Epidemiology and Outcomes of IA in the 21st Century:

Strengths and Weaknesses of Surveillance Databases

Dionissios Neofytos, MD, MPH

Transplant & Oncology Infectious Diseases

The Johns Hopkins University

School of Medicine

Disclosures

• Consultant (Pfizer, LifeCell)• Research grant (Pfizer)

Overview

• Compare and contrast the data from single and multicenter databases• What we learned and not• Specific problems

– Number of patients– Case definition– Case capture

• Suggestions

Incidence of IA: 1987-1998

Wald A, Clin Infect Dis, 1996Marr KA, Blood, 2002

Timing and risk factors of IA post HSCT

Wald A, Clin Infect Dis, 1996Kontoyiannis D, Med Myc, 2008

Combination therapy for IA

Marr KA, Clin Infect Dis, 2004Garcia-Vidal C, Clin Infect Dis, 2009

Single-center databases

• Benefits: – Clinical data availability– Homogeneity in:

• Case capture

• Case definitions

• Clinical practices

– Long follow-up

• Deficiencies: – Small numbers of patients– Decreased patient and practice variability– Are results generalizable?

• Prophylaxis, diagnosis, and treatment practices

• Case capture rates

Variability in attack rates

National databases

• Administrative healthcare surveillance databases– National Hospital Discharge Survey (NHDS)– National Inpatient Sample (NIS)– Kid’s Inpatient Database (KID)

• Excellent tools for:– Inter-institutional comparison– Clinical research

• Benefits: – Assess the magnitude & temporal aspects of IA on population basis– Big numbers of patients

Nationwide Inpatient Sample

• NIS– 20% discharges from US community

hospitals– Data: demographics, diagnosis (ICD-9),

procedures, length of stay (LOS), charges, payer type, patient disposition

– 1996: 19 states, 906 hospitals, 6.5 million records1

– 2003: 28 states, 994 hospitals, 7.5 million records2

1 Dasbach E, Clin Infect Dis, 20002 Tong K, Int J Infect Dis, 2008

19961

N=10,19020032

N=10,400

Age (Mean), years

53 55.6

Incidence (per million)

34.263 36

+ IA - IA + IA - IA

LOS, days 17.3 5.0 17.7 7.9

Cost 62426 10647 96731 44318

Mortality, in hospital

19.3% 2.5% 17.1% NR

National database problems

• Lack of clinical data– Inability to adjust for severity of disease differences– Differences at individual and institutional level

• Lack of longitudinal follow-up – Patients not individually identified– Re-admission vs. transfer

• Under-representation of tertiary care centers– NIS

• ICD-9 coding– Designed for financial & administrative purposes– Incentives to maximize payments– Experience of billing staff & coding verification

ICD-9 coding and accuracy of IA diagnosis

Chang DC, Inf Control Hosp Epid, 2008

IDC-9 codes triggered MR review for 64 pts: 16 (25%) with IA

Multicenter databases

• Transplant Associated Infections Surveillance Network (TRANSNET)

– 2001-2006– Prospective surveillance data on

transplant recipients with IFIs– 23 transplant centers in the US

• Prospective Antifungal Therapy (PATH) Alliance®

– 2003-2008– Prospectively collected data on

patients with IFIs– 23 centers in North America

Horn D, DMID, 2007Pappas P, In Press

Epidemiology & outcomes of IA in HSCT

Marr KA, Blood, 2002Upton A, Clin Infect Dis, 2008Kontoyiannis D, in pressNeofytos D, Clin Infect Dis, 2009

Decreased incidence

Better survival

Multicenter database challenges

• Can we predict which data we need to capture?– Disease / Clinical practice-related data– New diagnostic methods– New clinical practices

• Can we always capture the data we need? – Total number of at risk patient population– Antifungal prophylaxis

• Can we always effectively translate data?– Antifungal therapies with >1 agent

– Sequential vs. concomitant treatment

How complete is case capture?

• Case identification– Microbiology & pathology databases– Attending physicians’ reporting– Consultation records– Medical & pharmacy records

• TRANSNET internal audit– Medical record review of randomly selected patients– HSCT: 20-30% highest risk group – SOT: lung transplant recipients– <5% of total cases identified

Horn D, DMID, 2007Pappas P, In PressChang DC, Inf Control Hosp Epid, 2008

Case reporting

Pappas P, In Press

• SOT - TRANSNET – Overall by site 12-month cumulative incidence of IFIs: 1.2-6.1%– SOT specific 12-month cumulative incidence of IFIs:

– Liver: 0-15.5%– Pancreas: 0-20.0%– Lung/Heart-lung: 0-25.9%

• HSCT - TRANSNET– 12-month cumulative incidence of IFIs: 3.4% (range, 0.9-13.2%)– 6 of 21 sites: 80% of IFIs in MMR HSCT (range, 3.1-20.6%)

The diagnosis challenge

• Patients at risk:– Center based clinical practices– Geography

• Diagnosis based on:– Diagnostic practices vary

– By center– By patient population

– Interaction between Infectious Disease service with other services– Hematology, BMT, Surgery, Pulmonary, Microbiology

– Availability of diagnostic assays on site

Neofytos D, Clin Infect Dis, 2009Neofytos D, Tran Infect Dis, 2010

Are multicenter database results comparable?

HSCT Type IFI Frequency Aspergillus spp. Candida spp.

Autologous Allogeneic IA IC Zygo A. fum Unknown C. alb C. gla C. par

TRANSET 21% 78% 43% 28% 8% 44% 26% 20% 33% 14%

PATH Alliance

31.2% 68.8% 59.2% 24.8% 7.2% 37.2% 52.7% 24.2% 43.5% 11.3%

Kontoyiannis D, In PressNeofytos D, Clin Infect Dis, 2009

Multi-Center Databases

• Benefits: – High numbers of patients– Patient and practice diversity

• Deficiencies: – Heterogeneity in:

• Case capture• Case definitions• Clinical practices

– Differences in endemicity– Limited clinical data– Inadequate follow-up– Inability to capture “late events” related to:

• Transplant-associated complications• Underlying disease relapse• Infections

How are data affected by changes in practice?

1980 1990 2000 2010

Diagnostics

Therapeutics

IFI definitions

GMA EIA

Voriconazole Combination therapy

PCR

Prophylaxis with anti-mould agents

Acknowledgments

• Acknowledgments– Peter Pappas, MD– David Horn, MD– Kieren Marr, MD

• Thanks for your attention