Paper
A NEW SMARTPHONE APPLICATION TO PREDICT HEMATOLOGIC
ACUTE RADIATION SYNDROME BASED ON BLOOD CELL COUNT
CHANGES—THE H-MODULE APP
Matthäus Majewski,1 Marco Rozgic,2 Patrick Ostheim,1 Matthias Port,1 and Michael Abend1
Abstract—Treatment regimens for acute radiation syndrome have
Downloaded from http://journals.lww.com/health-physics by BhDMf5ePHKbH4TTImqenVIiuKVF7qTxsAaM1kdR/ot/BxSsGcAvgg5mHcDl0FgGP on 07/04/2020
been improved over the past years. The application of appropriate
therapy relies on rapid and high-throughput tests ideally con-
ducted in the first 3 d after a radiation exposure event. We have
examined the utility of blood cell counts (BCCs) 3 d post irradia-
tion to predict clinical outcome for hematologic acute radiation
syndrome (HARS). The BCCs and HARS severity information
originated from data available in the System-for-Evaluation-
and-Archiving-of-Radiation Accidents-based-on-Case-Histories
(SEARCH). We found an almost complete discrimination of unex-
posed (HARS score H0) vs. irradiated individuals during model
development and validation (negative predictive value > 94%)
when using BCC data for all 3 d. We also found that BCC data in-
creased the correct prediction of exposed individuals from day 1 to
day 3. We developed spreadsheets to calculate the likelihood of cor-
rect diagnoses of the worried-well, requirement of hospitalization
(HARS 2-4), or development of severe hematopoietic syndrome
(HARS 3-4). In two table-top exercises, we found the spreadsheets
were confusing and cumbersome, so we converted the spreadsheets
into a smartphone application, named the H-module App, designed
for ease of use, wider dissemination, and accommodation of co-
morbidities in the HARS severity prediction algorithm.
Health Phys. 119(1):64–71; 2020
Key words: accidents, nuclear; blood; health effects; radiation effects
INTRODUCTION
PHYSICIANS AND health care providers require prompt guid-
ance for diagnosis and therapeutic interventions for radiation
injury patients after radiological or nuclear events (e.g., ter-
rorist attacks, nuclear power plant accidents, or use of an im-
provised nuclear device). Physical examination of patients
1
Bundeswehr Institute of Radiobiology, Munich, Germany. 2Helmut
Schmidt University, Hamburg, Germany
For correspondence contact: Michael Abend, Bundeswehr Institute of
Radiobiology, Neuherbergstr. 11, 80937 Munich, Germany, phone: +49 89
992 692 2280 or email: michaelabend@bundeswehr.org.
The authors declare no conflicts of interest.
(Manuscript accepted 11 November 2019)
0017-9078/20/0
Copyright © 2020 Health Physics Society
DOI: 10.1097/HP.0000000000001247
64
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and basic laboratory tests [blood cell counts (BCC)] of
lymphocytes, granulocytes, and thrombocytes are universally
available and integrate the extent of irradiation (total or par-
tial body) and individual response of each patient. Diagnostic
guidance and treatment protocols for acute health effects after
absorption of high radiation doses have been established
(Friesecke et al. 2001) and updated (Friesecke et al. 2001;
Gorin et al. 2006). The Medical Treatment Protocols for
Radiation Accident Victims (METREPOL) is a resource
for physicians treating acute radiation syndrome (ARS)
patients. Hematologic changes, such as the development
of severe immune deficiency due to lymphocytopenia
and granulocytopenia or bleeding due to thrombocytope-
nia, represent some of the challenges in appropriate clin-
ical management of hematologic ARS (HARS). Patient
outcomes are improved when treatment decisions benefit
from early diagnosis (within the first 3 d post-irradiation).
For instance, administration of cytokines is recommended
within the first day after exposure. Recently, filgrastim (G-
CSF) was approved for the treatment of patients with HARS
(Hérodin and Drouet 2005; Farese and MacVittie 2015).
In our work, we have focused on several immediate
clinical priorities to be addressed within the first 3 d and be-
fore the onset of disease manifestation: identify the unex-
posed (the “worried well”) to avoid misdirection of limited
clinical resources and differentiate between exposed indi-
viduals who will require hospitalization from those who will
develop a severe hematopoietic syndrome necessitating
specialized intensive therapy. Because BCC measurements
are commonly used and are standard diagnostic tests, we
assessed their possible use in a triage setting after radiation
exposure (Sproull et al. 2017). We measured changes in
peripheral BCCs (namely lymphocytes, granulocytes, and
thrombocytes) over 3 d and correlated them with the resulting
severity category of HARS: H0 (unexposed), H2-4 (exposed),
and H3-4 (highly exposed) (Sproull et al. 2017). For this effort,
we used exposure and clinical case history data from the
System for Evaluation and Archiving of Radiation Accidents
based on Case Histories (SEARCH) that included 70 major
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 H-Module App development c M. MAJEWSKI ET AL.
events like Chernobyl (Friesecke et al. 2000). We developed
a prediction model in spreadsheet form to provide early and
prompt diagnostic predictions and therapeutic recommenda-
tions for the unexposed, the requirement of hospitalization, or
development of severe hematopoietic syndrome.
These models improved the provisional classification
of HARS. We tested this application during a NATO exer-
cise with experts in the field and introduced the spreadsheet
to a medical management class for radiobiology students
with very good results (Dörr et al. 2017; Majewski et al.
2018). We showed that the clinical outcome of radiation in-
jury patients can be rapidly predicted within the first 3 d
post-irradiation using peripheral BCC and our model. How-
ever, we found limitations of versatility in the spreadsheet
version of our “H-module.” For instance, only BCCs from
two consecutive days (e.g., day 1 and day 2 could be added
to the spreadsheet, but not day 2 only), and each day required
an individual spreadsheet, making it confusing and cumber-
some. It was difficult to incorporate other clinical data, such
as acute or chronic infection, and this required additional ma-
nipulation. We sought to improve the H-module spreadsheet
tool for possible mass application in the hands of medical
personnel less familiar with ARS. Large-scale events will
probably overwhelm the capacity of the few trained experts
dealing with radiological or nuclear (RN) events who could
quickly deploy (Coleman et al. 2011). Access to ARS triage
knowledge for responding medical personnel will be critical
to handle a large-scale radiation event, particularly since
physical dosimetry will likely be unavailable. We chose
to focus our H-module improvement efforts on medical
significance and to simplify the application, as this would
most benefit the responding health care providers. So we
transformed the spreadsheet version into a smartphone
application (App). The goal was to provide an H-module
App that (1) was more complete and versatile, (2) had a sim-
ple interface, (3) was easy to distribute, and (4) provided a
link to experts for support and diagnostics after triage.
MATERIALS AND METHODS
Prerequisites originating from previous study
(Port et al. 2017)
Aligned with our previous approach (Port et al. 2017),
hematologic severity scores were organized into the follow-
ing binary clinical outcome categories:
1. H0 vs. H1-4 (never vs. ever radiation exposure);
2. H0-1 vs. H2-4 (none to mild vs. moderate-fatal hemato-
logic damage); and
3. H0-2 vs. H3-4 (none to moderate vs. severe-fatal hema-
tologic damage).
We evaluated BCCs from day 1 post-irradiation for the
lymphocyte, granulocyte, and thrombocyte values individually
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65
(univariate) and combined (multivariate) to discriminate
among the three binary outcome categories (Table 1).
We assessed whether discrimination abilities improved
with the multivariate model vs. the univariate model. For days
2 and 3 post-irradiation, we examined which BCC values from
that same day or which combination of BCCs from previous
days (sequential diagnosis) provided the best model for dis-
criminating the three binary categories. By doing so, we con-
sidered varied scenarios for which BCCs might be available on
different days. For instance, in the first model for day 2, we as-
sumed that BCCs would be available on day 2 only, and in the
second model we assumed BCC availability on days 1 and 2
(sequential diagnostic values, Table 1).
The calculated r square (r2) from these models refers to
the variability explained by the BCC values used in the
model. For instance, an r2 close to 1 suggests an almost
complete separation of both categories. Descriptive statis-
tics and weighting factors for the BCC variables (maximum
likelihood estimates, MLE) as well as P values (chi-square
tests) were calculated. We constructed a classification table
for sensitivity, specificity, and false positive/negative predic-
tive values and calculated a receiver-operator characteristic
(ROC) curve. An area under the ROC curve close to 1 rep-
resents the model’s ability to completely discriminate the bi-
nary categories of HARS severity. The statistical package
SAS, version 9.1.3 (Cary, NC), was used for computations.
The independent validation of these models generated
positive and negative predictive values (PPV and NPV, re-
spectively), which were implemented into the spreadsheet
screens (for details see Port et al. 2017), as well as the newly
developed H-module App. With the most recent validation,
we also addressed the impact of acute/chronic infections/
diseases on our predictions (Port et al. 2017). Acute infec-
tions examined comprised gastroenteritis, meningitis, herpes
zoster, or acute infection of unclear origin, among others.
Chronic infections included, for example, hepatic encepha-
lopathy, hepatitis, colitis ulcerosa, or liver cirrhosis. These
diseases are associated with a granulocytosis resembling a
HARS but are missing a lymphocyte depletion that discrim-
inates them from a HARS. This explains that the PPV for the
prediction of more severe HARS in the binary category was
altered considerably in those models comprising granulocyte
counts for prediction of the HARS. Next, we converted our
validated models and prediction values to easily understand-
able Excel spreadsheets. BCCs were input into all three predic-
tion models for each day, and the predicted HARS severity
scores were shown on the screen (Fig. 1). Multiple HARS se-
verity scores originating from these models were aggregated
into one outcome to avoid contradictory predictions (for
details see Port et al. 2017). Corresponding therapeutic de-
cisions, based on HARS severity diagnosis, were also
shown. We found the predictions, in particular PPV, were
strongly influenced by the presence of acute infection or
 66

Table 1. Model characteristics used for discriminating binary hematologic severity score categories on days 1–3 post-irradiation.
H 0 vs. 1−4 H 0−1 vs. 2−4 H 0−2 vs. 3−4
time after p-values p-values p-values
irradiation (d) Model Variables MLE (Chi Square) r-square ROC area Variables MLE (Chi Square) r-square ROC area Variables MLE (Chi Square) r-square ROC area

1 intercept 3.4953 <.0001 intercept 3.3751 <.0000 intercept −3.8245 <.0000

lymphocytes −2.8365 <.0001 0.6905 0.937 lymphocytes −2.9125 <.0001 0.6989 0.939 granulocytes 0.5372 <.0001 0.5738 0.912
2 intercept −0.9051 0.2418 intercept 0.1501 0.8297 intercept −0.5500 0.3617
lymphocytes −2.7399 <.0001 lymphocytes −2.4989 <.0001 granulocytes 0.3868 <.0001
1 granulocytes 0.8931 <.0001 0.8610 0.981 granulocytes 0.5076 <.0001 0.8134 0.969 lymphocytes −2.0239 <.0001 0.7464 0.952
3 intercept 1.3259 0.2425 intercept 1.5908 0.1483 intercept 1.1819 0.2821
lymphocytes −2.6708 <.0001 lymphocytes −2.1287 <.0001 granulocytes 0.8697 <.0001
granulocytes 1.0343 <.0001 granulocytes 0.8706 <.0001 lymphocytes −1.8271 <.0001
thrombocytes −0.0135 0.0107 0.8706 0.983 thrombocytes −0.0153 0.0019 0.8431 0.978 thrombocytes −0.0194 0.0002 0.8444 0.981
1 intercept 1.5368 0.0089 intercept 2.2677 0.0003 intercept 2.7729 <.0001
lymphocytes −3.6983 <.0001 lymphocytes −3.7882 <.0001 lymphocytes −3.3406 <.0001 0.7085 0.940
2nd day 2nd day 2nd day
granulocytes 0.7586 <.0001 0.8131 0.967 granulocytes 0.5076 0.0008 0.8124 0.969
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2nd day 2nd day

2 intercept 0.4489 0.6716 intercept 0.4774 0.6035 intercept −0.1454 0.8969
2
lymphocytes −2.8576 0.0007 lymphocytes −5.6453 <.0001 lymphocytes −5.5248 <.0001
2nd day 2nd day 2nd day
granulocytes 1.0533 0.0001 granulocytes 0.8964 0.0002 0.9283 0.995 granulocytes 0.7316 0.0020 0.9109 0.992

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1st day 1st day 1st day
lymphocytes −2.7805 0.0149 0.9137 0.993
1st day
1 intercept 1.2508 0.0442 intercept 3.4583 <.0000 intercept 2.7168 <.0001
lymphocytes −4.0019 <.0001 lymphocytes −3.7535 <.0001 0.7944 0.965 lymphocytes −3.8260 <.0001 0.7515 0.960
3rd day 3rd day 3rd day
granulocytes 0.7296 <.0001 0.8418 0.977
July 2020, Volume 119, Number 1

3rd day
3
2 intercept 1.3656 0.0367 intercept 2.5722 0.0028 intercept −0.9468 0.4387
lymphocytes −4.4345 <.0001 lymphocytes −6.4853 <.0001 lymphocytes −5.1316 <.0001
2nd day 2nd day 2nd day
granulocytes 0.7565 <.0001 0.8683 0.980 granulocytes 0.8131 0.0009 0.9074 0.992 granulocytes 0.8062 <.0001 0.9036 0.992

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3rd day 3rd day 1st day
a
Weighting factors for all variables (maximum likelihood estimate, MLE) as well as p-value (chi-square statistic), refer to their discrimination significance. The explained variability (r2) and discrimination ability (area
under the receiver-operator characteristic [ROC] curve) indicating one of the two binary categories enable a comparison among the different models. Sequence of models refers to the discrimination significance with
most predictive single variables followed by combinations on day 1 postirradiation. For days 2 and 3 postirradiation, only two models are shown. The first model refers to blood cell counts (BCCs) available from one day
only (day 2 or 3). The second model assumes BCCs to be available from several days (sequential diagnosis). The most predictive models are shown.
 H-Module App development c M. MAJEWSKI ET AL. 67

Fig. 1. The figure to the left (a) shows a screen shot of the earlier version of the H-module using an Excel spread sheet. An excel macro translates
the mathematical models into diagnostic and therapeutic recommendations. After the blood cell counts (per nl) are entered for, e.g., day 1 postir-
radiation, three different models automatically develop predictions indicating a particular binary HARS severity category comprising combinations
of hematologic severity scores (e.g. H0 versus H1-4). Hematologic severity scores are categorized as no radiation exposure (H0), or low, medium,
severe or fatal (H1–H4, respectively) hematologic damage caused by absorbed radiation dose. These results are summarized in one statement ad-
dressing diagnostic and therapeutic issues (Actions). The tables in the middle panel (b) reflect 16 different spreadsheets, because in Excel these
many spreadsheets were required for entering blood cell counts on days 1–3 and considering the infection status. In the H-module App all these
spreadsheets are integrated into one entry interface (c). Abbreviation: PPV, positive predictive value for prediction of the higher HARS category.
inflammatory disease. This co-morbid acute disease infor- Since the user interface and the calculation parts are separated,
mation necessitated an additional spreadsheet. it becomes fairly easy to implement new models. The logic
follows the ordering of the layers. Suppose a new model
Algorithms generated for the H-module App needed to be added to the existing model. As a first step, the
Logistic regression models. The H-module App con- conditions the model is trying to capture are defined as an if-
tains four layers, and each layer sets the stage for the next statement; e.g., the new model is valid for day 2 after irradia-
step/layer as outlined in the insert to the right of Fig. 2. tion and requires lymphocytes and granulocytes of the first
The fourth layer provides a shortened (overview) and coded day and lymphocytes of the second day. The resulting state-
version of models reflected in Table 1. The first digit reflects the ment would then simply read:
day, and the second is the model number (see Table 1). For in-
if (day1 == true & day2 == true & day3 == false){
stance, model 1–2 consists of lymphocytes and granulocytes
var hars_day2v1 = -1;
combined, and this model is used for HARS degree prediction
if(lym1 !==0 & lym2 !==0 & gran1 !==0){
on day 1 when thrombocyte counts are missing. In case the
hars_day2v1 = myNewModel(lym1, gran1, throm1,
thrombocyte counts are known, another model (1–3) will be
lym2, gran2, throm2, infection);
used automatically. The concert of the 21 models, depend-
}
ing on the BCCs availability at certain days for diagnosis,
}
is reflected in the third layer of the H-module App (Fig. 2).
(Abbreviations: lym, lymphocytes; gran, granulocytes;
Programming. The user interface of the H-module throm, thrombocytes).
App was created with Qt-Quick. The calculations according Note: The stacked blocks are to make sure the conditions
to the third and fourth layer were written in Java Script. on the days after irradiation and the corresponding BCCs are
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68 Health Physics July 2020, Volume 119, Number 1

Fig. 2. The H-module App consists of four layers and each layer provides the basis for the next step/layer (insert with overlapping layers to the
right). The layers are labeled (1–4) and shown in full on the left and below the insert.

separated. Next, the model itself, in this case myNewModel, Enter the computation and decision block, which needs
has to be defined as a function. Because all models are logistic only small modifications. The correct input variables must
regression models, the function that is to be written follows a be used at the corresponding position (e.g., lymd1), and
strict structure, which is explained in the following: the desTreeNew function has to conform with the number
Provide the inputs for the intercepts, coefficients of days post irradiation; here it is day 2.
(alpha, beta, gamma), and cut-offs for the identified function myNewModel(lymd1, grand1, thromd1, lymd2,
model for the binary classifications “H0 vs. H1-4,” grand2, thromd2, infection){
“H0-1 vs. H2-4,” and “H0-2 vs. H3-4.” The ordering for .
the cut-off’s in the cutOffs array is first <=, then >= for .
the corresponding classification. .
var prob_valueh0vsh1_4 = intercept[0] +alpha[0]
function myNewModel(lymd1, grand1, thromd1, lymd2, *lymd2 + beta[0]*grand1 +gamma[0]*lymd1;
grand2, thromd2, infection){ prob_valueh0vsh1_4 = Math.exp(prob_valueh0vsh1_4);
var intercept = [i1,i2, i3]; prob_valueh0vsh1_4 = prob_valueh0vsh1_4/(1+prob_
var alpha = [a1, a2, a3]; valueh0vsh1_4);
var beta = [b1, b2, b3];
var gamma = [g1, g2, g3]; var prob_valueh01vsh2_4 = intercept[1] +alpha[1]
// the cutOffs are <= then >= *lymd2 + beta[1]*grand1 +gamma[1]*lymd1;
var cutOffs = [c11, c12, c21, c22, c31, c32]; prob_valueh01vsh2_4 = Math.exp(prob_valueh01vsh2_4);
. prob_valueh01vsh2_4 = prob_valueh01vsh2_4/(1
. +prob_valueh01vsh2_4);
. var prob_valueh02vsh3_4 = intercept[2] +alpha[2]
} *lymd2 + beta[2]*grand1 +gamma[2]*lymd1;
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 H-Module App development c M. MAJEWSKI ET AL. 69

prob_valueh02vsh3_4 = Math.exp(prob_valueh02vsh3_4);
prob_valueh02vsh3_4 = prob_valueh02vsh3_4/(1+prob_
valueh02vsh3_4);
var hars_day2 = desTreeNew(cutOffs,
prob_valueh0vsh1_4,
prob_valueh01vsh2_4,
prob_valueh02vsh3_4,
2,infection);
return(hars_day2)
} the next model at level 3 will be recruited to further narrow
So, basically, only the parameters of the identified model
have to be provided, as the subsequent computation and deci-
sion making follow a strict protocol that needs only slight
changes. This allows for easy addition of further models.
The resulting HARS severity prediction is given (a) for
each day and (b) aggregated, taking all information into ac-
count. The final allocation of a HARS category based on
the three binary HARS prediction models in the App results
from a decision tree as depicted in Fig. 3. Our intent for the
decision tree was to apply the models sequentially, not in
parallel as was done in the spreadsheet. In this way, we de-
fined the clinical outcomes more precisely; e.g., a H0 or
H1 category instead of a range H0-1. The decision tree
worked as follows: at each of three decision levels, a pre-
viously identified binary clinical outcome model depen-
dent on the inputs was used. Arrows originating from
the left or the right side of the binary model refer to the
corresponding binary HARS-category. For instance, if
an arrow originates from the left side of the “H0 vs.
H1-4” binary clinical outcome (level 1), the corresponding
model will choose the left side of the formulation resulting
in H0 HARS severity degree. The prediction will end
here with the identification of a specific HARS sever-
ity degree.
If the arrow originates from the right side of the same
model, it refers to the right-sided set of HARS categories,
namely H1-4. At this point, the second binary clinical out-
come model is conscripted (H0-1 vs. H2-4, level 2). If the
higher HARS severity category was predicted (H2-4), then
the specific HARS severity degree. Assuming the model
predicts H3-4, then the final HARS severity degree will
be H3-4, which was identified based on the predictions of
H1-4 at level 1, H2-4 at level 2, and H3-4 at level 3. An ar-
row originating from the center indicates that the model was
unable to classify one or the other clinical outcome cate-
gory. For instance, if no classification of the model “H0
vs. H1-4” at level 1 was possible, then the program will au-
tomatically proceed to the next model (H0-1 vs. H2-4) at
level 2. Assuming no classification could be done here as
well, the model “H0-2 vs. H3-4” at level 3 will be con-
sidered. No classification at this level finally leads to a
“H0-4” prediction meaning that the H-module App
could not classify the entered BCC data.
According to METREPOL, HARS severity categories
indicate therapeutic recommendations. These recommenda-
tions are provided in the App, and they correspond to the ap-
proach we used in the spreadsheet version.
Our new method yields a more precise final model
(HARS-category), aggregating the various levels as we described.

Fig. 3. Shown is the decision tree used in the H-module App. At each of three decision levels, a previously identified binary clinical outcome
model, depending on the input data, is corresponding to a hematologic acute radiation syndrome (HARS) category. For instance, if an arrow orig-
inates from the left side of the “H0 versus H1-4” binary clinical outcome, the corresponding model selected the left side of the formulation resulting
in H0 HARS severity degree. If the arrow originates from the right side of the same model, it refers to the right-sided HARS category, namely H1-4.
An arrow originating from the center indicates that the model could not distinguish either clinical outcome category.
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70 Health Physics
To estimate the performance of the new approach, we employed
the previously determined PPVand NPV values and constructed
intervals from these values.
Following work by Port et al. (2017), the infection status
was also considered. So we further evaluated infection co-
morbidity in estimating the corresponding PPV and NPV.
In addition to the computation of the HARS category,
the App offers a function to store a patient database. Patients
can be added or removed, and their respective BCCs can be
added when they become available.
RESULTS
The H-module App consists of a start screen that
graphically depicts the analysis steps beginning with the in-
put data of, for example, granulocyte and lymphocyte
counts. These are modeled into a ROC curve and converted
into clinically relevant information regarding diagnosis and
therapy (first layer, Fig. 2). After a few seconds, the start
screen is replaced by the main screen called “Quick Data
Entry” (second layer, Fig. 2). Here, the user adds BCC per
nl for the first three days after exposure depending on when
the data were available. After adjusting for known infection
via the button placed below the upper table, the input is
completed. Depressing the “evaluate” button will generate
the output. The output comprises (1) HARS severity score,
(2) diagnosis, and (3) clinical/therapeutic recommenda-
tions. These are visualized below the table (layer 2, Fig. 2).
Clicking the button “Save To Database” will result in
an upload to a patient database (Fig. 1). Built-in icons for
brief explanations make the main window self-explanatory
(Fig. 1). The “Help” button provides expert help contacts,
background information, and references.
DISCUSSION AND CONCLUSION
We took advantage of a real-case history database
(SEARCH) to obtain blood cell counts of radiation patients,
primarily originating from the Chernobyl accident (Friesecke
et al. 2000). These persons were followed over time so that a
clinical severity category of HARS could be determined ac-
cording to METREPOL guidelines. Preliminarily we dem-
onstrated the high-throughput approach of a spreadsheet
version of our H-module, which allowed for early predic-
tion of developing HARS as a later sequelae. The prediction
was based on data available within the first 3 d post-
irradiation. It also provided relevant clinical recommenda-
tions on therapeutic decision making for radiation injury
patients. To our knowledge, this approach was based on
the largest database available and included 519 persons
with 729 BCC in order to predict clinical outcomes. The
spreadsheet version was successfully used in an international
NATO exercise (Dörr et al. 2017). There the goal was to
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July 2020, Volume 119, Number 1
determine HARS severity category and hospitalization
recommendations from prodromal symptoms (e.g., vomiting,
diarrhea, erythema) and changes in BCC using the spreadsheet
version of the H-module (Port et al. 2017). This spreadsheet
H-module version was also used for teaching purposes
(Medical Management course on ARS in a Master’s Program
in Radiobiology; Majewski et al. 2018). Masters-level stu-
dents without a background in ARS diagnosis performed as
well as NATO experts in this field (Majewski et al. 2018).
This underscores the potential of our tool and our motivation
to provide an easily implemented interface to handle clini-
cally relevant information, even to non-experts in this
field. However, the spreadsheet H-module version proved
cumbersome during various testing exercises, and we real-
ized improvements could be made, which resulted in the
H-module App. Other than the spreadsheet version, the
H-module App now allows (1) blood cell count inputs from
each combination of all three days or single days after expo-
sure on one screen only instead of using 16 spreadsheets;
(2) input of lymphocytes and granulocytes with and without
thrombocyte counts, because forward deployable BCC in-
struments sometimes do not provide thrombocyte counts;
(3) infectious diseases are considered with a simple click
on the main screen and no new screen is required; and (4)
other standard features of Apps were included (e.g., the im-
plementation of a patient database, employing built-in icons
for brief explanations and a “Help” button providing back-
ground information, references and expert contacts).
Our H-module App complements already existing
software tools such as BAT, WinFRAT or HEMODOSE
(Uniformed Services University; Jayaraman and Sethi
2009; Hu et al. 2015). Our App uses only BCCs to pro-
vide clinically relevant information. BAT, HEMODOSE,
and WinFRAT either provide a dose estimate (BAT,
HEMODOSE) or they provide clinically relevant information
from the individual dose estimate(s) (Forces Radiobiology
Research Institute 2018). We recently discussed some
limitations using radiation dose only and the prediction
of HARS severity in a range between 1–5 Gy (Port et al.
2018). Nevertheless, both approaches (dose estimation
and immediate clinical outcome prediction) are comple-
mentary. Several tabletop exercises have supported the use
of all available tools to provide the best predictions of clin-
ical outcomes (Dörr et al. 2017, Majewski et al. 2018).
In October this year, a workshop was organized in Paris
(StTARS – Software tools for Triage of the Acute Radiation
Syndrome: a practical workshop). This workshop focused
on early and high-throughput ARS diagnostic methods
and the introduction of software tools to accomplish rapid
diagnosis and treatment recommendations. This practical
workshop culminated in an exercise using 191 case histories
for which the participants used the software tools. After the
workshop, all these materials were made available to the
 H-Module App development c M. MAJEWSKI ET AL.
participants for teaching purposes (teach the teacher). This
workshop was very successful: the 31 participants correctly
identified 93–94% of all individuals in need of hospitaliza-
tion and those who will later develop a HARS of different
degree. All participants unanimously recommended to or-
ganize another workshop on this topic, which will be held
in the US [Radiation Emergency Assistance Center/
Training Site (REAC/TS) from 29 September until 2
October 2020].
Our approach bears some advantages and disadvan-
tages. For instance, the performance of the aggregated
model implemented in the H-module App is estimated
by taking the results (PPV and NPV) from the single
models into account. With each step along the decision
tree, the likelihood in favor of a HARS-category should
increase, but it is difficult modeling that. Instead, we pro-
vide a range of all PPV/NPV taken from all single models
considered along the decision tree. That certainly reduces
the precision of the predicted outcome, but it correctly re-
flects the range of the PPV/NPV along the decision find-
ing procedure. Also, PPV and NPV are estimates that
strongly depend on the validation set; they only give a
rough guideline and make sense only for the binary clas-
sifications made with the individual models. However,
the database functionality of the H-module App allows
for the construction of validation sets and a future assessment
of the modified model’s prediction accuracy.
In summary, the H-module App provides an easily ma-
nipulated, intuitive, and high-throughput tool that can be ap-
plied in a preclinical as well as a clinical setting. The App
can be widely distributed, if necessary. It is more compre-
hensive, adaptable, and can be used by persons untrained
in radiation emergency situations.
Acknowledgments—This work was supported by the German Ministry of
Defense.
Design of the H-Module was done by M. Port and M. Abend. Program-
ming of the app was done by M. Rozgic. Testing of the app was done by M.
Majewski. Figures and tables were developed by M. Majewski and P. Ostheim.
The manuscript was written by M. Abend, M. Majewski, and M. Rozgic. All
authors reviewed the manuscript.
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