Supplementary appendix

Transcription

1 Supplementary appendix This appendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors. Supplement to: Dayer MJ, Jones S, Prendergast B, et al. Incidence of infective endocarditis in England, : a secular trend, interrupted time-series analysis. Lancet 2014; published online Nov 18.

2 Appendix Contents Page 1. Supplementary Methods Method for identifying high-risk and lower-risk individuals 2 Method for identifying the causal organism for IE cases identified through HES data Supplementary Results Other factors that could have influenced the incidence of infective endocarditis (IE) 3 3. Supplementary Tables Table S1. ICD-10 & OPCS-4 codes used to identify high-risk patients 4 Table S2. Number of high-risk and lower-risk IE patients in different categories 5 Table S3. ICD-10 codes used to identify IE cases where the causal organism was likely to be streptococcal or staphylococcal 6 4. Supplementary Figures Figure S1. Incidence of IE cases (superspells) and deaths per month (uncorrected for populationchange) 7 Figure S2. Change-point analysis of uncorrected IE incidence 8 Figure S3. Incidence of IE cases per month in high-risk and lower-risk individuals (uncorrected for population-change) 9 Figure S4. Other factors that could have influenced IE incidence 10 Figure S5. The population of England Supplementary References 11 1

3 1. Supplementary Methods Method for identifying high-risk and lower-risk individuals All patients admitted to UK hospitals have standard Hospital Episode Statistics (HES) data recorded using the ICD-10 coding system ( to provide their primary discharge diagnosis and up to 12 secondary diagnoses. Individual patient level analysis of secondary codes and correlation with preceding hospital admissions was used to identify patients at high-risk of developing IE, as defined by AHA 1 and ESC 2 guidelines. All other patients were defined as lower-risk (i.e. moderate or low-risk ). Individual National Health Service (NHS) patient numbers were used to identify any previous IE admission. Those with a pre-existing prosthetic valve were identified by inclusion of a Z95.2 ICD-10 supplementary code (presence of prosthetic heart valve) or an earlier OPCS-4 operative procedure code (prosthetic replacement or repair of heart valve) within the HES data record (Table S1). Patients with congenital heart disease repaired with prosthetic material are regarded as high-risk for 6 months after the procedure. 1,2 Thus, OPCS-4 codes were used to identify any such procedures in the 6 months prior to an IE admission. Patients with unrepaired cyanotic congenital heart disease and those with a palliative shunt or conduit were identified using similar coding analysis (Table S1). We were unable to identify two categories of high-risk individual using HES data: (i) those with congenital heart disease and a persistent residual defect at the site of implantation of a prosthetic device, and (ii) cardiac transplant recipients who develop valvulopathy. Although such individuals represent a very small proportion of high-risk individuals, we were unable to include them in our subanalysis of this group. Method for identifying the causal organism for IE cases identified through HES data. An initial detailed inspection of a patient level data extract of a 1,000 IE cases was used to identify all those pathogen-specific supplementary ICD-10 codes that were recorded in IE cases that could indicate if the likely causal organism was Streptococcal or Staphylococcal in origin (see Table S3 and below). All data records identified as having an IE diagnosis using the I33.0 ICD-10 code in the HES database were examined for the presence of any of these secondary or supplemental pathogen-specific ICD-10 codes that could identify the nature of the likely causal organism. ICD-10 codes A A40.3 and B B95.3, respectively, were used to identify Group A, B, D streptococci and Streptococcus pneumoniae as causal organisms. Codes A40.8, A40.9, A49.1, B95.4 and B95.5 were used to identify other or unspecified streptococci and since there are no specific codes for oral viridans group streptococci (OVGS), we assumed that this cluster encompassed all possible cases caused by this group of organisms. This assumption may not be correct, however, and the data on OVGS-related IE can only be regarded as an approximation. For comparison, ICD-10 codes A A41.2, A49.0 and B B95.8 were used to identify IE cases related to staphylococci. ICD-10 codes used are listed in Table S3. It should be noted that this methodology does not enable us to determine if the secondary or supplemental code identifies the organism responsible for IE or another concurrent infection in someone whose primary diagnosis is IE (e.g. pneumonia, urinary tract or wound infection). We can therefore only deduce that it is likely, but not certain, that the secondary or supplemental code relates to the organism causing IE. 2

4 2. Supplementary Results Other factors that could have influenced the incidence of infective endocarditis (IE) There was no sudden change in the overall frequency of valve surgery. Although we identified a small fall in the annual number of mechanical heart valves inserted over the study period, the overall volume of prosthetic valve surgery increased steadily due to a concomitant rise in the use of bioprosthetic valves and valve repair procedures using prosthetic material (Figure S4a). The number of new diagnoses of cyanotic congenital heart disease rose steadily (Figure S4b) while the number of palliative surgical procedures for congenital heart disease was almost constant. There was, however, a dramatic increase in the number of percutaneous repair procedures for congenital heart disease commencing in , peaking in (at around 1,600/annum), and falling thereafter as the reservoir of newly treatable cases was presumably depleted (Figure S4b). Although lead- and valve-related IE are frequent complications of device infection (usually due to staphylococcal contamination at the time of implantation), neither the AHA or ESC guidelines define patients with pacemakers or cardioverter defibrillators as high-risk. 3 Although the annual number of these procedures rose steadily over the study period, there was no sudden change that could account for the rise in incidence of IE in 2008 (Figure S4c). An increase in the incidence of IE could also be explained by a large rise in the number of individuals undergoing invasive dental procedures, or an overall deterioration in the oral health of individuals at risk of IE as a result of restricted access to dental services or other reasons. Although we could not obtain specific data for individuals at risk of IE, there was no significant change in the overall proportion of the English population receiving dental treatment that could account for the observed change in IE incidence (Figure S4d). 3

5 3. Supplementary Tables Table S1. ICD-10 & OPCS-4 codes used to identify high-risk 1 patients ICD-10 code for infective endocarditis: I33.0 OPCS-4 codes for prosthetic replacement of a heart valve: K25.1-K25.4, K26.1-K26.4, K27.1-K27-4, K28.1-K28.4 or K29.1-K29.4 OPCS-4 codes for valve repair using prosthetic material: K25.5, K25.8, K25.9, K26.8, K26.9, K27.6, K27.8, K27.9, K28.8, K28.9, K29.8, K29.9, K30.1-K30.5, K30.8, K30.9, K33.1- K33.9, K34.1-K34.3, K35.8+Z32.4. OPCS-4 codes for congenital heart disease repaired with prosthetic material 2 : K09.1, K09.2, K10.1, K11.1, K11.7, K12.1, K13.1-K13.5, K13.8, K13.9, K16.3, K16.5, L03.1, L07.5, L10.1, L23.3 OPCS-4 codes for congenital heart disease patients in whom a palliative shunt or conduit had been used: K04.1, K04.2, K06.3, K17.1, K17.3, K17.4, K18.1-K19.9, K76.1, K76.8, K76.9, L05.1-L05.3, L05.8, L05.9, L07.1-L07.3, L07.8, L07.9 ICD-10 codes for a pre-existing congenital cyanotic heart condition: Q20.0-Q20.4, Q21.2-Q21.8, Q26.2 OPCS-4 codes for prosthetic heart/ventricular assist device: K02.3, K02.5, K54.1 Note: 1. Patients at high-risk of developing IE were identified by determining whether they had been diagnosed with a high-risk condition (ICD-10 codes) or undergone a high-risk procedure (OPCS-4 codes) at any time in the past (within the available records for that individual). 2. Since patients with congenital heart disease repaired with prosthetic material are only considered high-risk for 6 months following the procedure, the search was restricted to 6 months for these individuals. 4

6 Period Previous IE Replacement Heart Valve Repaired Heart Valve Repaired Congenital Heart Dis Palliative Shunt or Conduit Cyanotic Heart Disease Prosthetic Heart/VAD Lower-Risk Table S2. Number of high-risk and lower-risk IE patients in different categories Jan-Mar Apr-Jun Jul-Sep Oct-Dec Jan-Mar Apr-Jun Jul-Sep Oct-Dec Jan-Mar Apr-Jun Jul-Sep Oct-Dec Jan-Mar Apr-Jun Jul-Sep Oct-Dec Jan-Mar Apr-Jun Jul-Sep Oct-Dec Jan-Mar Apr-Jun Jul-Sep Oct-Dec Jan-Mar Apr-Jun Jul-Sep Oct-Dec Jan-Mar Apr-Jun Jul-Sep Oct-Dec Jan-Mar Apr-Jun Jul-Sep Oct-Dec Jan-Mar Apr-Jun Jul-Sep Oct-Dec Jan-Mar Apr-Jun Jul-Sep Oct-Dec Jan-Mar Apr-Jun Jul-Sep Oct-Dec Jan-Mar Apr-Jun Jul-Sep Oct-Dec Jan-Mar Red line indicates the time point at which the NICE guidelines were introduced 5

7 Table S3. ICD-10 codes used to identify IE cases where the causal organism was likely to be streptococcal or staphylococcal A40 Streptococcal sepsis A40.0 Sepsis due to streptococcus, group A A40.1 Sepsis due to streptococcus, group B A40.2 Sepsis due to streptococcus, group D A40.3 Sepsis due to Streptococcus pneumoniae A40.8 Other streptococcal sepsis A40.9 Streptococcal sepsis, unspecified A41 Other sepsis A41.0 Sepsis due to Staphylococcus aureus A41.1 Sepsis due to other specified staphylococcus Sepsis due to coagulase-negative staphylococcus A41.2 Sepsis due to unspecified staphylococcus A49 Bacterial infection of unspecified site A49.0 Staphylococcal infection, unspecified site A49.1 Streptococcal infection, unspecified site B95 Streptococcus and staphylococcus as the cause of diseases classified to other chapters B95.0 Streptococcus, group A, as the cause of diseases classified to other chapters B95.1 Streptococcus, group B, as the cause of diseases classified to other chapters B95.2 Streptococcus, group D, as the cause of diseases classified to other chapters B95.3 Streptococcus pneumoniae as the cause of diseases classified to other chapters B95.4 Other streptococcus as the cause of diseases classified to other chapters B95.5 Unspecified streptococcus as the cause of diseases classified to other chapters B95.6 Staphylococcus aureus as the cause of diseases classified to other chapters B95.7 Other staphylococcus as the cause of diseases classified to other chapters B95.8 Unspecified staphylococcus as the cause of diseases classified to other chapters Notes re B Codes: These categories should never be used in primary coding. They are provided for use as supplementary or additional codes when it is desired to identify the infectious agent(s) in diseases classified elsewhere. 6

8 4. Supplementary Figures Figure S1. Incidence of IE cases (superspells) and deaths per month (uncorrected for populationchange) Figure S1 - Legend The number of IE cases (spells) recorded each month (solid BLACK line) and associated in-patient mortality (solid RED line). The vertical dashed black line indicates March 2008, the month in which cessation of antibiotic prophylaxis for IE was recommended by NICE. Trend lines for IE incidence (dashed BLACK line) and associated in-patient mortality (dashed RED line) before and after introduction of the NICE guidelines are also shown. NOTE: The change in IE incidence trend remains statistically significant after removal of the outlier value in March 2012 (change in level = -1 37, CI , p=0 79; change in slope = 0 55, CI , p<0 001). 7

9 Figure S2. Change-point analysis of uncorrected IE incidence Figure S2 - Legend The number of IE cases per month (solid BLACK line). The vertical dashed black line indicates March 2008, the month in which cessation of antibiotic prophylaxis for IE was recommended by NICE. The red lines show the result of change-point analysis, indicating that the change occurred in June

10 Figure S3. Incidence of IE cases per month in high-risk and lower-risk individuals (uncorrected for population-change) Figure S3 - Legend The number of IE cases recorded each month affecting lower-risk (solid BLACK line) and high-risk (solid RED line) individuals. The vertical dashed black line indicates March 2008, the month in which cessation of antibiotic prophylaxis for IE was recommended by NICE. Trend lines for lower-risk (dashed BLACK lines) and high-risk (dashed RED lines) individuals before and after introduction of the NICE guidelines are also shown. 9

11 Figure S4. Other factors that could have influenced IE incidence Figure S4 - Legend Contemporaneous trends which could influence IE incidence: (a) volume of heart valve surgery performed/year/10 million of the population (ORANGE), sub-divided into valve repair (GREEN) and valve replacement (PURPLE) - valve replacement procedures are further sub-divided into those using mechanical (BLUE), bioprosthetic (YELLOW) and homograft (RED) valves; (b) number of new inpatient diagnoses of cyanotic congenital heart disease/year/10 million of the population (CHD) (GREEN) and palliative shunt or conduit procedures (BLUE) - also shown is the total number of CHD repair procedures performed using prosthetic material (PURPLE), subdivided into those performed 10

12 using percutaneous (RED) or other (ORANGE) techniques; (c) number of implantable pacemakers and cardioverter defibrillators inserted/year/10 million of the population; (d) proportion of the total (GREEN), adult (BLUE) and child (RED) population of England who were seen by a dentist in the previous 24 months. Figure S5. The population of England Supplementary References 1. Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation 2007; 116(15): Habib G, Hoen B, Tornos P, et al. Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009): the Task Force on the Prevention, Diagnosis, and Treatment of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the International Society of Chemotherapy (ISC) for Infection and Cancer. Eur Heart J 2009; 30(19): Baddour LM, Epstein AE, Erickson CC, et al. Update on cardiovascular implantable electronic device infections and their management: a scientific statement from the American Heart Association. Circulation 2010; 121(3):