Prolonged grief disorder: Psychometric validation of criteria proposed for DSM-V and ICD-11

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Prolonged Grief Disorder: Psychometric Validation of
Criteria Proposed for
DSM-V
and
ICD-11
Holly G. Prigerson
1,2,3
*, Mardi J. Horowitz
4
, Selby C. Jacobs
5
, Colin M. Parkes
6
, Mihaela Aslan
7
,
Karl Goodkin
8,9
, Beverley Raphael
10
, Samuel J. Marwit
11
, Camille Wortman
12
, Robert A. Neimeyer
13
,
George Bonanno
14
, Susan D. Block
1,2,3
, David Kissane
15
, Paul Boelen
16
, Andreas Maercker
17
,
Brett T. Litz
18,19,20
, Jeffrey G. Johnson
21
, Michael B. First
21
, Paul K. Maciejewski
1,2
1Department ofPsychiatry, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America, 2Center for Psycho-Oncology and PalliativeCare Research, Dana
Farber Cancer Institute, Boston, Massachusetts, United States of America, 3Harvard Medical School Center for Palliative Care, Boston, Massachusetts, United States of America,
4Department of Psychiatry, University of California Schoolof Medicine, San Francisco, California, United Statesof America, 5Department of Psychiatry,Yale University School of
Medicine, New Haven, Connecticut, United States of America, 6St. Christopher’s Hospice, Sydenham, and St. Joseph’s Hospice, Hackney, England, 7Department of Internal
Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America, 8Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai
Medical Center, Los Angeles, California, United States of America, 9Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of
California at Los Angeles, Los Angeles, California, United States of America, 10Department of Population Mental Health and Disasters, University of Western Sydney Medical
School, New South Wales, Australia, 11Department of Psychology, University of Missouri, St. Louis, Missouri, United States of America, 12Department of Psychology, State
University of New York at Stony Brook, New York, United States of America, 13 Department of Psychology, The University of Memphis, Memphis, Tennessee, United States of
America, 14Department of Counseling and Clinical Psychology, Teachers College, Columbia University, New York, New York, United States of America, 15 Department of
Psychiatry and Behavioral Sciences, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America, 16Department of Clinical and Health Psychology,
Utrecht University, Utrecht, The Netherlands, 17 Department of Clinical Psychology, University of Zu
¨rich, Zu
¨rich, Switzerland, 18 Veterans Affairs Boston Healthcare System,
Boston, Massachusetts, United States of America, 19 National Center for PTSD, Boston, Massachusetts, United States of America, 20 Boston University School of Medicine,
Boston, Massachusetts, United States of America, 21 Department of Psychiatry, Columbia University, New York, New York, United States of America
Abstract
Background:
Bereavement is a universal experience, and its association with excess morbidity and mortality is well
established. Nevertheless, grief becomes a serious health concern for a relative few. For such individuals, intense grief
persists, is distressing and disabling, and may meet criteria as a distinct mental disorder. At present, grief is not recognized
as a mental disorder in the DSM-IV or ICD-10. The goal of this study was to determine the psychometric validity of criteria for
prolonged grief disorder (PGD) to enhance the detection and potential treatment of bereaved individuals at heightened risk
of persistent distress and dysfunction.
Methods and Findings:
A total of 291 bereaved respondents were interviewed three times, grouped as 0–6, 6–12, and 12–
24 mo post-loss. Item response theory (IRT) analyses derived the most informative, unbiased PGD symptoms. Combinatoric
analyses identified the most sensitive and specific PGD algorithm that was then tested to evaluate its psychometric validity.
Criteria require reactions to a significant loss that involve the experience of yearning (e.g., physical or emotional suffering as
a result of the desired, but unfulfilled, reunion with the deceased) and at least five of the following nine symptoms
experienced at least daily or to a disabling degree: feeling emotionally numb, stunned, or that life is meaningless;
experiencing mistrust; bitterness over the loss; difficulty accepting the loss; identity confusion; avoidance of the reality of
the loss; or difficulty moving on with life. Symptoms must be present at sufficiently high levels at least six mo from the
death and be associated with functional impairment.
Conclusions:
The criteria set for PGD appear able to identify bereaved persons at heightened risk for enduring distress and
dysfunction. The results support the psychometric validity of the criteria for PGD that we propose for inclusion in DSM-V and
ICD-11.
Please see later in the article for the Editors’ Summary.
Citation: Prigerson HG, Horowitz MJ, Jacobs SC, Parkes CM, Aslan M, et al. (2009) Prolonged Grief Disorder: Psychometric Validation of Criteria Proposed for DSM-
Vand ICD-11. PLoS Med 6(8): e1000121. doi:10.1371/journal.pmed.1000121
Academic Editor: Carol Brayne, University of Cambridge, United Kingdom
Received March 10, 2008; Accepted June 25, 2009; Published August 4, 2009
Copyright: ß2009 Prigerson et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: HGP was supported by National Institute of Mental Health grants MH56529 and MH63892, and National Cancer Institute grant CA106370. PKM was
supported by NIH grant NS044316. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: MBF received consultant fees over the past 5 years from Roche, Corcept, Wyeth, Cephalon, Astra-Zeneca, Shire, GSK, and Eli Lilly for
preparing diagnostic interviews and/or conducting diagnostic trainings at investigator meetings.
Abbreviations: 2-PL, two-parameter logistic; DIF, differential item functioning; DSM-IV,Diagnostic Statistical Manual of Mental Disorders, 4th Edition; GAD,
generalized anxiety disorder; ICD-10,International Statistical Classification of Diseases and Related Health Problems; ICG-R, Inventory of Complicated Grief—Revised;
IIF, item information function; IRM, item response model; IRT, item response theory; MDD, major depressive disorder; PG, prolonged grief; PGD, prolonged grief
disorder; PTSD, posttraumatic stress disorder; SCID, Structured Clinical Interview for DSM-IV; WPS, Widowed Persons Service; YBS, Yale Bereavement Study.
* E-mail: Holly_Prigerson@dfci.harvard.edu
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Introduction
Bereavement is a universal experience to which most individuals
adequately adjust. Nevertheless, numerous studies have shown
that bereaved individuals have higher rates of disability and
medication use than their nonbereaved counterparts [1–7], and
are themselves at heightened risk of death [8–11]. The excess
morbidity and mortality is likely to be concentrated in a grief-
stricken few. The challenge has been to identify vulnerable
bereaved individuals so that interventions could reduce their risk
of adverse outcomes.
Following a major loss, such as the death of a spouse, a
noteworthy minority of bereaved individuals experiences ‘‘a
clinically significant behavioral or psychological syndrome or
pattern that occurs in an individual and that is associated with
present distress or disability’’ [12]. These are the requirements for
meeting the definition of a mental disorder in the Diagnostic
Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) [12].
Nevertheless, the DSM-IV excludes grief as a disorder on the
grounds that it is ‘‘an expectable and culturally sanctioned
response to a particular event’’ [12]. In the DSM-IV, bereavement
is classified as a ‘‘V’’ code; that is, an ‘‘other condition that may be
a focus of clinical attention’’ [12]. Similarly, in the International
Statistical Classification of Diseases and Related Health Problems, Tenth
Revision (ICD-10) [13], bereavement is classified as a ‘‘Z’’ code,
which refers to ‘‘occasions when circumstances other than a
disease or injury result in an encounter or are recorded by
providers as problems or factors that influence care’’ [14].
The DSM-IV and ICD-10 focus on the distinction between
‘‘normal’’ grief and major depressive disorder (MDD), but neglect
to acknowledge that grief, per se, may be pathological. Studies
have shown that symptoms denoting complicated, or prolonged,
grief are distinguishable from symptoms of uncomplicated grief
[15–18] and that only the former are associated with significant
impairment [15–25]. The aim of the present study is to validate
criteria for prolonged grief disorder (PGD) proposed for inclusion
in DSM-V and ICD-11. The justification for validating criteria for
PGD and proposing inclusion in DSM-V and ICD-11 lies in the
distinctive phenomenology, etiology, course, response to treat-
ment, and adverse outcomes associated with PGD symptoms.
PGD symptomatology—variously referred to as ‘‘complicated
grief’’ (CG) [15,17–20,22,25–28], ‘‘traumatic grief’’ (TG)
[21,23,24,29], and complicated grief disorder (CGD) [22]—have
repeatedly been shown to be different from the symptoms of other
DSM-IV and ICD-10 disorders (e.g., MDD). For example, in
studies of bereaved individuals from a variety of different
countries, yearning loads highly on the grief factor, but not on
depression or anxiety factors, whereas sadness loads highly only on
a depression factor, and feeling nervous and worried loads highly
only on an anxiety factor [15,19,20,26,28–31]. A study of negative
cognitions among bereaved individuals found that being over-
whelmed by the loss (i.e., ‘‘If I would fully realize what the death of
___ meant, I would go crazy’’) was a cognition specific to PGD,
but not depression [32]. The distinction between the symptoms of
grief and depressive symptoms found in bereaved individuals has
also been shown in advanced cancer patients [30] and caregivers
of nursing home residents with advanced dementia [31,33].
The set of risk factors and clinical correlates of PGD includes a
history of childhood separation anxiety [34], controlling parents
[35], parental abuse or death [36], a close kinship relationship to
the deceased (e.g., parents) [37,38], insecure attachment styles
[39], marital supportiveness and dependency [39,40], and lack of
preparation for the death [41,42]—all suggesting that attachment
issues are salient in creating a vulnerability to PGD. For example,
we find that feelings of emotional dependency on the dying patient
is associated with symptoms of grief, but not with symptoms of
depression in patient caregivers [39] and recently bereaved
persons [40]. We have also found that childhood separation
anxiety uniquely predicts PGD, but not MDD, posttraumatic
stress disorder (PTSD), or generalized anxiety disorder (GAD)
following bereavement later in life [34]. The identified grief
symptoms have been shown not to relate to the changes of
electroencephalographic (EEG) sleep physiology associated with
MDD [43]. Most recently, a functional magnetic resonance
imaging (fMRI) study by O’Connor et al. [44] has demonstrated
that only patients with complicated grief showed reward-related
neural activity in the nucleus accumbens in response to reminders
of the deceased. The nucleus accumbens cluster ‘‘was positively
associated with yearning, but not with time since death,
participant age, or positive/negative affect’’ [44]. Taken together,
these findings suggest distinct clinical correlates of grief symptoms
relative to depressive symptoms.
PGD symptoms also demonstrate incremental validity in that they
are associated with elevated rates of suicidal ideation and attempts,
cancer, immunological dysfunction, hypertension, cardiac events,
functional impairments, hospitalization, adverse health behaviors,
and reduced quality of life in adults [19,21,24,25,30,45] and in
children and adolescents [46], after controlling for the effects of
depression and/or anxiety. In a Swedish sample of bereaved parents
4–9 y after the death of their child from cancer, parents with
unresolved grief were at risk for long-term mental and physical
impairments, increased health service use, and increased sick leave
over and above the effects of depression and anxiety [47]. These
findings highlight the enduring nature of bereavement-related distress
and disability, and the societal consequences of unresolved grief.
The course and response to treatment of PGD differ from those of
normal grief [48,49] and depression [48–52]. Tricyclic antidepres-
sants alone and with interpersonal psychotherapy have proven
ineffective relative to placebo for the reduction of PGD symptoms
[50–52]. By contrast, randomized, controlled trials of psychother-
apy designed specifically for PGD have demonstrated efficacy for
PGD symptom reduction [53,54]. The efficacy of a PGD-specific
treatment highlights the benefits of an accurate diagnosis.
Although the results above suggest that symptoms of grief
constitute a syndrome that operationally defines a mental disorder,
no agreed upon and tested diagnostic algorithm for PGD exists.
Psychiatrists such as Lindemann [55], Parkes [56], Raphael [57],
Horowitz [22], and Jacobs [58] have noted the suffering associated
with intense and/or chronic mourning. Nevertheless, no explicit
criteria developed from a consensus process have been assessed and
then tested in a community-based sample of bereaved individuals.
The absence of explicit and agreed upon (i.e., standardized) criteria
for PGD has hampered efforts for its inclusion in the DSM and ICD
systems. The establishment of standardized criteria for PGD would
enable researchers to investigate the prevalence, risk factors,
outcomes, neurobiology, prevention, and treatment of this disorder.
Such criteria would also assist clinicians in the accurate detection
and treatment, as well as reimbursement for treatment, of PGD.
As a first step toward the development of consensus criteria for
PGD, we convened a group of experts in bereavement, mood and
anxiety disorders, and psychiatric nosology to review the evidence
justifying the development of diagnostic criteria [23]. Following
the panel’s conclusion that the evidence merited the development
of a diagnostic algorithm for a grief disorder, they engaged in a 2-d
workshop culminating in the formulation of consensus criteria. A
preliminary testing of the criteria analyzed the most relevant, yet
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incomplete, data available at the time—data lacking the full set of
proposed consensus criteria and an independent rating to diagnose
PGD. Results of this preliminary report supported the sensitivity
and specificity of the initially proposed algorithm [23].
Here, we report the results of a field trial designed specifically to
develop and evaluate diagnostic algorithms for PGD based on
symptoms proposed by the consensus panel. The aim of this study
was to establish the psychometric validity of, and propose criteria
for, a new syndrome, PGD.
Methods
Sample
Data were obtained for the Yale Bereavement Study (YBS) (e.g.,
[25,34–36,40,41,45,48]), a National Institute of Mental Health
(NIMH)-funded (MH56529) investigation to conduct a field trial of
consensus criteria [23] for PGD. The YBS was a longitudinal,
interview-based study of community-dwelling bereaved individuals
in Connecticut. The YBS was approved by the institutional review
boards (IRBs) of all participating sites and was in accordance with
Health Insurance Portability and Accountability Act (HIPAA)
regulations.
Recruitment involved locating family survivors bereaved 6 mo
or less found on contact lists of the Greater Bridgeport/Fairfield
American Association of Retired Persons (AARP) Widowed
Persons Service (WPS), a community-based outreach program.
The contact lists provided names of recently widowed persons who
a volunteer widowed person would contact to describe the WPS
program. Fewer than 5% of those contacted participated in any
WPS program; the lists included those approached, but not
necessarily actively involved in, the WPS. A comparison between
vital records and the WPS contact list revealed that WPS listings
provide an unbiased and comprehensive ascertainment of recently
widowed people. Participants were also recruited from pastoral
care offices in the New Haven area. Participants from this
alternative source (117/317 = 37.0% of study participants) did not
differ significantly from WPS participants (200/317 = 63.0% of
study participants) on gender, income, education, race/ethnicity,
or quality of life, but they were younger than WPS participants
(p= 0.05) (mean age = 59.7 y, standard deviation [SD] = 16.4
versus 63.2 y, SD = 11.5 y, respectively).
Of the 575 potential participants contacted, 317 (55.1%) agreed
to participate. Reasons for nonparticipation included reluctance to
participate in research (n= 11; 4.3%); being too busy (n= 46; 17.8%)
or too upset (n= 27; 10.5%); ‘‘doing fine’’ (n= 23; 8.9%); ‘‘not
interested’’ or ‘‘no reason’’ (n= 145; 56.2%); and ‘‘other’’ reasons
(n= 6; 2.3%). Nonparticipants were more likely to be male (37.2%
versus 25.9%, p,0.001) and older (mean age = 68.8 y versus 61.7 y,
p,0.001) than participants. Written informed consent was obtained
from all study participants. Interviews were conducted by master’s
degree–level interviewers trained by YBS investigators (HGP, SCJ).
Interviewers were required to demonstrate nearly perfect agreement
(k$0.90) with the YBS investigators for diagnoses of psychiatric
disorders (e.g., MDD) and PGD in five pilot interviews before being
permitted to interview for the study.
The 317 YBS participants were interviewed at baseline an
average of 6.3 mo (SD= 7.0 mo) post-loss. First follow-up inter-
views (n= 296, 93.4% of participants) were completed an average of
10.9 mo (SD = 6.1 mo) post-loss; second follow-up interviews
(n= 263, 83.0% of participants) at an average of 19.7 mo
(SD = 5.8 mo) post-loss. The average age of participants was
61.8 y (SD = 18.7 y), most were female (73.7%), white (95.3%),
educated beyond high school (60.4%), and spouses of the deceased
(83.9%). Data were restructured such that assessments were
grouped into more uniform post-loss time periods (0–6 mo, 6–
12 mo, and 12–24 mo post-loss). A single assessment within each
time period was randomly selected for each participant to remove
cases in which two assessments occurred within the same interval.
The present study sample (n= 291; 91.8% of YBS participants)
included participants interviewed at least once within 12 mo post-
loss and who provided sufficient information to evaluate PGD.
Assessment of Symptoms of PGD
Symptoms of PGD were assessed with the rater version of
the Inventory of Complicated Grief—Revised (ICG-R) [34–
36,40,41,45,59], a structured interview designed to assess a wide
variety of potential PGD symptoms, using five-point scales to
represent increasing levels of symptom severity. The ICG-R is a
modification of the Inventory of Complicated Grief (ICG) [15]
that includes all the symptoms proposed by the consensus panel
[23] and additional symptoms enabling the testing of alternative
diagnostic algorithms [22]. The ICG-R and the original ICG have
both proven highly reliable (e.g., [15,25,36,41]) (e.g., Cronbach’s
a.0.90; test-retest reliability coefficient = 0.80 [15]) and to possess
criterion validity [15,21,24,25,45]. Based on prior work [23,59], a
symptom was considered present if rated 4 or 5, and absent if rated
1, 2, or 3, on its five-point scale. Interviewers were trained by
project investigators (HGP, SJC) to provide a separate evaluation
of whether or not the participant represented a current ‘‘case’’ of
PGD.
Assessment of Psychiatric Disorders
Psychiatric disorders were assessed using the Structured Clinical
Interview for DSM-IV (SCID Non-Patient Version) [60]. The
rater-administered SCID assessed criteria for DSM-IV anxiety
disorders (GAD, PTSD, and panic disorder [PD]) and mood
disorders (MDD). Research has supported the reliability and
validity of SCID diagnoses [61].
Assessment of Additional Outcomes
Positive responses to one or more of the four Yale Evaluation of
Suicidality [25] screening questions were categorized as having
suicidal ideation. The Established Populations for Epidemiological
Studies of the Elderly [62] measured performance of activities of
daily living [63] and physical functioning [64]. Individuals with at
least ‘‘some difficulty’’ with at least one of the 14 tasks (e.g., bathing)
were considered functionally impaired in order to make the measure
sensitive to impairment in a highly functioning sample. Scores less
than 5 (below the lowest quartile) on the Medical Outcomes Short-
Form [65] indicated inferior quality of life.
Analyses and Results
The psychometric validation of diagnostic criteria for PGD
proceeded through a cumulative series of analyses, with each
phase in the overall analysis having a distinct aim. In Phase 1 of
the analysis, the aim was to limit the set of candidate symptoms for
PGD to those that were informative and unbiased. In Phase 2 of
the analysis, the goal was to construct an objective, reliable, valid
symptom criterion standard for PGD by which to evaluate
alternative diagnostic algorithms for meeting symptom criteria for
PGD. The aim of Phase 3 of the analysis was to identify a specific,
optimum diagnostic algorithm for meeting symptom criteria for
PGD among a large set of candidate algorithms. Phase 4 of the
analysis was designed to evaluate the predictive validity for
temporal subtypes of meeting the optimal symptom criteria for
PGD as an empirical means to inform the specification of a
‘‘timing criterion’’ for the diagnosis of PGD. In Phase 5, the goal
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was to propose a complete set of ‘‘DSM-style’’ diagnostic criteria
based on results of the preceding phases in the analysis. Phase 6 of
the analysis evaluated the predictive validity of the final, complete,
proposed criteria for PGD.
Phase 1: deriving a set of informative, unbiased
symptoms of PGD. IRT [66], item information function (IIF)
analysis, and differential item functioning (DIF) analysis were used
to evaluate candidate symptoms for PGD assessed 0–12 mo post-
loss. IIF analysis was used to evaluate the amount of information
about the prolonged grief (PG) ‘‘attribute’’ (underlying construct)
provided by each of 22 dichotomous candidate symptoms for PGD.
Consistent with the use of IRT to construct a one-dimensional scale
for PG, Cattell’s scree test [67] indicated that grief, as measured by
these 22 symptoms, is one-dimensional. Figure 1 presents item
information functions for these 22 symptoms derived from a two-
parameter logistic (2-PL) item response model (IRM). Within the
framework of IRT, information for a given value of the latent PG
attribute is inversely related to its conditional standard error of
measurement. Greater information implies lower measurement
error, and greater measurement precision, for PG. Six symptoms
with maximum ‘‘peak’’ information less than 20% of that of the
most informative symptom were considered to be relatively
uninformative and removed from further consideration as possible
symptoms for assessing and diagnosing PGD. DIF analysis of
between-group differences in item location parameters was used to
evaluate potential biases in the assessment of the remaining 16
informative, candidate symptoms for PGD with respect to age (less
than 65 y versus greater than or equal to 65 y), gender (male versus
female), education (beyond versus not beyond high school),
relationship to the deceased (spouse versus nonspouse), and time
from loss (0–6 versus 6–12 mo post-loss). Figure 2 displays item
characteristic curves by group, spouse, and nonspouse, for two items
eliminated from consideration as possible symptoms for assessing
and diagnosing PGD due to evidence of DIF using a 16-item 2-PL
IRM. A total of four of 16 informative symptoms were found to be
biased with respect to time from loss, gender, and/or relationship to
the deceased. Table 1 provides a summary of results for these IRT
IIF and DIF analyses of candidate symptoms for assessing and
diagnosing PGD.
The following 12 informative, unbiased ICG-R symptoms were
retained for consideration in a diagnostic algorithm: yearning;
avoidance of reminders of the deceased; disbelief or trouble
accepting the death; a perception that life is empty or meaningless
without the deceased; bitterness or anger; emotional numbness or
detachment from others; feeling stunned, dazed or shocked; feeling
part of oneself died along with the deceased; difficulty trusting
others; difficulty moving on with life; on edge or jumpy; survivor
guilt (Cronbach’s a= 0.82).
Phase 2: deriving a criterion standard for assessing
diagnostic algorithms for symptoms of PGD. In the
Figure 1. Relative item information as a function of the prolonged grief attribute for 22 candidate symptoms for PGD. IRT IIF analysis
of 22 binary candidate symptoms for PGD was performed using a 2-PL IRM. This figure displays item information as a function of the PG attribute for
all 22 of these symptoms included in this IRM, relative to the maximum information for the most informative symptom, ‘‘inability to care about others
since the death.’’ The horizontal line in the figure represents the standard used to discriminate between 16 informative candidate symptoms retained
for further analysis, and six uninformative candidate symptoms excluded from further analysis (as indicated in Table 1).
doi:10.1371/journal.pmed.1000121.g001
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absence of an established, standard method for diagnosing PGD,
there was a need to develop a criterion standard for ‘‘caseness’’ of
PGD by which the performance of alternative algorithms for PGD
could be evaluated. As a potential criterion standard for PGD, the
rater determination of caseness of PGD had the advantage of
reflecting experienced clinical judgment. However, rater
assessments of PGD were subjective, were made without explicit
reference to any established criteria, and were not always
consistent with more objective, reliable assessments of PG as
measured with IRM scores for the underlying PG attribute (i.e.,
raters assign PGD to some individuals with low scores, and not to
others with high scores, on the PG attribute scale). It was decided
that a criterion standard for caseness should be informed by
clinical judgment, but should also be a function of PG symptom
severity. Dichotomized IRM PG attribute scores, informed by
rater assessments of PGD, would provide objective, reliable, valid
criterion standard diagnoses for PGD.
Scores from a 2-PL IRM for PG based on the 12 informative,
unbiased symptoms were used to order individuals in terms of PG
symptom severity. Agreement between rater and minimum-
threshold PG attribute assessments of caseness of PGD was
maximized to establish an optimum minimum threshold for
caseness of PGD along this IRM scale. As illustrated in Figure 3,
PGD ‘‘cases’’ determined by a minimum-threshold ‘‘cutoff’’ PG
attribute score of approximately 1.0 had the greatest agreement
(k= 0.68) with cases determined by the rater assessments. An IRM
PG attribute score above this minimum-threshold cutoff value
became our criterion standard for PGD caseness.
Phase 3: identifying an optimal diagnostic algorithm for
symptoms of PGD. Based on consensus opinion of the
previously mentioned expert panel [23], and confirmed by
results showing yearning was the most common (68.3%) and
most informative (I
max
= 0.94) of the 12 items and provided the
maximum information and the lowest degree of severity
(H
max
=20.53), yearning was specified as a mandatory
symptom. The analyses then sought to determine the number
and combination of the remaining 11 (nonmandatory) symptoms
in addition to yearning that would yield the most efficient (i.e.,
optimum balance between sensitive and specific) diagnosis for
PGD with respect to our criterion standard. Combinatorics [68],
the branch of mathematics that studies the number of different
ways of arranging sets, was used to enumerate alternative sets of
nonmandatory symptoms to construct alternative, candidate
diagnostic algorithms for meeting the symptom criterion for
PGD. Each of these diagnostic algorithms was specified in terms
one common, mandatory symptom, yearning, a specific set of n
other, nonmandatory symptoms, and some minimum number of
nonmandatory symptoms within this set, k, which one must have
to satisfy the symptom criterion for PGD. A total of 4,785 of these
algorithms for meeting the symptom criterion for PGD were
enumerated [i.e., the sum of (11 choose n6(n23) for n=5,6,7,8,
9, where (11 choose n) represents the number of ways of choosing n
of 11 nonmandatory symptoms, nM{5, 6, 7, 8, 9}, and (n23)
represents the number of values of kM{3, …, n21}, considered for
a given value of n] and subsequently evaluated with respect to the
criterion standard. Algorithms requiring yearning and as few as
three of five, and as many as eight of nine, additional symptoms
were considered.
Figure 4 displays results for a subset of the diagnostic algorithms
considered. Each data point in Figure 4 represents the sensitivity
and specificity of a unique diagnostic algorithm. The optimal,
most efficient algorithm included yearning and at least five of the
nine following symptoms: avoidance of reminders of the deceased;
disbelief or trouble accepting the death; a perception that life is
Figure 2. Differential item functioning for two biased symptoms. IRT DIF analysis of candidate symptoms for PGD was performed with
respect to age (less than 65 y versus greater than or equal to 65 y), gender (male versus female), education (beyond versus not beyond high school),
relationship to the deceased (spouse versus nonspouse), and time from loss (0–6 mo versus 6–12 mo post-loss). This figure displays IRT item
characteristic curves (ICCs) for two symptoms found to differ with respect to relationship to the deceased (spouse versus nonspouse). The horizontal
error bar associated with each ICC represents the standard error in the estimate of the location of the ICC with respect to the PG attribute. Of 16
informative symptoms examined, four symptoms displayed DIF and were excluded from further analysis (as indicated in Table 1).
doi:10.1371/journal.pmed.1000121.g002
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empty or meaningless without the deceased; bitterness or anger
related to the loss; emotional numbness; feeling stunned, dazed, or
shocked; feeling part of oneself had died along with the deceased;
difficulty trusting others; difficulty moving on with life (sensitivi-
ty = 1.00; specificity = 0.99; positive predictive value = 0.94; neg-
ative predictive value = 1.00). The optimal algorithm displayed
convergent validity with respect to the previously proposed
diagnostic algorithm for PGD (k= 0.68) and the rater diagnosis
of PGD (k= 0.68), and discriminant validity with respect to other
mood and anxiety disorders (Wwith MDD = 0.36; PTSD = 0.31;
GAD = 0.17).
Phase 4: evaluating the predictive validity for temporal
subtypes of PGD. Three subtypes of PGD were defined in
terms of patterns of meeting diagnostic criteria for PGD at 0–6
and 6–12 mo post-loss: acute = meeting the symptom criteria for
PGD at 0–6 mo, but not at 6–12 mo, post-loss; delayed = meeting
the symptom criteria for PGD at 6–12 mo, but not at 0–6 mo,
post-loss; and persistent = meeting the symptom criteria for PGD
both at 0–6 and at 6–12 mo post-loss. In Table 2, we see that the
acute temporal specification was not significantly associated with
any of the examined outcomes evaluated 12–24 mo post-loss.
Delayed was significantly (p,0.001) associated with suicidal
ideation and poor quality of life. Persistent was significantly
(p,0.01) associated with mental disorders (MDD, PTSD, or
GAD), suicidal ideation, and poor quality of life. Delayed or
persistent was significantly (p,0.05) associated with psychiatric
disorders (MDD, PTSD, or GAD), suicidal ideation, functional
disability, and poor quality of life. These results indicate that
diagnoses of PGD before 6 mo post-loss do not effectively identify
bereaved individuals at risk of long-term dysfunction, whereas
delayed and persistent temporal subtypes do.
Phase 5: proposing criteria for PGD. To reduce further
the likelihood of a false-positive diagnosis, a timing criterion
(Criterion D) was added to specify that a diagnosis not be made
until at least 6 mo have elapsed since the death. This would
exclude the acute cases described above in which a person with
initially high levels of grief in the first few months experiences
declines in grief intensity at and beyond 6 mo post-loss. To be
conservative in our diagnosis of PGD, we also added a
requirement that the symptomatic distress be associated with
functional impairment (Criterion E).
The ultimate consensus criteria set for PGD proposed for DSM-
Vand ICD-11 appears in Table 3. Diagnoses of PDG based on
these criteria demonstrated convergent validity with respect to the
diagnostic algorithm proposed by Horowitz et al. [22] (k= 0.69)
and the rater diagnosis of PGD (k= 0.52), and discriminant
validity with respect to other mood and anxiety disorders (Wwith
MDD = 0.48; PTSD = 0.23; GAD = 0.21).
Table 1. Evaluation of candidate symptoms for PGD (n= 287).
Candidate PGD Symptom Rate (%) IRT IIF Analysis
a
IRT DIF Analysis
b
I
maxc
H
maxd
Sex Spouse Time
Inability to care about others since the death 6.6 1.00 1.70 Biased
Yearning for, or preoccupation with, deceased 68.3 0.94 20.53
Life empty, meaningless without deceased 34.8 0.93 0.46
Stunned, dazed, or shocked about the death 19.2 0.58 1.07
Trouble accepting the death 32.7 0.56 0.56
Feel part of you died along with the deceased 37.6 0.49 0.41
Difficulty moving on with life without deceased 18.1 0.46 1.17
Sense of numbness since the death 13.6 0.46 1.41
Future holds no meaning without the deceased 14.6 0.38 1.40 Biased
Hard for you to trust others since the death 7.0 0.36 2.00
Avoid reminders of deceased 12.5 0.26 1.67
Survivor guilt 8.4 0.25 2.04
Loneliness as a result of the death 57.1 0.24 20.26 Biased Biased Biased
Lost sense of security since the death 23.3 0.23 1.09 Biased
Bitterness or anger related to the death 25.1 0.23 1.01
On edge, jumpy since the death 11.5 0.20 1.88
Envious of others who have not lost someone close 7.0 0.16 2.51
Memories of the deceased upset you 22.6 0.14 1.31
Drawn to places, things associated with deceased 31.0 0.14 0.86
Disturbed sleep since the death 23.3 0.13 1.28
The death has shattered your world view 28.6 0.13 1.02
Lost sense of control since the death 16.4 0.10 1.93
Relatively uninformative (I
max
,0.20) or biased symptoms are displayed in bold font. All others are informative, unbiased symptoms and were retained for further
analysis.
a
IRT IIF analysis was performed using all 22 symptoms, showing 16 to be informative (I
max
$0.20).
b
IRT DIF analysis was restricted to 16 relatively informative symptoms, showing four to be biased.
c
I
max
represents maximum item information relative to that of ‘‘inability to care about others….’’
d
H
max
represents location of I
max
for the item along the PG attribute scale.
doi:10.1371/journal.pmed.1000121.t001
Criteria for Prolonged Grief Disorder
PLoS Medicine | www.plosmedicine.org 6 August 2009 | Volume 6 | Issue 8 | e1000121

Phase 6: evaluating the predictive validity of the proposed
criteria for PGD. Among those not concurrently meeting DSM
criteria for MDD, PTSD, or GAD (n= 215), PGD diagnoses
assessed 6–12 mo post-loss (7/215 = 3.3%) were significantly
(p,0.01) associated with psychiatric diagnoses (MDD, PTSD, or
GAD), suicidal ideation, functional disability, and low quality of
life 12–24 mo post-loss (see Table 4). Among those concurrently
meeting DSM criteria for MDD, PTSD, or GAD (n= 27), PGD
diagnoses 6–12 mo post-loss (10/27 = 37.0%) were significantly
associated with psychiatric diagnoses (MDD, PTSD, or GAD) at
12–24 mo post-loss (relative risk = 2.38, p= 0.043).
Discussion
Our results indicate that PGD meets DSM criteria for inclusion as
a distinct mental disorder on the grounds that it is a clinically
significant form of psychological distress associated with substantial
disability. Findings from this field trial of consensus criteria for PGD
confirm prior work demonstrating the distinctiveness of the
symptoms of PGD (e.g., [15,18–20,22,26,27,29–31]). The proposed
diagnostic algorithm for PGD has quite incomplete overlap with
established mental disorders commonly occurring among recently
bereaved individuals (MDD, PTSD). Further, our results indicate
that in the absence of mental disorders found in DSM-IV (e.g.,
MDD), the proposed algorithm for PGD predicts substantial
dysfunction—impairment missed by the current psychiatric diag-
nostic system. Because standard treatments for depression have
not always proven effective for the reduction of PGD [49–52],
whereas psychotherapies designed specifically to ameliorate symp-
toms of PGD have demonstrated efficacy [53,54], there exists a
need for the accurate detection and specialized treatment of PGD.
Although the YBS data may appear unrepresentative of the
general US population, a comparison with US Census 2005
[48,69,70] data reveals similarities with the US widowed popula-
tion. For example, the YBS sample was 73.7% female compared
with 80.7% of the US widowed population and 95.3% white
compared with 80.2% of the US widowed population. Like the
population of US widowed individuals, the YBS sample is
disproportionately female, white, and elderly. Compared with the
US widowed population, however, the study participants were
somewhat younger, more likely to be male, and a higher proportion
was white and better educated. Future research should replicate the
analyses in older, nonwhite, less-educated widowed samples.
Although there is a need to confirm the results in nonwidowed
bereaved persons, we consider widowhood following an older
spouse’s death from natural causes to be the prototypical case of
bereavement. In the US, 84% of all deaths occur among
individuals who are 65 y and over [71], and less than 7% of
deaths are from unnatural causes (e.g., unintentional injuries,
assault, suicide) [72]. Given that in later life one’s spouse/partner
is the person most likely to be adversely affected by the death, a
sample of older widowed persons surviving the death of a spouse
from natural causes provides an important sample in which to
develop and test criteria for a bereavement-related mental
Figure 3. Agreement between rater diagnoses and dichotomized prolonged grief attribute score diagnoses of PGD as a function of
cutoff PG attribute score for diagnosis. Dichotomized IRM PG attribute scores provide objective, reliable criterion standard diagnoses for PGD.
This figure illustrates how rater diagnoses were used to establish a minimum-threshold cutoff PG attribute score for diagnosis of PGD (i.e., PG
attribute score$minimum-threshold cutoff PG attribute score). An optimal cutoff PG attribute score of 1 maximized agreement between rater
diagnoses and dichotomized IRM PG attribute score diagnoses of PGD.
doi:10.1371/journal.pmed.1000121.g003
Criteria for Prolonged Grief Disorder
PLoS Medicine | www.plosmedicine.org 7 August 2009 | Volume 6 | Issue 8 | e1000121

disorder. In addition, the symptoms retained were only those
proven to be invariant across gender, time from loss, and kinship
groups (e.g., IRT DIF analysis removed items that performed
differently based on whether or not the deceased was a spouse) and
a distinct advantage of IRT is that it produces generalizable results
regardless of sample characteristics [66]. Thus, the results are
expected to be generalizable to most bereaved individuals. The
generalizability of the results reported here is not intended to deny
the value in further confirmation of the findings in nonwidowed,
more traumatically bereaved, younger, less-educated, more male,
and ethnically and geographically diverse samples, and the need to
examine longer-term bereavement outcomes (e.g., 3, 5, and 10 y
post-loss).
Although the sample size may appear modest, the study was
designed and appropriately powered to evaluate a wide range of
potential diagnostic criteria (i.e., the first phases of the analyses
used the full sample [n= 291]). The YBS PGD prevalence rate was
obtained in a resilient community sample in which rates of mental
Figure 4. Alternative diagnostic algorithms for meeting symptom criteria for PGD. Each data point in this figure represents the
performance, in terms of sensitivity and specificity with respect to a criterion standard for PGD, of a unique ‘‘DSM-style’’ diagnostic algorithm for
meeting symptom criteria for PGD. Each algorithm is specified in terms of one common, mandatory symptom, yearning, a specific set of nother,
nonmandatory symptoms, and some minimum number of nonmandatory symptoms within this set, k, which one must have to satisfy the symptom
criterion for PGD. Based on the current data, the optimal, most efficient algorithm requires having yearning and at least five of the following nine
symptoms: avoidance of reminders of the deceased; trouble accepting the death; a perception that life is empty or meaningless without the
deceased; bitterness or anger related to the loss; emotional numbness; feeling stunned, dazed or shocked; feeling that part of oneself died along with
the deceased; difficulty in trusting others; and difficulty moving on with life.
doi:10.1371/journal.pmed.1000121.g004
Table 2. Mental health and functional consequences of meeting symptom criteria for PGD by temporal subtype.
Outcome (12–24 Mo Post-Loss) Relative Risk for Outcome Associated with PGD Temporal Subtype:
Acute
(15/172 [8.7%])
a
Delayed
(6/172 [3.5%])
a
Persistent
(12/172 [7.0%])
a
Delayed or persistent
(28/242 [11.6%])
b
RR 95% CI RR 95% CI RR 95% CI RR 95% CI
MDD, PTSD, or GAD 1.54 (0.20–11.98) 3.86 (0.55–27.22) 11.58*** (4.41–30.43) 10.19*** (4.72–21.99)
Suicidal ideation (n= 171:241)
c
1.97 (0.64–6.09) 4.93*** (1.92–12.64) 3.29* (1.28–8.43) 4.44*** (2.62–7.53)
Functional disability (n= 170:240)
c
0.51 (0.18–1.45) 1.54 (0.73–3.25) 1.40 (0.79–2.50) 1.65** (1.16–2.34)
Poor quality of life (n= 168:238)
c
0.76 (0.20–2.89) 3.78*** (1.93–7.40) 2.58* (1.23–5.41) 3.17*** (2.03–4.95)
Acute = meeting symptom criteria at 0–6 mo, but not at 6–12 mo, post-loss; Delayed = not meeting symptom criteria at 0–6 mo, but meeting symptom criteria at 6–
12 mo post-loss; Persistent = meeting symptom criteria at 0–6 and 6–12 mo post-loss.
a
The denominator included those assessed at both 0–6 and 6–12 mo post-loss.
b
The denominator included all those assessed at 6–12 mo post-loss, regardless of the 0–6-mo post-loss assessment.
c
Sample sizes (n) varied due to missing data. The first number in the parenthesis represents nfor those assessed at both 0–6 and 6–12 mo post-loss, the second number
after the colon represents nfor those assessed at 6–12 mo post-loss regardless of the 0–6-mo post-loss assessment.
*p,0.05; **p,0.01; ***p,0.001.
CI, confidence interval; RR, relative risk.
doi:10.1371/journal.pmed.1000121.t002
Criteria for Prolonged Grief Disorder
PLoS Medicine | www.plosmedicine.org 8 August 2009 | Volume 6 | Issue 8 | e1000121

illness were lower than those that have been reported in other
bereavement studies (e.g., 9% for MDD compared with 22% in
the first year of widowhood) [73]. The only analyses limited by
statistical power would have been the predictive validity analyses.
Here, we found large, statistically significant effects suggesting the
conservative nature of our estimates of functional impairment
associated with PGD.
Study participants may have been less distressed than study
nonparticipants. Given the relatively low rates of MDD in the YBS
sample and that 10.5% refused participation in the YBS due to
being ‘‘too upset,’’ the prevalence rate of PGD reported here may
be an underestimate. In addition, our statistical power to detect
significant effects of PGD on mental health and functional
impairment outcomes would be lower than would have been the
case if more distressed nonparticipants with PGD had been
included in the study sample.
Conclusion
This report provides psychometric validation of a diagnostic
algorithm for PGD. Although further validation work will, no
doubt, be needed, we consider the evidence sufficient to justify
PGD’s serious consideration for inclusion in DSM-V and ICD-11.
In light of the recent concerns about financial conflicts of interest
in psychiatric research, especially that which involves pharmaceu-
tical manufacturers, it is noteworthy that this study was federally
funded by the US NIMH, and no part of this research was
sponsored by producers of a potential therapeutic remedy for
PGD.
Although most bereaved individuals will eventually adapt to the
loss of a significant other more or less successfully, a significant,
identifiable minority will experience chronic and disabling grief. A
PGD diagnosis has the potential to enhance the detection and
effective treatment of a substantial cause of morbidity among
persons who have experienced the loss of a significant other. The
diagnosis and treatment of PGD offers the promise of reducing the
personal and societal toll taken by prolonged grief.
Author Contributions
ICMJE criteria for authorship read and met: HGP MJH SCJ CMP MA BR
SJM CW KG RAN GB SDB DK PB AM BL JGJ MF PKM. Agree with the
manuscript’s results and conclusions: HGP MJH SCJ CMP MA BR SJM
CW KG RAN GB SDB DK PB AM BL JGJ MF PKM. Designed the
experiments/the study: HGP MJH PKM. Analyzed the data: PKM HGP
MA. Collected data/did experiments for the study: HGP PKM. Enrolled
patients: HGP. Wrote the first draft of the paper:HGP PKM. Contributed to
the writing of the paper: HGP MJH SCJ CMP BR SJM CW RAN GB SDB
DK PB AM JGJ MF PKM. Contributed to the conceptualisation: BR.
Contributed items to the scale to assess PGD: CW. Assisted with
interpretation of the results and contributed to the writing of the final
manuscript, and reviewed and approved the contributions of others: RAN.
Table 3. Criteria for PGD proposed for DSM-V and ICD-11.
Category Definition
A. Event: Bereavement (loss of a significant other)
B. Separation distress: The bereaved person experiences yearning (e.g., craving, pining, or longing for the deceased; physical or emotional sufferingas
a result of the desired, but unfulfilled, reunion with the deceased) daily or to a disabling degree.
C. Cognitive, emotional, and behavioral symptoms: The bereaved person must have five (or more) of the following symptoms experienced daily or to
a disabling degree:
1. Confusion about one’s role in life or diminished sense of self (i.e., feeling that a part of oneself has died)
2. Difficulty accepting the loss
3. Avoidance of reminders of the reality of the loss
4. Inability to trust others since the loss
5. Bitterness or anger related to the loss
6. Difficulty moving on with life (e.g., making new friends, pursuing interests)
7. Numbness (absence of emotion) since the loss
8. Feeling that life is unfulfilling, empty, or meaningless since the loss
9. Feeling stunned, dazed or shocked by the loss
D. Timing: Diagnosis should not be made until at least six months have elapsed since the death.
E. Impairment: The disturbance causes clinically significant impairment in social, occupational, or other important areas of functioning (e.g., domestic
responsibilities).
F. Relation to other mental disorders: The disturbance is not better accounted for by major depressive disorder, generalized anxiety disorder, or
posttraumatic stress disorder.
doi:10.1371/journal.pmed.1000121.t003
Table 4. Mental health and functional impairment at 12–
24 mo post-loss associated with PGD among those not
meeting DSM criteria for MDD, PTSD, or GAD at 6–12 mo
post-loss (n= 215).
Outcome
(12–24 Mo Post-Loss)
PGD Diagnosis
(6–12 Mo Post-Loss)
Yes
(3.3%)
No
(96.7%) RR 95% CI
MDD, PTSD, or GAD 28.6% 3.4% 8.49** (2.14–33.72)
Suicidal ideation
a
(n= 214) 57.1% 10.1% 5.63*** (2.64–12.03)
Functional disability
a
(n= 213) 71.4% 35.9% 1.99** (1.20–3.29)
Poor quality of life
a
(n= 210) 83.3% 14.7% 5.67*** (3.48–9.22)
a
Sample sizes (n) varied due to missing data.
*p,0.05; **p,0.01; ***p,0.001.
CI, confidence interval; RR, relative risk.
doi:10.1371/journal.pmed.1000121.t004
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PLoS Medicine | www.plosmedicine.org 9 August 2009 | Volume 6 | Issue 8 | e1000121

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Editors’ Summary
Background. Virtually everyone loses someone they love
during their lifetime. Grief is an unavoidable and normal
reaction to this loss. After the death of a loved one, bereaved
people may feel sadness, anger, guilt, anxiety, and despair.
They may think constantly about the deceased person and
about the events that led up to the person’s death. They
often have physical reactions to their loss—problems
sleeping, for example—and they may become ill. Socially,
they may find it difficult to return to work or to see friends
and family. For most people, these painful emotions and
thoughts gradually diminish, usually within 6 months or so of
the death. But for a few people, the normal grief reaction
lingers and becomes increasingly debilitating. Experts call
this complicated grief or prolonged grief disorder (PGD).
Characteristically, people with PGD have intrusive thoughts
and images of the deceased person and a painful yearning
for his or her presence. They may also deny their loss, feel
desperately lonely and adrift, and want to die themselves.
Why Was This Study Done? PGD is not currently
recognized as a mental disorder although it meets the
requirements for one given in the American Psychiatric
Association’s Diagnostic and Statistical Manual of Mental
Disorders,4
th
Edition (DSM-IV) and in the World Health
Organization’s International Statistical Classification of
Diseases and Related Health Problems,10
th
Edition (ICD-10).
Before PGD can be recognized as a mental disorder (and
included in DSM-V and ICD-11), bereavement and mental-
health experts need to agree on standardized criteria for
PGD. Such criteria would be useful because they would allow
researchers and clinicians to identify risk factors for PGD and
to find ways to prevent PGD. They would also help to ensure
that people with PGD get appropriate treatments such as
psychotherapy to help them change their way of thinking
about their loss and re-engage with the world. Recently, a
panel of experts agreed on a consensus list of symptoms for
PGD. In this study, the researchers undertake a field trial to
develop and evaluate algorithms (sets of rules) for
diagnosing PGD based on these symptoms.
What Did the Researchers Do and Find? The researchers
used ‘‘item response theory’’ (IRT) to derive the most
informative PGD symptoms from structured interviews of
nearly 300 people who had recently lost a close family
member. These interviews contained questions about the
consensus list of symptoms; each participant was
interviewed two or three times during the two years after
their spouse’s death. The researchers then used
‘‘combinatoric’’ analysis to identify the most sensitive and
specific algorithm for the diagnosis of PGD. This algorithm
specifies that a bereaved person with PGD must experience
yearning (physical or emotional suffering because of an
unfulfilled desire for reunion with the deceased) and at least
five of nine additional symptoms. These symptoms (which
include emotional numbness, feeling that life is meaningless,
and avoidance of the reality of the loss) must persist for at
least 6 months after the bereavement and must be
associated with functional impairment. Finally, the
researchers show that individuals given a diagnosis of PGD
6–12 months after a death have a higher subsequent risk of
mental health and functional impairment than people not
diagnosed with PGD.
What Do These Findings Mean? These findings validate a
set of symptoms and a diagnostic algorithm for PGD.
Because most of the study participants were elderly
women who had lost their husband, further validation is
needed to check that these symptoms and algorithm also
apply to other types of bereaved people such as individuals
who have lost a child. For now, though, these findings
support the inclusion of PGD in DSM-V and ICD-11 as a
recognized mental disorder. Furthermore, the availability of a
standardized way to diagnose PGD will help clinicians
identify the minority of people who fail to adjust
successfully to the loss of a loved one. Hopefully, by
identifying these people and helping them to avoid the
onset of PGD (perhaps by providing psychotherapy soon
after a death) and/or providing better treatment for PGD, it
should now be possible to reduce the considerable personal
and societal costs associated with prolonged grief.
Additional Information. Please access these Web sites via
the online version of this summary at http://dx.doi.org/10.
1371/journal.pmed.1000121.
NThis study is further discussed in a PLoS Medicine
Perspective by Stephen Workman
NThe Dana Farber Cancer Institute has a page describing its
Center for Psycho-oncology and Palliative Care Research
NThe UK Royal College of Psychiatrists has a leaflet on
bereavement (in English, Welsh, Urdu, and Chinese)
NThe US National Cancer Institute also has information
about coping with bereavement for patients and health
professionals (in English and Spanish)
NMedlinePlus has links to other information about bereave-
ment (in English and Spanish)
NThe Journal of the American Medical Association has a
patient page on abnormal grief
NHarvard Medical School provides a short family health
guide about complicated grief
NInformation on DSM-IV and ICD-10 is available
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PLoS Medicine | www.plosmedicine.org 12 August 2009 | Volume 6 | Issue 8 | e1000121