BMJ Open. Pulmonary embolism and mortality following total ankle replacement: a data linkage study using the NJR dataset

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1 BMJ Open Pulmonary embolism and mortality following total ankle replacement: a data linkage study using the NJR dataset Journal: BMJ Open Manuscript ID bmjopen--0 Article Type: Research Date Submitted by the Author: -Mar- Complete List of Authors: Zaidi, Razi; UCL, Institute of Orthopaedics and Musculoskeletal Science MacGregor, Alex; University of East Anglia, Norwich Medical School Cro, Suzie; Medical Research Council, Clinical Trials Unit at UCL Goldberg, Andrew; University College London, Institute of Orthopaedics and Musculoskeletal Science <b>primary Subject Heading</b>: Surgery Secondary Subject Heading: Health informatics Keywords: Foot & ankle < ORTHOPAEDIC & TRAUMA SURGERY, ankle replacement, data linkage, registry

2 Page of BMJ Open Pulmonary embolism and mortality following total ankle replacement: a data linkage study using the NJR dataset

3 BMJ Open Page of Author: Razi Zaidi MBBS BSc MRCS Co-Authors: Alexander MacGregor MD, PhD, FRCP Suzie Cro BSc, MSc Andy Goldberg MD FRCS (Tr&Orth) Correspondence to Razi Zaidi razizaidi@doctors.net.uk Phone number: + Keywords: ankle replacement, ankle arthroplasty, national joint registry, data linkage, hospital episodes statistics. Word Count: Institute of Orthopaedics & Musculoskeletal Science Royal National Orthopaedic Hospital NHS Trust Brockley Hill Stanmore HA LP UK Norwich Medical School University of East Anglia Bob Champion Research & Education Bldg. MRC Clinical Trials Unit at UCL Kingsway London WCB NH

4 Page of BMJ Open Copyright for authors The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, a worldwide licence to the Publishers and its licensees in perpetuity, in all forms, formats and media (whether known now or created in the future), to i) publish, reproduce, distribute, display and store the Contribution, ii) translate the Contribution into other languages, create adaptations, reprints, include within collections and create summaries, extracts and/or, abstracts of the Contribution, iii) create any other derivative work(s) based on the Contribution, iv) to exploit all subsidiary rights in the Contribution, v) the inclusion of electronic links from the Contribution to third party material where-ever it may be located; and, vi) licence any third party to do any or all of the above.

5 BMJ Open Page of Abstract Objective To determine the mortality rate following Total Ankle Replacement (TAR) and incidence of 0 day pulmonary embolism (PE) along with the associated risk factors. Design Data-linkage study of the UK National Joint Registry (NJR) data and Hospital Episodes Statistics (HES) database. Linkage was performed in a deterministic fashion. HES episodes 0 days after the index procedure were analysed for pulmonary embolism. Mortality data was obtained pertaining to all the index procedures from the NJR for analysis. Participants All primary and revision ankle replacement patients captured on the NJR between February 0 and February. Results The 0-day mortality following TAR was 0.% (% CI 0.0 to 0.) and one-year mortality was 0.% (% CI 0.0 to.0), no deaths were as a result of PE. The incidence of PE within 0 days following primary TAR was 0.% (% CI 0. -.). There was only one PE following revision surgery. Patients with a RCS Charlson score greater than zero were at times greater risk of PE (p= 0.00). Conclusions There is low incidence of PE following TAR, but multiple co-morbidities are a leading risk factor for its occurrence.

6 Page of BMJ Open Article Summary Article Focus Mortality rate following Total Ankle Replacement Pulmonary embolism rate following Total Ankle Replacement Key Messages Mortality rate is low Multiple co-morbidities are the key risk factor for Pulmonary Embolism post Ankle Replacement Surgery. Strengths and limitations of this study The world s largest cohort of ankle replacements Data-linkage methodology reduces biases that are present in single surgeon, single centre reports of pulmonary embolism. Limited by linkage rate of %

7 BMJ Open Page of Introduction Total ankle replacement (TAR) provides patients with an improved functional outcome that is maintained at ten years with a cumulative annual failure rate of.%.[] The National Institute for Healthcare and Clinical Excellence (NICE) risk assessment tool categorises TAR as a high-risk procedure for pulmonary embolism (PE) [] but the true incidence of venous thromboembolism (VTE) following TAR is largely unknown, with several papers reporting wide variation in incidence ranging from 0-.% (Table ).[ ] These studies demonstrate ambiguity of definition of VTE; methodological flaws; and small single centre retrospective reviews. An estimated,000 people die from hospital acquired venous thromboembolism (VTE) in the UK every year.[] Indeed, mortality is a key quality of care indicator outlined by the Keogh Report and its reduction a vital ambition of the UK National Health Service.[] VTE events are rare and difficult to capture in a single centre, but can be detected in sufficient numbers by large scale national registries. It has been mandatory to input every TAR into the NJR since. A further advantage to using registry data for analysis is the diversity regarding patient population, surgeon and implant choice. It is therefore representative of real world practice. In England any patient admitted to an NHS hospital is recorded on the Hospital Episode Statistics (HES) database; currently more than million records are captured each year. Almost all suspected PEs are admitted to hospital and should be recorded on the HES database. Between April to April, patients were admitted to NHS hospitals in England with pulmonary embolism.[]

8 Page of BMJ Open The aims of our study therefore were to answer the following research questions using linked NJR- HES data:. What is the rate of mortality following TAR?. What is the 0 day incidence of pulmonary embolism and associated risk factors? Methods Data Linkage Data from the NJR was linked to HES data in a deterministic fashion. Deterministic linkage requires an exact match of the fields being linked from both datasets in order to say that they are from the same patient. NJR records for primary and revision procedures (From Feb 0 to Feb ) ( records) were linked to five years of HES records (which equates to 0 million records) (Figure ). This is in contrast to probabilistic linkage which estimates the likelihood that two records are for the same individual, even if they disagree on some fields.[] Linkage was conducted by the Health & Social Care Information Centre (HSCIC). This was in line with best linkage practice with application of the separation principle to allow the most ethical workflow.[] This principle is used to protect patient data, with patient identifying components and clinical components of a dataset kept separate. Identifying data is used by a group to perform data linkage while the research group uses non- identifying data to perform the analysis., NJR records were linked to NJR data that was captured on minimal dataset forms completed by the surgeon at the time of surgery and submitted by the performing hospital. This is a mandated requirement in the UK National Health Service. For a primary ankle replacement the form is entitled an A form and for a revision ankle replacement, an A form.[,] The forms capture patient

9 BMJ Open Page of demographics such as patient age, gender, and BMI. The unit where the surgery is performed is captured with the grade of surgeon performing the surgery. The grade of surgeon is sub-divided into a consultant surgeon or trainee. Indication for surgery, details of pre-operative deformity and range of motion are also collected. Further to this the prosthesis type, surgical approach, associated procedures, intra-operative complications and prophylaxis against venous thromboembolic disease are recorded. [,] Identification of pulmonary embolism The ICD- (International Classification of Disease Version ) codes were used to search the linked data for episodes of PE after the index procedure.[] DVT was excluded from our analysis as these patients are not admitted to hospital but instead are treated in the community and hence are not recorded on the HES database. [] Identification of deaths following TAR Mortality data was obtained separately from the NJR. The NJR tracks mortality via its link with the Office of National Statistics and automatically flags deaths at 0-days, year, years and -years. Analytical Approach Factors related to increased risk of PE following primary TAR were assessed. Several variables were investigated including: age, sex, body-mass index, length of stay, indication for surgery, implant type and fixation, thromboprophylaxis, preoperative range of motion and deformity, where the implant was performed (NHS vs. independent sector), and co-morbidities.

10 Page of BMJ Open Co-morbid conditions were defined using the Royal College of Surgeons Charlson Score applied to HES records in the months preceding the index operation for every patient. This is a validated tool that is a count of chronic co-morbid conditions that may affect the outcome of surgery.[] We combined the co-morbidity count to form two groups for analysis this was due to small numbers of PEs in each group. An assessment of the similarities between the background characteristics and surgical factors of the PE and no PE patient groups was conducted. The normality of each continuous factor when broken down by the PE or no PE patient groups was assessed using the Shapiro Wilk test. T-tests were used to test whether there was a difference in the means between the two groups when normality was upheld. Mann-Whitney tests were used to test whether the medians of the distributions were different for skew distributions. The Chi-squared or Fisher s exact tests were used to test whether there was an association between a categorical factor and patient group membership. As the number of PE outcome events were small, the ratio of outcome events per factor was not sufficient to enable multivariable analysis of the effect of multiple factors on PE. For the purpose of analysis, age was divided into three groups; less than, - and greater than. BMI was divided into three categories; a BMI of less than. is underweight;.- was classed as normal, and a BMI of greater than was classified as overweight, with no further breakdown for obesity. PE rate was also analysed in the context of unit volume. We identified that those units performing more than per year ( units) accounted for half of all ankle replacements performed and those that did less than per year ( units) accounted for the other half. We therefore classed high volume units as those carrying out ankle replacements or more per year and low volume units as those that performed less than per year.

11 BMJ Open Page of Due to the low occurrence of PE we combined ASA grades to form two groups. Analysis was conducted using R v.0. (R Foundation for Statistical Computing, Vienna, Austria). Estimates of mortality rates were derived by the Kaplan-Meier method using Stata/IC version.0 (StataCorp, College Station, TX, USA). Results There were a total of, NJR records comprising of, primary operations and revisions. The overall match rate with HES was % with, matched primary procedures and revisions. The mean patient age of patients undergoing primary total ankle replacement (TAR) was. (SD.). % of these patients were female. of NJR records gave details on patient BMI, the mean BMI was. (SD ). % of the primary procedures were done as a result of osteoarthritis with % having rheumatoid arthritis as the indication..% were uncemented operations with % were done via an anterior approach. The mean patient age of patients undergoing revision operation was (SD.). 0% of these patients were female. of NJR records gave details on patient BMI, the mean BMI was. (SD.). The main indication for revision was infection (%) followed by persistent pain (%) and aseptic loosening of the tibia (%). % were uncemented revisions to another ankle replacement..% involved fusion of the ankle joint form a TAR. Mortality Rate Survival data was available for, primary procedure patients. The median follow-up time was months (range to ), during which patients died. The 0-day mortality following TAR was

12 Page of BMJ Open % (% CI 0.0 to 0.) and one-year mortality was 0.% (% CI 0.0 to.0) (Table ). None of the deaths were as a result of PE. When compared to the ONS age and sex standardised death rates in the UK for the 0-day were times lower and one-year death rate was. times lower for patients who had a TAR. No deaths were observed amongst the revision patients who had a median follow-up time of months (range 0 to ). Pulmonary Embolism Rate Of the, linked primary procedures, had a PE within 0 days of surgery, giving an incidence rate of 0.% (% CI 0. -.) at a mean of days. All patients with a PE had an uncemented prosthesis via an anterior approach and received both mechanical and chemical thromboprophylaxis. Only of the revision procedures was recorded as having a PE. There were no fatal PEs. Although no statistical significance was noted (p=0.0) the 0 day rate of PE was greater amongst the - age group (0.0%), and over s (0.%) in comparison to the under age group where no PE s occurred (Table ). All the patients that had a PE were overweight. No occurrences of PE were found in patients with a BMI of less than (p=0.). Seventy three percent of the patients that did not suffer a PE (no PE Group) had received both mechanical and chemical prophylaxis. Three percent of patients received no thromboprophylaxis and yet none of them suffered a PE (Table ). Distribution of ASA Grade was similar in patients that suffered and did not suffer a PE (Table ). Patients with a RCS Charlson score greater than zero were at times greater risk of PE (p= 0.00). When looking at ankle deformity and range of motion we found a higher rate of PE with varus deformity and fixed equinus, but the differences were not statistically significant (Table ).

13 BMJ Open Page of Discussion The 0-day mortality rate following TAR is 0.%. This is lower than that reported for hip replacement (0.%) and knee replacement (0.%).[] The incidence of pulmonary embolism within 0 days of ankle replacement surgery is 0.% (% CI 0. -.), with a mean event time of days after surgery. A review of the literature suggests the published rate of PE to be 0.% (Table ), which is significantly lower than the incidence revealed by this study. This may represent reporting bias in that, in other reported series, patients were admitted under medical teams and not picked up by the surgical team. The strength in our methodology is that it has the ability to capture readmissions anywhere in the UK under any clinician regardless of where the TAR was performed and hence meets one of our key aims to use registry data to determine a true incidence of pulmonary embolism following ankle replacement. A previous study used HES data only to determine PE rates following TAR determined by a search of a series of relevant treatment codes (ICD) and reported a PE rate of 0.0% post TAR.[] The current study used a more robust data linkage methodology to identify several more PEs. This highlights the advantage of using one dataset to validate another to ensure that data is not lost. A national audit of a large UK trust into clinical coding revealed that in orthopaedics % of diagnosis and % procedures are coded inaccurately.[] Therefore although we employed a robust method to identify ankle replacement more accurately the actual identification of PE was still limited by accuracy of clinical coding. All patients who suffered PE had both mechanical and chemical prophylaxis. Other studies have shown similar rates of PE in foot and ankle surgery and argued that evidence for routine

14 Page of BMJ Open thromboprophylaxis use is weak.[,] It is difficult to argue that thromboprophylaxis is not warranted based on negative findings in a treated group, however, this study showed that in the % of patients that received no routine thromboprophylaxis, none of them suffered a PE (Table ). Comorbidity surfaced as the leading predictor of PE in patients undergoing TAR with a co-morbidity count greater than 0 leading to increased risk of PE by a multiple of. The RCS Charlson score looks at disease categories developed by a consensus group.[] Until now the existing literature has focused on the PE rates in foot and ankle surgery as a whole and mostly including trauma cases due to the higher volumes compared to elective surgery. Some have shown that the presence of any co-morbid conditions double the rate of PE[] and Jameson et al found that a Charlson score of or more significantly increased the risk of PE in ankle fractures treated operatively. Other groups have shown specific co-morbidity, such as diabetes double the risk of PE.[] The existing body of work is supported by the current study in the emphasising the importance of comorbidity and PE risk. We showed a trend towards increased risk of PE with age over and by being overweight. This is similar to the finding of Shibuya et al who found a significant increase in PE risk with increasing age and BMI when looking at lower limb trauma.[] Our findings however did not reach statistical significance. A limitation of this study is that we were unable to record DVT as well as PE to give an overall VTE rate. This is largely because the HES database only records admissions to hospital whereas DVTs are invariably treated in the outpatient setting and hence not admitted[] As a result the national rate of VTE associated with TAR is unknown. None the less the PE rate is more accurate as PE s and expected PE s are invariably admitted to hospital. Another limitation was that only % of the NJR records were linked to the HES database. This % of non linked records includes both patients that

15 BMJ Open Page of did not sign their consent to enable data linkage, and also patients where the surgery was carried out in the independent sector where no HES record is kept.[0] Despite these limitations this still represents data from the largest cohort of ankle replacements to date. A further limitation is not having available data on the duration of surgery and tourniquet use, which are possible factors that might influence VTE. None of this data is captured on the NJR nor the HES database. Due to the small number of PE events, it is possible that a type II error occurred and that risk factors existed but did not reach statistical significance with the cohort size in this study. These risk factors will become clear as the number of NJR records increase over time. Increasing patient consent and ability to link records from the independent sector will also increase the power of any future analysis. Conclusion The current study demonstrates that the rate of PE following TAR is low (0. %) and that within the initial three year period of the UK National Joint Registry, no fatal PE s occurred. The 0-day mortality rate following TAR is 0.%, which is lower than that reported for hip replacement and knee replacement. Multiple co-morbidity is the leading risk factor for PE and must be taken into account in the treatment and informed consenting process for patients undergoing TAR.

16 Page of BMJ Open Acknowledgement We thank the patients and staff of all the hospitals in England, Wales and Northern Ireland who have contributed data to the National Joint Registry. We are grateful to the Healthcare Quality Improvement Partnership (HQIP), the NJR Research Sub-Committee and staff at the NJR Centre for facilitating this work. The authors have conformed to the NJR s standard protocol for data access and publication. The views expressed represent those of the authors and do not necessarily reflect those of the National Joint Registry Steering Committee or the Health Quality Improvement Partnership (HQIP) who do not vouch for how the information is presented. The Healthcare Quality Improvement Partnership ( HQIP ) and/or the National Joint Registry ( NJR ) take no responsibility for the accuracy, currency, reliability and correctness of any data used or referred to in this report, nor for the accuracy, currency, reliability and correctness of links or references to other information sources and disclaims all warranties in relation to such data, links and references to the maximum extent permitted by legislation.

17 BMJ Open Page of Figures HES > 0 million records NJR A and A records Primary Procedures Deterministic Linkage NJR-HES linked records Revision Procedures Figure Flow chart showing the linkage of the NJR and HES databases. % of the records remained unlinked due to non-consent and the procedures being carried out in non-nhs institutions where no HES record is created.

18 Page of BMJ Open Tables Number of Death Rate (% CI) SMR 0 Days 0. (0.0-0.) 0.0 Year 0. (0.0-.0) 0. Years 0. (0.0-.) 0. Years 0. (0.-.) 0. Table Kaplan Meier estimates of the cumulative percentage probability of mortality at 0 days,, and years post operation [% CI]. Standardised Mortality Ratio was calculated using the age and sex adjusted mortality data from the ONS.[] SMR = Mortality rate in TAR/age+sex adjusted mortality rate in general population. Study Source Number in study Total VTE events Number and percentage Deep vein thrombosis Number and percentage Pulmonary embolism Number and percentage Barg sc/ms, (.), (.) na Haskell 0 mc/ms, (.0) na na Hobson 0 sc/ss 0, (0) 0, (0) 0, (0) Jameson HES, (0.0) 0, (0), (0.0) Karantana database sc/ss 0, (0) 0, (0) 0, (0) Knecht 0 sc/ss, (.) 0, (0), (.) Kumar 0 sc/ss 0, (0) 0, (0) 0, (0) Lee 0 sc/ss 0 0, (0) 0, (0) 0, (0) Rippstein sc/ms, (.), (.) 0, (0) Rodrigues-Pinto mc/ms 0, (0) 0, (0) 0, (0) Saltzman sc/ss, (.), (.) 0, (0) Schweitzer mc/ms, (.) 0, (0), (.) Table Studies reporting on thromboembolic events post TAR. sc= single centre, mc= multicentre, ss= single surgeon, ms= multiple surgeons, n = number.

19 BMJ Open Page of PE No PE PE rate Significance test Age n (proportion) n (proportion) < 0 (0) (0.) 0.00% p=0.0 - (0.) (0.) 0.0% > (0.) (0.) 0.% Length of stay mean (range) mean (range). (-). (0-) p=0. BMI n (proportion) n (proportion) underweight 0 (0) (0.0) 0.00% p=0. normal 0 (0) (0.) 0.00% overweight () (0.) 0.% Missing data Gender percentage percentage female p= 0. Indications n (proportion) n (proportion) osteoarthritis (.0) (0.) 0.0% p=0. rheumatoid arthritis 0 (0) (0.0) 0.00% inflammatory 0 (0) (0.0) 0.00% other 0 (0) (0.0) 0.00% Operation n (proportion) n (proportion) uncemented (.0) (0.) 0.% p=0. cement 0 (0) (0.0) 0.00% hybrid 0 (0) (0.00) 0.00% ASA n (proportion) n (proportion) - (0.) (0.) 0.% p=0. - (0.) (0.) 0.0% Charlson n (proportion) n (proportion) 0 0.% p = 0.00 >0.0% Prophylaxis n (proportion) n (proportion) both () 0 (0.).0% p=0. chemical only 0 (0) (0.) 0.0% mechanical only 0 (0) (0.0) 0.0% none 0 (0) (0.0) 0.0% Deformity n (proportion) n (proportion) Neutral (0.) (0.) 0.% p=0. Valgus (0.) (0.).0% Varus (0.) (0.).% Missing data Dorsiflexion n (proportion) n (proportion) - (0.) (0.) 0.% p=0. Neutral (0.) (0.) 0.% Fix equinus (0.) (0.) 0.% Plantarflexion n (proportion) n (proportion) - (0.) (0.) 0.0% p = 0. - (0.) (0.) 0.0% Missing data

20 Page of BMJ Open Unit Volume per year n (proportion) n (proportion) > (0.) (0.) 0.% p = 0. < (0.) (0.) 0.% Organisation Type n (proportion) n (proportion) NHS Hospital (0.) (0.) 0.% p = 0. Independent hospital (0.) (0.0).% Independent treatment centre (0.) (0.0).% Previous Operation n (proportion) n (proportion) None (0.) (0.) 0.% p = 0. Fusion 0 (0) (0.0) 0.0% Ankle ORIF 0 (0) (0.0) 0.0% Tibial Osteotomy 0 (0) (0.00) 0.0% Other 0 (0) (0.0) 0.0% Previous fracture (0.) (0.) 0.% Missing data Table Analysis of patients that had PE vs no-pe 0 days post primary TAR. n=number of patients, ASA, American Society of Anesthesiologists.

21 BMJ Open Page of Conflict of Interest We have read and understood the BMJ Group policy on declaration of interests and have no relevant interests to declare. Data Sharing No additional data available Authorship RZ, AG and AM were all involved in the conception of the study. RZ and AG were responsible for obtaining the linked data. AM was involved in gaining approval for all the data used. RZ and SC did the data analysis. AG, SC and RZ were involved in data interpretation. RZ, AG, SC and AM involved in drafting, revising and final approval of the version to be published. Funding This research received no specific grant from any funding agency in the public, commercial or notfor-profit sectors.

22 Page of BMJ Open References Zaidi R, Cro S, Gurusamy K, et al. The outcome of total ankle replacement: A systematic review and meta-analysis. Bone Joint J ;-B:00. doi:.0/00- X.B. No Authors Listed. Venous thromboembolism : reducing the risk Reducing the risk of venous.. Barg A, Barg K, Schneider SW, et al. Thrombembolic complications after total ankle replacement. Curr Rev Musculoskelet Med ;:. doi:.0/s-0-- Haskell A, Mann RA. Foot & Ankle International. Published Online First:. doi:./00000 Hobson S a, Karantana A, Dhar S. Total ankle replacement in patients with significant preoperative deformity of the hindfoot. J Bone Joint Surg Br 0;:. doi:.0/00- X.B. Jameson SS, Augustine A, James P, et al. FOOT AND ANKLE Venous thromboembolic events following foot and ankle surgery in the English National Health Service. ;:0. doi:.0/00-x.b. Karantana A, Hobson S, Dhar S. The scandinavian total ankle replacement: survivorship at and years comparable to other series. Clin Orthop Relat Res ;:. doi:.0/s-00-0-y Knecht SI, Estin M, Callaghan JJ, et al. The Agility total ankle arthroplasty. Seven to sixteenyear follow-up. J Bone Joint Surg Am 0;-A:. (accessed Oct). Kumar A, Dhar S. Total ankle replacement: Early results during learning period. Foot Ankle Surg 0;:. doi:./j.fas Lee K-B, Cho S-G, Hur C-I, et al. Perioperative complications of HINTEGRA total ankle replacement: our initial 0 cases. Foot Ankle Int 0;:. doi:./fai.0.0 Rippstein PF, Huber M, Coetzee JC, et al. Total ankle replacement with use of a new threecomponent implant. J Bone Joint Surg Am ;:. doi:./jbjs.j.00 Rodrigues-Pinto R, Muras J, Martín Oliva X, et al. Functional results and complication analysis after total ankle replacement: early to medium-term results from a Portuguese and Spanish prospective multicentric study. Foot Ankle Surg ;:. doi:./j.fas..0.0 Saltzman CL, Kadoko RG, Suh JS. Treatment of isolated ankle osteoarthritis with arthrodesis or the total ankle replacement: a comparison of early outcomes. Clin Orthop Surg ;:. doi:.0/cios... Schweitzer KM, Adams SB, Viens N a, et al. Early prospective clinical results of a modern fixed-bearing total ankle arthroplasty. J Bone Joint Surg Am ;:0. doi:./jbjs.l.00 No Authors Listed. Health Committee The Prevention of Venous Thromboembolism in. 0. Keogh B. Review into the quality of care and treatment provided by hospital trusts in England : overview report..

23 BMJ Open Page of No. Hospital Episode Statistics, Admitted Patient Care, England--.. Search?productid=&q=title:+ Admitted+Patient+Care+- +England &sort=relevance&size=&page=&area=both#top (accessed Jan). Zhu Y, Matsuyama Y, Ohashi Y, et al. When to conduct probabilistic linkage vs. deterministic linkage? A simulation study. J Biomed Inform ;:0. doi:./j.jbi..0.0 Kelman CW, Bass AJ, Holman CDJ. Research use of linked health data--a best practice protocol. Aust N Z J Public Health 0;:. (accessed Oct). No Authors Listed. NJR A Form. ;:. A.pdf No Authors Listed. NJR A form. collection forms/mdsv.0_a_v00.pdf No Authors Listed. ICD codes for VTE.. Armitage JN, van der Meulen JH. Identifying co-morbidity in surgical patients using administrative data with the Royal College of Surgeons Charlson Score. Br J Surg ;:. doi:.0/bjs.0 Wishart N, Beaumont R, Young E, et al. NJR th Annual Report.. Spencer SA, Davies MP. Hospital episode statistics: improving the quality and value of hospital data: a national internet e-survey of hospital consultants. BMJ Open ;. doi:./bmjopen--00 Metz R, Verleisdonk E-JMM, Heijden GJMG. Insufficient Evidence for Routine Use of Thromboprophylaxis in Ambulatory Patients with an Isolated Lower Leg Injury Requiring Immobilization: Results of a Meta-Analysis. Eur J Trauma Emerg Surg 0;:. doi:.0/s y Griffiths JT, Matthews L, Pearce CJ, et al. Incidence of venous thromboembolism in elective foot and ankle surgery with and without aspirin prophylaxis. J Bone Joint Surg Br ;:. doi:.0/00-x.b. Shibuya N, Frost CH, Campbell JD, et al. Incidence of acute deep vein thrombosis and pulmonary embolism in foot and ankle trauma: analysis of the National Trauma Data Bank. J Foot Ankle Surg;:. doi:./j.jfas...0 SooHoo NF, Krenek L, Eagan MJ, et al. Complication rates following open reduction and internal fixation of ankle fractures. J Bone Joint Surg Am 0;:. doi:./jbjs.h.00 0 No Authors Listed. National Joint Registry for England, Wales and Northern Ireland, th Annual Report.. No Authors Listed. Statistical Bulletin Deaths Registered in England and..

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25 BMJ Open Page of 0 0 Section/Topic Item # STROBE 0 (v) Statement Checklist of items that should be included in reports of cohort studies Recommendation Reported on page # Title and abstract (a) Indicate the study s design with a commonly used term in the title or the abstract and Introduction (b) Provide in the abstract an informative and balanced summary of what was done and what was found and Background/rationale Explain the scientific background and rationale for the investigation being reported - Objectives State specific objectives, including any prespecified hypotheses - Methods Study design Present key elements of study design early in the paper Setting Describe the setting, locations, and relevant dates, including periods of recruitment, exposure, follow-up, and data collection Participants (a) Give the eligibility criteria, and the sources and methods of selection of participants. Describe methods of follow-up (b) For matched studies, give matching criteria and number of exposed and unexposed Variables Clearly define all outcomes, exposures, predictors, potential confounders, and effect modifiers. Give diagnostic criteria, if Data sources/ measurement applicable * For each variable of interest, give sources of data and details of methods of assessment (measurement). Describe comparability of assessment methods if there is more than one group Bias Describe any efforts to address potential sources of bias Study size Explain how the study size was arrived at Quantitative variables Explain how quantitative variables were handled in the analyses. If applicable, describe which groupings were chosen and why Statistical methods (a) Describe all statistical methods, including those used to control for confounding Results (b) Describe any methods used to examine subgroups and interactions (c) Explain how missing data were addressed and (d) If applicable, explain how loss to follow-up was addressed (e) Describe any sensitivity analyses na na

26 Page of BMJ Open 0 0 Participants * (a) Report numbers of individuals at each stage of study eg numbers potentially eligible, examined for eligibility, confirmed eligible, included in the study, completing follow-up, and analysed (b) Give reasons for non-participation at each stage na Descriptive data (c) Consider use of a flow diagram * (a) Give characteristics of study participants (eg demographic, clinical, social) and information on exposures and potential confounders (b) Indicate number of participants with missing data for each variable of interest (c) Summarise follow-up time (eg, average and total amount) Outcome data * Report numbers of outcome events or summary measures over time na Main results (a) Give unadjusted estimates and, if applicable, confounder-adjusted estimates and their precision (eg, % confidence na interval). Make clear which confounders were adjusted for and why they were included (b) Report category boundaries when continuous variables were categorized (c) If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time period Na Other analyses Report other analyses done eg analyses of subgroups and interactions, and sensitivity analyses na Discussion Key results Summarise key results with reference to study objectives Limitations Interpretation Give a cautious overall interpretation of results considering objectives, limitations, multiplicity of analyses, results from similar studies, and other relevant evidence Generalisability Discuss the generalisability (external validity) of the study results Other information Funding Give the source of funding and the role of the funders for the present study and, if applicable, for the original study on which the present article is based *Give information separately for cases and controls in case-control studies and, if applicable, for exposed and unexposed groups in cohort and cross-sectional studies. In figures Note: An Explanation and Elaboration article discusses each checklist item and gives methodological background and published examples of transparent reporting. The STROBE checklist is best used in conjunction with this article (freely available on the Web sites of PLoS Medicine at Annals of Internal Medicine at and Epidemiology at Information on the STROBE Initiative is available at

27 BMJ Open Pulmonary embolism and mortality following total ankle replacement: a data linkage study using the NJR dataset Journal: BMJ Open Manuscript ID bmjopen--0.r Article Type: Research Date Submitted by the Author: -May- Complete List of Authors: Zaidi, Razi; UCL, Institute of Orthopaedics and Musculoskeletal Science MacGregor, Alex; University of East Anglia, Norwich Medical School Cro, Suzie; Medical Research Council, Clinical Trials Unit at UCL Goldberg, Andrew; University College London, Institute of Orthopaedics and Musculoskeletal Science <b>primary Subject Heading</b>: Surgery Secondary Subject Heading: Health informatics Keywords: Foot & ankle < ORTHOPAEDIC & TRAUMA SURGERY, ankle replacement, data linkage, registry

28 Page of BMJ Open Pulmonary embolism and mortality following total ankle replacement: a data linkage study using the NJR dataset

29 BMJ Open Page of Author: Razi Zaidi MBBS BSc MRCS Co-Authors: Alexander MacGregor MD, PhD, FRCP Suzie Cro BSc, MSc Andy Goldberg MD FRCS (Tr&Orth) Correspondence to Razi Zaidi razizaidi@doctors.net.uk Phone number: + Keywords: ankle replacement, ankle arthroplasty, national joint registry, data linkage, hospital episodes statistics. Word Count: Institute of Orthopaedics & Musculoskeletal Science Royal National Orthopaedic Hospital NHS Trust Brockley Hill Stanmore HA LP UK Norwich Medical School University of East Anglia Bob Champion Research & Education Bldg. MRC Clinical Trials Unit at UCL Kingsway London WCB NH

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31 BMJ Open Page of Abstract Objective To determine the mortality rate following Total Ankle Replacement (TAR) and incidence of 0 day pulmonary embolism (PE) along with the associated risk factors. Design Data-linkage study of the UK National Joint Registry (NJR) data and Hospital Episodes Statistics (HES) database. Linkage was performed in a deterministic fashion. HES episodes 0 days after the index procedure were analysed for pulmonary embolism. Mortality data was obtained pertaining to all the index procedures from the NJR for analysis. Participants All primary and revision ankle replacement patients captured on the NJR between February 0 and February. Results The 0-day mortality following TAR was 0.% (% CI 0.0 to 0.) and one-year mortality was 0.% (% CI 0.0 to.0), no deaths were as a result of PE. The incidence of PE within 0 days following primary TAR was 0.% (% CI 0. -.). There was only one PE following revision surgery. Patients with a RCS Charlson score greater than zero were at times greater risk of PE (p= 0.00). Conclusions There is low incidence of PE following TAR, but multiple co-morbidities are a leading risk factor for its occurrence.

32 Page of BMJ Open Article Summary Article Focus Mortality rate following Total Ankle Replacement Pulmonary embolism rate following Total Ankle Replacement Key Messages Mortality rate is low Multiple co-morbidities are the key risk factor for Pulmonary Embolism post Ankle Replacement Surgery. Strengths and limitations of this study The world s largest cohort of ankle replacements Data-linkage methodology reduces biases that are present in single surgeon, single centre reports of pulmonary embolism. Limited by linkage rate of %

33 BMJ Open Page of Introduction Total ankle replacement (TAR) provides patients with an improved functional outcome that is maintained at ten years with a cumulative annual failure rate of.%.[] The National Institute for Healthcare and Clinical Excellence (NICE) risk assessment tool categorises TAR as a high-risk procedure for pulmonary embolism (PE) [] but the true incidence of venous thromboembolism (VTE) following TAR is largely unknown, with several papers reporting wide variation in incidence ranging from 0-.% (Table Error! Reference source not found.).[ ] These studies demonstrate ambiguity of definition of VTE; methodological flaws; and small single centre retrospective reviews. An estimated,000 people die from hospital acquired venous thromboembolism (VTE) in the UK every year.[] Indeed, mortality is a key quality of care indicator outlined by the Keogh Report and its reduction a vital ambition of the UK National Health Service.[] VTE events are rare and difficult to capture in a single centre, but can be detected in sufficient numbers by large scale national registries. It has been mandatory to input every TAR into the NJR since. A further advantage to using registry data for analysis is the diversity regarding patient population, surgeon and implant choice. It is therefore representative of real world practice. In England any patient admitted to an NHS hospital is recorded on the Hospital Episode Statistics (HES) database; currently more than million records are captured each year. Almost all suspected PEs are admitted to hospital and should be recorded on the HES database. Between April to April, patients were admitted to NHS hospitals in England with pulmonary embolism.[]

34 Page of BMJ Open The aims of our study therefore were to answer the following research questions using linked NJR- HES data:. What is the rate of mortality following TAR?. What is the 0 day incidence of pulmonary embolism and associated risk factors? Methods Data Linkage Data from the NJR was linked to HES data in a deterministic fashion. Deterministic linkage requires an exact match of the fields being linked from both datasets in order to say that they are from the same patient. NJR records for primary and revision procedures (From Feb 0 to Feb ) ( records) were linked to five years of HES records (which equates to 0 million records) (Figure Figure ). This is in contrast to probabilistic linkage which estimates the likelihood that two records are for the same individual, even if they disagree on some fields.[] Linkage was conducted by the Health & Social Care Information Centre (HSCIC). This was in line with best linkage practice with application of the separation principle to allow the most ethical workflow.[] This principle is used to protect patient data, with patient identifying components and clinical components of a dataset kept separate. Identifying data is used by a group to perform data linkage while the research group uses non-identifying data to perform the analysis., NJR records were linked to NJR data that was captured on minimal dataset forms completed by the surgeon at the time of surgery and submitted by the performing hospital. This is a mandated requirement in the UK National Health Service. For a primary ankle replacement the form is entitled an A form and for a revision ankle replacement, an A form.[,] The forms capture patient

35 BMJ Open Page of demographics such as patient age, gender, and BMI. The unit where the surgery is performed is captured with the grade of surgeon performing the surgery. The grade of surgeon is sub-divided into a consultant surgeon or trainee. Indication for surgery, details of pre-operative deformity and range of motion are also collected. Further to this the prosthesis type, surgical approach, associated procedures, intra-operative complications and prophylaxis against venous thromboembolic disease are recorded. [,] Identification of pulmonary embolism The ICD- (International Classification of Disease Version ) codes were used to search the linked data for episodes of PE after the index procedure.[] DVT was excluded from our analysis as these patients are not admitted to hospital but instead are treated in the community and hence are not recorded on the HES database. [] Identification of deaths following TAR Mortality data was obtained separately from the NJR. The NJR tracks mortality via its link with the Office of National Statistics and automatically flags deaths at 0-days, year, years and -years. Analytical Approach Factors related to increased risk of PE following primary TAR were assessed. Several variables were investigated including: age, sex, body-mass index, length of stay, indication for surgery, implant type and fixation, thromboprophylaxis, preoperative range of motion and deformity, where the implant was performed (NHS vs. independent sector), and co-morbidities.

36 Page of BMJ Open Co-morbid conditions were defined using the Royal College of Surgeons Charlson Score applied to HES records in the months preceding the index operation for every patient. This is a validated tool that is a count of chronic co-morbid conditions that may affect the outcome of surgery.[] We combined the co-morbidity count to form two groups for analysis this was due to small numbers of PEs in each group. An assessment of the similarities between the background characteristics and surgical factors of the PE and no PE patient groups was conducted. The normality of each continuous factor when broken down by the PE or no PE patient groups was assessed using the Shapiro Wilk test. T-tests were used to test whether there was a difference in the means between the two groups when normality was upheld. Mann-Whitney tests were used to test whether the medians of the distributions were different for skew distributions. The Chi-squared or Fisher s exact tests were used to test whether there was an association between a categorical factor and patient group membership. As the number of PE outcome events were small, the ratio of outcome events per factor was not sufficient to enable multivariable analysis of the effect of multiple factors on PE. For the purpose of analysis, age was divided into three groups; less than, - and greater than. BMI was divided into three categories; a BMI of less than. is underweight;.- was classed as normal, and a BMI of greater than was classified as overweight, with no further breakdown for obesity. PE rate was also analysed in the context of unit volume. We identified that those units performing more than per year ( units) accounted for half of all ankle replacements performed and those that did less than per year ( units) accounted for the other half. We therefore classed high volume units as those carrying out ankle replacements or more per year and low volume units as those that performed less than per year.

37 BMJ Open Page of Due to the low occurrence of PE we combined ASA grades to form two groups. Analysis was conducted using R v.0. (R Foundation for Statistical Computing, Vienna, Austria). Estimates of mortality rates were derived by the Kaplan-Meier method using Stata/IC version.0 (StataCorp, College Station, TX, USA). Results There were a total of, NJR records comprising of, primary operations and revisions. The overall match rate with HES was % with, matched primary procedures and revisions. The mean patient age of patients undergoing primary total ankle replacement (TAR) was. (SD.). % of these patients were female. of NJR records gave details on patient BMI, the mean BMI was. (SD ). % of the primary procedures were done as a result of osteoarthritis with % having rheumatoid arthritis as the indication..% were uncemented operations with % were done via an anterior approach. The mean patient age of patients undergoing revision operation was (SD.). 0% of these patients were female. of NJR records gave details on patient BMI, the mean BMI was. (SD.). The main indication for revision was infection (%) followed by persistent pain (%) and aseptic loosening of the tibia (%). % were uncemented revisions to another ankle replacement..% involved fusion of the ankle joint form a TAR. Mortality Rate Survival data was available for, primary procedure patients. The median follow-up time was months (range to ), during which patients died. The 0-day mortality following TAR was

38 Page of BMJ Open % (% CI 0.0 to 0.) and one-year mortality was 0.% (% CI 0.0 to.0) (Table ). None of the deaths were as a result of PE. When compared to the ONS age and sex standardised death rates in the UK for the 0-day were times lower and one-year death rate was. times lower for patients who had a TAR. No deaths were observed amongst the revision patients who had a median follow-up time of months (range 0 to ). Pulmonary Embolism Rate Of the, linked primary procedures, had a PE within 0 days of surgery, giving an incidence rate of 0.% (% CI 0. -.) at a mean of days. All patients with a PE had an uncemented prosthesis via an anterior approach and received both mechanical and chemical thromboprophylaxis. Only of the revision procedures was recorded as having a PE. There were no fatal PEs. Although no statistical significance was noted (p=0.0) the 0 day rate of PE was greater amongst the - age group (0.0%), and over s (0.%) in comparison to the under age group where no PE s occurred (Table ). All the patients that had a PE were overweight. No occurrences of PE were found in patients with a BMI of less than (p=0.). Seventy three percent of the patients that did not suffer a PE (no PE Group) had received both mechanical and chemical prophylaxis. Three percent of patients received no thromboprophylaxis and yet none of them suffered a PE (Table ). Distribution of ASA Grade was similar in patients that suffered and did not suffer a PE (Table ). Patients with a RCS Charlson score greater than zero were at times greater risk of PE (p= 0.00). When looking at ankle deformity and range of motion we found a higher rate of PE with varus deformity and fixed equinus, but the differences were not statistically significant (Table ).

39 BMJ Open Page of Discussion The 0-day mortality rate following TAR is 0.%. This is lower than that reported for hip replacement (0.%) and knee replacement (0.%).[] The incidence of pulmonary embolism within 0 days of ankle replacement surgery is 0.% (% CI 0. -.), with a mean event time of days after surgery. A review of the literature suggests the published rate of PE to be 0.% (Error! Reference source not found.table ), which is significantly lower than the incidence revealed by this study. This may represent reporting bias in that, in other reported series, patients were admitted under medical teams and not picked up by the surgical team. The strength in our methodology is that it has the ability to capture readmissions anywhere in the UK under any clinician regardless of where the TAR was performed and hence meets one of our key aims to use registry data to determine a true incidence of pulmonary embolism following ankle replacement. A previous study used HES data only to determine PE rates following TAR determined by a search of a series of relevant treatment codes (ICD) and reported a PE rate of 0.0% post TAR.[] The current study used a more robust data linkage methodology to identify several more PEs. This highlights the advantage of using one dataset to validate another to ensure that data is not lost. A national audit of a large UK trust into clinical coding revealed that in orthopaedics % of diagnosis and % procedures are coded inaccurately.[] Therefore although we employed a robust method to identify ankle replacement more accurately the actual identification of PE was still limited by accuracy of clinical coding.