Febrile IVDU Hospitalization: Occult Illness & Decision Factors

Hospitalization
Decision in Febrile Intravenous Drug Users
JEFFREY H. SAMET, M.D., ABBY SHEVITZ, M.D., JANET FOWLE, M.D., DANIEL E. SINGER, M.D.,
Boston,
Massachusetts
PURPOSE:
To determine the frequency and to
identify predictive factors of occult major illness in
febrile intravenous drug users (MXJs) presenting
to an emergency room.
PATIENTS
AND METHODS:
A prospective follow-up
study was performed involving a consecutive series
of 296 presentations of febrile IVDUs to a public
hospital emergency room. Follow-up information
was obtained for 283 presentations (95.6%). Physicians’ initial assessment was obtained for 204 presentations (70%). Illness was classified as major or
minor using explicit criteria. Frequency of occult
major ilhmss was determined among patients without obvious major illness on presentation. Risk factors for occult major illness were determined.
RESULTS:
Occult major illness occurred in 11 patients (4%). This represented 11% of the 103 presentations without obvious major illness on presentation. Pneumonia and cellulitis occurred in 128 of
180 patients (71%) with obvious major ilhmss on
presentation. Racteremia was present in seven of
11 patients with occult major illness. Physician
predictions were not sufficiently sensitive to provide the basii of the hospitalization decision in febrile IVDUs. The best combination of features suggesting major illness were last use of intravenous
drugs less than 5 days and fever greater than
388°C (102.0’F) (sensitivity 64%, specificity 77%).
CONCLUSION:
Clinical tests and physician assessments are unable to distinguish occult major illness
from minor illness among febrile IVDUs at presentation. Occult major illness is best identified by
blood culture. If patient follow-up is unreliable,
then hospitalization of febrile IVDUs, while awaiting blood culture results, remains a wise policy.
From the Section of General Internal Medicine, Department of Medrcine,
and Thorndike Memorial Laboratory, Boston City Hosprtal and Boston Universitv School of Medicine. Boston. Massachusetts:
and the General Internal Medicine Unrt. Department of Medictne. Massachusetts
General Hosprtal and Harvard Medical School, Boston, Massachusetts.
Dr. Samet was
supported by a training grant for faculty development
in general internal
medrcrne by the Health Resources
Services Admimstration
(2 028
PE51006-04). Dr. Singer was partially supported as a Henry J. Kaiser Family Foundation Scholar in General Internal Medicine. Requests for reprints
should be addressed to Jeffrey H. Samet, M.D.. Section of General Internal
Medicine, Boston City Hospital, 818 Harrison Avenue, Boston, Massachusetts 02118. Manuscript submitted December 11, 1989. and accepted in
revised form March 30. 1990.
drug use is a prevalent social and mediIsonsntravenous
cal disease affecting an estimated 1.2 million perin the United States and associated with many
medical complications [l-5]. Fever may be the initial
clinical feature of minor illness or life-threatening disease in the intravenous drug user (IVDU) [6].
The presentation of a febrile IVDU is common in
some municipal hospitals [7]. The possibility of occult
life-threatening disease makes the presentation of an
IVDU with fever a difficult clinical problem. This difficulty has led to the recommendation to hospitalize
all febrile IVDUs [7]. The necessity of this costly policy is uncertain.
Life-threatening
diseases described in IVDUs include infective endocarditis, osteomyelitis, and pneumonia [8-lo]. The frequency of endocarditis among
febrile IVDUs presenting to an emergency room was
found to be 13% in one series [7]. This disease’s presentation may range from fulminant to occult. Although
occult life-threatening disease is the chief motivation
for universal hospitalization of this population, the
frequency of this threat is uncertain. The usefulness of
clinical and laboratory information and initial physician impression in the detection of occult life-threatening disease among those febrile IVDUs with apparent minor illness at presentation is uncertain. This
information is essential for consideration of a policy
concerning selective hospitalization of febrile IVDUs.
To address these issues, we performed a prospective
follow-up study of a consecutive series of febrile
IVDUs presenting to a public hospital emergency
room.
PATIENTS AND METHODS
Patients
Between January 11,1988, and January 10,1989, we
enrolled all persons who presented to the Boston City
Hospital emergency room (ER) with admitted illicit
use of intravenous drugs within the previous 6 months
and a documented temperature of 378°C (lOO.O’F) or
greater. Initial identification of appropriate patients
was performed by ER physicians, and daily review of
medical admissions was carried out to identify any
appropriate patients not enrolled in the ER. Hospitalization of febrile IVDUs was the accepted ER practice
during the study period and occurred in 95% of the
study patients. Comprehensive accrual of patients in
the ER and review of all medical admissions enabled
us to enroll essentially all febrile IVDUs. The study
protocol was approved by the Human Subjects Institutional Review Board.
Data Collection
A standard data form was completed at the time of
enrollment by the ER physician responsible for the
patient (70%) or, if unavailable, by one of the study
investigators (30%). This form contained the following: I2 historical or demographic questions (age, sex,
race, duration of parenteral drug use, last use of intraJuly 1990
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HOSPITALIZATION
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/ SAMET
ET AL
venous drugs, history of endocarditis, antibiotic use
within 48 hours, hospitalization within 3 months or
within 12 months, history of heart murmur, history of
cardiac valvular disease, reason for seeking care), 12
specifically defined symptoms (dyspnea, hemoptysis,
pleuritic chest pain, cough, vomiting, diarrhea, weight
loss, headache, arthralgias, myalgias, night sweats,
and sore throat), 12 specifically defined physical signs
(temperature, pulse, systolic blood pressure, meningismus, Roth spots, cardiac murmur, petechiae, pustules, Janeway lesions, Osler’s nodes, splenomegaly,
and hepatomegaly), and three questions concerning
physician’s assessment (percent likely to be bacteremit, percent likely to have infective endocarditis, and
primary diagnoses). All forms were reviewed within 1
week by one of the investigators to ensure comprehensiveness and uniformity of data collection.
A separate standard follow-up data form was completed by one of the study investigators on each patient. This form contained the following information:
from the ER-complete
blood count, creatinine, blood
urea nitrogen, serum bicarbonate, erythrocyte sedimentation rate; within 72 hours of presentation-albumin, bilirubin, serum glutamic oxaloacetic transaminase @GOT), hepatitis B surface antigen and surface
antibody; within 24 hours of presentation-urinalysis
and chest radiographic results; during hospitalization-all culture results; and discharge diagnoses. Follow-up data were obtained until the time of discharge
by review of patient charts and computerized laboratory and culture results.
For analysis, temperature was corrected to equal the
oral temperature. As rectal or tympanic membrane
temperature determinations
reflect core body temperature, each of these observed temperatures was reduced by 0.44”C [ll]. If the route of temperature determination
was not specified,
then the more
commonly used oral route was assumed.
All data were entered onto an RBASE System V
database development and management system [12].
After entry, all data on the computerized database
were checked against the original forms and appropriate corrections were made.
Definition of Outcomes
Diseases that were believed by the investigators to
require hospitalization are classified in this study as
“major illness” and those believed not to require hospitalization, as “minor illness.” After completion of
the data collection for the entire cohort, patients were
categorized into one of three outcome groups: Group
l-major
illness that was clinically obvious on presentation to the ER; Group 2-minor
illness; Group 3major illness that was not clinically apparent (occult)
on presentation to the ER.
Criteria for major illness included any of the following findings: (1) a new radiographic pulmonary infiltrate, (2) a physician’s determination
of cellulitis
based on physical evidence of warmth, erythema, and
induration, or (3) endocarditis as diagnosed by strict
criteria: definite if pathologic confirmation; probable
if two or more positive blood cultures and a new regurgitant murmur or peripheral or pulmonary embolic
phenomena; possible if two or more positive blood cultures and a known abnormal cardiac valve [13]. Additionally, all IVDUs with two or more positive blood
cultures, no known underlying cardiac valvular dis54
July 1990
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ease, and no discernable focus of infection were defined as having presumed endocarditis. A number of
other diagnoses not meeting the aforementioned criteria but requiring hospitalization were also designated
as major illness (Appendix).
Minor illness (Group 2) included presumed viral
syndrome (uncomplicated headache, myalgias, cough,
diarrhea, or pharyngitis), streptococcal pharyngitis
(throat culture positive for group A /3-hemolytic streptococci), hepatitis B (elevation of SGOT greater than
40 mU/mL and positive serology for hepatitis B surface antigen without complications of ascites, coagulopathy, or altered mental status), and no established
diagnosis with spontaneous resolution of the fever
(empiric antibiotics administered less than 48 hours).
Several other diagnoses not requiring hospitalization
were also designated as minor illness (Appendix).
Patients with major illness were assigned to Group 1
(obvious on presentation) if any of the following criteria were satisfied: (1) new infiltrate on initial chest
radiograph, (2) ER physician’s diagnosis of cellulitis,
or (3) diagnosis of another major illness by the ER
physician (e.g., abscess, arthritis, meningitis) and a
discharge diagnosis of the same major illness. Patients
with major illness were assigned to Group 3 (occult at
presentation) if the etiology of the fever as ultimately
diagnosed was not known at the time of presentation.
In the rare event that an ER diagnosis was a major
illness that differed from the actual discharge major
illness, the patient was classified into Group 1, since a
need for admission based on a major illness was obvious in the ER. Patients had incomplete follow-up if no
diagnosis was clear at presentation and the clinical
course was not known.
For purposes of tabulating overall disease frequency, the following rules were followed: only one diagnosis was assigned to each patient; pneumonia was defined as a new radiographic pulmonary infiltrate and
blood cultures negative for Staphylococcus aureus.
The assessment of final diagnosis was based on all
available information. In the event of dual diagnoses,
the priority for diagnosis used for tabulating overall
disease frequency was in decreasing order: infective
endocarditis, septic arthritis, acute renal insufficiency, pneumonia, and cellulitis.
Methods of Analysis
Comparisons of differences in variables between patient subgroups were performed using the chi-square
test or Fisher’s exact test for categoric variables and
Student’s t-test for continuous variables [14]. A twotailed p value <0.05 was considered statistically significant. When appropriate, continuous variables were
analyzed as categoric variables using clinically meaningful cut-points.
We analyzed all variables in the database to compare patients in Group 2 (minor illness) to those in
Group 3 (occult major illness). These analyses were
carried out in two ways: using all presentations, and
using only the first presentation of those patients who
had more than one presentation to the ER during the
study period. We describe results based on all febrile
IVDU presentations, since using only first presentations of patients with multiple ER visits during the
study period did not substantially alter the study results. Relative risks and 95% confidence intervals were
calculated using the SAS command “proc freq” [15].
HOSPlTALlZATlON
RESULTS
Description of Cohort
Figure 1 provides an overview of the study population. During the 12-month period, 296 IVDUs presented to the ER with a temperature greater than 37PC
(lOO.O”F). Follow-up was inadequate in 13 patients
who left the hospital against medical advice or were
transferred to other facilities. Thus, 283 presentations
(95.6% of all presentations) were evaluated. Of these,
180 (64%) had a major illness that was obvious in the
ER (Group l), and 103 (36%) had no obvious major
illness in the ER (Groups 2 and 3). Of the latter group,
92 (89%) were ultimately diagnosed with minor illness
(Group 2) and 11 (11%) were diagnosed with major
illness (Group 3).
The 296 presentations involved 244 different patients. Table I summarizes demographic and clinical
characteristics of the 244-patient cohort.
Spectrum of Illness
Figure 2 illustrates the distribution of major diseases in which the need to hospitalize the febrile IVDU
was apparent at presentation (Group 1). Two diagnoses, pneumonia and cellulitis, were evident on the
basis of physical examination or a chest radiograph.
These two infectious diseases accounted for 71% (128
of 180) of Group 1. Infective endocarditis and abscess
each comprised 6%. Several other diagnoses each accounted for fewer than 4% of Group 1 (Appendix).
The 11 patients with occult major illness on presentation (Group 3) are described in Table II. Seven of
these 11 patients were bacteremic and diagnosed with
endocarditis. Two patients were ultimately diagnosed
with pneumonia after initial clear chest radiographs.
One patient with nonspecific clinical characteristics
consistent with a viral syndrome developed disseminated intravascular coagulation. One patient was
found by venogram to have a deep femoral venous
thrombosis after more than 7 days of hospitalization
for fever without an evident source.
Among the 92 patients with minor illness (Group 2),
the most common diagnosis was presumed viral syndrome in 44 patients (47%). No established diagnosis
with spontaneous resolution of fever occurred in 18
patients (20%). Streptococcal pharyngitis and hepatitis B accounted for four and three patients, respectively. The other diagnoses are included in the Appendix.
Predictors of Major Illness
Among the 103 febrile IVDUs without apparent major illness at presentation, we identified three univariate predictors of occult major illness (Table III).
These included last use of intravenous drugs less than
5 days, fever greater than 38.8”C (102.O”F), and proteinuria greater than trace by dipstick. Temperature
greater than 38.8”C (102.0°F) and last use of intravenous drugs less than 5 days were both present in seven
of the 11 patients in Group 3 (sensitivity 64%). These
same two features were present in 21 of 92 patients in
Group 2 (specificity 77%). The other combinations of
significant univariate predictors yielded very low
sensitivities.
Other clinical and laboratory features that did not
predict major illness included duration of intravenous
drug use, prior history of endocarditis, recent hospitalization, presence of a cardiac murmur, serum bicarbonate, and erythrocyte sedimentation rate. We did
296
IN FEBRILE
IVDUs
/ SAMET
ET AL
Total # cf presentations
to ER
I
--
2
1 3 Presentations
follow-up
8 3 Presentations
evaluated
180(64%)
1 o3(369/O)
with Inadequate
Presentations wth
apparent ma,or Illness
(Group 1)
Prewntations
wlthout
Presentations
minor illness
(Group 2)
with
apparent
1 1 ~4%/x’:~:..,
Presentations wth
inapparent major illness
(Group 3)
Figure
1. Overview
of the study population,
presentations
of febrile
intravenous
drug
emergency
users.
room
TABLEI
Demographicand ClinicalCharacteristicsof 244 Febrile
IntravenousDrug UsersPresentingto an EmergencyRoom
Characteristic
Se;,;;e243)*
Male
Ra;h$;thnicity
82 (33.7%)
161 (66.3%)
(n = 240)
Black
Hispanic
Other
History of endocarditis (n = 215)
Hospitalization within the
past 1 year (n = 203)
Age (mean years) (n = 226)
Duration of intravenous
drug use (median years) (n = 215)
Time since last use of
intravenousdrugs(mediandays)(n
= 241)
46 (19.2%)
154 (64.2%)
3; $\.’
24(li.&)
103 (50.7%)
33.6(range,
19-64)
10 (range, O-40)
1 (range, O-180)
* “n” values are the number of different patients about whom the specific characteristic
is known
TABLEII
Diagnosisand Sourceof BacteremiaIn Patientswith
OccultMajor Illness
Patient
Diagnosis
1
Infective endocarditis
(possible)
Infective endocarditis
(definite)
Infective endocarditis
(presumed)
Infective endocarditis
(possible)
Infective endocarditis
(probable)
Infective endocarditis
(presumed)
Infective endocarditis
(possible)
Pneumonia
Pneumonia
Disseminated intravascular
coagulation
Deep venous thrombosis
2
3
4
5
6
7
9”
10
11
July 1990
The American
Bacteremia
Journal
Group G @-hemolytic
streptococcus
Staphylococcus
aureus
Staphylococcus
aureus
Staphylococcus
aureus
Staphylococcus
aureus
Staphylococcus
aureus
Streptococcus
viridans
None
None
None
None
of Medicine
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89
55
HOSPITALIZATION IN FEBRILE IVDUs /SAMET ET AL
sentations (Group 3) were associated with positive
blood cultures, while only one of the 91 minor illness
presentations (Group 2) was bacteremic. This single
bacteremic patient in Group 2 had a painful exudative
pharyngitis and showed growth of group A f)-hemolytic streptococci on both blood and throat cultures.
Cellulitis (37%)
\
:: ;-~'- c 11 :
,
67
\
\
Infective
-~~:·~'7 endocarditis (6%)
~~~Abscess (6%)
~~:::.::..\~~:;~~>
-~. ·"-"-~~'-.'Y"
Other apparent
major illnesses (17%)
Figure 2. Distribution of major illnesses at presentation in febrile intravenous drug users (Group 1, n = 180). Other apparent major illnesses are listed in the Appendix.
TABLE Ill
Significant Univariate Predictors of Major Illness (Among 103
Febrile Intravenous Drug Users without Apparent Major Illness
at Presentation)
Predictors
RR*
95% Cit
Historical
Last use of intravenous drugs <5
days
6.30*
1.05-37.79
Symptoms and signs
Cough
Headache
Sore throat
Temperature >38.8°C
Meningismus
2.32
0.40
1.09
4.76*
0.66
0.56-9.52
0.13-1.30
0.30-3.93
1.52-14.89
0.04-10.13
Laboratory results
White blood cell count> 104 jmm3
Neutrophils >70%
Creatinine> 1.3 mgjdL
Albumin <3.5 gjdL
Proteinuria > trace§
1.69
1.40
3.33
2.44
4.44*
0.53-5.36
0.42-4.64
0.53-20.97
0.79-7.52
1.27-15.5
• RR denotes relative risk.
t Cl denotes confidence interval. The relative risk and their 95% confidence intervals
were calculated using SAS ··proc freq.""
"<0.05.
§Proteinuria scaling is qualitative based on standard dipstick procedure.
not analyze human immunodeficiency virus serology
as a predictor since this information was available in
only 28% of all presentations.
Physician Predictions
Physicians' estimates of the probability of bacteremia and endocarditis were obtained for 204 presentations (70%). Table IV lists the numbers of patients
with bacteremia and endocarditis stratified by the ER
physician's estimate of likelihood to have these diseases. Cases were distributed through all quintiles of
risk. Although the actual risk of bacteremia or endocarditis tended to increase with higher physician risk
category, the relationship was not smooth and was
poorly calibrated (i.e., the actual risks were not near
the midpoints of the physician risk category). The lowest quintile included 24% of all patients with bacteremia and 37% of all patients with endocarditis, indicating substantial inaccuracy.
Bacteremia
Blood cultures were obtained in 276 of 283 presentations (98%). Seven of the 11 occult major illness pre56
July 1990 The American Journal of Medicine Volume 89
COMMENTS
Our study examined the possibility of more selective
hospitalization for febrile IVDUs. We utilized a cohort
over three times the size of the previously studied
group of febrile IVDUs, and an analytic framework
focused on the most critical clinical problem, the identification of major illness among those patients without obvious major illness on presentation [7].
We provide data on which a policy concerning triage
of febrile IVDUs can be based. The majority of febrile
IVDUs presented with obvious major illness in the ER,
and the risk of occult major illness was low. Our results
may be used as a basis for two very different approaches. The fiscally conservative would argue that since
nearly 90% of patients with no apparent major illness
would be appropriately triaged, none should be admitted to the hospital. Outpatient follow-up would be
adequate. The medically conservative would suggest
that all febrile IVDUs should be hospitalized since
greater than 10% of those without obvious major illness may have occult major illness. Outpatient followup is often poor in this particular population. Since
bacteremia was present in 64% of cases of occult major
illness, the hospitalization decision in febrile IVDUs
could depend on the possibility of reliably informing
patients of blood culture results.
This approach raises the key questions of the clinical importance of occult bacteremia in this setting and
the risk of waiting 24 to 48 hours to institute therapy.
Although there is uncertainty about both these questions, the clinical meaning of occult bacteremia is generally assumed to indicate serious illness in this population. Institution of antibiotic therapy is not without
risk, since central intravenous access is frequently
required.
Bacteremia was found in patients in Group 3, in part
because its presence alone defined "presumed endocarditis." Nonetheless, the occurrence of bacteremia
in an IVDU without obvious major illness does change
the hospitalization decision. In this study, bacteremia
was a striking discriminator between those with minor
illness and those with occult major illness (Groups 2
and 3). However, because blood culture information is
not available for 24 to 48 hours, it is not useful for
initial triage purposes. If a technology that determined bacteremia within a matter of hours could be
developed, this might improve triage decisions for febrile IVDUs.
Although other clinical or laboratory features (i.e.,
last use of intravenous drugs less than 5 days, temperature greater than 38.8°C [102.0°F], and proteinuria greater than trace [by dipstick]) were significantly
associated with occult major illness, the associations
were not sufficiently strong to direct the triage
decision.
Physicians' estimates of the probability of bacteremia or endocarditis revealed the uncertainty of this
clinical problem. Although physicians' higher risk categories did include greater proportions of patients
with true disease (Table IV), their assessments were
HOSPITALIZATION
TABLEIV
EmergencyRoom PhysicianPredictionof Bacteremiaand
Endocarditis
Physician
Prediction
(% likely to have)
Number of
Patients with
Bacteremia
O-20%
21-40%
41-60%
Percent of
Prediction
Category
Actually with
9% (7/79)f
5% (2/44)t
29% (10/35)t
61-80%
81-100%
18x(5/28)7
29% (5/17)t
29 (loo)*
Total
Endocarditir
-
\Ol”G.J
O-20%
21-40%
41-60%
U-80%
81-100%
2 (13)*
Total
16 (100)’
II,
)/,olO11,115553
015
pa
4% (6/ 140)*
8% (2/25)t
21% (5/24)f
9%(1/11)~
50% (2/4)*
LmlL~~~c..
r Values rn parentheses are number of pabents wrth bacteremra rn the specific risk
qurntile/number of all patients rn specrfic risk quintile.
t Values rn parentheses are number of patients with endocarditis in the specrfic risk
qurntile/number of all patients in specrfic rusk quintrle.
IN FEBRILE
IVDUs
/ SAMET
ET AL
warfarin, Pneumocystis carinii pneumonia (PCP)
with a negative chest radiograph but positive sputum
stain, PCP with a negative chest radiograph treated
presumptively with a full course of therapy, hip fracture, small bowel obstruction, coma, pelvic inflammatory disease, pneumonia with a negative chest radiograph but with evidence of consolidation (egophony)
on physical examination, hepatitis with ascites, biliary
colic, new-onset seizures, disseminated gonococcal infection, and multiple trauma.
The following diagnoses were designated as minor
illness, in addition to presumed viral syndrome, streptococcal pharyngitis, uncomplicated hepatitis B, and
no established diagnosis with spontaneous resolution
of fever (values in parentheses are the number of patients involved, if two or more): heroin withdrawal (4),
sinusitis (3), adenopathy (2), acquired immunodeficiency syndrome with no other source of fever (2),
vaginitis, venous insufficiency, buttock hematoma,
prostatitis, superficial thrombophlebitis,
secondary
syphilis, otitis externa, acute gouty arthritis, uncomplicated pyelonephritis (without vomiting, leukocytosis), mild possible pelvic inflammatory disease, chronic nonhealing right middle lobe infiltrate, gonococcal
urethritis, and urinary tract infection.
ACKNOWLEDGMENT
fraught with error. In particular, physician assessments were too insensitive to provide the basis of the
hospitalization decision. This finding confirms the
previous experience in a small physician cohort (n =
40) 171.
In conclusion, the need for hospitalization is apparent at presentation in the majority of febrile IVDUs.
Although we found three clinical or laboratory features associated with infrequent occult major illness, it
is unlikely that these or other clinical tests currently
available at initial patient evaluation will be adequate
to guide triage of febrile IVDUs. Development of a
rapid assay for bacteremia may improve triage decisions for these patients and reduce unnecessary hospitalizations. At the present time, the hospitalization
decision in the febrile IVDUs rests primarily on the
need for patient follow-up after blood culture results
are known. If 24- and 48-hour follow-up is not possible,
then hospitalization of the febrile IVDU remains a
wise policy.
APPENDIX: MAJOR AND MINOR ILLNESSES
The following diagnoses did not meet the criteria for
major illness but were considered to require hospitalization (values in parentheses are the number of patients involved, if two or more): deep venous thrombosis (4), septic arthritis (4), pyelonephritis (3), acute
renal insufficiency (2) (new elevation of serum creatinine greater than 1.5 mg/dL [130 rmol/L]), cryptococcal meningitis (2), altered mental status (2), bleeding
diathesis (hematocrit = 21%) in a patient receiving
We thank the house staff in the Departments of Medrcine, Emergency Medicine.
and Surgery at Boston City Hospital for their active parbcipabon in this study. We
also thank Donald Craven, M.D., John Noble, M.D.. Kenneth Freedberg, M.D., and
John Rrch, M.D., for therrcntical revrew of themanuscnpt,
andTerry Field, M.P.H.,
for her assrstance with the statrstrcal analyses.
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