key: cord-0683650-6n4nmf96 authors: Rahamat‐Langendoen, Janette; Groenewoud, Hans; Kuijpers, Judith; Melchers, Willem J.G.; van der Wilt, Gert Jan title: Impact of molecular point‐of‐care testing on clinical management and in‐hospital costs of patients suspected of influenza or RSV infection: a modeling study date: 2019-04-14 journal: J Med Virol DOI: 10.1002/jmv.25479 sha: d2a10af0fb0028bc94c66c22059a695c755d8862 doc_id: 683650 cord_uid: 6n4nmf96 BACKGROUND: At hospital admission, patients suspected of infection with influenza or respiratory syncytial virus (RSV) are placed in isolation, pending the outcome of diagnostics. In a significant number, isolated care proves unnecessary. We investigated the potential impact of molecular point‐of‐care (POC) diagnostics on patient management and in‐hospital costs. METHOD: Prospective collection of data on resource utilization within the hospital from consecutive patients 18 years or older presenting at our university medical center with symptoms of respiratory tract infection from December 2016 to April 2017. A cost analysis was conducted using Markov modeling comparing the actual course of events (on the basis of routine diagnostic tests) with two hypothetical scenarios: when POC would impact time to diagnosis only (scenario 1) or on discharge from the hospital, too (scenario 2). RESULTS: A total of 283 patients were included, of whom 217 (76.7%) were admitted. Influenza and RSV were detected in 31% and 7% of the patients, respectively. Fifty‐four percent of patients tested negative, of which 79% were kept in isolated care waiting for test results, with a median duration of 24 hours. Median length of stay was 6.0 days. Mean total in‐hospital costs per patient were € 5243. Introducing POC would lower mean costs per patient to € 4904 (scenario 1) and € 4206 (scenario 2). At the hospital level, this would result in a total cost reduction of € 95 937 to € 293 471 in a single influenza season. CONCLUSIONS: Introducing POC testing for patients presenting with symptoms of viral respiratory tract infection can reduce time‐to‐diagnosis, hospital stay and, thereby, in‐hospital costs. If no single-persons room is available, a multiple-person room may be used for a single patient resulting in the loss of admission capacity. This highly impacts hospital resource utilization and healthcare costs. Furthermore, because of the clinical uncertainty about the cause of disease (viral versus bacterial), many patients will be treated empirically with nontargeted antibiotic therapy until results of microbiological diagnostics are known, whereas only some will actually need it. Rapid detection of respiratory viral pathogens has therefore also the potential of reducing the duration of empirically started antibiotics and initiation of appropriate antiviral treatment, as an antiviral treatment for influenza should be started within 48 hours after onset of disease to be effective. The aim of this study is to assess the potential impact of a POC test for influenza and RSV on patient management and associated hospital costs. From December 2016 to April 2017, all patients aged 18 years and older with suspicion of respiratory viral infection were included, either admitted to our hospital or ambulatory. Our hospital is a tertiary referral academic center in The Netherlands. Respiratory samples were taken on the basis of the clinical judgment of the physician. Patient characteristics were collected (sex, age, underlying illness, length of hospital stay, admission to ICU, and mortality). Respiratory samples were divided in two aliquots, one for the routine laboratory molecular testing, and one for the cobas ® Liat System. Aliquots for the cobas Liat System were stored in minus 80°C for retrospective testing at the end of the study. Patients were followed up, collecting data on resource utilization within the hospital until the time of final diagnosis and discharge. Time of admission, time of collection of respiratory material, time spent in isolation for respiratory illness, time to arrival of the specimen in the laboratory, time to result of the diagnostic test, and data on antimicrobial were retrieved from our electronic patient record system and laboratory information system. For routine detection of influenza virus and RSV the Diagenode assay was performed as described by Templeton et al. 8 Testing by the cobas ® Liat Influenza/RSV assay was carried out according to the manufacturer's instructions, which required 200 µL of patient sample to be pipetted into the supplied assay tube and tested on the cobas ® Liat analyzer. 9 A Markov decision model was developed to compare costs in three scenarios: actual clinical management, compared with two hypothetical scenarios, in which clinical management would have been based on the cobas ® Liat (POC). In both hypothetical scenarios, a correct diagnosis was assumed to be made within an hour upon admission. In one scenario, the impact of reduced time-to-diagnosis on in-hospital resource utilization and associated costs was modeled (scenario 1), whereas the second model took into account reduced hospital stay as well (scenario 2). Patients presenting at the out-patient clinic were distinguished from those presenting at the emergency department. A Markov model was constructed to reflect the in-hospital routing of patients, distinguishing seven specific states ( Figure 1 ). In each scenario, patients started at the outpatient clinic or the emergency department (state 1). They could either remain in that state, be discharged (ie, not hospitalized, state 7), or they could be hospitalized, in isolated care (state 2) or not (state 3). In both cases, their infection status was unknown. From state 2 they could either remain in that state, or progress to the state "isolated care, infectious state established/need for isolated care confirmed" (state 4), progress to the state "not isolated care, infectious state established/need for isolated care disconfirmed" (ie no influenza or RSV detected, state 5), or progress to state 6 ("not isolated care, infectious state is known, absence of isolation confirmed"). From state 3 ("hospitalized, not isolated care, infectious state unknown"), patients could remain in that state, or progress to state 6 or 4. Patients in states 4, 5 or 6 could remain in that state, or progress to state 7 ("discharge from hospital"). In addition, patients in state 4 or 5 could progress to state 6. The costs for routine and POC diagnostic tests were on the basis of estimated cost prices of the assay. Where available, standard cost prices on the basis of national guidelines were used to calculate mean costs per patient. 10 Costs for admission in isolated care were assumed to be twice the costs for non-isolated admission. This would reflect the additional protective equipment for patient and personnel, the use of a one-person room or multiple room occupancy by a single patient, the extra workload for staff (eg need for finding capacity within own hospital or in other neighboring hospitals) and loss of productivity because of inability to admit patients because of lack of capacity. Table 1 represents an overview of the costs used in the model. All analyses were performed using the TreeAge Pro software Retrospective testing using the cobas ® Liat Influenza/RSV assay was possible in 225 patients; for 58 patients either results using the cobas ® Liat assay were invalid and no material was left for re-testing (n = 21), or no respiratory material was left after initial routine testing (n = 37). All patients who tested influenza A, influenza B or RSV positive in the routine PCR had comparable results using the cobas ® Liat Influenza/RSV assay (Table 3 ). Four out of 115 patients who tested negative in the routine PCR turned out influenza A (n = 2) or RSV (n = 2) positive using the cobas ® Liat Influenza/RSV assay. In one of these patients, routine PCR on sputum was negative for RSV, but positive on subsequent BAL material. Initial sputum was positive for RSV using the cobas ® Liat Influenza/RSV assay. For the other three patients, no other respiratory material was available for further testing to distinguish between true or false positive findings using the cobas ® Liat Influenza/RSV assay. The results of the Markov modeling are presented in Figure 2 . The When compared with this reference scenario, scenario 1 represents the impact of POC testing on time-to-diagnosis only ( Figure 2B ). In scenario 2, POC testing also impacts discharge from the hospital ( Figure 2C) The costs associated with in-hospital care for patients suspected of influenza or RSV infection are presented in Table 4 . Cost estimates were on the basis of the average length of stay of patients in the various model states (1-7) , combined with unit cost prices (Table 1) . T A B L E 4 Mean duration in the various model states (hours) and associated costs (euros) per patient suspected of influenza or RSV infection, in case of care as usual and in case of reduced time-to-diagnosis as result of POC (scenario 1) and in case of additional impact of POC on length of stay (scenario 2). For total costs, the 90% confidence interval is presented on the basis of first-order Monte Carlo simulation of the three models (numbers between brackets). In the scenario "usual care," mean costs per patient amounted to € 5243 (€ 288-10 105). Introducing POC would lower in-hospital costs to € 4904 (€ 253-9604) and € 4206 (€ 253-8267) in scenarios 1 and 2, respectively. Our study suggests that introducing a POC test for influenza and in a timelier manner. 4, 5, [14] [15] [16] [17] [18] [19] Two randomized studies showed a significant reduction in turn-around-time and a positive effect on the timely prescription of antiviral therapy; however, no effect was observed on the length of hospital stay and on antibiotic use. 20, 21 The impact of POC respiratory virus testing on clinical decision making in patients with respiratory symptoms at the emergency department was assessed in two recent reports. 13, 22 In approxi- The study was financially supported by an unrestrictive grant by Roche LTD. The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication. 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Rahamat-Langendoen http://orcid.org/0000-0003- Willem J.G. Melchers http://orcid.org/0000-0002-5446-2230