Primary and
hospital care
infective endocarditis endocarditis board guidelines

Five years’ experience of the ­endocarditis team in a tertiary ­referral centre

Review Article
infective endocarditis endocarditis board guidelines
Christiane Gruner
Weitere Autoren
Carlos A. Mestres, Barabara Hasse, Alberto Weber, Robert Bauernschmitt, Annelies S Zinkernagel, Thierry Carrel, Felix Tanner, Dominique Bettex, Frank Ruschitzka, Dre Michelle Frank, Matthias Greutmann, Oscar A. Cuevas, David Siemer, Peter Bode, Ronny R. Büchel, Alexander Breitenstein, Adrian Schmid, Mathias Van Hemelrick
Ausgabe
2022/04
DOI:
https://doi.org/10.4414/cvm.2022.02210
Cardiovasc Med. 2022;25:w02210

Publiziert am 01.07.2022

Current European guidelines recommend a multidisciplinary team approach in infective endocarditis in order to ensure adequate treatment and follow-up.

A key role in the treatment of cardiovascular infections

Introduction

Cardiovascular infections, and infective endocarditis in particular, are complex diseases. Even if treated properly, current studies still show high mortality in the acute phase (20–30%) [1–4]. In developing countries, infective endocarditis has a subacute and more chronic course, mainly due to underlying rheumatic heart disease. Treatment of streptococcal throat infections as well as endocarditis prophylaxis have almost eradicated this disease among the native population in  western countries. However, occasional rheumatic heart disease cases are diagnosed among people with a migration background [5].
Epidemiological studies have shown changes in patient characteristics and pathogens over past decades with a current incidence of up to 10 cases per 100,000 patients/year [6–8]. Native valve infective endocarditis (NVIE) is still the most frequent form [9]. However, the incidence of prosthetic valve infective endocarditis (PVIE), cardiac device- and vascular graft-related endocarditis has increased in recent years, mainly due to more frequent surgical and interventional procedures in patients having received a prior cardiovascular implant and broader indications [3, 9]. Also, the increase of transcatheter interventions, implantation of repair devices and the rising number of patients with congenital heart disease reaching adulthood contribute to the risk of infection [10]. Diagnosis of infective endocarditis relies on the modified Duke criteria [11–13] (table 1). Despite adequate antimicrobial treatment and diagnosis, cardiac surgery is required in 40–50% of cases [13].
Table 1:
Modified Duke Criteria with task force recommendations [12].
Major criteria1. Blood culture positive for infective endocarditis
 a. Typical microorganisms consistent with IE from 2 separate blood cultures
  • Viridans streptococci, Streptococcus gallolyticus (bovis), HACEK group, Staphylococcus aureus or
  • Community-acquired enterococci, in the absence of a primary focus or
 b. Microorganisms consistent with IE from persistently positive blood cultures:
  • ≥2 positive blood cultures of blood samples drawn >12h apart or
  • All of 3 or a majority of ≥4 separate cultures of blood (with first and last samples drawn ≥1 h apart); or
 c. Single positive blood culture for Coxiella burnetii or phase I IgG antibody titre >1:800
 2. Imaging positive for IE
 a. Echocardiography positive for IE
  • Vegetation
  • Abscess, pseudoaneurysm, intracardiac fistula
  • Valvular perforation or aneurysm
  • New partial dehiscence of prosthetic valve
 b. Abnormal activity around the site of prosthetic valve implantation detected by 18F-FDG PET/ (only if the prosthesis was implanted for >3 months) or radiolabelled leukocytes SPECT/
 c. Definite paravalvular lesions by cardiac CT
Minor criteria1. Predisposing Heart conditions: previous IE, CHD, prosthetic valve, IVU
 2. Fever (> 38°C)
 3. Immunological findings: glomerulonephritis, Roth’s spots, Osler’s nodes and positive rheumatoid factor
 4. Vascular findings: arterial emboli, septic (mycotic) pulmonary infarcts, intracranial haemorrhage, conjunctival haemorrhages and Janeway’s lesions
 5. Microbiological evidence not meeting major criteria or serological evidence of active infection with organism consistent with IE
IE: infective endocarditis; HACEK group: Aggregatibacter aprophilus, Aggregatibacter actinomycetencomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae; IgG: Immunoglobulin G; FDG: fluorodeoxyglucose; PET: positron emission tomography; CT: computed tomography; SPECT: single-photon emission computed tomography; CHD: congenital heart disease; IVU: intravenous drug users
A multidisciplinary team approach is currently recommended in tertiary care institutions [1, 14, 15]. Recent experiences suggest and support that a multidisciplinary team reduces mortality rates [1, 2, 14, 15]. This approach was incorporated into the 2015 ESC Guidelines for the Management of Infective Endocarditis as a Class IIa B recommendation [12]. In this article, we aim to describe the work of the Endocarditis Board at the University Hospital of Zurich  and to report the initial management and outcome data of patients with short-term follow-up information.

Methods

Endocarditis Board mission and vision ­statement

In recent years, the value of an endocarditis board in the diagnosis and treatment has been well highlighted by individual institutions and scientific societies (such as the European Society of Cardiology [ESC]). Therefore, the Endocarditis Board was created in order to stan­dardise and improve the quality of care for patients with infective endocarditis by developing a workflow algorithm and a multidisciplinary team to facilitate interdisciplinary communication, decrease the possibility of treatment errors, expedite surgical indications and to pursue continued quality improvement.

Setting

The University Hospital of Zurich is a tertiary care teaching hospital with about 900 beds and a large referral centre for heart surgery covering the northeastern part of Switzerland. The Endocarditis Board was established in 2016 and since then meets on a weekly basis. The meeting is scheduled as a hybrid event with either physical or virtual presence. Referring hospitals can participate by Skype™-based video conferencing services. The list of patients who are scheduled for discussion is e-mailed to the participants one day ahead of the next meeting. The list includes basic information such as demographics, responsible physician, valve affected, isolated pathogen (if any), antimicrobial therapy and available images. The core team is available at any time during the week for emergency and urgent cases.

Structure of the Endocarditis Board

The Endocarditis Board includes specialists in:
  • Anesthesiology
  • Cardiovascular Surgery
  • Cardiology
  • Infectious Disease
  • Intensive Care
  • Neurology
  • Nuclear Medicine
  • Pathology
The complexity of the disease may require the participation of other departments that are not listed above but are consulted when necessary. Research nurses play an important role and are actively involved in data abstraction, Endocarditis Board discussion compilation, blood sampling and patient support.

Workflow

Each case is presented and the likelihood of infective endocarditis is evaluated according to the modified Duke criteria.
Imaging findings such as transthoracic or transoesophageal echocardiography (TTE/TOE), computed tomography (CT) or positron emission tomography computed tomography (PET/CT) scans are presented by the corresponding specialists. Valve dysfunction is quantified, vegetation, fistula, abscesses and other pathological echocardiographic findings are identified, and cardiac function is documented. Patients without clear signs and a low probability of infective endocarditis are excluded, but always with the possibility of re-evaluation. After infective endocarditis is confirmed an ­appropriate treatment strategy is recommended, antimicrobial therapy and treatment duration are determined in accordance with international treatment guidelines. Additionally, the ideal timing of surgery, if required, is discussed. Once consensus on the treatment strategy is reached, the team issues an official statement, which is documented in the electronical medical record. If feasible, each case will be reassessed at the next Endocarditis Board and the outcome presented (fig. 1).
Figure 1:
Workflow.
Another goal is to support the continuity of outpatient management after hospital discharge and to gather follow-up information. After initial intravenous antimicrobial therapy according to microbiology results, patients may be discharged and allocated to outpatient parenteral antibiotic therapy [16] or referred to other centres for treatment continuation. This may eventually change in accordance with a recent trial, which supports oral continuation therapy for 4 weeks in ­selected groups of patients [17]. Most of the patients discussed at the Endocarditis Board meetings are also enrolled in our internal prospective infective endocarditis registry (ENVALVE).

When to refer a patient to a tertiary centre

Patients are frequently referred from other centres without cardiovascular surgery. Hence, it is important that referring clinics stay in continuous contact with the Endocarditis Board (fig. 2), in order to ascertain optimal timing for transfer. Indications for transferring a patient to a tertiary referral centre are summarised in table 2. For patients not meeting these criteria, periodic communication with the Endocarditis Board is re­commended.
Figure 2: 
Suggested management by referring clinics.
Table 2:
Indications for transfer to a tertiary centre.
Cardiogenic Shock / Heart FailureSigns of heart failure with unstable haemodynamics (inotropic support, mechanical ventilation)
Acute valvular regurgitation
Uncontrolled InfectionAbscesses, fistula or septic aneurysms
Non-responders to antibiotic therapy
NeurologyEmbolic events
Ischaemic or haemorrhagic stroke
Prosthetic Valve Endocarditis
Cardiac-device related Endocarditis

Case management

Figure 3 depicts the suggested algorithm when infective endocarditis is suspected. The first recommendation in the case of clinically suspected infective endocarditis is to call the emergency medical service of the Department of Infectious Diseases and Hospital Epidemiology, as well as the Heart Team. Initially, three sets of blood cultures must be drawn. Empirical antimicrobial treatment starts as soon as blood cultures have been taken. Simultaneously or within 48 hours, a TTE should be performed in order to disclose typical signs of infective endocarditis and assess cardiac function. Patients with heart failure and/or cardiogenic shock, as well as those with PVIE and device-related infective endocarditis need to be admitted and daily assessment is mandatory in order to detect a worsening in the patient's condition and be able to adjust treatment without any delay. TOE is performed in inconclusive cases when TTE cannot provide definite information, in PVIE and in those patients with an infected intracardiac device. An intraoperative TOE is also always performed. CT or MRI scans are performed to rule out cerebro- and/or renovisceral embolism, but they not replace TTE/TOE examinations. Generally we perform whole body CT scans in all types of Staphylococcus aureus ­endocarditis to exclude peripheral embolisms and in mechanical aortic valve prosthesis endocarditis to ­exclude locoregional complications, which can be difficult to diagnose because of acoustic shadowing. PET/CT scans are mainly reserved for patients with prosthetic materials (PVIE, vascular graft- and device-associated infections) when endocarditis can not be confirmed by all other modalities and clinical suspicion remains high. Lately we tend to replace CT scans with PET/CT scans in complex cases with multiple prosthetic materials (intracardiac and extracardiac), allowing locoregional complications/infections as well as peripheral embolisms and infections to be excluded.
Figure 3:
Daily assessment (suspected infection).

Indication for and timing of surgery

Between 40% and 50% of all infective endocarditis-patients will need surgical treatment in the acute phase [8, 13]. Three different scenarios are considered: emergency (within 24 hours), urgent (within a few days, <7 days) and elective (between 1 and 2 weeks) ­surgery. ­Indications for surgical treatment of infective ­endocarditis at any valve location are summarised in table 3.
Table 3:
Indications and timing for surgery (ESC / Eurupean Association for Cardio-Thoracic surgery Guidelines [12]).
Indications for surgeryTimingClassLevel
1. Cardiogenic shock / heart failure   
Aortic or mitral NVE or PVE with severe acute regurgitation, obstruction or fistula causing refractory pulmonary oedema or cardiogenic shockEmergencyIB
Aortic or mitral NVE or PVE with severe regurgitation or obstruction causing symptoms of heart failure or echocardiographic signs of poor haemodynamic toleranceUrgentIB
Uncontrolled infection   
Locally uncontrolled infection (abscess, false aneurysm, fistula, enlarging vegetation)UrgentIB
Infection caused by fungi or multiresistent organismsUrgent/electiveIC
Persistent positive blood cultures despite appropriate antibiotic therapy and adequate control of septic metastatic fociUrgentIIaB
PVE caused by staphylococci or non-HACEK Gram-negative bacteriaUrgent/electiveIIaC
Prevention of embolism   
Aortic or mitral NVE or PVE with persistent vegetations >10 mm after one or more embolic episode despite ­appropriate antibiotic therapyUrgentIB
Aortic or mitral NVE with vegetations >10 mm, associated with severe valve stenosis or regurgitation, and low ­operative riskUrgentIIaB
Aortic or mitral NVE or PVE with isolated very large vegetations (>30 mm)UrgentIIaB
Aortic or mitral NVE or PVE with isolated large vegetations (>15 mm) and no other indication for surgeryUrgentIIbC
HACEK: Aggregatibacter aprophilus, Aggregatibacter actinomycetencomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae; NVE: native valve endocarditis; PVE: prosthetic valve endocarditis

Ethics

The Zurich Cantonal Ethics Commission waived the necessity for a formal ethical evaluation based on the Swiss Federal Human Research Act. Due to the ethics waiver, no informed consent had to be requested. Moreover, a large number of the discussed patients are enrolled in our institutional prospective infective endocarditis registry ENVALVE, where all participants provide written informed consent.

Results

Time frame

The Endocarditis Board at the University Hospital Zurich started its activities in May 2016.

Patient assessment

Between May 2016 and December 2020, 595 consecutive patients with suspected infective endocarditis were discussed, leading to 1145 case-discussion episodes. The Endocarditis Board rejected by consensus the diagnosis of a cardiovascular infection in 128 patients. Of the 467 patients with cardiovascular infections (113 female, median age 68 years) 346 (70%) had an infective endocarditis (218 NVIE / 122 PVIE / 6 marantic), 73 (16%) had device-associated and 48 (10%) vascular graft infections. Concerning microbiology, Gram-positive bacteria predominated (S. aureus (141, 30%); coagulase-negative staphylococci (53, 11%); Streptococcus spp (120, 26%) and Enterococcus spp (51, 11%), other pathogens (103, 22%)). Surgery was performed in 190 (40.2 %) patients. Follow-up clinical data showed that the 30-day and 1-year mortality due to infective endocarditis were 9.6% and 14%, respectively.

Discussion

The endocarditis Board is currently considered the cornerstone of decision-making in infective endocarditis [2, 14, 15, 18–28]. An official Endocarditis Board meeting is held on a weekly basis at our institution. There is a structured protocol with documentation of pre- and post-discussion activities in the electronic medical ­record. This enhances the value of the joint decisions taken by the Endocarditis Board Team.
Our initial results correlate with current epidemiological studies, where NVIE continues to be the most ­common form of infective endocarditis [9]. We found almost equal PVIE and device-related infective endocarditis cases, pointing out the importance of changing epidemiology in this setting. Similar to the ­available literature, S. aureus was the most common causative pathogen [7, 9] and surgery was required in more than 40% of cases [1, 2, 29].
Some sources in the literature have analysed the effects of Endocarditis Boards on patient outcomes [15, 19, 25, 29] and seem to support an active role of these internal bodies in clinical practice. Although specific outcomes may be subject to institutional differences in patient referral and internal team factors, the role of the Endocarditis Board multidisciplinary team is being increasingly accepted, with more teams reporting institutional experiences, from organisational matters to clinical impact [2, 14, 15, 18–28]. Of note is that individual physician perception of the Endocarditis Board multidisciplinary team is an important part of the topic, as the hospital physicians will be able to register patients online for the weekly meeting and assess the effect of discussions on outcomes. This has been recently addressed by El-Dalati et al. [28] supporting a wider adoption of the Endocarditis Board multidisciplinary team model.
Other aspects of the Endocarditis Board multidisciplinary team not addressed here may require further ­separate discussion. The educational role of the Endocarditis Board multidisciplinary team cannot be ­neglected. By pooling a number of different specialists together, patients enrolled in ENVALVE get educated during follow-up visits. Educational materials like individual departmental specific brochures, well drafted by the involved departments (Cardiology, Cardiac Surgery, Infectious Diseases) are given to patients on admission and after discharge. This contributes to create and reinforce awareness on the disease and its possible late consequences.
Research is another critical aspect of the Endocarditis Board. Data is collected and an institutional registry is maintained (ENVALVE). As briefly reported in the methods section, the existence of an approved protocol guarantees uniform collection of data aiming at evaluating pre-specified outcomes including mortality (early and late), the analysis of recurrences and relapses, surgical outcomes, etc. Our Institutional Registry can be used to determine the indications and optimal timings of different therapeutic approaches including surgery, antimicrobial therapy for complex infections and comparisons. Quality improvement, clinical and basic research are fundamental goals [30, 31].

Limitations

This is a description of a local operational working scheme that may differ from other practices, although the Endocarditis Board is currently contemplated in practice guidelines. The referral patterns, considering the type of admitting institution and case-mix with high complexity, make our patient population skewed towards high-risk and mortality, and may not represent a regular practice. Furthermore, those shown here are preliminary and descriptive results that warrant more detailed prospective investigation.

Conclusion

The Endocarditis Board is currently an integrated part in the treatment of infective endocarditis and is the standard of care at our institution following international recommendations [12]. Current ESC European Practice Guidelines for the management of infective endocarditis [12] suggest the need of an Endocarditis Team in order to effectively treat this highly lethal disease. Multidisciplinary consensual decisions might also enable optimization of standards of care in vascular graft infections. Preliminary results are in line with current epidemiological studies.
No financial support and no other potential conflict of interest relevant to this article was reported.
Michelle Frank, MD
Department of Cardiology
University Heart Centre Zurich
University Hospital Zurich
Rämistrasse 100
CH-8091 Zürich
Michelle.frank[at]usz.ch
1.  Impact of a multidisciplinary management strategy on the outcome of patients with native valve infective endocarditis. Am J Cardiol. 2013 Oct;112(8):1171–6. http://dx.doi.org/10.1016/j.amjcard.2013.05.060 PubMed
2.  Influence of a multidisciplinary alert strategy on mortality due to left-sided infective endocarditis. Rev Esp Cardiol (Engl Ed). 2014 May;67(5):380–6. http://dx.doi.org/10.1016/j.rec.2013.09.010 PubMed
3.  Clinical features and changes in epidemiology of infective endocarditis on pacemaker devices over a 27-year period (1987-2013). Europace. 2016 Jun;18(6):836–41. http://dx.doi.org/10.1093/europace/euv377 PubMed
4. . The Changing Epidemiology of Infective Endocarditis in the Twenty-First Century. Curr Infect Dis Rep. 2017 May;19(5):21. http://dx.doi.org/10.1007/s11908-017-0574-9 PubMed
5.  Global, Regional, and National Burden of Rheumatic Heart Disease, 1990-2015. N Engl J Med. 2017 Aug;377(8):713–22. http://dx.doi.org/10.1056/NEJMoa1603693 PubMed
6.  Epidemiological trends of infective endocarditis: a population-based study in Olmsted County, Minnesota. Mayo Clin Proc. 2010 May;85(5):422–6. http://dx.doi.org/10.4065/mcp.2009.0585 PubMed
7. . Staphylococcus aureus endocarditis: a consequence of medical progress. JAMA. 2005 Jun;293(24):3012–21. http://dx.doi.org/10.1001/jama.293.24.3012 PubMed
8. . Infective endocarditis. Lancet. 2016 Feb;387(10021):882–93. http://dx.doi.org/10.1016/s0140-6736(15)00067-7   http://dx.doi.org/10.1016/S0140-6736(15)00067-7 PubMed
9. . Clinical presentation, etiology, and outcome of infective endocarditis in the 21st century: the International Collaboration on Endocarditis-Prospective Cohort Study. Arch Intern Med. 2009 Mar;169(5):463–73. http://dx.doi.org/10.1001/archinternmed.2008.603 PubMed
10.  Association Between Transcatheter Aortic Valve Replacement and Subsequent Infective Endocarditis and In-Hospital Death. JAMA. 2016 Sep;316(10):1083–92. http://dx.doi.org/10.1001/jama.2016.12347 PubMed
11. . New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Am J Med. 1994 Mar;96(3):200–9. http://dx.doi.org/10.1016/0002-9343(94)90143-0 PubMed
12. . 2015 ESC Guidelines for the management of infective endocarditis: The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J. 2015 Nov;36(44):3075–128. http://dx.doi.org/10.1093/eurheartj/ehv319 PubMed
13.  The timing of surgery influences mortality and morbidity in adults with severe complicated infective endocarditis: a propensity analysis. Eur Heart J. 2011 Aug;32(16):2027–33. http://dx.doi.org/10.1093/eurheartj/ehp089 PubMed
14.  The infective endocarditis team: recommendations from an international working group. Heart. 2014 Apr;100(7):524–7. http://dx.doi.org/10.1136/heartjnl-2013-304354 PubMed
15. . Organization and Functioning of a Multidisciplinary Team for the Diagnosis and Treatment of Infective Endocarditis: A 30-year Perspective (1985-2014). Rev Esp Cardiol (Engl Ed). 2015 May;68(5):363–8. http://dx.doi.org/10.1016/j.rec.2014.10.006 PubMed
16. . Efficacy and safety of outpatient parenteral antibiotic therapy for infective endocarditis: a ten-year prospective study. Enferm Infecc Microbiol Clin. 2011 Oct;29(8):587–92. http://dx.doi.org/10.1016/j.eimc.2011.05.007 PubMed
17.  Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis. N Engl J Med. 2019 Jan;380(5):415–24. http://dx.doi.org/10.1056/NEJMoa1808312 PubMed
18.  Standards for heart valve surgery in a ‘Heart Valve Centre of Excellence’. Open Heart. 2015 Jul;2(1):e000216. http://dx.doi.org/10.1136/openhrt-2014-000216 PubMed
19. . [Infective endocarditis: a serious and rare condition that needs to be handled in experienced hospitals]. Rev Esp Cardiol. 2005 Oct;58(10):1145–7. http://dx.doi.org/10.1157/13079907 PubMed
20.  A Multidisciplinary Pathway for the Diagnosis and Treatment of Infectious Endocarditis. Crit Pathw Cardiol. 2020 Dec;19(4):187–94. http://dx.doi.org/10.1097/HPC.0000000000000224 PubMed
21.  Management of infective endocarditis and multidisciplinary approach. Med Mal Infect. 2019 Feb;49(1):17–22. http://dx.doi.org/10.1016/j.medmal.2018.06.007 PubMed
22.  Case conferences for infective endocarditis: A quality improvement initiative. PLoS One. 2018 Oct;13(10):e0205528. http://dx.doi.org/10.1371/journal.pone.0205528 PubMed
23. . [Infective endocarditis in Morocco through the experience of a hospital department]. Ann Cardiol Angeiol (Paris). 2019 Apr;68(2):87–93. http://dx.doi.org/10.1016/j.ancard.2018.10.014 PubMed
24. . Practical implementation of the Endocarditis Team in ‘functional’ reference centres: the Italian hospital network experience and recommendations of the Italian Society of Echocardiography and Cardiovascular Imaging. J Cardiovasc Med (Hagerstown). 2019 Jul;20(7):414–8. http://dx.doi.org/10.2459/JCM.0000000000000810 PubMed
25.  Impact of Setting up an “Endocarditis Team” on the Management of Infective Endocarditis. Open Forum Infect Dis. 2019 Jul;6(9):ofz308. http://dx.doi.org/10.1093/ofid/ofz308 PubMed
26. . The value of an “Endocarditis Team”. Ann Cardiothorac Surg. 2019 Nov;8(6):621–9. http://dx.doi.org/10.21037/acs.2019.09.03 PubMed
27.  EACVI survey on the evaluation of infective endocarditis. Eur Heart J Cardiovasc Imaging. 2020 Aug;21(8):828–32. http://dx.doi.org/10.1093/ehjci/jeaa066 PubMed
28.  Physician perceptions of a multidisciplinary endocarditis team. Eur J Clin Microbiol Infect Dis. 2020 Apr;39(4):735–9. http://dx.doi.org/10.1007/s10096-019-03776-9 PubMed
29.  [Short- and long-term prognosis of infective endocarditis in non-injection drug users: improved results over 15 years (1987-2001)]. Rev Esp Cardiol. 2005 Oct;58(10):1188–96. http://dx.doi.org/10.1016/s1885-5857(06)60398-8   http://dx.doi.org/10.1016/S1885-5857(06)60398-8 PubMed
30.  Polyester Vascular Graft Material and Risk for Intracavitary Thoracic Vascular Graft Infection. Emerg Infect Dis. 2020 Oct;26(10):2448–52. http://dx.doi.org/10.3201/eid2610.191711 PubMed
31. . International Society of Cardiovascular Infectious Diseases Guidelines for the Diagnosis, Treatment and Prevention of Disseminated Mycobacterium chimaera Infection Following Cardiac Surgery with Cardiopulmonary Bypass. J Hosp Infect. 2020 Feb;104(2):214–35. http://dx.doi.org/10.1016/j.jhin.2019.10.009 PubMed

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