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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

E-mail: [email protected]

Keywords: Pneumonia, Severity assessment, mortality, meta-analysis

mailto:[email protected]

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ADDITIONAL METHODS

Definition of Severity scores

Pneumonia Severity Index[1]

The Pneumonia Severity Index is a well-validated prediction scale for 30-day mortality in

community-acquired pneumonia is composed of the following twenty characteristics:

demographics including age, sex and nursing home residence; co-morbid illness including

neoplastic disease, cerebrovascular disease, congestive cardiac failure, chronic renal disease

and chronic liver disease; physical examination findings including altered mental status,

respiratory rate > 30/min, systolic blood pressure <90mmHg, temperature <35oC or >40oC

and pulse >125/min; laboratory findings including pH <7.35, blood urea >10.7 mmol/L,

sodium <130 mEq/L, glucose >13.9 mmol/L, haematocrit <30% and PaO2 <60mmHg;

radiographic findings including pleural effusion.

Using these data, patients are classified into 5 risk classes. In the original Pneumonia Patient

Outcome Research Team cohort study, 30-day mortality ranged from 0.1% for patients with a

class 1 rating to 27% for patients with a class 5 rating. Typically, patients with PSI class IV/V

are regarded as severe pneumonia and recommended for hospitalization. For the purposes of

this meta-analysis, 2x2 tables were constructed for mortality in both PSI class IV/V and class

V alone.

CURB65/CRB65[2]

CURB65 is a validated method of predicting inpatient mortality associated with CAP that is

recommended by the British Thoracic Society. It consists of new onset mental confusion,

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urea >7 mmol/L, respiratory rate >30 breaths/min, systolic blood pressure <90mmHg or

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.

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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]


CURB65, PSI

Melbourne, Australia,

2003-2006

722 Median 74

In-hospital mortality

9.8% Derivation of a new severity score (CORB)

Capelastegui , A[27]


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]


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]


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


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

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Fine MJ- PORT[7]


PSI 5 Hospitals, USA and Canada, 1991-1994

2287 NR 30-day mortality

4.9% Validation of PSI

Flanders, WD[46]


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


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)


7.1% Derivation of simplified score.

Goss CH[49] Prospective cohort study

PSI Seattle, WA, USA 1994-1996

522 46 (range 18-100)


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

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Menendez, R[31]


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]


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


PSI 14 hospitals, Catalonia, Spain,

2003

853 Mean 65 28 day mortality

6.3% Validation of PSI in European population

Querol-Ribelles JM[52]


PSI Valencia, Spain, 2000


6.2% Validation of PSI

Restrepo, M[53]


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


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

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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)


12.4% Assessment of TREM-1 as a prognostic marker in CAP

Van der Eerden[56]


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

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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)

Events8

33342

145

13132

2011110

130

Total120

1952140

100661

5084058262402056472061035063

6532

Events1

232

12165

103282111

78

Total120

1952140

100661

5084058262402056472061035063

6532

Weight3.1%

18.6%4.0%8.3%2.4%

10.4%7.3%

12.4%7.2%3.4%

12.5%5.4%1.8%1.8%1.4%

100.0%

M-H, Random, 95% CI8.00 [1.02, 62.98]1.43 [0.85, 2.43]1.50 [0.25, 8.84]0.33 [0.11, 1.03]

2.00 [0.19, 21.48]2.33 [0.90, 6.02]1.00 [0.29, 3.43]1.30 [0.57, 2.95]

4.33 [1.25, 15.01]1.00 [0.14, 7.03]2.50 [1.11, 5.63]

5.50 [1.23, 24.51]1.00 [0.06, 15.77]1.00 [0.06, 15.55]0.33 [0.01, 8.03]

1.63 [1.11, 2.40]

Observed Predicted Risk Ratio Risk RatioM-H, Random, 95% CI

0.05 0.2 1 5 20Favours experimental Favours control

CURB65 group 2



Events164720369

201427237

5121434

302

Total13377511947448

3332384213151303061311027238

3635

Events127011434

30213828122812963

327

Total13377511947448

3332384213151303061311027238

3635

Weight6.4%

10.7%6.6%9.8%3.6%8.2%7.0%9.1%8.4%4.9%9.7%6.9%3.5%2.7%2.4%

100.0%

M-H, Random, 95% CI1.33 [0.66, 2.71]0.67 [0.47, 0.96]1.82 [0.91, 3.63]0.84 [0.55, 1.28]2.25 [0.74, 6.81]0.67 [0.39, 1.15]0.67 [0.35, 1.28]0.71 [0.44, 1.14]0.82 [0.48, 1.39]0.58 [0.24, 1.43]1.82 [1.18, 2.81]1.75 [0.90, 3.41]0.44 [0.14, 1.40]0.50 [0.13, 1.92]1.33 [0.32, 5.56]

0.95 [0.74, 1.21]


0.1 0.2 0.5 1 2 5 10Favours experimental Favours control

CURB65 group 3-5

[Type text]


Total (95% CI)Total eventsHeterogeneity: Tau² = 0.11; Chi² = 57.58, df = 14 (P < 0.00001); I² = 76%Test for overall effect: Z = 0.27 (P = 0.78)

Events39655679317431665127

1129

262414

704

Total15545416029677

38423940427611828936

12410436

3152

Events35

1033667178754916227658

28248

712

Total15545416029677

38423940427611828936

12410436

3152

Weight6.8%7.9%7.2%7.9%5.9%8.0%6.8%7.9%7.5%6.2%8.1%3.5%6.1%5.9%4.1%

100.0%

M-H, Random, 95% CI1.11 [0.75, 1.66]0.63 [0.48, 0.84]1.56 [1.09, 2.22]1.18 [0.89, 1.56]1.82 [1.11, 3.01]0.85 [0.65, 1.12]0.57 [0.38, 0.86]0.73 [0.55, 0.96]0.82 [0.59, 1.15]1.00 [0.63, 1.60]1.72 [1.33, 2.23]1.13 [0.49, 2.59]0.93 [0.58, 1.49]1.00 [0.61, 1.64]1.75 [0.84, 3.65]

1.03 [0.84, 1.25]



CRB65 score

CRB65 0

Study or SubgroupBarlow 2008Bauer 2006Capelastegui 2006Chalmers 2008Ewig 2009Man 2007Menendez 2009Schuetz 2008Zuberi 2008


Events0004

15213140

1533

Total71

659716276

6426712879

10934

66339

Events1663

5781110

597

Total71

659716276

6426712879

10934

66339

Weight6.7%7.8%7.8%

17.0%30.0%10.9%8.3%

11.4%

100.0%

M-H, Random, 95% CI0.33 [0.01, 8.05]0.08 [0.00, 1.36]0.08 [0.00, 1.36]1.33 [0.30, 5.90]2.63 [2.39, 2.89]

3.00 [0.32, 28.46]1.00 [0.06, 15.71]4.00 [0.45, 35.21]

Not estimable

1.15 [0.45, 2.94]



CRB65 1-2

[Type text]


Total (95% CI)Total eventsHeterogeneity: Tau² = 0.19; Chi² = 81.46, df = 8 (P < 0.00001); I² = 90%Test for overall effect: Z = 0.77 (P = 0.44)

Events49668353

3731058183513

37685

Total281

1231980803

27789078331925994

282640

Events23

1007965

225096326218

22894

Total281

1231980803

27789078331925994

282640

Weight10.7%12.4%12.4%11.9%13.9%12.0%9.5%

10.2%7.1%

100.0%

M-H, Random, 95% CI2.13 [1.34, 3.40]0.66 [0.49, 0.89]1.05 [0.78, 1.41]0.82 [0.57, 1.16]1.66 [1.63, 1.68]0.92 [0.65, 1.30]0.69 [0.39, 1.24]1.67 [1.00, 2.78]1.63 [0.71, 3.74]

1.13 [0.83, 1.55]



CRB65 3-4



Events30143651

15903261725

16084

Total676980

19046249

1054959

46823

Events21222559

14430331523

14610

Total676980

19046249

1054959

46823

Weight9.0%5.7%

10.3%14.7%42.4%9.2%5.9%1.0%1.8%

100.0%

M-H, Random, 95% CI1.43 [0.92, 2.22]0.64 [0.36, 1.14]1.44 [0.96, 2.16]0.86 [0.63, 1.19]1.10 [1.08, 1.12]0.79 [0.51, 1.22]1.13 [0.64, 2.00]1.00 [0.22, 4.56]1.67 [0.56, 4.97]

1.06 [0.91, 1.23]



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


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


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


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

[Type text]

Di agnost i c O dds Rat i o0. 011 91. 81

Ananda- Rajah 21. 23 ( 12. 13 - 37. 15)Aujesky, D 9. 04 ( 6. 16 - 13. 27)Capelast egui, A 21. 25 ( 14. 04 - 32. 18)Chalm er s, JD 9. 21 ( 6. 09 - 13. 94)Char les, P 6. 60 ( 3. 66 - 11. 90)Chen CZ 7. 34 ( 3. 01 - 17. 94)Davydov L 7. 88 ( 3. 44 - 18. 02)Dedier J 11. 04 ( 6. 42 - 18. 98)Ewig, S 4. 04 ( 2. 07 - 7. 88)Fine, M J 14. 28 ( 9. 55 - 21. 36)G ar au J 6. 87 ( 5. 30 - 8. 91)G ar cia- Vazquez 8. 15 ( 2. 57 - 25. 81)G oss CH 12. 66 ( 4. 32 - 37. 16)Huang, DT 2. 37 ( 1. 39 - 4. 04)Johnst one, J 5. 72 ( 4. 57 - 7. 16)M an, SY 4. 76 ( 3. 01 - 7. 52)M edisgr oup 1 9. 73 ( 8. 64 - 10. 95)M edisgr oup 2 8. 67 ( 8. 08 - 9. 31)M enendez R 9. 18 ( 4. 46 - 18. 86)M iglior at i PL 20. 11 ( 4. 40 - 91. 80)O r t ega L 4. 26 ( 0. 40 - 45. 23)Phau J 13. 92 ( 9. 73 - 19. 91)Pneum ocom 1 9. 97 ( 6. 34 - 15. 69)Pneum ocom 2 25. 28 ( 12. 64 - 50. 55)Q uer ol- Ribelles JM 22. 33 ( 6. 61 - 75. 44)Rest r epo M 4. 40 ( 2. 52 - 7. 69)Roson, B 7. 38 ( 4. 07 - 13. 36)Schuet z, P 2. 75 ( 1. 33 - 5. 67)Tejer a A 3. 29 ( 1. 44 - 7. 52)Van Der Eer den, M M 8. 46 ( 3. 19 - 22. 46)

Di agnost i c O R ( 95% CI )

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)



[Type text]

Speci f i ci t y0 0. 2 0. 4 0. 6 0. 8 1




[Type text]

Posi t i ve LR0. 224 4. 51




[Type text]

Negat i ve LR0. 004 267. 01




[Type text]

PSI V

[Type text]

Sensi t i vi t y0 0. 2 0. 4 0. 6 0. 8 1

Ananda-Rajah 0. 74 ( 0. 65 - 0. 82)Aujesky, D 0. 32 ( 0. 25 - 0. 41)Capelast egui, A 0. 62 ( 0. 53 - 0. 71)Chalm ers, JD 0. 58 ( 0. 48 - 0. 67)Char les, P 0. 58 ( 0. 43 - 0. 72)Chen CZ 0. 77 ( 0. 58 - 0. 90)Davydov L 0. 54 ( 0. 33 - 0. 74)Dedier J 0. 66 ( 0. 53 - 0. 77)Ewig, S 0. 51 ( 0. 35 - 0. 68)Fine, MJ 0. 54 ( 0. 44 - 0. 63)G ar au J 0. 48 ( 0. 42 - 0. 54)G ar cia-Vazquez 0. 67 ( 0. 38 - 0. 88)G oss CH 0. 71 ( 0. 44 - 0. 90)Huang, DT 0. 18 ( 0. 11 - 0. 27)Johnst one, J 0. 56 ( 0. 51 - 0. 61)Man, SY 0. 46 ( 0. 35 - 0. 57)Medisgroup 1 0. 66 ( 0. 64 - 0. 69)Medisgroup 2 0. 68 ( 0. 66 - 0. 69)Menendez R 0. 56 ( 0. 38 - 0. 72)M iglior at i PL 0. 89 ( 0. 65 - 0. 99)O r t ega L 0. 25 ( 0. 01 - 0. 81)Phau J 0. 68 ( 0. 61 - 0. 75)Pneumocom 1 0. 56 ( 0. 46 - 0. 66)Pneumocom 2 0. 80 ( 0. 66 - 0. 89)Q uer ol-Ribelles JM 0. 73 ( 0. 45 - 0. 92)Rest r epo M 0. 31 ( 0. 21 - 0. 43)Roson, B 0. 57 ( 0. 43 - 0. 71)Schuet z, P 0. 32 ( 0. 18 - 0. 48)Tejer a A 0. 64 ( 0. 44 - 0. 81)Van Der Eer den, MM 0. 33 ( 0. 17 - 0. 54)


Pooled Sensit ivit y = 0. 63 ( 0. 62 t o 0. 64)Chi-squar e = 331. 38; df = 29 ( p = 0. 0000)I nconsist ency ( I - squar e) = 91. 2 %

[Type text]

Speci f i ci t y0 0. 2 0. 4 0. 6 0. 8 1

Ananda-Rajah 0. 88 ( 0. 84 - 0. 92)Aujesky, D 0. 95 ( 0. 94 - 0. 96)Capelast egui, A 0. 93 ( 0. 91 - 0. 94)Chalmers, JD 0. 87 ( 0. 85 - 0. 89)Char les, P 0. 83 ( 0. 80 - 0. 85)Chen CZ 0. 69 ( 0. 63 - 0. 75)Davydov L 0. 87 ( 0. 85 - 0. 89)Dedier J 0. 85 ( 0. 83 - 0. 87)Ewig, S 0. 79 ( 0. 75 - 0. 83)Fine, MJ 0. 92 ( 0. 91 - 0. 93)G ar au J 0. 88 ( 0. 87 - 0. 89)G ar cia-Vazquez 0. 80 ( 0. 73 - 0. 87)G oss CH 0. 84 ( 0. 80 - 0. 87)Huang, DT 0. 92 ( 0. 90 - 0. 93)Johnst one, J 0. 82 ( 0. 80 - 0. 83)Man, SY 0. 85 ( 0. 82 - 0. 87)Medisgroup 1 0. 83 ( 0. 83 - 0. 84)Medisgroup 2 0. 81 ( 0. 80 - 0. 81)Menendez R 0. 88 ( 0. 84 - 0. 91)Migliorat i PL 0. 72 ( 0. 63 - 0. 79)O r t ega L 0. 93 ( 0. 87 - 0. 97)Phau J 0. 87 ( 0. 84 - 0. 89)Pneum ocom 1 0. 89 ( 0. 86 - 0. 91)Pneum ocom 2 0. 87 ( 0. 84 - 0. 89)Q uerol-Ribelles JM 0. 89 ( 0. 84 - 0. 93)Rest repo M 0. 91 ( 0. 88 - 0. 93)Roson, B 0. 85 ( 0. 81 - 0. 88)Schuet z, P 0. 86 ( 0. 81 - 0. 89)Tejer a A 0. 65 ( 0. 58 - 0. 71)Van Der Eerden, M M 0. 94 ( 0. 91 - 0. 97)

Speci f i ci t y (95% CI )

Pooled Specif icit y = 0. 84 ( 0. 84 t o 0. 83)Chi- squar e = 1212. 99; df = 29 ( p = 0. 0000)I nconsist ency ( I -squar e) = 97. 6 %

[Type text]

Posi t i ve LR0. 048 21. 11

Ananda- Rajah 6. 25 ( 4. 51 - 8. 67)Aujesky, D 6. 43 ( 4. 86 - 8. 52)Capelast egui, A 8. 66 ( 6. 93 - 10. 82)Chalmers, JD 4. 48 ( 3. 60 - 5. 57)Char les, P 3. 35 ( 2. 54 - 4. 43)Chen CZ 2. 48 ( 1. 88 - 3. 28)Davydov L 4. 15 ( 2. 76 - 6. 24)Dedier J 4. 40 ( 3. 50 - 5. 52)Ewig, S 2. 48 ( 1. 74 - 3. 54)Fine, MJ 7. 11 ( 5. 68 - 8. 90)G ar au J 4. 06 ( 3. 47 - 4. 75)G ar cia-Vazquez 3. 38 ( 2. 07 - 5. 53)G oss CH 4. 43 ( 3. 03 - 6. 47)Huang, DT 2. 12 ( 1. 36 - 3. 31)Johnst one, J 3. 06 ( 2. 72 - 3. 44)Man, SY 3. 03 ( 2. 30 - 3. 98)Medisgroup 1 3. 96 ( 3. 75 - 4. 18)Medisgroup 2 3. 48 ( 3. 38 - 3. 59)Menendez R 4. 63 ( 3. 13 - 6. 85)Migliorat i PL 3. 12 ( 2. 27 - 4. 29)O r t ega L 3. 44 ( 0. 56 - 21. 05)Phau J 5. 09 ( 4. 25 - 6. 11)Pneumocom 1 4. 94 ( 3. 81 - 6. 39)Pneumocom 2 5. 95 ( 4. 76 - 7. 42)Q uerol-Ribelles JM 6. 69 ( 4. 14 - 10. 80)Rest repo M 3. 34 ( 2. 21 - 5. 06)Roson, B 3. 72 ( 2. 72 - 5. 07)Schuet z, P 2. 19 ( 1. 30 - 3. 69)Tejer a A 1. 82 ( 1. 30 - 2. 54)Van Der Eerden, MM 5. 97 ( 2. 82 - 12. 66)

Posi t i ve LR (95% CI )

Random Ef f ect s ModelPooled Posit ive LR = 4. 05 (3. 67 t o 4. 47)Cochran- Q = 239. 30; df = 29 (p = 0. 0000)I nconsist ency ( I - squar e) = 87. 9 %Tau- squared = 0. 0488

[Type text]

Negat i ve LR0. 042 23. 91

Ananda-Rajah 0. 29 ( 0. 21 - 0. 41)Aujesky, D 0. 71 ( 0. 64 - 0. 80)Capelast egui, A 0. 41 ( 0. 32 - 0. 51)Chalmers, JD 0. 49 ( 0. 39 - 0. 60)Char les, P 0. 51 ( 0. 37 - 0. 70)Chen CZ 0. 34 ( 0. 18 - 0. 65)Davydov L 0. 53 ( 0. 34 - 0. 81)Dedier J 0. 40 ( 0. 28 - 0. 56)Ewig, S 0. 61 ( 0. 44 - 0. 85)Fine, MJ 0. 50 ( 0. 41 - 0. 61)G ar au J 0. 59 ( 0. 53 - 0. 66)G ar cia-Vazquez 0. 42 ( 0. 20 - 0. 85)G oss CH 0. 35 ( 0. 17 - 0. 73)Huang, DT 0. 90 ( 0. 82 - 0. 98)Johnst one, J 0. 54 ( 0. 48 - 0. 60)Man, SY 0. 64 ( 0. 52 - 0. 77)Medisgroup 1 0. 41 ( 0. 38 - 0. 44)Medisgroup 2 0. 40 ( 0. 38 - 0. 42)Menendez R 0. 50 ( 0. 35 - 0. 73)M iglior at i PL 0. 16 ( 0. 04 - 0. 58)O r t ega L 0. 81 ( 0. 46 - 1. 43)Phau J 0. 37 ( 0. 30 - 0. 45)Pneum ocom 1 0. 50 ( 0. 40 - 0. 62)Pneum ocom 2 0. 24 ( 0. 14 - 0. 40)Q uer ol-Ribelles JM 0. 30 ( 0. 13 - 0. 69)Rest r epo M 0. 76 ( 0. 65 - 0. 89)Roson, B 0. 50 ( 0. 37 - 0. 69)Schuet z, P 0. 80 ( 0. 65 - 0. 99)Tejer a A 0. 55 ( 0. 33 - 0. 92)Van Der Eerden, MM 0. 71 ( 0. 54 - 0. 92)

Negat i ve LR (95% CI )

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

[Type text]


Ananda- Rajah 21. 23 ( 12. 13 - 37. 15)Aujesky, D 9. 04 ( 6. 16 - 13. 27)Capelast egui, A 21. 25 ( 14. 04 - 32. 18)Chalm er s, JD 9. 21 ( 6. 09 - 13. 94)Char les, P 6. 60 ( 3. 66 - 11. 90)Chen CZ 7. 34 ( 3. 01 - 17. 94)Davydov L 7. 88 ( 3. 44 - 18. 02)Dedier J 11. 04 ( 6. 42 - 18. 98)Ewig, S 4. 04 ( 2. 07 - 7. 88)Fine, M J 14. 28 ( 9. 55 - 21. 36)G ar au J 6. 87 ( 5. 30 - 8. 91)G ar cia- Vazquez 8. 15 ( 2. 57 - 25. 81)G oss CH 12. 66 ( 4. 32 - 37. 16)Huang, DT 2. 37 ( 1. 39 - 4. 04)Johnst one, J 5. 72 ( 4. 57 - 7. 16)M an, SY 4. 76 ( 3. 01 - 7. 52)M edisgr oup 1 9. 73 ( 8. 64 - 10. 95)M edisgr oup 2 8. 67 ( 8. 08 - 9. 31)M enendez R 9. 18 ( 4. 46 - 18. 86)M iglior at i PL 20. 11 ( 4. 40 - 91. 80)O r t ega L 4. 26 ( 0. 40 - 45. 23)Phau J 13. 92 ( 9. 73 - 19. 91)Pneum ocom 1 9. 97 ( 6. 34 - 15. 69)Pneum ocom 2 25. 28 ( 12. 64 - 50. 55)Q uer ol- Ribelles JM 22. 33 ( 6. 61 - 75. 44)Rest r epo M 4. 40 ( 2. 52 - 7. 69)Roson, B 7. 38 ( 4. 07 - 13. 36)Schuet z, P 2. 75 ( 1. 33 - 5. 67)Tejer a A 3. 29 ( 1. 44 - 7. 52)Van Der Eer den, M M 8. 46 ( 3. 19 - 22. 46)



CURB65

CURB65 1+

[Type text]

Sensi t i vi t y0 0. 2 0. 4 0. 6 0. 8 1

Lim, WS 0. 99 ( 0. 94 - 1. 00)Capelast egui, A 1. 00 ( 0. 97 - 1. 00)Aujesky, D 0. 96 ( 0. 91 - 0. 98)Menendez, R 0. 97 ( 0. 85 - 1. 00)Schuet z, P 0. 93 ( 0. 80 - 0. 98)Man, SY 0. 99 ( 0. 94 - 1. 00)Zuber i FF 1. 00 ( 0. 81 - 1. 00)Tejer a A 1. 00 ( 0. 88 - 1. 00)Bar low G 1. 00 ( 0. 95 - 1. 00)Shindo Y 1. 00 ( 0. 89 - 1. 00)Ananda- Rajah 1. 00 ( 0. 94 - 1. 00)Challen K 1. 00 ( 0. 92 - 1. 00)Phau J 0. 98 ( 0. 94 - 0. 99)

Sensi t i vi t y (95% CI )

Pooled Sensit ivit y = 0. 98 ( 0. 97 t o 0. 99)Chi- squar e = 22. 38; df = 12 (p = 0. 0335)I nconsist ency ( I - squar e) = 46. 4 %

Speci f i ci t y0 0. 2 0. 4 0. 6 0. 8 1

Lim, WS 0. 20 ( 0. 18 - 0. 23)Capelast egui, A 0. 38 ( 0. 36 - 0. 40)Aujesky, D 0. 34 ( 0. 33 - 0. 36)Menendez, R 0. 15 ( 0. 12 - 0. 19)Schuet z, P 0. 25 ( 0. 21 - 0. 30)Man, SY 0. 11 ( 0. 09 - 0. 13)Zuber i FF 0. 22 ( 0. 15 - 0. 30)Tejer a A 0. 09 ( 0. 05 - 0. 13)Bar low G 0. 17 ( 0. 13 - 0. 22)Shindo Y 0. 12 ( 0. 08 - 0. 16)Ananda-Rajah 0. 08 ( 0. 05 - 0. 11)Challen K 0. 10 ( 0. 06 - 0. 17)Phau J 0. 28 ( 0. 26 - 0. 31)



[Type text]

Posi t i ve LR0. 600 1. 71

Lim , WS 1. 24 ( 1. 19 - 1. 29)Capelast egui, A 1. 60 ( 1. 54 - 1. 67)Aujesky, D 1. 45 ( 1. 39 - 1. 52)Menendez, R 1. 15 ( 1. 07 - 1. 23)Schuet z, P 1. 24 ( 1. 12 - 1. 38)Man, SY 1. 11 ( 1. 08 - 1. 15)Zuber i FF 1. 25 ( 1. 11 - 1. 41)Tejer a A 1. 08 ( 1. 01 - 1. 15)Bar low G 1. 20 ( 1. 14 - 1. 26)Shindo Y 1. 12 ( 1. 05 - 1. 19)Ananda- Rajah 1. 07 ( 1. 04 - 1. 12)Challen K 1. 11 ( 1. 04 - 1. 18)Phau J 1. 37 ( 1. 31 - 1. 43)


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

[Type text]

Negat i ve LR0. 001 1446. 81

Lim, WS 0. 06 ( 0. 01 - 0. 39)Capelast egui, A 0. 01 ( 0. 00 - 0. 17)Aujesky, D 0. 13 ( 0. 06 - 0. 28)Menendez, R 0. 18 ( 0. 03 - 1. 29)Schuet z, P 0. 29 ( 0. 10 - 0. 87)Man, SY 0. 10 ( 0. 01 - 0. 72)Zuber i FF 0. 12 ( 0. 01 - 1. 87)Tejer a A 0. 20 ( 0. 01 - 3. 17)Bar low G 0. 04 ( 0. 00 - 0. 58)Shindo Y 0. 13 ( 0. 01 - 2. 09)Ananda- Rajah 0. 10 ( 0. 01 - 1. 65)Challen K 0. 11 ( 0. 01 - 1. 78)Phau J 0. 08 ( 0. 03 - 0. 20)


Random Ef f ect s ModelPooled Negat ive LR = 0. 12 ( 0. 07 t o 0. 18)Cochr an- Q = 9. 24; df = 12 (p = 0. 6825)I nconsist ency ( I - squar e) = 0. 0 %Tau- squared = 0. 0000


Lim , WS 22. 56 ( 3. 12 - 163. 08)Capelast egui, A 145. 86 ( 9. 05 - 2, 349. 59)Aujesky, D 11. 23 ( 4. 94 - 25. 54)M enendez, R 6. 23 ( 0. 84 - 46. 29)Schuet z, P 4. 29 ( 1. 29 - 14. 26)M an, SY 10. 88 ( 1. 50 - 78. 92)Zuber i FF 10. 49 ( 0. 61 - 179. 84)Tejer a A 5. 50 ( 0. 32 - 93. 95)Bar low G 33. 04 ( 2. 02 - 540. 53)Shindo Y 8. 49 ( 0. 51 - 141. 77)Ananda- Rajah 10. 53 ( 0. 63 - 175. 10)Challen K 10. 17 ( 0. 60 - 173. 68)Phau J 17. 67 ( 6. 50 - 48. 03)



CURB65 2+

[Type text]

Sensi t i vi t y0 0. 2 0. 4 0. 6 0. 8 1

Lim , WS 0. 94 ( 0. 87 - 0. 98)Capelast egui, A 0. 97 ( 0. 92 - 0. 99)Aujesky, D 0. 76 ( 0. 67 - 0. 83)M enendez, R 0. 94 ( 0. 81 - 0. 99)Schuet z, P 0. 73 ( 0. 57 - 0. 86)M an, SY 0. 85 ( 0. 76 - 0. 92)Char les, P 0. 90 ( 0. 78 - 0. 97)Huang, DT 0. 88 ( 0. 80 - 0. 93)Zuber i FF 1. 00 ( 0. 81 - 1. 00)Tejer a A 0. 96 ( 0. 82 - 1. 00)Bar low G 0. 96 ( 0. 89 - 0. 99)Shindo Y 0. 97 ( 0. 83 - 1. 00)Ananda- Rajah 0. 87 ( 0. 77 - 0. 94)Challen K 0. 95 ( 0. 84 - 0. 99)Phau J 0. 89 ( 0. 84 - 0. 93)



Speci f i ci t y0 0. 2 0. 4 0. 6 0. 8 1




[Type text]

Posi t i ve LR0. 383 2. 61




[Type text]

Negat i ve LR0. 003 311. 51








CURB65 3+

[Type text]

Sensi t i vi t y0 0. 2 0. 4 0. 6 0. 8 1

Lim , WS 0. 70 ( 0. 59 - 0. 79)Capelast egui, A 0. 66 ( 0. 57 - 0. 75)Aujesky, D 0. 45 ( 0. 37 - 0. 53)Buising, KL 0. 52 ( 0. 41 - 0. 64)Chalm er s, JD 0. 69 ( 0. 60 - 0. 78)M enendez, R 0. 75 ( 0. 58 - 0. 88)Schuet z, P 0. 22 ( 0. 11 - 0. 38)M an, SY 0. 59 ( 0. 48 - 0. 69)Char les, P 0. 62 ( 0. 47 - 0. 75)Huang, DT 0. 62 ( 0. 52 - 0. 71)Zuber i FF 0. 78 ( 0. 52 - 0. 94)Tejer a A 0. 86 ( 0. 67 - 0. 96)Bar low G 0. 71 ( 0. 60 - 0. 81)Shindo Y 0. 84 ( 0. 66 - 0. 95)Ananda- Rajah 0. 62 ( 0. 49 - 0. 74)Challen K 0. 74 ( 0. 58 - 0. 86)Phau J 0. 61 ( 0. 54 - 0. 68)



Speci f i ci t y0 0. 2 0. 4 0. 6 0. 8 1




[Type text]

Posi t i ve LR0. 134 7. 51



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

[Type text]

Negat i ve LR0. 096 10. 41








CURB65 4+

[Type text]

Sensi t i vi t y0 0. 2 0. 4 0. 6 0. 8 1

Lim, WS 0. 37 (0. 27 - 0. 48)Capelast egui, A 0. 27 (0. 19 - 0. 36)Aujesky, D 0. 10 (0. 05 - 0. 16)Chalmers, JD 0. 40 (0. 30 - 0. 49)Menendez, R 0. 39 (0. 23 - 0. 57)Schuet z, P 0. 02 (0. 00 - 0. 13)Man, SY 0. 23 (0. 15 - 0. 33)Zuber i FF 0. 17 (0. 04 - 0. 41)Tejer a A 0. 57 (0. 37 - 0. 76)Bar low G 0. 37 (0. 26 - 0. 48)Shindo Y 0. 58 (0. 39 - 0. 75)Ananda-Rajah 0. 30 (0. 19 - 0. 43)Challen K 0. 43 (0. 28 - 0. 59)Phau J 0. 27 (0. 21 - 0. 34)


Pooled Sensit ivit y = 0. 29 ( 0. 26 t o 0. 32)Chi- squar e = 93. 21; df = 13 (p = 0. 0000)I nconsist ency ( I - squar e) = 86. 1 %

Speci f i ci t y0 0. 2 0. 4 0. 6 0. 8 1

Lim, WS 0. 93 ( 0. 91 - 0. 94)Capelast egui, A 0. 98 ( 0. 97 - 0. 98)Aujesky, D 0. 98 ( 0. 98 - 0. 99)Chalmer s, JD 0. 90 ( 0. 88 - 0. 92)Menendez, R 0. 94 ( 0. 91 - 0. 96)Schuet z, P 0. 99 ( 0. 98 - 1. 00)Man, SY 0. 94 ( 0. 93 - 0. 96)Zuber i FF 0. 97 ( 0. 92 - 0. 99)Tejer a A 0. 85 ( 0. 79 - 0. 90)Bar low G 0. 92 ( 0. 89 - 0. 95)Shindo Y 0. 92 ( 0. 88 - 0. 95)Ananda- Rajah 0. 92 ( 0. 88 - 0. 94)Challen K 0. 92 ( 0. 86 - 0. 96)Phau J 0. 97 ( 0. 95 - 0. 98)


Pooled Specif icit y = 0. 95 ( 0. 95 t o 0. 96)Chi-squar e = 242. 38; df = 13 ( p = 0. 0000)I nconsist ency ( I - squar e) = 94. 6 %

[Type text]

Posi t i ve LR0. 023 43. 71

Lim , WS 5. 12 ( 3. 56 - 7. 37)Capelast egui, A 11. 14 ( 7. 28 - 17. 06)Aujesky, D 5. 14 ( 2. 94 - 9. 01)Chalm er s, JD 3. 96 ( 2. 97 - 5. 27)M enendez, R 6. 49 ( 3. 71 - 11. 34)Schuet z, P 4. 05 ( 0. 38 - 43. 68)M an, SY 4. 11 ( 2. 58 - 6. 55)Zuber i FF 4. 96 ( 1. 21 - 20. 36)Tejer a A 3. 77 ( 2. 38 - 5. 97)Bar low G 4. 80 ( 3. 00 - 7. 68)Shindo Y 7. 21 ( 4. 43 - 11. 73)Ananda- Rajah 3. 59 ( 2. 15 - 5. 99)Challen K 5. 14 ( 2. 70 - 9. 80)Phau J 8. 27 ( 5. 53 - 12. 36)



[Type text]

Negat i ve LR0. 301 3. 31

Lim, WS 0. 68 (0. 58 - 0. 80)Capelast egui, A 0. 75 (0. 67 - 0. 84)Aujesky, D 0. 92 (0. 87 - 0. 97)Chalmers, JD 0. 67 (0. 58 - 0. 78)Menendez, R 0. 65 (0. 50 - 0. 84)Schuet z, P 0. 98 (0. 93 - 1. 03)Man, SY 0. 82 (0. 73 - 0. 92)Zuber i FF 0. 86 (0. 70 - 1. 06)Tejer a A 0. 51 (0. 33 - 0. 78)Bar low G 0. 69 (0. 58 - 0. 81)Shindo Y 0. 46 (0. 30 - 0. 69)Ananda-Rajah 0. 76 (0. 65 - 0. 90)Challen K 0. 62 (0. 48 - 0. 81)Phau J 0. 75 (0. 69 - 0. 82)


Random Ef f ect s ModelPooled Negat ive LR = 0. 73 ( 0. 65 t o 0. 83)Cochran- Q = 186. 21; df = 13 ( p = 0. 0000)I nconsist ency ( I - squar e) = 93. 0 %Tau- squared = 0. 0450


Lim , WS 7. 55 ( 4. 57 - 12. 49)Capelast egui, A 14. 87 ( 8. 91 - 24. 82)Aujesky, D 5. 59 ( 3. 03 - 10. 28)Chalm er s, JD 5. 90 ( 3. 85 - 9. 03)M enendez, R 9. 98 ( 4. 56 - 21. 82)Schuet z, P 4. 13 ( 0. 37 - 46. 52)M an, SY 5. 03 ( 2. 84 - 8. 92)Zuber i FF 5. 75 ( 1. 17 - 28. 22)Tejer a A 7. 47 ( 3. 21 - 17. 35)Bar low G 7. 00 ( 3. 81 - 12. 86)Shindo Y 15. 81 ( 6. 92 - 36. 12)Ananda- Rajah 4. 71 ( 2. 43 - 9. 09)Challen K 8. 25 ( 3. 53 - 19. 30)Phau J 11. 00 ( 6. 89 - 17. 57)



CRB65

CRB65 1+

[Type text]

Sensi t i vi t y0 0. 2 0. 4 0. 6 0. 8 1

Lim, WS 0. 98 ( 0. 92 - 1. 00)Man SY 0. 97 ( 0. 90 - 0. 99)Capelast egui A 1. 00 ( 0. 97 - 1. 00)Menendez, R 0. 97 ( 0. 85 - 1. 00)Chalmer s JD 0. 96 ( 0. 90 - 0. 99)Bauer , TT 1. 00 ( 0. 95 - 1. 00)Schuet z, P 0. 90 ( 0. 77 - 0. 97)Zuber i FF 1. 00 ( 0. 81 - 1. 00)Bar low G 1. 00 ( 0. 95 - 1. 00)Ewig S 0. 94 ( 0. 95 - 0. 94)



Speci f i ci t y0 0. 2 0. 4 0. 6 0. 8 1



Pooled Specif icit y = 0. 38 ( 0. 38 t o 0. 38)Chi- squar e = 690. 28; df = 9 (p = 0. 0000)I nconsist ency ( I - squar e) = 98. 7 %

[Type text]

Posi t i ve LR0. 599 1. 71

Lim, WS 1. 35 (1. 28 - 1. 43)Man SY 1. 12 (1. 06 - 1. 17)Capelast egui A 1. 61 (1. 54 - 1. 67)Menendez, R 1. 20 (1. 12 - 1. 29)Chalmer s JD 1. 17 (1. 12 - 1. 23)Bauer , TT 1. 53 (1. 47 - 1. 59)Schuet z, P 1. 32 (1. 17 - 1. 49)Zuber i FF 1. 37 (1. 19 - 1. 57)Bar low G 1. 26 (1. 19 - 1. 33)Ewig S 1. 54 (1. 53 - 1. 54)


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

[Type text]

Negat i ve LR0. 001 1462. 41



Random Ef f ect s ModelPooled Negat ive LR = 0. 15 ( 0. 10 t o 0. 22)Cochr an- Q = 11. 92; df = 9 (p = 0. 2176)I nconsist ency ( I - squar e) = 24. 5 %Tau- squar ed = 0. 0888


Lim , WS 16. 68 ( 4. 07 - 68. 38)M an SY 4. 35 ( 1. 36 - 13. 98)Capelast egui A 147. 65 ( 9. 17 - 2, 378. 37)M enendez, R 8. 20 ( 1. 11 - 60. 76)Chalm er s JD 5. 16 ( 1. 88 - 14. 20)Bauer , TT 87. 00 ( 5. 39 - 1, 405. 14)Schuet z, P 4. 28 ( 1. 49 - 12. 32)Zuber i FF 14. 93 ( 0. 88 - 254. 69)Bar low G 42. 18 ( 2. 58 - 688. 66)Ewig S 10. 51 ( 10. 12 - 10. 90)



CRB65 2+

[Type text]

Sensi t i vi t y0 0. 2 0. 4 0. 6 0. 8 1

Lim, WS 0. 78 ( 0. 67 - 0. 86)Man SY 0. 68 ( 0. 57 - 0. 77)Capelast egui A 0. 77 ( 0. 68 - 0. 84)Menendez, R 0. 86 ( 0. 71 - 0. 95)Chalmers JD 0. 75 ( 0. 65 - 0. 83)Bauer , TT 0. 65 ( 0. 54 - 0. 75)Schuet z, P 0. 27 ( 0. 14 - 0. 43)Zuber i FF 0. 83 ( 0. 59 - 0. 96)Bar low G 0. 73 ( 0. 62 - 0. 83)Buising KL 0. 88 ( 0. 78 - 0. 94)



Speci f i ci t y0 0. 2 0. 4 0. 6 0. 8 1

Lim, WS 0. 64 ( 0. 60 - 0. 67)Man SY 0. 63 ( 0. 60 - 0. 67)Capelast egui A 0. 83 ( 0. 81 - 0. 85)Menendez, R 0. 65 ( 0. 60 - 0. 70)Chalmer s JD 0. 57 ( 0. 54 - 0. 61)Bauer , TT 0. 79 ( 0. 77 - 0. 81)Schuet z, P 0. 90 ( 0. 86 - 0. 93)Zuber i FF 0. 72 ( 0. 63 - 0. 80)Bar low G 0. 59 ( 0. 53 - 0. 64)Buising KL 0. 55 ( 0. 52 - 0. 59)



[Type text]

Posi t i ve LR0. 192 5. 21



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

[Type text]

Negat i ve LR0. 082 12. 31



Random Ef f ect s ModelPooled Negat ive LR = 0. 39 (0. 28 t o 0. 54)Cochran- Q = 69. 83; df = 9 (p = 0. 0000)I nconsist ency ( I - squar e) = 87. 1 %Tau- squared = 0. 2229


Lim , WS 6. 02 ( 3. 59 - 10. 10)M an SY 3. 65 ( 2. 28 - 5. 84)Capelast egui A 16. 01 ( 10. 29 - 24. 91)M enendez, R 11. 50 ( 4. 38 - 30. 21)Chalm er s JD 4. 11 ( 2. 54 - 6. 64)Bauer , TT 6. 95 ( 4. 34 - 11. 16)Schuet z, P 3. 21 ( 1. 48 - 6. 99)Zuber i FF 13. 03 ( 3. 54 - 47. 95)Bar low G 3. 95 ( 2. 29 - 6. 80)Buising KL 8. 71 ( 4. 26 - 17. 82)



CRB65 3+

[Type text]

Sensi t i vi t y0 0. 2 0. 4 0. 6 0. 8 1

Lim. WS 0. 44 ( 0. 33 - 0. 55)Man SY 0. 30 ( 0. 21 - 0. 41)Capelast egui A 0. 30 ( 0. 22 - 0. 39)Menendez. R 0. 47 ( 0. 30 - 0. 65)Chalmer s JD 0. 47 ( 0. 37 - 0. 58)Bauer . TT 0. 18 ( 0. 10 - 0. 28)Schuet z. P 0. 05 ( 0. 01 - 0. 17)Zuber i FF 0. 28 ( 0. 10 - 0. 53)Bar low G 0. 38 ( 0. 27 - 0. 50)Ewig S 0. 29 ( 0. 29 - 0. 29)



Speci f i ci t y0 0. 2 0. 4 0. 6 0. 8 1

Lim. WS 0. 90 ( 0. 88 - 0. 92)Man SY 0. 91 ( 0. 90 - 0. 93)Capelast egui A 0. 97 ( 0. 96 - 0. 98)Menendez. R 0. 92 ( 0. 89 - 0. 95)Chalmers JD 0. 87 ( 0. 85 - 0. 89)Bauer . TT 0. 97 ( 0. 96 - 0. 98)Schuet z. P 0. 99 ( 0. 97 - 1. 00)Zuber i FF 0. 97 ( 0. 92 - 0. 99)Bar low G 0. 89 ( 0. 85 - 0. 92)Ewig S 0. 91 ( 0. 91 - 0. 91)



[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)



[Type text]

Negat i ve LR0. 420 2. 41

Lim. WS 0. 63 ( 0. 52 - 0. 75)Man SY 0. 77 ( 0. 67 - 0. 88)Capelast egui A 0. 72 ( 0. 64 - 0. 81)Menendez. R 0. 57 ( 0. 42 - 0. 78)Chalmer s JD 0. 60 ( 0. 50 - 0. 73)Bauer . TT 0. 85 ( 0. 77 - 0. 94)Schuet z. P 0. 96 ( 0. 89 - 1. 03)Zuber i FF 0. 75 ( 0. 56 - 1. 00)Bar low G 0. 70 ( 0. 58 - 0. 83)Ewig S 0. 78 ( 0. 78 - 0. 78)


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


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)



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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[Type text]

SUPPLEMENTAL FIGURE LEGENDS

Figure E1: Forest plots for positive likelihood ratio, negative likelihood ratio and Diagnostic odds

ratio for Pneumonia severity index.

Figure E2: Forest plots for positive likelihood ratio, negative likelihood ratio and Diagnostic odds

ratio for the CURB65 score.

Figure E3- Forest plots of positive likelihood ratio, negative likelihood ratio and Diagnostic odds ratio

for the CURB65 score.

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