","given":"M W J M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Weijl","given":"N I","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tanis","given":"B C","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tollenaar","given":"R A E M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Struikmans","given":"H","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nortier","given":"J W R","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland","id":"ITEM-1","issue":"10","issued":{"date-parts":[["2013","1"]]},"page":"e582-91","title":"Complicated postoperative recovery increases omission, delay and discontinuation of adjuvant chemotherapy in patients with Stage III colon cancer.","type":"article-journal","volume":"15"},"uris":[""]}],"mendeley":{"formattedCitation":"¹⁴","plainTextFormattedCitation":"14","previouslyFormattedCitation":"¹⁴"},"properties":{"noteIndex":0},"schema":""}14 used medical records, whereas the latter group used HES similar to our studyIn addition to complications, a stoma at the initial operation was a risk factor for delays. However from HES it is not possible to ascertain with certainty whether the stoma was a permanent or temporary bowel discontinuation. The lack of detail also precludes differentiating whether the higher proportion of reversals before AC in the delayed group were because of high output or a pre-operative plan to reverse before AC. The lower proportion of patients from the delayed AC group undergoing a reversal within 18 months may reflect more end stomas or the patient was no longer suitable for another procedure.Interestingly smoking was found to be an independent risk factor for a delay in AC. An interaction between smoking and complications or Charlson score was not demonstrated to explain this finding. A surgeon may decide to use a minimally invasive approach to reduce recovery timeADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"ISBN":"1086-8089","PMID":"18435886","abstract":"Background: The short-term benefits of laparoscopic surgery are well established, particularly within an enhanced recovery program. Early return to activity is to be expected but has not been quantified. The aim of this study was to measure the hospital stay and return to full activity following laparoscopic colorectal surgery and compare this with laparoscopic cholecystectomy and laparoscopic inguinal hernia repair. Methods: All totally laparoscopic gallbladder, inguinal hernia, and colorectal operations performed between January 2003 and October 2006 were included. Outcomes were collected from a prospective database and case notes. Post discharge information was collected by telephone interview. A comparison was made by creating 4 groups: laparoscopic cholecystectomy, laparoscopic inguinal hernia repair (Transabdominal PrePeritoneal [TAPP]), laparoscopic colorectal nonresectional, and re-sectional surgery. Results: The median hospital stay following laparoscopic colorectal resection was 7 days, while in the cholecystectomy and hernia group it was 1 day. The median return to full activity after discharge from the hospital was 4, 5, 3, and 7 days in the laparoscopic cholecystectomy, inguinal hernia repair, nonresection, and colorectal resection groups, respectively. Conclusions: Following laparoscopic colorectal surgery, patients can be expected to return to their usual activities within a week after discharge from the hospital and less than 2 weeks from surgery.","author":[{"dropping-particle":"","family":"Raymond","given":"Thomas M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dastur","given":"Jamasp K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Khot","given":"Umesh P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Parker","given":"Mike C.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"JSLS : Journal of the Society of Laparoendoscopic Surgeons","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2008"]]},"page":"143-149","title":"Hospital Stay and Return to Full Activity Following Laparoscopic Colorectal Surgery","type":"article-journal","volume":"12"},"uris":[""]}],"mendeley":{"formattedCitation":"¹⁵","plainTextFormattedCitation":"15","previouslyFormattedCitation":"¹⁵"},"properties":{"noteIndex":0},"schema":""}15. However, this study demonstrates there is no difference in using laparoscopy or open surgery in terms of reducing post-operative treatment delays after adjusting for complications. Our findings suggest patients who manage to start AC treatment despite experiencing a complication are no longer at risk of increased mortality due to the complication. This is similar to a previous studies by Tevis et al.ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1097/DCR.0b013e3182a857eb","ISSN":"1530-0358","PMID":"24201387","abstract":"OBJECTIVE: The objective of this study was to identify the risk factors for delays in chemotherapy after rectal cancer surgery and evaluate the effects of delayed therapy on long-term outcomes. We also sought to clarify what time frame should be used to define delayed adjuvant chemotherapy.\\n\\nBACKGROUND: Postoperative complications have been found to influence the timing of chemotherapy in patients with colon cancer. Delays in chemotherapy have been shown to be associated with worse overall and disease-free survival in patients with colorectal cancer, although the timing of delay has not been agreed upon in the literature.\\n\\nSTUDY DESIGN: We performed a retrospective review of a prospectively maintained rectal cancer database. Univariate analysis was used to identify risk factors for delayed chemotherapy. Kaplan-Meier curves were generated to compare overall and disease-free survival in patients based on complications and timing of chemotherapy.\\n\\nSETTINGS: This study was performed at the University of Wisconsin Hospital, Madison, Wisconsin, between 1995 and 2012.\\n\\nPATIENTS: Patients with rectal cancer who underwent proctectomy with curative intent were included in this study.\\n\\nOUTCOME MEASURES: Timing of chemotherapy, 30-day complications, and 30-day readmissions were the main outcome measures.\\n\\nRESULTS: Postoperative complications and 30-day readmissions were associated with delays in chemotherapy ≥8 weeks after surgery. Patients who received chemotherapy ≥8 weeks postoperatively were found to have worse local and distant recurrence rates and worse overall survival in comparison with patients who received chemotherapy within 8 weeks of surgery.\\n\\nLIMITATIONS: The limitations of this study include its retrospective nature and that it was performed at a single institution.\\n\\nCONCLUSIONS: We found complications and readmissions to be risk factors for delayed chemotherapy. Patients who received therapy ≥8 weeks postoperatively had worse disease-free and overall survival.","author":[{"dropping-particle":"","family":"Tevis","given":"Sarah E","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kohlnhofer","given":"Brittney M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stringfield","given":"Sarah","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Foley","given":"Eugene F","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Harms","given":"Bruce a","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Heise","given":"Charles P","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kennedy","given":"Gregory D","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Diseases of the colon and rectum","id":"ITEM-1","issued":{"date-parts":[["2013"]]},"note":"This study finds the obvious. Although they have not included data for co-founders - could this make the effect of timing insignificant?\n\nAlso our study could set out excatly when to give chemo and whether it is poinless after a certain amoint of weeks.\n\nWE could investigate which complications lead to delays\n\n\n\nThe median survival in patients who received delayed chemotherapy was 77.5 months (95% CI, 53.1–101.9). A Cox regression analy- sis was performed with the following potential cofounders: timing of chemotherapy, pathologic stage, margin status, neoadjuvant chemotherapy, comorbidity and postopera- tive complications; delays in chemotherapy remained a sig- nificant predictor of survival, local recurrence ,and distant recurrence (Table 3). These data suggest that delays in che- motherapy ≥8 weeks are associated with worse disease-free and overall survivThis study suggests the relationship between timimg of adjuvant therapy and survival has not been established\n\nProctectomy with TME\n\nOnly 355 patients initially - reduced to 136 with postop chemotherapy - - we should have more and also multi-instituional\n\nThese data show that the risk of death was significantly greater for patients with compli- cations who received adjuvant chemotherapy at ≥8 weeks compared with &lt;8 weeks. In patients without complica- tions, a similar trend in worse overall survival at ≥8 weeks was observed, but it lacked statistical significance.\n\ndeay chemo worsened disease free survival","page":"1339-48","title":"Postoperative complications in patients with rectal cancer are associated with delays in chemotherapy that lead to worse disease-free and overall survival.","type":"article-journal","volume":"56"},"uris":[""]}],"mendeley":{"formattedCitation":"⁵","plainTextFormattedCitation":"5","previouslyFormattedCitation":"⁵"},"properties":{"noteIndex":0},"schema":""}5 and Nachiappan et al.ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/codi.13308","ISSN":"14628910","author":[{"dropping-particle":"","family":"Nachiappan","given":"S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Askari","given":"A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mamidanna","given":"R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Munasinghe","given":"A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Currie","given":"A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stebbing","given":"J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Faiz","given":"O.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Colorectal Disease","id":"ITEM-1","issue":"11","issued":{"date-parts":[["2016"]]},"page":"1041-1049","title":"Initiation of adjuvant chemotherapy within 8?weeks of elective colorectal resection improves overall survival regardless of reoperation","type":"article-journal","volume":"18"},"uris":[""]}],"mendeley":{"formattedCitation":"¹⁶","plainTextFormattedCitation":"16","previouslyFormattedCitation":"¹⁶"},"properties":{"noteIndex":0},"schema":""}16. As expected a smoking historyADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1097/SLA.0b013e3182708cc5","ISSN":"0003-4932","PMID":"23059503","abstract":"OBJECTIVE:: The aim of this study was to delineate the impact of smoking on postoperative outcomes after colorectal resection for malignant and benign processes. BACKGROUND:: Studies to date have implicated smoking as a risk factor for increased postoperative complications. However, there is a paucity of data on the effects of smoking after colorectal surgery and in particular for malignant compared with benign processes. METHODS:: The American College of Surgeon's National Surgical Quality Improvement Program (2005-2010) database was queried for patients undergoing elective major colorectal resection for colorectal cancer, diverticular disease, or inflammatory bowel disease. Risk-adjusted 30-day outcomes were assessed and compared between patient cohorts identified as never-smokers, ex-smokers, and current smokers. Primary outcomes of incisional infections, infectious and major complications, and mortality were evaluated using regression modeling adjusting for patient characteristics and comorbidities. RESULTS:: A total of 47,574 patients were identified, of which 26,333 had surgery for colorectal cancer, 14,019 for diverticular disease, and 7222 for inflammatory bowel disease. More than 60% of patients had never smoked, 20.4% were current smokers, and 19.2% were ex-smokers. After adjustment, current smokers were at a significantly increased risk of postoperative morbidity [odds ratio (OR), 1.3; 95% confidence interval (CI), 1.21-1.40] and mortality (OR, 1.5; 95% CI, 1.11-1.94) after colorectal surgery. This finding persisted across malignant and benign diagnoses and also demonstrated a significant dose-dependent effect when stratifying by pack-years of smoking. CONCLUSIONS:: Smoking increases the risk of complications after all types of major colorectal surgery, with the greatest risk apparent for current smokers. A concerted effort should be made toward promoting smoking cessation in all patients scheduled for elective colorectal surgery.","author":[{"dropping-particle":"","family":"Sharma","given":"Abhiram","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Deeb","given":"Andrew-Paul","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Iannuzzi","given":"James C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rickles","given":"Aaron S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Monson","given":"John R.T.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fleming","given":"Fergal J.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Annals of Surgery","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2012"]]},"page":"296-300","title":"Tobacco Smoking and Postoperative Outcomes After Colorectal Surgery","type":"article-journal","volume":"258"},"uris":[""]}],"mendeley":{"formattedCitation":"¹⁷","plainTextFormattedCitation":"17","previouslyFormattedCitation":"¹⁷"},"properties":{"noteIndex":0},"schema":""}17 or an emergency admissionADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1002/bjs.4456","ISBN":"0007-1323 (Print)\\r0007-1323 (Linking)","ISSN":"00071323","PMID":"15122613","abstract":"BACKGROUND: Previous studies have reported that emergency presentation of colorectal cancer is associated with poor outcome. Many of these studies were small and most were not adjusted for case mix. The aim of this study was to establish, after adjusting for case mix, the magnitude of the differences in postoperative mortality and survival between patients undergoing elective surgery and those presenting as an emergency. METHODS: Three thousand two hundred patients who underwent surgery for colorectal cancer between 1991 and 1994 in Scotland were studied. Five-year survival rates and adjusted hazard ratios were calculated. RESULTS: Some 1603 (72.4 per cent) of 2214 elective patients had a potentially curative resection compared with 632 (64.1 per cent) of 986 patients who presented as an emergency (P < 0.001). Following curative resection, the postoperative mortality rate was 2.8 per cent after elective and 8.2 per cent after emergency operation (P < 0.001). Overall survival at 5 years was 57.5 per cent after elective and 39.1 per cent after emergency curative surgery (P < 0.001); cancer-specific survival at 5 years was 70.9 and 52.9 per cent respectively (P < 0.001). The adjusted hazard ratio for overall survival after emergency relative to elective surgery was 1.68 (95 per cent confidence interval (c.i.) 1.49 to 1.90; P < 0.001) and that for cancer-specific survival was 1.90 (95 per cent c.i. 1.62 to 2.22; P < 0.001). CONCLUSION: Following apparently curative resection for colorectal cancer, there was an excess of both cancer-related and intercurrent deaths in patients who presented as an emergency.","author":[{"dropping-particle":"","family":"McArdle","given":"C. S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hole","given":"D. J.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"British Journal of Surgery","id":"ITEM-1","issue":"December 1994","issued":{"date-parts":[["2004"]]},"page":"605-609","title":"Emergency presentation of colorectal cancer is associated with poor 5-year survival","type":"article-journal","volume":"91"},"uris":[""]}],"mendeley":{"formattedCitation":"¹⁸","plainTextFormattedCitation":"18","previouslyFormattedCitation":"¹⁸"},"properties":{"noteIndex":0},"schema":""}18 reduced overall survival. Patents treated between 2008 to 2011 demonstrated a better prognosis than those treated in 2000-2003. Between these periods our data demonstrate a reduction in the rate of emergency resections perhaps due to the NICE referral guidelines and/or screening. It could also reflect a change in practice to treat high risk stage II colon cancer with adjuvant chemotherapy, or the addition of oxaliplatin in chemotherapy regimensADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1093/jnci/djr524","ISSN":"1460-2105 (Electronic)","PMID":"22266473","abstract":"BACKGROUND: The addition of oxaliplatin to adjuvant 5-fluorouracil (5-FU) improves survival of patients with stage III colon cancer in randomized clinical trials (RCTs). However, RCT participants are younger, healthier, and less racially diverse than the general cancer population. Thus, the benefit of oxaliplatin outside RCTs is uncertain. SUBJECTS AND METHODS: Patients younger than 75 years with stage III colon cancer who received chemotherapy within 120 days of surgical resection were identified from five observational data sources-the Surveillance, Epidemiology, and End Results registry linked to Medicare claims (SEER-Medicare), the New York State Cancer Registry (NYSCR) linked to Medicaid and Medicare claims, the National Comprehensive Cancer Network (NCCN) Outcomes Database, and the Cancer Care Outcomes Research & Surveillance Consortium (CanCORS). Overall survival (OS) was compared among patients treated with oxaliplatin vs non-oxaliplatin-containing adjuvant chemotherapy. Overall survival for 4060 patients diagnosed during 2004-2009 was compared with pooled data from five RCTs (the Adjuvant Colon Cancer ENdpoinTs [ACCENT] group, n = 8292). Datasets were juxtaposed but not combined using Kaplan-Meier curves. Covariate and propensity score adjusted proportional hazards models were used to calculate adjusted survival hazard ratios (HR). Stratified analyses examined effect modifiers. All statistical tests were two-sided. RESULTS: The survival advantage associated with the addition of oxaliplatin to adjuvant 5-FU was evident across diverse practice settings (3-year OS: RCTs, 86% [n = 1273]; SEER-Medicare, 80% [n = 1152]; CanCORS, 88% [n = 129]; NYSCR-Medicaid, 82% [n = 54]; NYSCR-Medicare, 79% [n = 180]; and NCCN, 86% [n = 438]). A statistically significant improvement in 3-year overall survival was seen in the largest cohort, SEER-Medicare, and in the NYSCR-Medicare cohort (non-oxaliplatin-containing vs oxaliplatin-containing adjuvant therapy, adjusted HR of death: pooled RCTs: HR = 0.80, 95% CI = 0.70 to 0.92, P = .002; SEER-Medicare: HR = 0.70, 95% CI = 0.60 to 0.82, P < .001; NYSCR-Medicare patients aged >/=65 years: HR = 0.58, 95% CI = 0.38 to 0.90, P = .02). The association between oxaliplatin treatment and better survival was maintained in older and minority group patients, as well as those with higher comorbidity. CONCLUSION: The addition of oxaliplatin to 5-FU appears to be associated with better survival among patients receiving adjuvant col…","author":[{"dropping-particle":"","family":"Sanoff","given":"Hanna K","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Carpenter","given":"William R","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Martin","given":"Christopher F","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sargent","given":"Daniel J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Meyerhardt","given":"Jeffrey A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sturmer","given":"Til","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fine","given":"Jason P","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Weeks","given":"Jane","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Niland","given":"Joyce","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kahn","given":"Katherine L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schymura","given":"Maria J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schrag","given":"Deborah","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of the National Cancer Institute","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2012","2"]]},"language":"eng","page":"211-227","publisher-place":"United States","title":"Comparative effectiveness of oxaliplatin vs non-oxaliplatin-containing adjuvant chemotherapy for stage III colon cancer.","type":"article-journal","volume":"104"},"uris":[""]}],"mendeley":{"formattedCitation":"¹⁹","plainTextFormattedCitation":"19","previouslyFormattedCitation":"¹⁹"},"properties":{"noteIndex":0},"schema":""}19. Strengths and LimitationsThis is the first study to use linked data from CPRD as the source and so we have been able to consider post-discharge complications leading to delays in treatment. The number of colon cancer patients’ cases identified through our method compares well with the National Bowel Cancer AuditADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"abstract":"The National Bowel Cancer Audit is a high-profile, collaborative, national clinical audit for bowel cancer, including colon and rectal cancer.","author":[{"dropping-particle":"","family":"Partnership","given":"Healthcare Quality Improvement","non-dropping-particle":"","parse-names":false,"suffix":""}],"id":"ITEM-1","issued":{"date-parts":[["0"]]},"publisher":"Healthcare Quality Improvement Partnership","title":"National Bowel Cancer Audit","type":"article-journal"},"uris":[""]}],"mendeley":{"formattedCitation":"²⁰","plainTextFormattedCitation":"20","previouslyFormattedCitation":"²⁰"},"properties":{"noteIndex":0},"schema":""}20. In 2011 the latter reported 17161 patients underwent a colonic resection. From our data in 2010, 1242 had a resection, representing 7.2%. This is close to the 8% coverage of the national population by CPRD. However the proportion of patients receiving AC could be considered low, as previous studies have shown almost 20% of colon cancer patients receive treatmentADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1200/JCO.2004.09.059","ISSN":"0732183X","PMID":"15067028","abstract":"PURPOSE: Although it is well-established that fluorouracil- (FU-) based adjuvant therapy improves survival for patients with resected high-risk colon cancer, the magnitude of adjuvant therapy benefit across specific subgroups and for individual patients has been uncertain.\\n\\nPATIENTS AND METHODS: Using a pooled data set of 3,302 patients with stage II and III colon cancer from seven randomized trials comparing FU + leucovorin or FU + levamisole to surgery alone, we performed an analysis based on a Cox proportional hazards regression model. Treatment, age, sex, tumor location, T stage, nodal status, and grade were tested for both prognostic and predictive significance. Model derived estimates of 5-year disease-free survival and overall survival (OS) for surgery alone and surgery plus FU-based therapy were calculated for a range of patient subsets.\\n\\nRESULTS: Nodal status, T stage, and grade were the only prognostic factors independently significant for both disease-free survival and OS. Age was significant only for OS. In a multivariate analysis, adjuvant therapy showed a beneficial treatment effect across all subsets. Treatment benefits were consistent across sex, location, age, T-stage, and grade. A significant stage by treatment interaction was present, with treatment benefiting stage III patients to a greater degree than stage II patients.\\n\\nCONCLUSION: Patients with high-risk resected colon cancer obtain benefit from FU-based therapy across subsets of age, sex, location, T stage, nodal status, and grade. Model estimates of survival stratified by T stage, nodal status, grade, and age are available at . This information may improve patients' and physicians' understanding of the potential benefits of adjuvant therapy.","author":[{"dropping-particle":"","family":"Gill","given":"Sharlene","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Loprinzi","given":"Charles L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sargent","given":"Daniel J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Thomé","given":"Stephan D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Alberts","given":"Steven R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Haller","given":"Daniel G.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Benedetti","given":"Jacqueline","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Francini","given":"Guido","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shepherd","given":"Lois E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Seitz","given":"Jean Francois","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Labianca","given":"Roberto","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chen","given":"Wei","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cha","given":"Stephen S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Heldebrant","given":"Michael P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Goldberg","given":"Richard M.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Clinical Oncology","id":"ITEM-1","issue":"10","issued":{"date-parts":[["2004"]]},"page":"1797-1806","title":"Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: Who benefits and by how much?","type":"article-journal","volume":"22"},"uris":[""]}],"mendeley":{"formattedCitation":"¹","plainTextFormattedCitation":"1","previouslyFormattedCitation":"¹"},"properties":{"noteIndex":0},"schema":""}1. This is likely related to the completeness of chemotherapy coding in HES which has improved in latter years. As the accuracy of CPRDADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1093/ije/dyv098","ISSN":"0300-5771","PMID":"26050254","abstract":"The Clinical Practice Research Datalink (CPRD) is an ongoing primary care database of anonymised medical records from general practitioners, with coverage of over 11.3 million patients from 674 practices in the UK. With 4.4 million active (alive, currently registered) patients meeting quality criteria, approximately 6.9{%} of the UK population are included and patients are broadly representative of the UK general population in terms of age, sex and ethnicity. General practitioners are the gatekeepers of primary care and specialist referrals in the UK. The CPRD primary care database is therefore a rich source of health data for research, including data on demographics, symptoms, tests, diagnoses, therapies, health-related behaviours and referrals to secondary care. For over half of patients, linkage with datasets from secondary care, disease-specific cohorts and mortality records enhance the range of data available for research. The CPRD is very widely used internationally for epidemiological research and has been used to produce over 1000 research studies, published in peer-reviewed journals across a broad range of health outcomes. However, researchers must be aware of the complexity of routinely collected electronic health records, including ways to manage variable completeness, misclassification and development of disease definitions for research.","author":[{"dropping-particle":"","family":"Herrett","given":"Emily","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gallagher","given":"Arlene M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bhaskaran","given":"Krishnan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Forbes","given":"Harriet","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mathur","given":"Rohini","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Staa","given":"Tjeerd","non-dropping-particle":"van","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Smeeth","given":"Liam","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"International Journal of Epidemiology","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2015","6"]]},"page":"827-836","title":"Data Resource Profile: Clinical Practice Research Datalink (CPRD)","type":"article-journal","volume":"44"},"uris":[""]}],"mendeley":{"formattedCitation":"²¹","plainTextFormattedCitation":"21","previouslyFormattedCitation":"²¹"},"properties":{"noteIndex":0},"schema":""}21 and HESADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1093/pubmed/fdr054","ISSN":"1741-3850","PMID":"21795302","abstract":"INTRODUCTION: Routinely collected data sets are increasingly used for research, financial reimbursement and health service planning. High quality data are necessary for reliable analysis. This study aims to assess the published accuracy of routinely collected data sets in Great Britain.\n\nMETHODS: Systematic searches of the EMBASE, PUBMED, OVID and Cochrane databases were performed from 1989 to present using defined search terms. Included studies were those that compared routinely collected data sets with case or operative note review and those that compared routinely collected data with clinical registries.\n\nRESULTS: Thirty-two studies were included. Twenty-five studies compared routinely collected data with case or operation notes. Seven studies compared routinely collected data with clinical registries. The overall median accuracy (routinely collected data sets versus case notes) was 83.2% (IQR: 67.3-92.1%). The median diagnostic accuracy was 80.3% (IQR: 63.3-94.1%) with a median procedure accuracy of 84.2% (IQR: 68.7-88.7%). There was considerable variation in accuracy rates between studies (50.5-97.8%). Since the 2002 introduction of Payment by Results, accuracy has improved in some respects, for example primary diagnoses accuracy has improved from 73.8% (IQR: 59.3-92.1%) to 96.0% (IQR: 89.3-96.3), P= 0.020.\n\nCONCLUSION: Accuracy rates are improving. Current levels of reported accuracy suggest that routinely collected data are sufficiently robust to support their use for research and managerial decision-making.","author":[{"dropping-particle":"","family":"Burns","given":"E M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rigby","given":"E","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mamidanna","given":"R","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bottle","given":"A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Aylin","given":"P","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ziprin","given":"P","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Faiz","given":"O D","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of public health (Oxford, England)","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2012","3"]]},"page":"138-48","title":"Systematic review of discharge coding accuracy.","type":"article-journal","volume":"34"},"uris":[""]}],"mendeley":{"formattedCitation":"²²","plainTextFormattedCitation":"22","previouslyFormattedCitation":"²²"},"properties":{"noteIndex":0},"schema":""}22 in terms of complications compared to patients notes is unclear, it is not possible to conclude with confidence that wound infections recorded in CPRD and not in HES were de novo diagnoses in primary care or missing cases. The accuracy of these two datasets would have improved in the latter years. We are unable to ascertain the percentage of patients that had a delay in treatment due to administrative issues unrelated to the resection, such as unavailability of services, or did not complete the treatment regimen. The latter has been shown to effect overall survivalADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1038/sj.bjc.6603627","ISBN":"0007-0920","ISSN":"00070920","PMID":"17299387","abstract":"Two recent North American studies have shown that completion of 5-fluorouracil (5FU)-based adjuvant chemotherapy is a major prognostic factor for the survival of elderly stage III colon cancer patients. The aim of the present study was to confirm this finding in a population-based series from Australia. The study cohort comprised 851 stage III colon cancer patients treated by surgery alone and 461 who initiated the Mayo chemotherapy regime. One-third of patients who initiated chemotherapy failed to complete more than three cycles of treatment. Independent predictors for failure to complete were treatment in district or rural hospitals, low socioeconomic index and treatment by a low-volume surgeon. Patients who failed to complete chemotherapy showed worse cancer-specific survival compared not only to those who completed treatment (HR=2.24; 95% confidence interval (CI) (1.66-3.03), P<0.001) but also to those treated by surgery alone (HR=1.37; 95% CI (1.09-1.72), P=0.008). The current and previous studies demonstrate the importance of completing adjuvant 5-FU-based chemotherapy for colon cancer. Further prospective studies are required to identify better the physiological and socioeconomic factors responsible for failure to complete chemotherapy so that appropriate improvements in health service delivery can be made.","author":[{"dropping-particle":"","family":"Morris","given":"M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Platell","given":"C","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fritschi","given":"L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Iacopetta","given":"B","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"British journal of cancer","id":"ITEM-1","issue":"5","issued":{"date-parts":[["2007"]]},"page":"701-707","title":"Failure to complete adjuvant chemotherapy is associated with adverse survival in stage III colon cancer patients.","type":"article-journal","volume":"96"},"uris":[""]}],"mendeley":{"formattedCitation":"²³","plainTextFormattedCitation":"23","previouslyFormattedCitation":"²³"},"properties":{"noteIndex":0},"schema":""}23. As we could not include stage, we assumed the presence of AC episodes, and the exclusion of patients with metastases was sufficient to identify patients receiving AC for curative purposes. CONCLUSIONRelying only on secondary care data will underestimate the rate of complications following colonic resection. After adjusting for potential confounders such as type of surgical access and emergency admission, this study demonstrated complications, identified in primary care and in the hospital, are associated with a delay in AC following resection for colon cancer. The significant reduction in survival following a delay in AC should encourage the clinician to ensure all steps are taken to reduce complications and manage them effectively. REFERENCESADDIN Mendeley Bibliography CSL_BIBLIOGRAPHY 1. Gill S, Loprinzi CL, Sargent DJ, et al. Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: Who benefits and by how much? J Clin Oncol. 2004;22(10):1797-1806. doi:10.1200/JCO.2004.09.059.2. Biagi JJ, Raphael MJ, Mackillop WJ, Kong W, King WD, Booth CM. Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer: a systematic review and meta-analysis. JAMA. 2011;305(22):2335-2342. doi:10.1001/jama.2011.749.3. Des Guetz G, Nicolas P, Perret G-Y, Morere J-F, Uzzan B. Does delaying adjuvant chemotherapy after curative surgery for colorectal cancer impair survival? A meta-analysis. Eur J Cancer. 2010;46(6):1049-1055. doi:10.1016/j.ejca.2010.01.020.4. Hershman D, Hall MJ, Wang X, et al. Timing of adjuvant chemotherapy initiation after surgery for stage III colon cancer. Cancer. 2006;107(11):2581-2588. doi:10.1002/cncr.22316.5. Tevis SE, Kohlnhofer BM, Stringfield S, et al. Postoperative complications in patients with rectal cancer are associated with delays in chemotherapy that lead to worse disease-free and overall survival. Dis Colon Rectum. 2013;56:1339-1348. doi:10.1097/DCR.0b013e3182a857eb.6. Herrett E, Thomas SL, Schoonen WM, Smeeth L, Hall AJ. Validation and validity of diagnoses in the General Practice Research Database: A systematic review. Br J Clin Pharmacol. 2010;69:4-14. doi:10.1111/j.1365-2125.2009.03537.x.7. Williams T, van Staa T, Puri S, Eaton S. Recent advances in the utility and use of the General Practice Research Database as an example of a UK Primary Care Data resource. Ther Adv drug Saf. 2012;3(2):89-99. doi:10.1177/2042098611435911.8. Khan NF, Harrison SE, Rose PW. Validity of diagnostic coding within the General Practice Research Database: A systematic review. Br J Gen Pract. 2010;60(March):199-206. doi:10.3399/bjgp10X483562.9. Nachiappan S, Askari A, Mamidanna R, et al. The impact of adjuvant chemotherapy timing on overall survival following colorectal cancer resection. Eur J Surg Oncol. 2015;41(12):1636-1644. doi:10.1016/j.ejso.2015.09.009.10. Sundararajan V, Henderson T, Perry C, Muggivan A, Quan H, Ghali WA. New ICD-10 version of the Charlson comorbidity index predicted in-hospital mortality. J Clin Epidemiol. 2004;57(12):1288-1294. doi:10.1016/j.jclinepi.2004.03.012.11. Hendren S, Birkmeyer JD, Yin H, Banerjee M, Sonnenday C, Morris AM. Surgical complications are associated with omission of chemotherapy for stage III colorectal cancer. Dis Colon Rectum. 2010;53(12):1587-1593. doi:10.1007/DCR.0b013e3181f2f202.12. Xu F, Rimm AA, Fu P, Krishnamurthi SS, Cooper GS. The impact of delayed chemotherapy on its completion and survival outcomes in stage II colon cancer patients. PLoS One. 2014;9(9):e107993. doi:10.1371/journal.pone.0107993.13. Cheung WY, Neville BA, Earle CC. Etiology of delays in the initiation of adjuvant chemotherapy and their impact on outcomes for Stage II and III rectal cancer. Dis Colon Rectum. 2009;52(6):1054-63; discussion 1064. doi:10.1007/DCR.0b013e3181a51173.14. van der Geest LGM, Portielje JEA, Wouters MWJM, et al. Complicated postoperative recovery increases omission, delay and discontinuation of adjuvant chemotherapy in patients with Stage III colon cancer. Colorectal Dis. 2013;15(10):e582-91. doi:10.1111/codi.12288.15. Raymond TM, Dastur JK, Khot UP, Parker MC. Hospital Stay and Return to Full Activity Following Laparoscopic Colorectal Surgery. JSLS J Soc Laparoendosc Surg. 2008;12(2):143-149.16. Nachiappan S, Askari A, Mamidanna R, et al. Initiation of adjuvant chemotherapy within 8?weeks of elective colorectal resection improves overall survival regardless of reoperation. Color Dis. 2016;18(11):1041-1049. doi:10.1111/codi.13308.17. Sharma A, Deeb A-P, Iannuzzi JC, Rickles AS, Monson JRT, Fleming FJ. Tobacco Smoking and Postoperative Outcomes After Colorectal Surgery. Ann Surg. 2012;258(2):296-300. doi:10.1097/SLA.0b013e3182708cc5.18. McArdle CS, Hole DJ. Emergency presentation of colorectal cancer is associated with poor 5-year survival. Br J Surg. 2004;91(December 1994):605-609. doi:10.1002/bjs.4456.19. Sanoff HK, Carpenter WR, Martin CF, et al. Comparative effectiveness of oxaliplatin vs non-oxaliplatin-containing adjuvant chemotherapy for stage III colon cancer. J Natl Cancer Inst. 2012;104(3):211-227. doi:10.1093/jnci/djr524.20. Partnership HQI. National Bowel Cancer Audit. . Accessed November 9, 2016.21. Herrett E, Gallagher AM, Bhaskaran K, et al. Data Resource Profile: Clinical Practice Research Datalink (CPRD). Int J Epidemiol. 2015;44(3):827-836. doi:10.1093/ije/dyv098.22. Burns EM, Rigby E, Mamidanna R, et al. Systematic review of discharge coding accuracy. J Public Health (Oxf). 2012;34(1):138-148. doi:10.1093/pubmed/fdr054.23. Morris M, Platell C, Fritschi L, Iacopetta B. Failure to complete adjuvant chemotherapy is associated with adverse survival in stage III colon cancer patients. Br J Cancer. 2007;96(5):701-707. doi:10.1038/sj.bjc.6603627.TABLE AND FIGURE LEGENDSTable 1 - Summary statistics comparing patients with first episode adjuvant chemotherapy before and after eight weeks n (%)Figure SEQ Figure \* ARABIC 1 - Frequency distribution of patients according to first adjuvant chemotherapy episodeTable 2 - Complications recorded after colonic resection and before start of adjuvant chemotherapy treatment 1Includes acute renal failure, pneumonia, venothromboembolic event, cerebrovascular event and myocardial infarction 2Managed without an operation. Table 3 - Odds ratio (OR) for first adjuvant chemotherapy treatment after eight weeks or moreFigure 2 - Kaplan Meier analysis and life tables for first adjuvant chemotherapy episode before or after 8 weeks or moreTotalLess than 8 weeksN = 598 (47.2)8 weeks or moreN = 668 (52.8)p valueAgeUnder 60361 (28.5)180 (49.9)181 (50.1)0.06760 to 75698 (55.1)335 (48.0)363 (52.0)Over 75207 (16.4)83 (40.1)124 (59.9)GenderMale693 (54.7)337 (48.6)356 (51.4)0.275Female573 (45.3)261 (45.5)312 (54.5)Year of resection2000 to 2003307 (24.2)157 (51.1)150 (48.9)0.1322004 to 2007386 (30.5)187 (48.4)199 (51.6)2008 to 2011573 (45.3)80 (44.3)88 (55.7)Stoma at resectionNo Stoma1089 (86.0)537 (49.3)552 (50.7)< 0.005Stoma177 (14.0)61 (34.5)116 (65.5)Admission typeElective916 (72.4)442 (48.3)474 (51.7)0.241Emergency350 (27.6)156 (44.6)194 (55.4)Surgical accessOpen1035 (81.8)490 (47.3)545 (52.7)0.871Laparoscopic231 (18.2)108 (46.8)123 (53.2)Charlson scoreZero975 (77.0)466 (47.8)509 (52.2)0.465I or more291 (23.0)132 (45.4)157 (54.6)Table SEQ Table \* ARABIC 1 Summary statistics comparing patients with first episode adjuvant chemotherapy before and after eight weeks?Interval to adjuvant chemoBefore 8 weeks n (%)8 weeks or more n (%)Total n (%)p valueHESSystemic1 20 (3.3)46 (6.9)66 (12.1)<0.005Re-operation 20 (3.3)47 (7.0)67 (5.3)< 0.005Bowel obstruction2 52 (8.7)70 (10.5)122 (9.6)0.283Wound infection2 4 (0.7)5 (0.7)9 (0.7)0.895CPRDPneumonia000-VTE6 (1.0)10 (1.5)16 (1.3)0.432VTE not in HES2 (0.3)4 (0.6)6 (0.5)0.494Wound infection 22 (3.7)37 (5.5)59 (4.7)0.042Wound infection not in HES 20 (3.3)37 (5.5)57 (4.5)0.040At least one complicationHES 88 (14.7)142 (21.3)230 (18.2)<0.005HES and CPRD 109 (18.2)177 (26.5)286 (22.6)<0.0005Table 2 - Complications recorded after colonic resection and before start of adjuvant chemotherapy treatment 1Includes acute renal failure, pneumonia, venothromboembolic event, cerebrovascular event and myocardial infarction 2Managed without an operation. OR (95% CI)p valueAge (years)Over 75ref60 to 750.73 (0.53 to 1.01)0.056Under 600.65 (0.46 to 0.93)0.019GenderMalerefFemale1.17 (0.93 to 1.46)0.182SmokerNorefYes1.60 (1.08 to 2.35)0.018Charlson ScoreZerorefOne or more1.00 (0.76 to 1.32)0.997Surgical AccessOpenrefLaparoscopic1.12 (0.80 to 1.56)0.514AdmissionElectiverefEmergency1.10 (0.84 to 1.45)0.485StomaNorefYes1.79 (1.26 to 2.52)0.001Resection year2000 to 2003ref2004 to 20071.04 (0.77 to 1.42)0.7862008 to 20111.15 (0.85 to 1.57)0.373ComplicationNorefYes1.53 (1.16 to 2.03)0.003Table 3 – Multivariate analysis demonstrating the odds ratio (OR) for first adjuvant chemotherapy treatment after eight weeks or moreAppendix A – ICD-10 diagnosis for colon cancerC18.0Malignant neoplasm of cecumC18.1Malignant neoplasm of appendixC18.2Malignant neoplasm of ascending colonC18.3Malignant neoplasm of hepatic flexureC18.4Malignant neoplasm of transverse colonC18.5Malignant neoplasm of splenic flexureC18.6Malignant neoplasm of descending colonC18.7Malignant neoplasm of sigmoid colonC18.8Malignant neoplasm of overlapping sites of colonC18.9Malignant neoplasm of colon, unspecifiedD37.4Neoplasm of uncertain behavior of colonAppendix B – OPCS codes for a colon cancer procedureH04-Total excision of colon and rectumH05-Total excision of colonH06-Extended excision of right hemicolonH07-Other excision of right hemicolonH08-Excision of transverse colonH09-Excision of left hemicolonH10-Excision of sigmoid colonH11-Other excision of colonH29-Subtotal excision of colonG72.5Anastomosis of ileum to anus and creation of pouchAppendix C – OPCS code for chemotherapyX35.2Intravenous chemotherapyX72.1Delivery of complex chemotherapy for neoplasm including prolonged infusional treatment at first atX72.2Delivery of complex parenteral chemotherapy for neoplasm at first attendanceX72.3Delivery of simple parenteral chemotherapy for neoplasm at first attendanceX72.4Delivery of subsequent element of cycle of chemotherapy for neoplasmX72.8Other specified delivery of chemotherapy for neoplasmX72.9Unspecified delivery of chemotherapy for neoplasmX73.1Delivery of exclusively oral chemotherapy for neoplasmX73.8Other specified delivery of oral chemotherapy for neoplasmX73.9Unspecified delivery of oral chemotherapy for neoplasmX74.8Other specified other chemotherapy drugsX74.9Unspecified other chemotherapy drugsAppendix D – ICD code for metastastic diseaseC78.0Secondary malignant neoplasm of lungC78.1Secondary malignant neoplasm of mediastinumC78.2Secondary malignant neoplasm of pleuraC78.3Secondary malignant neoplasm of other and unspecified respiratory organsC78.4Secondary malignant neoplasm of small intestineC78.5Secondary malignant neoplasm of large intestine and rectumC78.6Secondary malignant neoplasm of retroperitoneum and peritoneumC78.7Secondary malignant neoplasm of liver and intrahepatic bile ductC78.8Secondary malignant neoplasm of other and unspecified digestive organsC79Secondary malignant neoplasm of other and unspecified sitesC79.0Secondary malignant neoplasm of kidney and renal pelvisC79.1Secondary malignant neoplasm of bladder and other and unspecified urinary organsC79.2Secondary malignant neoplasm of skinC79.3Secondary malignant neoplasm of brain and cerebral meningesC79.4Secondary malignant neoplasm of other and unspecified parts of nervous systemC79.5Secondary malignant neoplasm of bone and bone marrowC79.6Secondary malignant neoplasm of ovaryC79.7Secondary malignant neoplasm of adrenal glandC79.8Secondary malignant neoplasm of other specified sitesC79.9Secondary malignant neoplasm, unspecified siteAppendix EWound operations including dehiscenceS608, S068, S604, S069, S089, S242, S571, S573, S572, S574, S575, S576, S577, S578, S579, S472, S474, S478, S432, S434, S438, S439, S476, S352, S358, S359, S628, S132, S152, T282, T283, S424, S428, T288, T289, S421, S422, S423, S429, T315, T316, T318, T963 Re-enter abdomen for bleedingT301, Y321, G523, H212, H242, J104, J105Further resectionAs appendix S2Relief of bowel obstruction inc. adhesionlysis or stentT412, T413, T415, T423, Y181, H310, H311, H312, H313, H314, H315, H318, H319, H170, H175, H176, H178, H179, H211, H214, H243, H244, G611, G618, G589, G638, G535, G538, G699, G513, G781, G514, G518, G519, G692, G693, G694, G698, G711, G712, G713, G714, G715, G718, G721, G722, G723, G731, G733, G768, G782, G786, G788, G822, T374, G674, G671, G634, G734, G738, G762, G763, G828, G584, G588, G728, G782, G824Peritoneal washoutT331, T411, T414, T418, T419, T428, T431, T432, T488, T341, T342, T343, T348, T349, T461, T462, T463, T468, T469, T450, T451, T452, T453, T454, T458, T459Formation or attention to stomaG733, G739, G741, G742, G743, G748, G749, G751, G752, G753, G754, G755, G758, G759, H141, H142, H148, H149, H151, H152, H153, H155, H156, H158, H159, H321Repair of organ inc perforationG784, G633, J203, G362, G532, G350, G351, G352, G358, G359, G521, G522, M372, M212, M218, M162, M221, M228, M264, M373, M378, M379, M202, M258, M274, M335, M228, M136, M292, P253, P258, J041, J042, J043, J048, J049, J721, J722, J723, J724, J725, J728, J729, M222, M223, M275, M276, M277, M278, M279, M300, M302SplenectomyJ691, J692, J693, J698, J699Repair of herniaT251, T252, T253, T258, T259, T261, T262, T263, T264, T268, T269, T271, T272, T273, T274, T278, T279Perineal operationN242, N248, N249, P111, P131, P138, H531, H558, H581, H582, H583, H588, H589, H412, H418, H419, H464, H468, H469, H541, H568, H444, H448, Q552, H556. H444Attention to anastomosisG731, G734, G738, G739Re-enter abdomen NECT300, T302, T303, T304, T308, T309Operation on mesenteryT381, T382, T383, T384, T388, T389 ................
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