Task Force Microbiology: Reimbursement Proposal Template (version 01/08/2019) PROPOSAL: SUMMARY X NEW TEST O TEST WITHDRAWAL O CHANGE REIMBURSEMENT RULES OR PRICING Test descrip?on: NAAT detec?on of at least 10 different respiratory microorganisms in a respiratory sample Sample type(s): Respiratory samples (nasopharyngeal aspirates, pooled bilateral nasopharyngeal and throat flocked swabs, sputum, bronchial aspirates, BAL, pleural fluid, lung biopsies) Procedure: NAAT detec?ng at least 10 respiratory microorganisms.

Condi?on(s): hospitalized, cri?cally ill pa?ents.

Absolute requirement: short TAT (answer within < 24h, controlled TAT >= 95%)

Accredita?on warranted: yes, ISO 15189 (art 24 bis) – with control of TAT

Can be ordered by: Intensive care physician, pneumologist, intensive care paediatrician

Maximum/ Replica limit: 1 test/episode ; max 3/year Pricing: B2000 Es?mated number of tests/year: 15.600 (total of a survey of the numbers of respiratory panels performed in 12 large Belgian laboratories represented in MWG in2018).

Es?mated evolu?on over the next five years: increasing Es?mated total budget/year: 1.017.526 €/year (= 100% honoraria. Based on the results of a survey of the numbers of Panel tests performed in 12 large Belgian laboratories represented in MWG) Es?mated cost savings/year: withdrawal of viral culture (550631-550642 B1400) 2017: 211.000€

PLUS reduc?on of cost in an?gen tes?ng (B250; 552016-552020) in 2017: 1.400.000€ (es?mated reduc?on 25 to 50%) PLUS reduc?on in cost of an?bio?c use (es?ma?on: un?l 52%); PLUS reduc?on of hospitaliza?on cost (es?ma?on: un?l 26%) PLUS alterna?ve cost saving (reduced complementary laboratory tes?ng, reduc?on of unnecessary medical procedures: bronchoscopy, lung biopsy, or overly aggressive therapy with cor?costeroids and bronchodilators for presumed asthma) PLUS beker infec?on control ! PLUS improvement in clinical competence of trainee clinical staff (less easily quan?fiable in economic terms)

Numbers; References:

- Differen3a3ng viral CAP from mixed infec3on and bacterial CAP remains challenging, but beAer diagnos3c approaches could reduce an3bio3c overuse.

References: CAT template UZ-Leuven LAG ISO 15189 Price C. Evidence-based Laboratory Medicine: Supporting Decision-Making. Clinical Chemistry 46;8, 1041-1050 (2000) STARD initiative (http://www.stard-statement.org)

Task Force Microbiology: Reimbursement Proposal Template (version 01/08/2019)

- But since 2004 many addi3onal evidence-based data about CAP by solely a RV infec3on, even in adults. Ref. Cesario TC. CID 2012; Pavia AT. Infect Dis Clin N Am 2013.

Tests that become obsolete and can be withdrawn from reimbursement: Reduc?on of viral an?gen tes?ng in children and adults. Stopping of viral cultures in clinical laboratories (only necessary in ref labs for surveillance & epidemiology, examina?on of sensi?vity/resistance profiles)

Expected impact of (new) concurrent test ordering: -In immunocompetent paediatric and adult pa?ents:

- Significantly reduced hospitaliza?on dura?on - Significantly reduced an?bio?c use (reduced cost, reduced development of resistance) - Significantly reduced laboratory u?liza?on (clinical biology) and other technical

examina?ons -Beker management of SARI and of immunosuppressed hospitalized pa?ents (rapid start of directed an?viral therapy, beker prognosis, shorter hospitaliza?on! less nosocomial infec?ons) -Beker infec?on control (isola?on management) and bed management

Access for other disciplines: Less medical imaging possibly, less technical acts

Excel template: akached

CLINICAL/DIAGNOSTIC SCENARIO Short descrip-on: Why is this test proposed for reimbursement? ■ About 200 million cases of viral CAP occur each year: 100 million in adults & 100 million in children. Molecular diagnos3c tools have increased our understanding of the role of viruses in pneumonia, and findings indicate that the incidence of viral pneumonia has been underes3mated. (Ref. Ruuskanen O et al. Lancet 2011;377:1264-75) ■ Respiratory viruses are detected in 45% to 75% of children and in 15% to 54% of adults hospitalized with CAP. (Ref. Pavia AT 2013)

■ There is substan3al evidence that the risk of serious bacterial infec3on is low in children with laboratory confirmed viral infec3on. (IDSA guidelines 2011. Management of CAP in children)

References: CAT template UZ-Leuven LAG ISO 15189 Price C. Evidence-based Laboratory Medicine: Supporting Decision-Making. Clinical Chemistry 46;8, 1041-1050 (2000) STARD initiative (http://www.stard-statement.org)

Task Force Microbiology: Reimbursement Proposal Template (version 01/08/2019)

■ Molecular tests are the first choice in clinical seZng:

1) Rapid answer (within 4-24h with NAAT - compared to viral culture: Broad screening (with subtyping and resistance profile) possible in one test/amplifica3on reac3on

2) Gain in diagnos3c recovery compared to viral culture: in paediatrics + 30-45% (own data, presented at ESPID 2009, 2010, 2014); in adults + 33%-64% (Ref.Templeton KE et al, CID 2005; Van de Pol et al, JCM 2007). Differences in diagnos3c gain from culture to PCR differ from virus to virus (RSV + 12%; FluA-B: +50%).

3) Viral culture more sensi3ve for varia3ons in pre-analy3cal phase (transport condi3ons, temperature shock, delay before inocula3on) compared to NAAT

■ Start of an3viral therapy preferably within first 24-48h (effect decreases aeer delayed start of therapy) ■ Coinfec3on with viruses and bacteria is common (4% to 30% of adults hospitalized with CAP). ■ The role of Streptococcus pneumonia rela3ve to viral causes of CAP may have decreased because of widespread use of pneumococcal conjugate vaccines in children. ■ Since most viral respiratory tract infec3ons can present with similar symptoms and signs (from sinusi3s or rhini3s to fulminant bilateral pneumonia) it is impossible to differen3ate between an important respiratory infec3on such as influenza that would require a different management and infec3on control measures and a less severe infec3on with, say, coronavirus OC43, by clinical presenta3on only.

Data OLVZ-Aalst: de snotbarometer: h#ps://www.olvz.be/zorgverleners/de-snotbarometer-virussen-en-bacterien

Referen-es: Nichols et al. 2001 BBMT 7: 115; Mar-no et al. 2005 BBMT 11: 781; Chemaly et al. 2006 Medicine 85: 278; Khanna et al. 2008 CID 46. 402; Sung L et al. 2008 Ped Blood Canc 51(6): 784; Avetysian et al. 2009 Transplant 88: 1222; Shah & Chemaly 2011 Blood 117: 2755; Renaud C and Campbell AP. 2011 Curr Opin Infect Dis 24(4):333.

References: CAT template UZ-Leuven LAG ISO 15189 Price C. Evidence-based Laboratory Medicine: Supporting Decision-Making. Clinical Chemistry 46;8, 1041-1050 (2000) STARD initiative (http://www.stard-statement.org)

Task Force Microbiology: Reimbursement Proposal Template (version 01/08/2019)

Several reasons may jus?fy that a pa?ent is tested for respiratory pathogens (see above) 1) Treatment

Timely start of specific an?viral treatment (+/- IV Ig) Correct an?biotherapy Adapta?on of an?virals Decision about start of an?bio?cs or of immunosuppressive regimen

2) Isola?on: beker management of the isola?on of pa?ent, preven?on of outbreaks/nosocomial infec?ons.

The consequences of not rapidly iden3fying influenza virus in a large nursing home or busy hospital ward could result in an outbreak of 10−20 infected pa3ents within a single day, resul3ng in significant morbidity and mortality and lost revenue in the case of a hospital if bed closures are invoked.

3) Inves?ga?on of outbreaks (ICU, ...) for different respiratory viruses : Making the correct diagnosis of a respiratory virus infec3on is important in the context of respiratory outbreak management and in the event of a novel respiratory virus appearing in the human popula3on for the first 3me. Respiratory outbreaks in the community oeen go undiagnosed with no e3ological agent being detected. This is because subop3mal or insensi3ve methods are used or specific viral agents may not be tested for. In North America it is es3mated that in one quarter to one third of respiratory outbreaks no e3ological agent is ever detected. Use of broad molecular panels would certainly assist the public health authori3es in inves3ga3ng respiratory outbreaks given the large number of viruses that it can detect. Such tests has helped with the diagnosis of nursing home outbreaks of hMPV and rhinovirus and obviated the need for oseltamivir prophylaxis. Use of these tests in outbreak situa3ons will also increase our understanding of the epidemiology of outbreaks in the community and assist the public health authori3es in developing appropriate control measures. Molecular RV panels may also be useful in the event of a new outbreak of SARS, H5N1 influenza or other new agents since it can be used to rule out the “common agents” and therefore indicate the possibility that a new agent is circula3ng. Ref. Mahony B : The Clinical Need for the RVP test. J Clin Virol 2007, 40 (Suppl 1:S36-S38)

APPRAISAL 1) Analy3cal performance characteris3cs (analy3cal valida3on report)

1.Preanaly-cal considera-ons (pa-ent variables, sample stability)

• Biological varia3on (sampling -me (f.i. drug monitoring) At admission for CAP (Before treatment with an?virals)

• Interferences (medica-on, diet, ... ) Not known • Pa3ent variables (age, risk factors, gender, ... ) Higher viral load in samples of children

and immunodepressed pa?ents; longer viral shedding in same pa?ent groups • Sample stability (preserva-on, transporta-on, storage, ...) in transport medium 48 hours

aqer sampling at 2°c to 8°C, • Sample type (serum, swab, urine, ..) Respiratory samples (nasopharyngeal aspirates,

pooled bilateral nasopharyngeal and throat flocked swabs, sputum, bronchial aspirates, BAL, pleural liquid, lung biopsies)

• Sample volume: Depends on the test • Prevalence (es-ma-on of amount of posi-ve test percentage): See short descrip-on (cf

supra)

References: CAT template UZ-Leuven LAG ISO 15189 Price C. Evidence-based Laboratory Medicine: Supporting Decision-Making. Clinical Chemistry 46;8, 1041-1050 (2000) STARD initiative (http://www.stard-statement.org)

Task Force Microbiology: Reimbursement Proposal Template (version 01/08/2019)

▪ Sciensano (data SARI-network): A high Percentage of SARI pa?ents are infected with respiratory viruses In the SARI popula?on for the season 2012-2013

o 994 pa?ents 429 influenza posi?ves (with 13% coinfec?on with other viruses ) 295 other respiratory viruses posi?ve

o So 72% (724/994) = were infected by one respiratory viruses

▪ Data OLVZ-Aalst: de snotbarometer: h#ps://www.olvz.be/zorgverleners/de-snotbarometer-virussen-en-bacterien

▪ Data St. Jan: Jan 2013-Feb 2014: 1662 Children with LRTI: 86% posi?vity for RV (predominantly hRhV:747 samples; adeno; RSV and PIV1-4) or atypical bacteria (of which 19 B.pertussis/parapertussis; 12 C.pneumoniae; 16 M.pneumoniae, 1 Q-fever). 1480 adults with CAP or acute exacerba?on of asthma/COPD or SARI: 64% posi?ve for RV or atypical germs (including Pneumocys?s jirovecii, C.pneumoniae, C.psi#aci, M.pneumoniae, L.pneumophila, Coxiella burne?i)

• Target popula3on: 1) Acute respiratory failure (CAP or acute exacerba?on of asthma/COPD) in ICU

2) LRTI/SARI in following pa?ent groups:

oHSCT & SOT-recipients,

o (Premature) neonates

o Precarious elderly (> 65y) with underlying heart and lung disease

o pa?ents under immunosuppressive therapy (TNF alpha inhibitors, alemtuzumab, rituximab, high dose cor?costeroids, …) or acquired immunodeficiency

2.Analy-cal considera-ons (reproducibility, accuracy, correla-on, linearity, reference range) Depends on the test(s) that will be used, should be available in the valida3on files of the lab

3.Quality issues

• CTL (clinical tolerance limits) NA • Procedures available : YES (in house procedures and commercial tests) • Follow-up internal quality control YES • Does external quality control exist? (WIV, commercial, ...) YES (WHO , QCMD, …) for >

95%, but not for all pathogens

2) Diagnos3c performance

References: CAT template UZ-Leuven LAG ISO 15189 Price C. Evidence-based Laboratory Medicine: Supporting Decision-Making. Clinical Chemistry 46;8, 1041-1050 (2000) STARD initiative (http://www.stard-statement.org)

Task Force Microbiology: Reimbursement Proposal Template (version 01/08/2019)

1.Sensi-vity, specificity • What was used as gold standard “ culture” , Ag tests • Why is expected the test under inves-ga-on performing be_er than the exis-ng gold

standard (if there is one) Shorter turnaround ?me, higher sensi?vity • Health impact of false-posi-ves and false-nega-ves

false-posi?ve : unnecessary treatment, unnecessary isola?on measures false-nega?ve : risk of transmission (cessa?on of isola?on) , cessa?on of an?viral treatment although necessary, supplementary examina?ons will be performed

• Economic impact of false-posi-ves and false-nega-ves : cost of the test, cost of treatment and isola?on

• Propor-on of tests than can not be interpreted (due to inhibi-on) and their impact on health and cost: ≤ 1% (0.5-1/100 analyses)

2.Likelihood ra-o’s (LR) “Nega-ve predic-ve value- posi-ve predic-ve value “

3.NND (number needed to diagnose) one test/pa?ent/episode

4.Other • ROC-curves (other methods) • Are other results needed tot interpret this lab test? NO: clear-cut results (preferably

real-?me curves with indica?on of load)

2.5 Comparison with rapid viral tests

For influenza: The reference standards for laboratory confirmation of influenza virus infection are reverse transcription-polymerase chain reaction (RT-PCR) or viral culture. RIDTs can yield results in a clinically relevant time frame, i.e., approximately 15 minutes or less. However, RIDTs have limited sensitivity (in adults << in children) from 33-82% to detect influenza virus infection (varying from season to season in fonction of circulating viral strain -age of the patient -sample type, see table) and negative test results should be interpreted with caution given the potential for false negative results.

Table IV. Performance of Influenza A RAT (compared to culture) in function of the circulating subtype

Influenza Season

Predominant Subtype

N u m b e r o f Respiratory Samples

Sensitivity RAT (%) Specificity RAT (%)

References: CAT template UZ-Leuven LAG ISO 15189 Price C. Evidence-based Laboratory Medicine: Supporting Decision-Making. Clinical Chemistry 46;8, 1041-1050 (2000) STARD initiative (http://www.stard-statement.org)

Task Force Microbiology: Reimbursement Proposal Template (version 01/08/2019)

Rapid tests are available for RSV: - Ag RSV in POCT format; - IFA’s for RSV, Influenza: time consuming, laborious pre-analytical phase, requires experience,

more sensitive than ELISA/immunochromatography, less sensitive than NAAT

2.6 Available commercial tests for respiratory viruses

3) Clinical impact

1.Diagnos-c • Can other (non)-laboratory examina-ons be avoided by this test? Yes

An addi3onal major reason to iden3fy respiratory viruses relates to unnecessary medical procedures. Death has some3mes resulted from unnecessary procedures performed in pa3ents for whom RSV was not considered. Bronchoscopy,lung biopsy, or overly aggressive therapy with cor3costeroids and bronchodilators for presumed asthma can all pose a danger to these pa3ents, and some of these management decisions are best made with an accurate viral diagnosis. Iden3fica3on of viruses in pa3ents with ARI can alter pa3ent management by reducing the unnecessary use of an3bio3cs, blood work or other medical procedures. The correct diagnosis of viral ARI can also eliminate unnecessary blood work for bacterial workup (WBC differen3al and neutrophil counts). As the cost of an3bio3cs con3nues to rise and their indiscriminant use draws increasing aAen3on in the context of their contribu3on to the development of bacteria with increased an3bio3c resistance, an accurate and 3mely diagnosis of viral respiratory tract infec3on can help reduce the unnecessary use of an3bio3cs. This carries with it not only a cost saving to the health-care system but a posi3ve impact on the growing problem of an3bio3c resistance in bacteria

• Does the test supply addi-onal or more accurate informa-on, not provided by other (non)-laboratory examina-ons? YES, iden?fica?on of causal agent by screening of a broad panel of e?ologies within some hours (many of them not (or not ?mely) discoverable by tradi?onal techniques). No diagnos?c alterna?ves for many of them.

Coris* BinaxNOW** Coris* BinaxNOW**

2006-2007 A/H3N2 1171Δ 81.2 79.7 96.3 98.1

2007-2008 A/H1N1 3130Δ 56.0 99.8

2008-2009 2009-2010 2010-2011

A/H3N2 A/H1N1v2009 A/H1N1v2009

2375Δ 5046 3491

66.0 36.61

47.02 61.0

99.5 99.71

98.72 98.9

* Coris Influ-A&B Respi-Strip;**BinaxNOW Influenza A&B;Δ >93% of samples: nasopharyngeal aspirates; 1tested on 2763 samples;2on 2883 samples

References: CAT template UZ-Leuven LAG ISO 15189 Price C. Evidence-based Laboratory Medicine: Supporting Decision-Making. Clinical Chemistry 46;8, 1041-1050 (2000) STARD initiative (http://www.stard-statement.org)

Task Force Microbiology: Reimbursement Proposal Template (version 01/08/2019)

2.Treatment • Does the test allow (faster) star-ng of adequate therapy (or can useless therapy be

avoided)? Yes on both ques?ons. • Is there a be_er guidance of therapy by this test? Yes, star?ng or stopping of an?bio?cs,

an?virals • Can toxicity be avoided? Yes, less side effects and less therapeu?c (possibly dangerous)

interac?ons of an?bacterial or an?-mycological treatments. • Does condi-onal reimbursement of medica-on exist, based on test results? (eg. HSV and

acyclovir)? No

3.Health outcome • Can illness, complica-ons, morbidity, mortality be prevented? Yes,

-avoidance of poten?al side effects/interac?ons of an?bio?cs and an?myco?cs by stopping them at moment of diagnosis -postponing the induc?on of immunodepression schemes e.g. pre-transplant -avoidance of high doses cor?costeroids -reduc?on of morbidity and mortality when ?mely diagnosis and adequate interven?on (certainly in frail pa?ent groups: specific directed an?viral therapy, ?me-interval with reduc?on of immunosuppressive therapy, high dose Immunoglobulins

4.Other o Are there epidemiological interests to perform this test? Outbreak

monitoring? Yes: rapid infec?on control and preven?on of nosocomial transmission by aerosol or direct contact.

o Intra-hospital outbreak: a local confirma?on could accelerate the control measures. Only a few posi?ve tests are necessary to confirm the outbreak

o Intra-ins-tu-on: the isola?on measures should be taken on a syndromic base; The tests can confirm the source of the outbreak within some hours

• Is the test s-ll in research phase ? Several commercial test on the market but also a lot of in-house tests in use (different protocols). Each protocol should be extensively validated (analy?cally & clinically) !

• Improvement of infec-on control measures, including isola-on.

4) Organiza3onal impact

1.Impact in the hospital 2.Impact outside the hospital

• Pa-ent transporta-on (POCT, …)

5) Cost impact: in and outside the laboratory see above

1.(Ac-vity-Based) Cost/test (reagents, personnel, overhead (housing, QC, …)) • R&D cost if applicable (in-house tes-ng): rela?vely high (in house valida?on expensive

in order to be sure one can detect as much targets as possible) • How many reagent kits have been sold? • See also Excel template?

References: CAT template UZ-Leuven LAG ISO 15189 Price C. Evidence-based Laboratory Medicine: Supporting Decision-Making. Clinical Chemistry 46;8, 1041-1050 (2000) STARD initiative (http://www.stard-statement.org)

Task Force Microbiology: Reimbursement Proposal Template (version 01/08/2019)

2.Reimbursement • Can other tests be withdrawn?

3.Profit elsewhere in the hospital infec-ons noso

6) Decision making

1.Impact on the clinical decision making process and pa-ent management: huge

2.Overexploita-on/underu-liza-on

3.Incorporated in Clinical Prac-ce Recommenda-ons/Guidelines?

In the context of new emerging respiratory pathogens MERS-hCoV and H7N9 in 2013, some new recommenda3ons are made Namely by the WHO (see documents )

WHO Recommenda?ons

Collect respiratory and other specimens for laboratory testing Collect routine clinical specimens (e.g. blood and sputum bacterial cultures) for community-acquiredpneumonia,ideallybeforeantimicrobialuse.Alsocollectrespiratoryspecimensfromtheupper respiratory tract (i.e. nasal, nasopharyngeal and/or throat swab) and lower respiratorytract (i.e. sputum,endotrachealaspirate,bronchoalveolar lavage) forknownrespiratoryviruses(such as inAluenza A and B, inAluenza A virus subtypesH1, H3, and H5 in countries with H5N1virusescirculatingamongpoultry;RSV,parainAluenzaviruses,rhinoviruses,adenonviruses,humanmetapneumoviruses,andnon-SARScoronaviruses).Testingshouldbedonebyreverse-transcriptasepolymerasechainreaction(RT-PCR) ifpossible.Serial collectionof respiratoryspecimens frommultiplesitesonmultipledays (every2–3days)will inform viral shedding; and blood to assess viremia; conjunctival swabs if conjunctivitis isclinicallypresent;urine,stool,andcerebrospinal Aluid if lumbarpuncture isperformed.ContactWHOforinformationaboutlaboratoriesthatcantestforthepresenceofnovelcoronavirus.

In the same context , A recommenda?on by the Public health Agency in Canada

Protocol for Microbiological Inves?ga?ons of Severe Acute Respiratory Infec?ons (SARI) Influenza A and B by RT-PCR with subtyping (H3N2 or H1N1) should be the primary method for detec?on of influenza (24 hour turnaround ?me (TAT). Respiratory mul?plex RT-PCR for parainfluenza, human metapneumovirus, coronavirus, rhinovirus/enterovirus, adenovirus should be done on nega?ve influenza specimens (48 hour TAT) when there is a clinical indica?on to detect noninfluenza viruses.

ATTACHMENTS

RELEVANT EVIDENCE/REFERENCES

References: CAT template UZ-Leuven LAG ISO 15189 Price C. Evidence-based Laboratory Medicine: Supporting Decision-Making. Clinical Chemistry 46;8, 1041-1050 (2000) STARD initiative (http://www.stard-statement.org)

Task Force Microbiology: Reimbursement Proposal Template (version 01/08/2019) 1) Guidelines and Recommenda?ons (most recent topics on top)

• IDSA Guidelines August 2011. The Management of CAP in infants and children older than 3 months of age: clinical prac?ce guidelines by the pediatric infec?ous disease society and the infec?ous disease society of America. CID 2011.

• Guidance CDC for rapid tests hkp://www.cdc.gov/flu/professionals/diagnosis/rapidlab.htm

• Recommenda?on Public Health Canada for SARI pa?ents hAp://www.phac-aspc.gc.ca/eri-ire/proto-sari-iras-eng.php

• Intermim Guidance Document WHO : h k p : / / w w w . w h o . i n t / c s r / d i s e a s e / c o r o n a v i r u s _ i n f e c ? o n s /InterimGuidance_ClinicalManagement_NovelCoronavirus_11Feb13u.pdf

• Na-onal Guideline Clearinghouse (h_p://www.ngc.org) • The Na-onal Ins-tute for Clinical Excellence (http://www.nice.org.uk) • Ins-tute for Clinical Systems Improvement (h_p://www.icsi.org) • Health Technology Assessment Database (h_p://www.york.ac.uk/inst/crd/htahp.htm) • Clinical and Laboratory Standards Ins-tute (www.clsi.org) • Clinical Laboratory Improvement Amendments (CLIA; h_p://www.cms.hhs.gov/clia/) • Belgian Healthcare Knowledge Centre (h_p://www.kce.fgov.be) • Superior Health Council Belgium (h_ps://portal.health.fgov.be/portal/page?

_pageid=56,512429&_dad=portal&_schema=PORTAL) • Isenberg H. Clinical Microbiology Procedures Handbook, 2nd edi-on, ASM • CUMITECHS (Cumula-ve Techniques and Procedures in Clinical Microbiology), ASM (h_p://

estore.asm.org) • EUCAST (h_p://www.escmid.org/sites/index_f.aspx?par=2.4)

2) Systema?c Reviews and Meta-analyses • Cochrane (http://www.update-software.com/cochrane) • PubMed Clinical Queries (from 1966; h_p://www.ncbi.nlm.nih.gov/entrez/query.fcgi):

Systema-c Reviews; Clinical Queries using Research Methodology Filters (diagnosis + specific, diagnosis + sensi-ve, prognosis + specific)

• SUMSearch (h_p://sumsearch.uthscsa.edu/)

3) Reviews

4) Original Ar?cles

1)Woo P et al.: Cost-effec-veness of rapid diagnosis of viral respiratory tract infec-ons in pediatric pa-ents. JCM 1997, 35(6): 1579-1581. 2)Gonzales R, Malone DC, Maselli JH, Sande MA: Excessive an-bio-c use for acute respiratory infec-ons in the United States. Clin Infect Dis 2001, 33:757-762. 3)Bri_ain-Long R et al. : Access to a PCR targe-ng 13 respiratory viruses can reduce an-bio-cs. BMC Medicine 2011, 9:44. 4)Mahony B : The Clinical Need for the RVP test. J Clin Virol 2007, 40 (Suppl 1:S36-S38) 6) Pavia AT: What is the role of respiratory viruses in community-acquired pneumonia? Infect Dis Clin N Am 2013,27:157-175. References:

CAT template UZ-Leuven LAG ISO 15189 Price C. Evidence-based Laboratory Medicine: Supporting Decision-Making. Clinical Chemistry 46;8, 1041-1050 (2000) STARD initiative (http://www.stard-statement.org)

Task Force Microbiology: Reimbursement Proposal Template (version 01/08/2019) 5) Cesario TC. Viruses Associated With Pneumonia in Adults.Clinical Infec-ous Diseases 2012;55(1):107–13 7)Oosterheert JJ, van Loon AM, Schuurman R, Hoepelman AI, Hak E, Thijsen S, Nossent G, Schneider MM, Hus-nx WM, Bonten MJ: Impact of rapid detec-on of viral and atypical bacterial pathogens by real--me polymerase chain reac-on for pa-ents with lower respiratory tract infec-on. Clin Infect Dis 2005, 41:1438-1444. 8)Murdoch DR. CID 2005;41:1445-7.Editorial on: Impact of Rapid Microbiological Tes-ng on the Management of Lower Respiratory Tract Infec-on 9)Joan-Miquel Balada-Llasat, et al. Evalua-on of commercial ResPlex II v2.0, Mul-Code®-PLx, and xTAG® respiratory viral panels for the diagnosis of respiratory viral infec-ons in adults. Journal of Clinical Virology 2011;50(1): 42–45 10)Pillet S, Lardeux M, Dina J, Gra_ard F, Verhoeven P, et al. (2013) Compara-ve Evalua-on of Six Commercialized Mul-plex PCR Kits for the Diagnosis of Respiratory Infec-ons. PLoS ONE 8(8): e72174. doi:10.1371/journal.pone.0072174 11)Sanghavi SK et al. Clinical evalua-on of mul-plex Real--me PCR panels for rapid detec-on of respiratory viral infec-ons. J Med Virol 2012; 84:162-169 12) Pierre-Olivier Bridevaux et al. Incidence and outcomes of respiratory viral infec-ons in lung transplant recipients: a prospec-ve study. Thorax Online First, published on September 11, 2013 as 10.1136/thoraxjnl-2013-203581 13) Ruuskanen O et al. Viral pneumonia. Lancet 2011;377:1264-75 14) Schnell D et al. Burden of Respiratory Viruses in pa-ents with acute respiratory failure. J Med Virol 2013 15) Templeton KE et al. Improved diagnosis of the e-ology of community-acquired pneumonia with real--me polymerase chain reac-onCID 2005; 41:345-51 16) Van de Pol AC et al. Increased detec-on of respiratory syncy-al virus, influenza viruses, parainfluenza viruses, and adenoviruses with real--me PCR in samples from pa-ents with respiratory symptoms. J Clin Microbiol 2007;45:2360-63 17) Verboon-Maciolek MA et al. Human Parechovirus causes encephali-s with white ma_er injury in neonates. Ann Neurol 2008; 64:266-73. 18) Benschop K et al. High prevalence of Human Parechovirus genotypes in the Amsterdam region and the iden-fica-on of specific HPeV variants by direct genotyping of stool samples. JCM 2008

5) Reference Works, Handbooks and Databases • UpToDate Online (h_p://www.uptodate.com) • Murray P. Manual of Clinical Microbiology, ASM, 2007 • Mandell. Principles and Prac-ce of Infec-ous Diseases. 6th Edi-on (h_p://

www.ppidonline.com) • 1Viral diseases affec?ng the pleura. J Clin Virol 58 (2013):367-373. Jennings N et al.

6) Posters, “grey literature”, presenta?ons • CAT Library UZ-Leuven (h_p://www.uzleuven.be/UZroot/hos-ng/labo/Leermodule/EBLM/

EBLM_LM_CAT.htm)

References: CAT template UZ-Leuven LAG ISO 15189 Price C. Evidence-based Laboratory Medicine: Supporting Decision-Making. Clinical Chemistry 46;8, 1041-1050 (2000) STARD initiative (http://www.stard-statement.org)

Task Force Microbiology: Reimbursement Proposal Template (version 01/08/2019)

References: CAT template UZ-Leuven LAG ISO 15189 Price C. Evidence-based Laboratory Medicine: Supporting Decision-Making. Clinical Chemistry 46;8, 1041-1050 (2000) STARD initiative (http://www.stard-statement.org)