[Type text] ONLINE DATA SUPPLEMENT FOR: Severity assessment tools for predicting mortality in hospitalised patients with Community-Acquired Pneumonia: Systematic review and Meta-Analysis. James D Chalmers 1 , Aran Singanayagam 2 , Ahsan R Akram 2 , Pallavi Mandal 2 , Philip M Short 3 , Gourab Chowdhury 2 , Victoria Wood 1 , Adam T Hill 2 1. University of Edinburgh, Edinburgh, UK. 2. Department of Respiratory Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK 3. University of Dundee, Tayside, UK. Corresponding author Dr James Chalmers Department of Respiratory Medicine Royal Infirmary of Edinburgh 51 Little France Crescent Old Dalkeith Road Edinburgh EH16 4SA E-mail: [email protected]Keywords: Pneumonia, Severity assessment, mortality, meta-analysis
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[Type text]
ONLINE DATA SUPPLEMENT FOR:
Severity assessment tools for predicting mortality in hospitalised patients with Community-Acquired Pneumonia: Systematic review and Meta-Analysis.
James D Chalmers1, Aran Singanayagam2, Ahsan R Akram2, Pallavi Mandal2, Philip M Short3, Gourab Chowdhury2, Victoria Wood1, Adam T Hill2
1. University of Edinburgh, Edinburgh, UK.2. Department of Respiratory Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK3. University of Dundee, Tayside, UK.
Corresponding author
Dr James Chalmers
Department of Respiratory Medicine
Royal Infirmary of Edinburgh
51 Little France CrescentOld Dalkeith RoadEdinburghEH16 4SA
diastolic blood pressure <60 mmHg and age > 65 years.
British Thoracic Society guidelines suggest that patients with a CURB65 score of 0–1 be
considered for outpatient treatment; that patients with a CURB65 score of 2 be considered for
short inpatient hospital stay; and that patients with a CURB65 score >3 have severe
pneumonia that requires inpatient management, and intensive care or high dependency
environment care should be considered, particularly for patients with a CURB65 score >4.
For the purposes of this meta-analysis both > 3 and > 4 were used to construct 2 x 2 tables of
the relationship between CURB65 and mortality.
CRB65 is a simplified version of the CURB65 score that does not include the urea criterion.
It stratifies patients into low risk (CRB65= 0 or 1), intermediate risk (CRB65= 2) or high risk
groups (CRB65 = 3 or 4). CRB65 is recommended for outpatient use in the British Thoracic
Society guidelines.[3]
HAYDENS CRITERIA FOR QUALITY ASSESSMENT
The following table (Table E1) describe Haydens criteria.[4] These quality assessment criteria were modified to apply to observational studies of community acquired pneumonia severity scores.
Haydens criteria Components As applied to CAP studies
1. Study sample represents the
population of interest, design
appropriate to limit potential
bias
a) Source population
clearly defined
b) Study population
described
c) Study population
represents
i) Population limited
to CAP and
excludes other
diagnoses
ii) Requires Chest x-
ray confirmation
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population of
interest
and uses
recognised
definition
iii) Enrolls
consecutive,
unselected
patients
iv) Demographics are
representative of
CAP cohorts
internationally.
2. Loss to follow-up, study data
adequately represent the
sample
d) Completeness of
follow-up described
e) Completeness of
follow-up adequate
i) Appropriate follow
up to determine
mortality
ii) Limited number of
patients lost to
follow-up.
3. Prognostic factor of interest is
adequately measured in study
participants
f) Prognostic factors
defined
g) Prognostic factors
appropriately
measured
i)CURB65/CRB65/PSI
score calculated
according to standard
definition
II) Measurement made
on admission and
recorded
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prospectively
III) Missing values
minimised and
appropriately dealt
with
4. The outcomes of interest are
adequately measured in study
participants
h) Outcome defined
i) Outcome measured
appropriately
j) Mortality
k) 30-day mortality or
alternative outcome
determined
appropriately.
5. Important confounders are
accounted for.
l) Confounders
defined and
measured
m) Confounders
accounted for
Not applicable as prognostic
scores are used
independently.
6. Appropriate statistical analysis n) Analysis described
o) Analysis
appropriate
p) Analysis provides
sufficient
presentation of
data
l) Uses and reports
PPV/NPV/sensitivity/specificity
and/or receiver operator
characteristic curve for
pneumonia severity scores.
II) displays data for different
cut-points of each pneumonia
severity score
TABLE E1- Haydens Criteria for quality assessment, modified to apply to studies of community acquired pneumonia.
[Type text]
ADDITIONAL RESULTS
The Table (E2) provides details of each of the studies included in the meta-analysis.
First author name
Study Population
Score(s) assessed
Setting and design
N Age
(years)
Study Outcome
Mortality rate
Study Objective/
Conclusion
Ananda-Rajah[24]
Retrospective chart review
PSI, CURB65
Melbourne, Australia,
2002
408 72 +/- 16 30-day mortality
15.4% Comparison of PSI and CURB65
Aujesky, D[15] Guideline implementation trial
PSI, CURB65
32 hospitals in Pennsylvania, Connecticut USA
2001
3181 63 30-day mortality
4.6% Randomised controlled trial comparing effect of intensity of guideline implementation (PSI)
Barlow, G[25] Prospective, before and after quality improvement study
CURB65, CRB65
2 Hospitals, Tayside, UK. 2001-2003.
419 Median 74
30-day mortality
18.9% Study to increase proportion of patients receiving antibiotics within 4 hours of admission
Bauer, TT (CAPNETZ)[37]
Prospective cohort study
CRB65 10 inpatient and outpatient centres Germany,
2003-2004
1967 66 +/- 18 30-day mortality
4.3% Validation of CRB65
Buising, KL[26]
Prospective cohort study
CURB65, PSI
Melbourne, Australia,
2003-2006
722 Median 74
In-hospital mortality
9.8% Derivation of a new severity score (CORB)
Capelastegui , A[27]
Prospective cohort study
PSI, CURB65, CRB65
Galdakao Hospital, Basque region, Spain
2000-2004
1776 61.8 +/- 20.5
30-day mortality
6.7% Validation of severity scores
Challen, K[28] Retrospective case note review
CURB65 Manchester, UK 2005.
186 NR In-hospital mortality
22.6% Comparison of CURB65 with modified early warning score
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Chalmers, JD[20]
Prospective cohort study
PSI, CURB65, CRB65
2 hospitals, Edinburgh, UK 2005-2008
1007 66 (50-78)
30-day mortality
9.6% Modification of the CURB65 score.
Charles, PG[29]
Prospective cohort study
PSI, CURB65
Multicentre, Australia,
2004-2006.
882 65.1 +/- 19.9
30-day mortality
5.7% Derivation of new severity score (SMART-COP)
Chen CZ[41] Prospective cohort study
PSI Taiwan,
2005-2006
250 NR In hospital mortality
12% Evaluation of repeated measurements of PSI
Davydov L[42] Prospective cohort study
PSI Multicentre,
USA
1998-1999
875 66.5 +/- 17.7
In hospital mortality
2.7% Audit treatment of patients according to PSI class.
Dedier, J [43] Retrospective database
PSI 38 US Academic hospitals
1062 Median 64 (range 18-98)
Hospital mortality
6% Study the effect of processes of care on outcome.
Ewig, S[44] Prospective cohort study
PSI Single centre, unknown location, 1998-2001
489 67.8 +/- 17.1
In-hospital mortality within 30-days
6.8% Comparison of severity scores.
Ewig S[38] Retrospective administrative database
CRB65 Nationwide database, Germany
2005-2006
388,406
Median 76
In-hospital mortality
14.1% National epidemiological survey
Feagan, B[45] Retrospective chart review
PSI 20 hospitals across Canada
1996-1997
858 69.4 +/- 17.7
30-day in hospital mortality
14.1% Evaluate the treatment and outcome of CAP in Canada
Fine, MJ- Medisgroup[7]
Administrative database
PSI MEDISGROUP 1
78 hospitals in USA,
1989
MEDISGROUP 2
193 Hospitals in Pensylvania
1991
52,238
NR 30-day mortality
10.5% Derivation and internal validation of PSI
[Type text]
Fine MJ- PORT[7]
Prospective cohort study
PSI 5 Hospitals, USA and Canada, 1991-1994
2287 NR 30-day mortality
4.9% Validation of PSI
Flanders, WD[46]
Retrospective chart review
PSI 22 Hospitals, Atlanta, USA
1994-1995
1,024 NR Not reported. Assumed in-hospital mortality
4.8% Recalibration of PSI
Garau J[47] Retrospective care note review
PSI Multicentre, Spain 2001-2002
3233 66.6 +/- 18.5
In-hospital mortality
8.7% Investigating factors affecting length of stay and mortality.
Garcia-Vazquez E[48]
Retrospective study
PSI Murcia, Spain, 2003.
211 63 (range 13-100)
In hospital mortality
7.1% Derivation of simplified score.
Goss CH[49] Prospective cohort study
PSI Seattle, WA, USA 1994-1996
522 46 (range 18-100)
In hospital mortality
3.3% To evaluate resource utilisation among patients in low risk PSI groups.
Huang, DT[30] Prospective cohort study
PSI, CURB65
Multicentre, USA
2001-2003
1651 65 +/- 18.5
30-day mortality, 90 day mortality
6.4%
9.8%
Assessment of procalcitonin as a severity marker (GenIMS)
Johnstone, J[39]
Prospective, population based cohort study
PSI 6 hospitals, Alberta, Canada 2000-2002
2,906 68.9 +/- 17.9
1 year mortality (30-day mortality as secondary end-point)
13% Long term mortality and morbidity of CAP patients
Lim, WS[10] Combination of 3 prospective cohort studies
CURB65, CRB65
Nottingham, UK 1998-2000. Christchurch and Waikato, New Zealand
1999-2000. Alkmaar, Netherlands, 1998-2000.
1068 Mean 64.1
30-day mortality
8.3% Derivation of CURB65, CRB65
Man, SY[18] Prospective cohort study
PSI, CURB65, CRB65
Hong Kong
2004
1016 72 +/- 7.2 30-day mortality
8.6% Validation of severity scores for 30-day mortality
[Type text]
Menendez, R[31]
Prospective cohort study
PSI, CURB65, CRB65
2 Hospitals, Spain
2003-2004
453 67.3 +/- 17.1
Treatment failure
(includes mortality)
6.8% Investigation of CRP, cytokines and procalcitonin as markers of treatment failure
Migliorati, PL [50]
Retrospective chart review
PSI Single Centre, Italy
148 70.3 +/- 17.3
30-day mortality
12.2% Validation of PSI in Italy.
Ortega L[40] Prospective cohort study
PSI Barcelona, Spain, Dates not stated
128 64 +/- 8 In-hospital mortality
3.1% Evaluation of the pneumonia severity index
Phua, J[32] Retrospective cohort study
PSI, CURB65
Singapore,
2004-2007
1242 65.7 +/- 20.1
In hospital mortaity
14.7% Validation of IDSA/ATS criteria for severe CAP.
Renaud, B[8]
Pneumocom 1
Randomised controlled trial
PSI 16 Hospitals, France.
2002-2003
925 Mean 66 28 day mortality
10.6% Randomised controlled trial using PSI to determine site of care
Renaud, B[51]
Pneumocom 2
Prospective cohort study
PSI 14 hospitals, Catalonia, Spain,
2003
853 Mean 65 28 day mortality
6.3% Validation of PSI in European population
Querol-Ribelles JM[52]
Prospective cohort study
PSI Valencia, Spain, 2000
243 63 +/- 19 30-day mortality
6.2% Validation of PSI
Restrepo, M[53]
Retrospective chart review
PSI 2 hospitals, San Antonio, Texas, USA
1999-2002
730 59.2 +/- 16.2
30-day mortality
8.1% Compare patients admitted to the ward and intensive care units with CAP
Reyes Calzada S[54]
Prospective observational study
PSI Multicentre, Valencia, Spain Dates not stated
425 69 +/- 16 30-day mortality
8.2% Evaluate adherence to community-acquired pneumonia guidelines
Roson, B[55] Prospective cohort study
PSI Barcelona, Spain
1995-1997
533 Mean 64 30-day mortality
6.6% Use of PSI to determine site of care
Schuetz , P[33] Randomised controlled trial
PSI, CURB65, CRB65
Basel, Switzerland, 2002-2005
373 73 (59-82)
30-day mortality
11% Validation and recalibration of severity scores
[Type text]
Shindo, Y[34] Retrospective cohort study
CURB65 Handa City, Japan 2005-2007
329 75 +/- 15.7
30-day in hospital mortality
9.4% Compare CURB65 with ADROP (Alternative scoring system)
Tejera, A[35] Prospective cohort study
PSI, CURB65
Tenerife, Spain
Dates not available
226 74 (61-82)
In hospital mortality
12.4% Assessment of TREM-1 as a prognostic marker in CAP
Van der Eerden[56]
Prospective cohort study
PSI Alkmaar, Netherlands, 1998-2000
260 Mean 64 30-day mortality
10% Validation of PSI
Zuberi, FF[36] Prospective chart review
CURB65, CRB65
Karachi, Pakistan. 2006-2007
137 60.4 +/- 18.5
30-day mortality
13.1% Validation of CURB65/CRB65 in a developing country
TABLE E2- Characteristics of studies included in the meta-analysis (note- references refer to
those in the main document).
The following studies contained data on PSI, CURB65 or CRB65 but were excluded from the main analysis due to duplicate publication of data, or failure to meet the inclusion criteria of non-selected CAP populations. The reasons for exclusion are listed.
First author
name
year score(s) assessed Reason for exclusion
Angus DC[5] 2002 PSI Data contained in (1)
Arnold FW[6] 2003 PSI Low risk patients only
Bont J[7] 2008 CRB65 Outpatient only
Bruns, AH[8] 2008 PSI Limited to severe CAP (PSI IV and V)
Buising KL[9] 2007 CURB65, PSI Data contained in (10)
Cabre M[11] 2004 PSI Not consecutive, unselected CAP
[Type text]
patients. Data not presented.
Campbell, SG[12] 2006 PSI Patients discharged from emergency
department only.
Chalmers JD[13] 2008 PSI, CURB65, CRB65 Data contained in (14)
Chalmers, JD[15] 2008 PSI, CURB65, CRB65 Data contained in (14)
Cham, G[16] 2009 PSI No mortality data included.
Christ-Crain,
M[17]
2006 PSI Data reported in (18)
Curran, A[19] 2008 PSI HIV positive patients only
Dremsizov T[20] 2009 PSI Data reported in (1)
Escobar GJ[21] 2008 PSI Modified version of the PSI excluding
some parameters
Espana PP[22] 2006 PSI, CURB65 Data contained in (23)
Ewig S[24] 1999 PSI Limited to elderly patients (aged >65
years only)
Gotoh, S[25] 2008 PSI Data not reported
Haeuptle J[26] 2009 PSI Limited to Legionella pneumonia.
Hohenthal, U[27] 2009 PSI No mortality data presented.
Huang, DT[28] 2009 PSI, CURB65 Data contained in (29)
Ioachimescu 2004 PSI Limited to Streptococcus pneumoniae
[Type text]
OC[30] pneumonia patients only.
Kollef KE[31] 2008 CURB65 Single organism only (MRSA)
Kruger, S[32] 2008 CRB65 Data contained in (33)
Lin CC[34] 2005 PSI Data reported in (35)
Masia, M[36] 2005 PSI Data not reported.
Muller, B[37] 2007 PSI Not limited to CAP. Data reported in (17)
Myint, PK[38] 2006 CURB65 Limited to elderly patients only
Naito T[39] 2006 PSI Elderly patients aged >80 years only.
Pauls S[40] 2008 CRB65 Did not report mortality data.
Pilotto, A[41] 2009 PSI 1 year mortality as end-point. Age limited
to >65 years.
Prat, C [42] 2006 PSI Not exclusively CAP (including
tuberculosis and PCP).
Salluh JI[43] 2008 CURB65 Limited to severe CAP in ICU
Sanders KM[44] 2006 PSI Immunocompromised patients only
Sanz, F [45] 2009 PSI Low risk (PSI I-III) only.
Schaaf, B[46] 2007 CRB65 Limited to a single organism
(Streptococcus Pneumoniae)
Spindler, C[47] 2006 CURB65 Limited to a single organism
(Streptococcus Pneumoniae)
[Type text]
Teramoto, S [48] 2008 CURB65 Data not reported
Valencia, M[49] 2007 PSI, CURB65 Pneumonia severity index class V
patients only.
Vecchiarino, P
[50]
2004 PSI Data not presented.
Wilson PA[51] 2005 PSI ICU admitted patients only.
Yealy DM[52] 2005 PSI Data contained in (53)
Table E3- Studies of severity scores excluded from the meta-analysis.
ADDITIONAL RESULTS- PERFORMANCE CHARACTERISTICS AND FOREST PLOTS FOR SEVERITY SCORES
Calibration analysis
The performance of scores were compared to predicted values obtained from the initial
derivation studies. For PSI, fine et al reported mortality rates of 0.3%, 0.4%, 9.3% and 27%
for PSI classes I-II (lowest risk), PSI classes I-III (low risk), PSI class IV and class V
respectively. For CURB65, predicted values were 1.2% (CURB65 0-1), 9.0% (CURB65=2)
and 22.6% (CURB65 3-5). For CRB65, predicted mortality rates were 0.9% (CRB65 0),
8.1% (CRB65 1-2) and 31.2% (CRB65 3-4). The results of the calibration analysis are shown
in the forest plots below. The observed mortality in the validation studies was significantly
higher for both PSI and CURB65 for low risk patients (PSI I-III and CURB65 0-1) than
estimated in the original derivation studies. All 3 scores were well calibrated (p>0.05) at the
higher cut-offs, although significant heterogeneity was observed, suggesting variation in
[Type text]
mortality rates between different studies within these groups. Forest plots for each group are
displayed in the online supplement.
Pneumonia severity index I-II
Pneumonia severity index I-III
[Type text]
Pneumonia severity index class IV
[Type text]
Pneumonia severity index class V
[Type text]
CURB65 calibration
CURB65 0-1
[Type text]
Study or SubgroupAnanda Rajah 2007Aujesky 2007Barlow 2008Capelastegui 2006Challen 2007Chalmers 2008Charles 2008Huang 2008Man 2007Menendez 2009Phua 2009Schuetz 2008Shindo 2008Tejera 2007Zuberi 2008
Total (95% CI)Total eventsHeterogeneity: Tau² = 0.13; Chi² = 19.06, df = 14 (P = 0.16); I² = 27%Test for overall effect: Z = 2.50 (P = 0.01)
Observed Predicted Risk Ratio Risk RatioM-H, Random, 95% CI
0.2 0.5 1 2 5Favours experimental Favours control
Discrimination analysis
Pneumonia Severity Index
The Forest plots show the pooled sensitivity, specificity, positive likelihood ratio, pooled negative likelihood ratio and diagnostic odds ratio for the Pneumonia Severity Index. Forest plots are displayed for the following cut-offs
PSI III+
[Type text]
Sensi t i vi t y0 0. 2 0. 4 0. 6 0. 8 1
Ananda- Rajah 0. 98 ( 0. 91 - 1. 00)Aujesky, D 0. 97 ( 0. 92 - 0. 99)Capelast egui, A 0. 99 ( 0. 95 - 1. 00)Char les, P 0. 98 ( 0. 89 - 1. 00)Chen CZ 1. 00 ( 0. 88 - 1. 00)Davydov L 0. 96 ( 0. 79 - 1. 00)Dedier J 0. 95 ( 0. 87 - 0. 99)Ewig, S 0. 95 ( 0. 83 - 0. 99)Feagan B 1. 00 ( 0. 97 - 1. 00)Fine, M J 0. 97 ( 0. 92 - 0. 99)Flander s W 1. 00 ( 0. 93 - 1. 00)G ar au J 0. 95 ( 0. 92 - 0. 98)G ar cia- Vazquez E 1. 00 ( 0. 78 - 1. 00)G oss CH 0. 88 ( 0. 64 - 0. 99)Huang, DT 0. 95 ( 0. 88 - 0. 98)Johnst one, J 0. 99 ( 0. 97 - 1. 00)M an, SY 0. 98 ( 0. 92 - 1. 00)M edisgr oup 1 0. 98 ( 0. 97 - 0. 99)M edisgr oup 2 0. 99 ( 0. 98 - 0. 99)M enendez R 1. 00 ( 0. 90 - 1. 00)M iglior at i PL 1. 00 ( 0. 81 - 1. 00)O r t ega L 1. 00 ( 0. 40 - 1. 00)Phau J 0. 99 ( 0. 97 - 1. 00)Pneum ocom 1 0. 99 ( 0. 94 - 1. 00)Pneum ocom 2 0. 98 ( 0. 90 - 1. 00)Q uer ol- Ribelles JM 1. 00 ( 0. 78 - 1. 00)Rest r epo M 0. 88 ( 0. 77 - 0. 95)Roson, B 0. 97 ( 0. 85 - 1. 00)Schuet z, P 0. 98 ( 0. 87 - 1. 00)Tejer a A 1. 00 ( 0. 88 - 1. 00)Van Der Eer den, M M 0. 96 ( 0. 81 - 1. 00)
Sensi t i vi t y ( 95% CI )
Pooled Sensit ivit y = 0. 98 ( 0. 98 t o 0. 99)Chi- squar e = 60. 35; df = 30 ( p = 0. 0008)I nconsist ency ( I - squar e) = 50. 3 %
[Type text]
Speci f i ci t y0 0. 2 0. 4 0. 6 0. 8 1
Ananda- Rajah 0. 14 ( 0. 10 - 0. 18)Aujesky, D 0. 48 ( 0. 46 - 0. 50)Capelast egui, A 0. 49 ( 0. 46 - 0. 51)Char les, P 0. 30 ( 0. 27 - 0. 33)Chen CZ 0. 19 ( 0. 14 - 0. 24)Davydov L 0. 29 ( 0. 26 - 0. 33)Dedier J 0. 30 ( 0. 28 - 0. 33)Ewig, S 0. 30 ( 0. 26 - 0. 35)Feagan B 0. 23 ( 0. 20 - 0. 26)Fine, M J 0. 57 ( 0. 55 - 0. 59)Flander s W 0. 14 ( 0. 12 - 0. 16)G ar au J 0. 30 ( 0. 28 - 0. 32)G ar cia- Vazquez E 0. 30 ( 0. 24 - 0. 37)G oss CH 0. 40 ( 0. 35 - 0. 45)Huang, DT 0. 42 ( 0. 39 - 0. 44)Johnst one, J 0. 21 ( 0. 20 - 0. 23)M an, SY 0. 26 ( 0. 23 - 0. 29)M edisgr oup 1 0. 29 ( 0. 28 - 0. 30)M edisgr oup 2 0. 53 ( 0. 52 - 0. 54)M enendez R 0. 29 ( 0. 25 - 0. 34)M iglior at i PL 0. 18 ( 0. 12 - 0. 25)O r t ega L 0. 54 ( 0. 45 - 0. 63)Phau J 0. 36 ( 0. 33 - 0. 39)Pneum ocom 1 0. 35 ( 0. 32 - 0. 39)Pneum ocom 2 0. 39 ( 0. 35 - 0. 42)Q uer ol- Ribelles JM 0. 31 ( 0. 25 - 0. 38)Rest r epo M 0. 38 ( 0. 35 - 0. 42)Roson, B 0. 22 ( 0. 19 - 0. 26)Schuet z, P 0. 27 ( 0. 22 - 0. 32)Tejer a A 0. 12 ( 0. 08 - 0. 17)Van Der Eer den, M M 0. 35 ( 0. 29 - 0. 41)
Speci f i ci t y ( 95% CI )
Pooled Specif icit y = 0. 39 ( 0. 38 t o 0. 39)Chi- squar e = 3840. 00; df = 30 ( p = 0. 0000)I nconsist ency ( I - squar e) = 99. 2 %
[Type text]
Posi t i ve LR0. 361 2. 81
Ananda- Rajah 1. 14 ( 1. 08 - 1. 21)Aujesky, D 1. 85 ( 1. 77 - 1. 94)Capelast egui, A 1. 93 ( 1. 84 - 2. 03)Char les, P 1. 39 ( 1. 31 - 1. 48)Chen CZ 1. 21 ( 1. 13 - 1. 31)Davydov L 1. 36 ( 1. 24 - 1. 49)Dedier J 1. 37 ( 1. 28 - 1. 47)Ewig, S 1. 36 ( 1. 24 - 1. 50)Feagan B 1. 29 ( 1. 24 - 1. 34)Fine, M J 2. 28 ( 2. 15 - 2. 42)Flander s W 1. 15 ( 1. 11 - 1. 20)G ar au J 1. 36 ( 1. 31 - 1. 41)G ar cia- Vazquez E 1. 39 ( 1. 22 - 1. 58)G oss CH 1. 48 ( 1. 22 - 1. 79)Huang, DT 1. 62 ( 1. 51 - 1. 73)Johnst one, J 1. 25 ( 1. 22 - 1. 28)M an, SY 1. 32 ( 1. 25 - 1. 38)M edisgr oup 1 1. 39 ( 1. 37 - 1. 40)M edisgr oup 2 2. 10 ( 2. 07 - 2. 14)M enendez R 1. 39 ( 1. 29 - 1. 49)M iglior at i PL 1. 19 ( 1. 06 - 1. 32)O r t ega L 1. 96 ( 1. 38 - 2. 77)Phau J 1. 56 ( 1. 49 - 1. 63)Pneum ocom 1 1. 53 ( 1. 45 - 1. 61)Pneum ocom 2 1. 60 ( 1. 50 - 1. 71)Q uer ol- Ribelles JM 1. 41 ( 1. 24 - 1. 59)Rest r epo M 1. 43 ( 1. 28 - 1. 60)Roson, B 1. 25 ( 1. 16 - 1. 35)Schuet z, P 1. 34 ( 1. 23 - 1. 45)Tejer a A 1. 12 ( 1. 05 - 1. 20)Van Der Eer den, M M 1. 48 ( 1. 31 - 1. 66)
Posi t i ve LR ( 95% CI )
Random Ef f ect s M odelPooled Posit ive LR = 1. 44 ( 1. 32 t o 1. 57)Cochr an- Q = 3595. 65; df = 30 ( p = 0. 0000)I nconsist ency ( I - squar e) = 99. 2 %Tau- squar ed = 0. 0586
[Type text]
Negat i ve LR0. 001 885. 21
Ananda- Rajah 0. 11 ( 0. 02 - 0. 81)Aujesky, D 0. 07 ( 0. 03 - 0. 17)Capelast egui, A 0. 02 ( 0. 00 - 0. 12)Char les, P 0. 07 ( 0. 01 - 0. 47)Chen CZ 0. 09 ( 0. 01 - 1. 35)Davydov L 0. 14 ( 0. 02 - 0. 97)Dedier J 0. 15 ( 0. 05 - 0. 46)Ewig, S 0. 17 ( 0. 04 - 0. 66)Feagan B 0. 02 ( 0. 00 - 0. 29)Fine, M J 0. 05 ( 0. 02 - 0. 14)Flander s W 0. 07 ( 0. 00 - 1. 12)G ar au J 0. 16 ( 0. 09 - 0. 27)G ar cia- Vazquez E 0. 10 ( 0. 01 - 1. 60)G oss CH 0. 29 ( 0. 08 - 1. 08)Huang, DT 0. 13 ( 0. 05 - 0. 30)Johnst one, J 0. 06 ( 0. 03 - 0. 15)M an, SY 0. 09 ( 0. 02 - 0. 35)M edisgr oup 1 0. 06 ( 0. 04 - 0. 09)M edisgr oup 2 0. 02 ( 0. 02 - 0. 03)M enendez R 0. 05 ( 0. 00 - 0. 73)M iglior at i PL 0. 15 ( 0. 01 - 2. 32)O r t ega L 0. 19 ( 0. 01 - 2. 58)Phau J 0. 02 ( 0. 00 - 0. 11)Pneum ocom 1 0. 03 ( 0. 00 - 0. 20)Pneum ocom 2 0. 05 ( 0. 01 - 0. 33)Q uer ol- Ribelles JM 0. 10 ( 0. 01 - 1. 54)Rest r epo M 0. 31 ( 0. 15 - 0. 63)Roson, B 0. 13 ( 0. 02 - 0. 88)Schuet z, P 0. 09 ( 0. 01 - 0. 63)Tejer a A 0. 14 ( 0. 01 - 2. 18)Van Der Eer den, M M 0. 11 ( 0. 02 - 0. 73)
Negat i ve LR ( 95% CI )
Random Ef f ect s M odelPooled Negat ive LR = 0. 08 ( 0. 06 t o 0. 12)Cochr an- Q = 98. 67; df = 30 ( p = 0. 0000)I nconsist ency ( I - squar e) = 69. 6 %Tau- squar ed = 0. 6477
Random Ef f ect s M odelPooled Diagnost ic O dds Rat io = 8. 40 ( 7. 18 t o 9. 82)Cochr an- Q = 131. 39; df = 29 ( p = 0. 0000)I nconsist ency ( I - squar e) = 77. 9 %Tau- squar ed = 0. 1014
PSI 4+
[Type text]
Sensi t i vi t y0 0. 2 0. 4 0. 6 0. 8 1
Ananda- Rajah 0. 94 ( 0. 85 - 0. 98)Aujesky, D 0. 79 ( 0. 71 - 0. 85)Buising, KL 0. 88 ( 0. 79 - 0. 94)Capelast egui, A 0. 93 ( 0. 87 - 0. 97)Chalm er s, JD 0. 80 ( 0. 72 - 0. 87)Char les, P 0. 94 ( 0. 83 - 0. 99)Chen CZ 0. 88 ( 0. 77 - 0. 95)Davydov L 0. 88 ( 0. 68 - 0. 97)Dedier J 0. 86 ( 0. 75 - 0. 93)Ewig, S 0. 90 ( 0. 76 - 0. 97)Feagan B 0. 96 ( 0. 91 - 0. 99)Fine, M J 0. 94 ( 0. 88 - 0. 97)Flander s W 0. 78 ( 0. 63 - 0. 88)G ar au J 0. 88 ( 0. 84 - 0. 92)G ar cia- Vazquez E 0. 93 ( 0. 68 - 1. 00)G oss CH 0. 76 ( 0. 50 - 0. 93)Huang, DT 0. 80 ( 0. 68 - 0. 89)Johnst one, J 0. 93 ( 0. 90 - 0. 95)M an, SY 0. 84 ( 0. 74 - 0. 91)M edisgr oup 1 0. 93 ( 0. 92 - 0. 95)M edisgr oup 2 0. 92 ( 0. 91 - 0. 93)M enendez R 0. 94 ( 0. 81 - 0. 99)M iglior at i PL 0. 94 ( 0. 73 - 1. 00)O r t ega L 1. 00 ( 0. 40 - 1. 00)Phau J 0. 96 ( 0. 92 - 0. 98)Pneum ocom 1 0. 93 ( 0. 86 - 0. 97)Pneum ocom 2 0. 94 ( 0. 85 - 0. 99)Q uer ol- Ribelles JM 1. 00 ( 0. 78 - 1. 00)Rest r epo M 0. 75 ( 0. 62 - 0. 85)Reyes Calzada S 0. 91 ( 0. 77 - 0. 98)Roson, B 0. 86 ( 0. 70 - 0. 95)Schuet z, P 0. 90 ( 0. 77 - 0. 97)Tejer a A 0. 97 ( 0. 82 - 1. 00)Van Der Eer den, M M 0. 85 ( 0. 66 - 0. 96)
Sensi t i vi t y ( 95% CI )
Pooled Sensit ivit y = 0. 91 ( 0. 91 t o 0. 92)Chi- squar e = 115. 14; df = 33 ( p = 0. 0000)I nconsist ency ( I - squar e) = 71. 3 %
[Type text]
Speci f i ci t y0 0. 2 0. 4 0. 6 0. 8 1
Ananda- Rajah 0. 32 ( 0. 27 - 0. 37)Aujesky, D 0. 70 ( 0. 68 - 0. 71)Buising, KL 0. 47 ( 0. 43 - 0. 51)Capelast egui, A 0. 69 ( 0. 66 - 0. 71)Chalm er s, JD 0. 56 ( 0. 53 - 0. 59)Char les, P 0. 48 ( 0. 45 - 0. 52)Chen CZ 0. 39 ( 0. 32 - 0. 47)Davydov L 0. 51 ( 0. 47 - 0. 54)Dedier J 0. 50 ( 0. 47 - 0. 53)Ewig, S 0. 40 ( 0. 35 - 0. 44)Feagan B 0. 43 ( 0. 39 - 0. 47)Fine, M J 0. 72 ( 0. 70 - 0. 74)Flander s W 0. 73 ( 0. 70 - 0. 76)G ar au J 0. 53 ( 0. 51 - 0. 55)G ar cia- Vazquez E 0. 50 ( 0. 43 - 0. 57)G oss CH 0. 61 ( 0. 56 - 0. 66)Huang, DT 0. 62 ( 0. 60 - 0. 65)Johnst one, J 0. 47 ( 0. 45 - 0. 48)M an, SY 0. 50 ( 0. 47 - 0. 53)M edisgr oup 1 0. 50 ( 0. 49 - 0. 50)M edisgr oup 2 0. 44 ( 0. 43 - 0. 44)M enendez R 0. 51 ( 0. 46 - 0. 56)M iglior at i PL 0. 27 ( 0. 20 - 0. 35)O r t ega L 0. 70 ( 0. 61 - 0. 78)Phau J 0. 58 ( 0. 55 - 0. 61)Pneum ocom 1 0. 53 ( 0. 50 - 0. 57)Pneum ocom 2 0. 57 ( 0. 54 - 0. 61)Q uer ol- Ribelles JM 0. 54 ( 0. 48 - 0. 61)Rest r epo M 0. 58 ( 0. 54 - 0. 62)Reyes Calzada S 0. 44 ( 0. 39 - 0. 49)Roson, B 0. 45 ( 0. 41 - 0. 50)Schuet z, P 0. 48 ( 0. 42 - 0. 53)Tejer a A 0. 28 ( 0. 22 - 0. 35)Van Der Eer den, M M 0. 61 ( 0. 54 - 0. 67)
Speci f i ci t y ( 95% CI )
Pooled Specif icit y = 0. 50 ( 0. 49 t o 0. 50)Chi- squar e = 2327. 62; df = 33 ( p = 0. 0000)I nconsist ency ( I - squar e) = 98. 6 %
[Type text]
Posi t i ve LR0. 224 4. 51
Ananda- Rajah 1. 37 ( 1. 25 - 1. 51)Aujesky, D 2. 61 ( 2. 36 - 2. 88)Buising, KL 1. 67 ( 1. 50 - 1. 86)Capelast egui, A 2. 97 ( 2. 73 - 3. 24)Chalm er s, JD 1. 83 ( 1. 64 - 2. 05)Char les, P 1. 82 ( 1. 65 - 2. 00)Chen CZ 1. 46 ( 1. 26 - 1. 69)Davydov L 1. 77 ( 1. 50 - 2. 09)Dedier J 1. 72 ( 1. 53 - 1. 93)Ewig, S 1. 48 ( 1. 30 - 1. 69)Feagan B 1. 69 ( 1. 57 - 1. 82)Fine, M J 3. 37 ( 3. 10 - 3. 65)Flander s W 2. 86 ( 2. 39 - 3. 44)G ar au J 1. 89 ( 1. 78 - 2. 00)G ar cia- Vazquez E 1. 87 ( 1. 54 - 2. 27)G oss CH 1. 96 ( 1. 47 - 2. 62)Huang, DT 2. 14 ( 1. 85 - 2. 47)Johnst one, J 1. 74 ( 1. 66 - 1. 82)M an, SY 1. 68 ( 1. 50 - 1. 88)M edisgr oup 1 1. 85 ( 1. 81 - 1. 89)M edisgr oup 2 1. 64 ( 1. 62 - 1. 67)M enendez R 1. 94 ( 1. 71 - 2. 20)M iglior at i PL 1. 30 ( 1. 11 - 1. 51)O r t ega L 3. 00 ( 2. 02 - 4. 46)Phau J 2. 28 ( 2. 12 - 2. 46)Pneum ocom 1 1. 99 ( 1. 82 - 2. 19)Pneum ocom 2 2. 21 ( 1. 99 - 2. 45)Q uer ol- Ribelles JM 2. 12 ( 1. 80 - 2. 51)Rest r epo M 1. 77 ( 1. 49 - 2. 10)Reyes Calzada S 1. 64 ( 1. 44 - 1. 88)Roson, B 1. 56 ( 1. 34 - 1. 83)Schuet z, P 1. 72 ( 1. 49 - 1. 99)Tejer a A 1. 34 ( 1. 20 - 1. 50)Van Der Eer den, M M 2. 18 ( 1. 74 - 2. 73)
Posi t i ve LR ( 95% CI )
Random Ef f ect s M odelPooled Posit ive LR = 1. 89 ( 1. 78 t o 2. 00)Cochr an- Q = 769. 85; df = 33 ( p = 0. 0000)I nconsist ency ( I - squar e) = 95. 7 %Tau- squar ed = 0. 0271
[Type text]
Negat i ve LR0. 004 267. 01
Ananda- Rajah 0. 20 ( 0. 08 - 0. 52)Aujesky, D 0. 31 ( 0. 22 - 0. 42)Buising, KL 0. 25 ( 0. 14 - 0. 46)Capelast egui, A 0. 10 ( 0. 05 - 0. 19)Chalm er s, JD 0. 35 ( 0. 24 - 0. 51)Char les, P 0. 12 ( 0. 04 - 0. 37)Chen CZ 0. 30 ( 0. 14 - 0. 61)Davydov L 0. 25 ( 0. 09 - 0. 71)Dedier J 0. 28 ( 0. 15 - 0. 51)Ewig, S 0. 26 ( 0. 10 - 0. 66)Feagan B 0. 10 ( 0. 04 - 0. 23)Fine, M J 0. 09 ( 0. 04 - 0. 18)Flander s W 0. 31 ( 0. 18 - 0. 52)G ar au J 0. 22 ( 0. 16 - 0. 31)G ar cia- Vazquez E 0. 13 ( 0. 02 - 0. 89)G oss CH 0. 39 ( 0. 16 - 0. 91)Huang, DT 0. 32 ( 0. 19 - 0. 52)Johnst one, J 0. 15 ( 0. 11 - 0. 22)M an, SY 0. 32 ( 0. 20 - 0. 52)M edisgr oup 1 0. 13 ( 0. 11 - 0. 16)M edisgr oup 2 0. 18 ( 0. 16 - 0. 20)M enendez R 0. 11 ( 0. 03 - 0. 42)M iglior at i PL 0. 20 ( 0. 03 - 1. 40)O r t ega L 0. 14 ( 0. 01 - 1. 99)Phau J 0. 07 ( 0. 03 - 0. 14)Pneum ocom 1 0. 13 ( 0. 07 - 0. 27)Pneum ocom 2 0. 10 ( 0. 03 - 0. 29)Q uer ol- Ribelles JM 0. 06 ( 0. 00 - 0. 88)Rest r epo M 0. 44 ( 0. 28 - 0. 68)Reyes Calzada S 0. 19 ( 0. 07 - 0. 57)Roson, B 0. 32 ( 0. 14 - 0. 72)Schuet z, P 0. 21 ( 0. 08 - 0. 52)Tejer a A 0. 12 ( 0. 02 - 0. 86)Van Der Eer den, M M 0. 24 ( 0. 10 - 0. 60)
Negat i ve LR ( 95% CI )
Random Ef f ect s M odelPooled Negat ive LR = 0. 20 ( 0. 17 t o 0. 24)Cochr an- Q = 97. 66; df = 33 ( p = 0. 0000)I nconsist ency ( I - squar e) = 66. 2 %Tau- squar ed = 0. 1196
Random Ef f ect s ModelPooled Negat ive LR = 0. 50 (0. 44 t o 0. 58)Cochr an- Q = 489. 89; df = 29 ( p = 0. 0000)I nconsist ency ( I - squar e) = 94. 1 %Tau- squar ed = 0. 1104
Random Ef f ect s M odelPooled Diagnost ic O dds Rat io = 8. 40 ( 7. 18 t o 9. 82)Cochr an- Q = 131. 39; df = 29 ( p = 0. 0000)I nconsist ency ( I - squar e) = 77. 9 %Tau- squar ed = 0. 1014
Random Ef f ect s ModelPooled Posit ive LR = 1. 22 ( 1. 13 t o 1. 32)Cochr an- Q = 406. 41; df = 12 ( p = 0. 0000)I nconsist ency ( I - squar e) = 97. 0 %Tau- squar ed = 0. 0210
Random Ef f ect s M odelPooled Diagnost ic O dds Rat io = 11. 53 ( 7. 31 t o 18. 19)Cochr an- Q = 9. 41; df = 12 ( p = 0. 6680)I nconsist ency ( I - squar e) = 0. 0 %Tau- squar ed = 0. 0000
Random Ef f ect s M odelPooled Posit ive LR = 1. 71 ( 1. 54 t o 1. 89)Cochr an- Q = 198. 23; df = 14 ( p = 0. 0000)I nconsist ency ( I - squar e) = 92. 9 %Tau- squar ed = 0. 0364
Random Ef f ect s M odelPooled Negat ive LR = 0. 21 ( 0. 15 t o 0. 30)Cochr an- Q = 41. 11; df = 14 ( p = 0. 0002)I nconsist ency ( I - squar e) = 65. 9 %Tau- squar ed = 0. 2248
Random Ef f ect s M odelPooled Diagnost ic O dds Rat io = 8. 28 ( 5. 78 t o 11. 88)Cochr an- Q = 35. 54; df = 14 ( p = 0. 0012)I nconsist ency ( I - squar e) = 60. 6 %Tau- squar ed = 0. 2538
Random Ef f ect s M odelPooled Posit ive LR = 3. 06 ( 2. 67 t o 3. 49)Cochr an- Q = 92. 59; df = 16 ( p = 0. 0000)I nconsist ency ( I - squar e) = 82. 7 %Tau- squared = 0. 0615
Random Ef f ect s M odelPooled Negat ive LR = 0. 46 ( 0. 40 t o 0. 54)Cochr an- Q = 76. 51; df = 16 ( p = 0. 0000)I nconsist ency ( I - squar e) = 79. 1 %Tau- squar ed = 0. 0738
Random Ef f ect s M odelPooled Diagnost ic O dds Rat io = 6. 98 ( 5. 84 t o 8. 33)Cochr an- Q = 28. 74; df = 16 ( p = 0. 0257)I nconsist ency ( I - squar e) = 44. 3 %Tau- squar ed = 0. 0559
Random Ef f ect s M odelPooled Posit ive LR = 5. 38 ( 4. 41 t o 6. 56)Cochr an- Q = 28. 14; df = 13 ( p = 0. 0087)I nconsist ency ( I - squar e) = 53. 8 %Tau- squar ed = 0. 0698
Random Ef f ect s M odelPooled Diagnost ic O dds Rat io = 7. 77 ( 6. 26 t o 9. 64)Cochr an- Q = 19. 26; df = 13 ( p = 0. 1154)I nconsist ency ( I - squar e) = 32. 5 %Tau- squar ed = 0. 0515
Random Ef f ect s ModelPooled Posit ive LR = 1. 34 ( 1. 23 t o 1. 45)Cochr an- Q = 412. 28; df = 9 ( p = 0. 0000)I nconsist ency ( I - squar e) = 97. 8 %Tau- squar ed = 0. 0169
Random Ef f ect s M odelPooled Diagnost ic O dds Rat io = 9. 40 ( 5. 78 t o 15. 27)Cochr an- Q = 14. 06; df = 9 ( p = 0. 1202)I nconsist ency ( I - squar e) = 36. 0 %Tau- squar ed = 0. 1708
Random Ef f ect s ModelPooled Posit ive LR = 2. 39 (1. 93 t o 2. 95)Cochran- Q = 130. 43; df = 9 ( p = 0. 0000)I nconsist ency ( I - squar e) = 93. 1 %Tau- squared = 0. 1033
Random Ef f ect s M odelPooled Diagnost ic O dds Rat io = 6. 34 ( 4. 37 t o 9. 18)Cochr an- Q = 34. 74; df = 9 ( p = 0. 0001)I nconsist ency ( I - squar e) = 74. 1 %Tau- squar ed = 0. 2480
Pooled Specif icit y = 0. 91 ( 0. 91 t o 0. 91)Chi- squar e = 290. 58; df = 9 (p = 0. 0000)I nconsist ency ( I - squar e) = 96. 9 %
[Type text]
Posi t i ve LR0. 032 31. 41
Lim . WS 4. 30 ( 3. 15 - 5. 85)M an SY 3. 51 ( 2. 39 - 5. 16)Capelast egui A 11. 29 ( 7. 57 - 16. 84)M enendez. R 6. 07 ( 3. 75 - 9. 80)Chalm er s JD 3. 75 ( 2. 86 - 4. 92)Bauer . TT 5. 98 ( 3. 48 - 10. 28)Schuet z. P 5. 40 ( 0. 93 - 31. 36)Zuber i FF 8. 26 ( 2. 45 - 27. 93)Bar low G 3. 49 ( 2. 31 - 5. 28)Ewig S 3. 19 ( 3. 14 - 3. 25)
Posi t i ve LR ( 95% CI )
Random Ef f ect s M odelPooled Posit ive LR = 4. 73 ( 3. 61 t o 6. 18)Cochr an- Q = 57. 96; df = 9 ( p = 0. 0000)I nconsist ency ( I - squar e) = 84. 5 %Tau- squar ed = 0. 1242
Random Ef f ect s ModelPooled Negat ive LR = 0. 75 ( 0. 69 t o 0. 81)Cochr an- Q = 56. 61; df = 9 (p = 0. 0000)I nconsist ency ( I - squar e) = 84. 1 %Tau- squar ed = 0. 0116
Di agnost i c O dds Rat i o0. 022 46. 41
Lim . WS 6. 87 ( 4. 27 - 11. 03)M an SY 4. 59 ( 2. 74 - 7. 67)Capelast egui A 15. 70 ( 9. 60 - 25. 68)M enendez. R 10. 60 ( 5. 02 - 22. 37)Chalm er s JD 6. 24 ( 4. 00 - 9. 72)Bauer . TT 7. 03 ( 3. 72 - 13. 29)Schuet z. P 5. 62 ( 0. 91 - 34. 70)Zuber i FF 11. 06 ( 2. 63 - 46. 41)Bar low G 5. 01 ( 2. 84 - 8. 85)Ewig S 4. 09 ( 4. 00 - 4. 18)
Di agnost i c O R ( 95% CI )
Random Ef f ect s M odelPooled Diagnost ic O dds Rat io = 6. 73 ( 4. 77 t o 9. 50)Cochr an- Q = 48. 01; df = 9 ( p = 0. 0000)I nconsist ency ( I - squar e) = 81. 3 %Tau- squar ed = 0. 1999
SUBANALYSES
A priori the authors decided to conduct subgroup analyses to explore sources of heterogeneity in the
main analysis. Preplanned analyses included; analyses limited to studies only including hospital
inpatients; analysis limited to high quality studies only; analysis of prospective studies only. An
additional subanalysis was performed for studies directly comparing PSI and CURB65.
[Type text]
Analysis AUC
PSI
AUC
CURB65
AUC
CRB65
p-value
PSI v CURB65
p-value
PSI v CRB65
p-value
CURB65 v CRB65
Excluding outpatients
0.80 (+/- 0.010) 0.80 (+/- 0.008)
0.77 (+/- 0.014)
0.9 0.05 0.1
High quality only
0.82 (+/- 0.012) 0.80 (+/- 0.011)
0.80 (+/- 0.015)
0.3 0.2 0.7
Prospective studies only
0.81 (+/- 0.010) 0.81 +/- 0.011)
0.79 (+/- 0.014)
0.4 0.06 0.3
Direct comparison* PSI v CURB65
0.81 (+/- 0.014) 0.79 (+/- 0.010)
N/A 0.08 N/A N/A
Direct comparison*- PSI v CRB65
0.82 (+/- 0.024) N/A 0.79 (+/- 0.02)
N/A 0.3 N/A
Table E4- Subanalysis of severity scores for predicting mortality. *Comparisons made using the Hanley-MacNeil method for comparing data from the SAME set of cases.[
QUALITY ASSESSMENT
The following table contains the consensus quality assessment for each included study after applying Haydens criteria. There was significant agreement between reviewers in the quality assessment (kappa statistic 0.7).
First author
name
Population Follow-up Measurement
of severity
scores
Outcome
definition
Confounding Statistical analysis
Overall assessment by reviewers
Ananda-Rajah 2 3 U 3 2 3 2
Aujesky, D 3 3 3 3 2 3 3
Barlow GD 1 2 1 2 1 3 1
[Type text]
Bauer TT
(CAPNETZ)
3 3 2 3 2 3 3
Buising KL 3 2 2 3 3 3 2
Capelastegui ,
A
3 3 3 3 3 3 3
Challen, K 1 1 1 1 1 2 1
Chalmers JD 3 U 3 2 3 3 3
Chan, CZ 3 U 3 1 2 3 2
Charles, P 2 3 U 3 2 3 3
Davydov L 2 U U U 1 2 1
Dedier, J 1 2 3 3 1 3 2
Ewig, S 3 2 2 3 2 3 3
Ewig, S 2 2 3 3 3 3 3
Feagan B 1 1 1 U 1 2 1
Fine MJ-
PORT
3 3 3 3 3 3 3
Fine, MJ-
Medisgroup
1 1 1 1 1 3 1
Flanders, WD 1 1 1 U 1 2 1
Garau J 1 2 3 2 2 2 2
[Type text]
Garcia-
Vazquez E
1 2 1 2 2 2 1
Goss CH 3 U 2 U 2 3 2
Huang, DT 3 3 2 3 3 3 3
Johnstone, J 2 2 1 1 2 3 2
Lim, WS 3 3 3 3 3 2 3
Man, SY 3 U 3 3 3 3 3
Menendez R 3 3 2 3 3 3 3
Migliorati PL 2 1 2 2 1 2 1
Ortega L 2 2 U 2 2 3 2
Phau, J 2 3 2 2 2 3 2
Querol-
Ribelles JM
3 U 2 2 2 3 2
Renaud B
Pneumocom
1
3 U 3 3 3 3 3
Renaud B
Pneumocom
2
3 U 3 3 3 3 3
Restrepo MI 1 U 2 U 1 3 2
[Type text]
Reyes Calzada
S
1 2 3 3 1 3 2
Roson, B 3 3 3 3 3 3 3
Schuetz , P 2 3 3 3 2 3 2
Shindo, Y 1 1 1 2 1 3 1
Tejera, A 2 1 U 1 2 3 1
Van der
Eerden
3 3 3 3 3 3 3
Zuberi FF 2 2 U 2 2 3 2
TABLE E4- Quality assessment of included and excluded studies. U= unclear. 3= Good methodology, low likelihood of significant bias or confounding. 2= moderate methodology, possible confounding or bias. 1= Suboptimal methodology, significant likelihood of bias or confounding.
[Type text]
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