Support Care Cancer

DOI 10.1007/s00520-015-2843-1

ORIGINAL ARTICLE

An oral care self-management support protocol (OrCaSS)

to reduce oral mucositis in hospitalized patients with acute
myeloid leukemia and allogeneic hematopoietic stem cell
transplantation: a randomized controlled pilot study
Lynn Leppla 1,2 & Sabina De Geest 1 & Katharina Fierz 1 & Barbara Deschler-Baier 2 &
Antje Koller 1,2

Received: 30 November 2014 / Accepted: 6 July 2015

# Springer-Verlag Berlin Heidelberg 2015

Abstract
Introduction Oral mucositis (OM) is a common and debilitating side effect of chemoradiotherapy in patients awaiting allogeneic hematopoietic stem cell transplantation (aHSCT).
Purpose The aim of this pilot RCT was to compare an oral
care self-management support protocol (OrCaSS) to usual
pre-aHSCT care. Feasibility was tested, effect sizes calculated
for OM (primary outcome), and patient adherence was measured (secondary outcome).
Methods Eighteen AML patients awaiting aHSCT and hospitalized between August 2012 and April 2013 were randomized 1:1 to usual care (UCG) and intervention (IG) groups.
The OrCaSS protocol consisted of two sessions of educational
and behavioral interventions, the first delivered 1 week preadmission (T1), the second on admission day (T2). Via field
notes, practicability and acceptability were evaluated to explore the feasibility of intervention and study procedures.
OM data were collected at T1, T2, and daily for 28 days using
the WHO scale. The effect size r was calculated (r less than
0.1small and greater than or equal to 0.3medium). Patients adherence to the protocol was assessed at T1, T2, and
810 days post-HSCT (T3).
Results Research and intervention procedures were feasible.
OM incidence was 100 %. The IGs median highest OM grade
was 2.0 (IQR =2); the UCGs was 3.0 (IQR =2; r=0.1).
* Sabina De Geest
Sabina.DeGeest@unibas.ch
1

Institute of Nursing Science, University of Basel, Bernoullistrasse 28,

CH-4056 Basel, Switzerland

Department of Oncology, Hematology and Stem Cell

Transplantation, University Medical Center Freiburg,
Hugstetterstrasse 55, Freiburg 79106, Germany

Median OM durations were 12 days in the IG and 14 days

in the UCG (r=0.1). OM onset was 2 days later in the IG
than in the UCG (r=0.1). Over the course of the study, patient adherence decreased in both groups.
Conclusions OrCaSS is a promising intervention to delay and
reduce OM. These results can serve to plan a larger RCT.
Keywords Oral mucositis . Oral care protocol . Allogeneic
stem cell transplantation

Introduction
Oral mucositis (OM) is a common and debilitating side effect
of chemotherapy [1, 2], affecting about 75 % of patients undergoing allogeneic hematopoietic stem cell transplantation
(aHSCT) [3, 4]. Caused by cytotoxic therapies, OM presents
as an inflammation of oral mucosa and manifests as erythema
and/or ulceration. While the pathophysiology of OM is still
not entirely understood [2, 5], it results not only in pain and
difficulty eating and drinking but also in prolonged hospital
stays, additional costs, systemic infections, and increased mortality [6].
According to state of the art guidelines published by the
Multinational Association of Supportive Care in Cancer
(MASCC), only three strategies have proven efficacious in
preventing chemotherapy-induced OM: cryotherapy, lowlevel laser therapy (LLLT), and Palifermin (keratinocyte
growth factor) [79]. However, these approaches have limited
viability. Cryotherapy is only effective with short acting chemotherapeutic agents such as bolus 5-fluorouracil and highdose melphalane [10]; LLLT can only be provided in settings
in which clinicians are trained and the required equipment is

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available, and the use of Palifermin was limited to patients

undergoing total body irradiation and autologous HSCT [7].
Despite a lack of high-level evidence, particularly in highrisk groups such as aHSCT patients, the value of basic oral
care in preserving mucosal health, and in reducing the risk of
chemotherapy-induced OM, is commonly accepted [11].
While no consensus exists regarding the details of oral care
protocols [7, 11, 12], it is accepted that all cancer treatment
modalities should include initial and ongoing assessment, OM
self-management, toothbrushing, flossing, and basic oral
rinses [11]. Along with the most useful methods of assessment, the optimal timing and types of rinses remain unclear.
To foster patient adherence, though, guidelines agree that oral
care protocols should be feasible and easily applied, should
include patient education, self-assessment, and should be applied systematically [13].
We performed a thorough analysis of the MASCC guidelines [7, 11, 13, 14] and additional literature to extract the most
suitable and effective nonpharmacological components for the
oral care protocol. Four intervention components showed a
tendency to be efficacious: self-care instructions, pre-aHSCT
dental treatment [1520] instructions regarding tongue and
toothbrushing technique, and the use of foam brushes to reduce pain or bleeding [17, 18, 21].
In most studies, oral care protocols were tested in combination with highly effective components, e.g., cryotherapy,
LLLT, or Palifermin [19, 20]. However, it must be assumed
that there is significant interaction between these highly effective components and oral care. Therefore, to test oral care in
patients who do not receive highly effective components is
indicated.
In summary, research to reduce OM in aHSCT patients via
structured oral care protocols is limited. Therefore, the aim of
this pilot study was to develop an oral care self-management
support protocol (OrCaSS), to test its feasibility, and to estimate its effect sizes regarding incidence, severity, and duration
of OM as the primary outcome and to measure patient adherence as the secondary outcome.

Methods
Design, sample, setting
A randomized controlled pilot study was performed between
August 2012 and April 2013 in the Hematology Department
of the University Medical Center Freiburg, Germany. In our
department, approximately 100 aHSCT are performed annually. AML patients awaiting aHSCT were recruited consecutively if they were at least 18 years of age; able to speak, read,
and write German; free of OM; able to perform oral self-care;
and provided written informed consent. We assumed that patients with second aHSCT were at higher risk to develop OM.

Therefore, a stratified computer-generated permuted blocks

procedure was used to randomize patients 1:1 to the intervention group (IG) or usual care (UCG) (stratum 1: first aHSCT;
stratum 2: second aHSCT). To ensure blinding of the interventionist for the recruitment procedure regarding group allocation, opaque envelopes were prepared by an independent
nurse and only opened by the interventionist at the time of
randomization. Patients were not blinded to the intervention.
Interventions
Usual care
Usual care was based on an implemented nursing guideline
which included daily assessment, provision of an OM information sheet to patients, and a list of oral rinses from which
nurses could choose (e.g., chlorhexidine-containing rinses,
sage infusion, normal saline). Dose and timing of usual care
may have varied considerably (e.g., depending on the staff
nurses workloads and individual experience). Cryotherapy,
Palifermin, and LLLT were not provided due to the previous
mentioned reasons.
The OrCaSS intervention
As recommended by Rycroft-Malone et al., the OrCaSS protocol content was developed based on empirical evidence
[79, 11, 1321], clinical experience, contextual factors, and
patient preferences [22]. Its components were OM assessment
as well as self-assessment, brushing techniques, frequencies of
rinses, and written materials. For self-assessment, patients
were asked to complete the pediatric Oral Mucositis Daily
Questionnaire (OMDQ) and were instructed to use the modified Bass toothbrushing technique [2326]. This questionnaire and brushing technique were chosen largely for their
ease of administration. Self-assessment was used to enhance
adherence and empower patients to adapt their oral care on a
daily basis. By using the OMDQ, patients were asked to selfassess their oral status daily by rating their highest pain level
in the last 24 h and pain they experience while swallowing,
drinking, eating, speaking, or sleeping from 0 = no
pain/restrictions to 4=severe pain/restrictions. Furthermore,
all patients received a laminated measure sheet and were
instructed on how to base the choice and frequency of mouth
rinses on their self-assessment (Table 1).
Contextual factors and patient preferences were added
based on availability of materials and a feasibility check regarding one patient. The application of the intervention was
based on seven behavioral change techniques following the
taxonomy developed by Michie et al. [27]. Michie et al. based
this taxonomy on an extensive literature review to yield the
most effective techniques to support behavior change. For
OrCaSS, we chose the most suitable techniques from this

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Table 1

Literature-based classification and taxonomy of the oral care self-management support protocol (OrCaSS)

Behavior change techniques Michie et al. (2013)

Content of OrCaSS

Educational/cognitive

Information about health consequences

(insufficient oral care)a
Behavioral practice/instructions on how
to perform a behavior a,b

Oral and written information about pathogenesis, impact, complications, and

prevention of oral mucositis tailored to the patients level of knowledge
Recommendation of professional tooth cleaning before admission
Explanation and practice of the German pediatric Oral Mucositis Daily
Questionnaire (OMDQ) as self-assessment instrument for the oral cavity.
Information and practicing how to adapt frequencies of rinses according to the
oral care protocol:
Grade 0: basic rinsing with mineral water, toothbrushing, and tongue
brushing two to three times a day within 30 min, after meals, daily selfassessment
Grade 1: +increase frequency of rinses to four times daily
Grade 2: +increase frequency of rinses to six times daily + alcohol and
chlorhexidine free rinse (Octenidol), pain medication if necessary
Grade 3: +local application of disinfecting solutions (Octenidol), pain
medication if necessary
Grade 4: +rinsing as often as possible, pain medication if necessary
Foam swabs instead of toothbrushes when gum bleeding occurred. Weekly
change of toothbrushes

Behavioral/Counseling

Self-monitoring of outcome of behaviora,b

Demonstration of the behaviora,b
Goal settinga,b
Prompts/cuesb

Instructions for a daily self-assessment of the oral cavity with the OMDQ
Demonstration of the modified Bass tooth brushing technique for at least 90 s
and air-drying of the toothbrush afterward
Goals were set together with the patient according to patients self-assessed
ability to implement recommended strategies into daily life and were
evaluated in the next intervention/assessment
Demonstration how to use reminders such as mobile phone alerts if patients had
difficulties adhering to the protocol

Oral care kita

All patients in the IG were equipped with following supportive materials

1 laminated booklet with OMDQ and oral care protocol
1 bottle sparkling mineral water as basic oral mouthwash
2 bottles chlorhexidine- and alcohol-free antiseptic mouthwash (Octenidol)
5 extra soft tooth brushes
20 foam swabs
1 tooth paste
1 lip balm
5 sugar free chewing gums
1 hourglass-style timer for tooth brushing and rinsing

Was addressed in the first intervention session 1 week before admission to the transplant unit

Was addressed in the second intervention session 1 week later at day of admission

evidence-based taxonomy. For a detailed description of the

relatedness between OrCaSS and the taxonomy, see Table 1.
OrCaSS was provided in two sessions: the first 1 week
before admission and the second on the day of admission
(Fig. 1). Depending on individual patient needs and learning
abilities, each session took 2035 min. All interventions were
performed by the principal investigatora specialized
hemato-oncology nurse trained by a dentist on oral examination and hygiene techniquesfollowing the intervention
protocol.

(baseline=T1), on admission day (T2), and at the expected

time of nadir 810 days after aHSCT (T3). The two intervention sessions were performed at T1 and T2.
Demographic and clinical data
Demographic and clinical data are listed in Table 2. These
were derived at baseline from medical charts or patient interviews as appropriate.
Feasibility

Variables and measurement

Figure 1 provides an overview of the variables used, along
with the timing of data collection and intervention components. Data were collected 1 week before admission

In addition to practicability (i.e., how practical was the intervention in daily practice) and acceptability (i.e., was the intervention well accepted and implemented by the participants),
the OrCaSS protocols feasibility was assessed in view of

Support Care Cancer

Fig. 1 Overview of intervention
and assessment times

Intervention
Session 1

Intervention
Session 2

Intervention
R
Usual care

T2

T1

T3

Day
-14

-7

+10

+20

R = Randomization
T1 = Time one (one week before admission): demographic data, oral mucositis and quality of life
T2 = Time two (at day of admission): Adherence via questionnaire, plaque index
T3 = Time three (days 8,9 or 10 after aHSCT): Adherence via questionnaire, plaque index, quality of life
= OM Assessment first day of chemotherapy until day +20 after aHSCT

recruitment, attrition, and data collection procedures. To monitor recruitment and attrition, the achieved recruitment level
was constantly compared with the level required; patients who
declined were asked for reasons. To assess practicability and
acceptability during data collection, field notes and comments
were recorded by all study personnel (principal investigator
[PI; LL], last author [AK], study nurses). The interviews to
assess the BAASIS yielded additional information about patients implementation and acceptance of the protocol. At the
end of the study, the PI asked all patients open-ended questions to evaluate their experiences of the oral care protocol.
Table 2 Demographic and
clinical characteristics of sample
Age in years, median (IQR)

Oral mucositis
For 28 days starting with the first chemotherapy, OM was measured daily according to the World Health Organization
(WHO) scale [28]. Currently the most widely used assessment
instrument, this measures OM symptoms according to objective, subjective, and functional criteria. Grades range from 0
(no OM), to 1 (soreness and or erythema), 2 (erythema, ulcers,
ability to eat solids), 3 (ulcers, requiring liquid diet), and 4 (oral
alimentation impossible). Collection of the daily OM status
data were performed by blinded study nurses and recorded on
UCG (n=10)

IG (n=8)

Total group

44.0 (22)

47.5 (14.8)

46.5 (15.3)

6 (60.0)
11.5 (4)
24.8 (7.0)

6 (75.0)
13.0 (4)
24.9 (6.1)

12 (66.7)
13.0 (4)
24.8 (5.9)

Gender, n (%)
Female
Education in years, median (IQR)
Body mass index, median (IQR)
Smoking habits, n (%)
No
Number of transplantations, n (%)
First
Second

9 (90.0)

8 (100.0)

17 (94.4)

9 (90.0)
1(10.0)

7 (87.5)
1 (12.5)

16 (88.9)
2 (11.1)

Conditional treatment, n (%)a

BU/CY
FBM
FLUTT

6 (60.0)
3 (30.0)
1 (10.0)

3 (37.5)
4 (50.0)
1 (12.5)

9 (50.0)
7 (38.9)
2 (11.1)

UCG usual care group, IG intervention group, IQR interquartile range

BU/CY=busulfane (3, 2 mg/kg/day 7 to 4)+cyclophosamide (60 mg/kg/day 2 to 1); FBM=fludarabine
(30 mg/m2 /day 7 to 4), carmustine (150 mg/m2 /day 4 to 2), melphalane (110 mg/m2 140 mg/m2 /day 2,
depending on age); FLUTT=fludarabine (30 mg/m2 /day 7 to 4), thiotepa (5 mg/kg/day 7 to 5)

Support Care Cancer

a separate WHO assessment sheet. Despite its wide use, the

psychometric properties of the WHO scale are unknown.
Incidence of OM was rated when patients developed any
score >0 at the WHO scale during the period of measurement.
For maximum severity, the highest score within the study
period was used (OMmax). To assess OM duration, beginning
with onset, all days with scores >0 were counted. Time of OM
onset was dichotomized as Bbefore T3^ or Bafter T3.^
Patient adherence
Patient adherence to OrCaSS was measured via two methods.
First, the German translation of an adapted version of the
Basel Assessment of Adherence to Immunosuppressive Medication Scale (BAASIS) was used at T2 and T3. This five-item
questionnaire was designed to measure immunosuppressive
medication adherence [29] via interviews. For this pilot study,
the BAASIS was adapted by exchanging each occurrence of
Bmedication^ with Boral care^ and shortening the recollection
time span from 4 weeks to 1. Materials used for oral care and
the two dimensionsimplementation (taking, timing, holiday
o f o r a l c a r e or d o s e r e d u c t i o n ) a n d p e r s i s t e n c e
(discontinuation) of oral care over the past weekwere
assessed via yes/no questions. A positive answer to any question implied nonadherence. Patients also rated their adherence
to oral care over the past week on a visual analogue scale with
a score from 0 to 100 %. The BAASIS is validated to measure
adherence to immunosuppressive medication [30, 31].
Second, patient adherence was measured at T1, T2, and T3
with the modified Quigley-Hein Plaque Index (QPI) [32], an
objective measure of reduction or cessation of oral care. At
each measurement point, six predefined teeth were dyed and
examined for plaque coverage. Possible scores ranged from 0
(no plaque) to 5 (plaque covering two thirds or more of the
crown of the tooth). The index value was calculated by dividing the sum of the individual tooth scores by the number of
assessed teeth. The QPI is a widely used instrument; however,
its psychometric properties have yet to be tested. Change
scores were calculated by subtracting QPI scores at T1 from
those at T2 and T3.
Study procedures
All patients scheduled for aHSCT attended routine preparatory meetings with the PI and a physician 1 week before aHSCT.
Those who met inclusion criteria were provided detailed information about the study. After giving their written informed
consent, patients were randomly assigned to either the IG or
the UCG. Once baseline data had been collected patients in
the IG received their first OrCaSS session. The second intervention session was delivered after the T2 data were collected
[33]. In a random intervention session, the last author verified
fidelity of the interventionist with the intervention protocol.

The intervention protocol was used as a checklist; adherence

was more than 95 % and was therefore regarded as sufficient.
Clinicians on the transplant unit were blinded to group
allocation. Daily OM assessment and the adherence assessment at T3 was performed by blinded study nurses. To achieve
a high quality of data collection and study procedures (i.e.,
high inter-rater reliability concerning OM grading), meetings
were held between the study nurses and the interventionist to
discuss assessed WHO ratings. In these meetings, feasibility
issues were also discussed and recorded. Ethical approval was
obtained from the local ethics board.
Data analysis
Data were analyzed using IBM SPSS 21.0 after screening for
out of range values and data inconsistencies. Data entry error
rates were found to be 0.2 %; where possible, identified errors
were corrected. Overall, 3 % of the OM data were missing.
Missing scores were imputed via interpolation where no more
than two consecutive scores were missing [34]. After completing interpolation, OM data were 100 %. There were no missing data in the adherence measures.
Descriptive statistics were applied as appropriate for all
variables. Baseline characteristics, incidence, severity, and duration of OM between the intervention and the usual care
group were compared using the Mann-Whitney U Test. Differences between groups regarding onset of OM were compared by applying Kaplan-Meier analyses. For the primary
outcome OM, the effect size r for nonparametric testing (r=
z/N) was calculated classing r greater than or equal to 0.1 as
a small reduction, r less than 0.1 and greater than or equal to
0.3 as medium, and r less than 0.3 and greater than or equal
to 0.5 as large [34]. Statistical tests were pilot-tested but not
evaluated for statistical significance.

Results
Demographic and clinical characteristics
Patients were comparable regarding baseline characteristics
(Table 2). In each group, one patient required an additional
dose of chemotherapy due to persistent leukemic cells. One
the UCG patientdied at day 7 of measurement (UCG; attrition rate=5.5 %), while the other developed long and severe
OM (IG).
Feasibility of study and intervention procedures
Recruitment, retention, and data collection
During the 8 months of the study, 31 patients were assessed
for eligibility, of whom five failed to meet the inclusion

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criteria. Of the 26 patients who met the inclusion criteria, six

were not approached due to organizational problems (e.g.,
lack of interventionist availability), while two more (10 %)
declined to participate due to a high perceived study burden.
The remaining 18 patients were successfully recruited, with 8
allocated to the IG and 10 to the UCG (Fig. 2; recruitment rate
18/26100=69.2 %; response rate 18/20100=90 %). Data
collection was feasible for both OM and adherence. Three
patients required assistance completing the questionnaires at
T3 because of cognitive difficulties.
Practicability and acceptability of the intervention
The IGs two intervention sessions were scheduled 1 week
apart and were expected to last roughly 25 min each. In three
cases, delayed admission (e.g., because of withdrawal of the
donor) extended the interval between the sessions (median=
15 days). The first session took an average of 30 min (SD=
6 min), the second 22 min (SD=5 min), both of which the
patients considered acceptable. Only two patients (25 %)
Fig. 2 Flowchart of participant
involvement

managed to schedule appointments for professional dental

plaque removal before admission.
The study nurses field notes within the BAASIS interview
revealed that, due to treatment-related complications, a high
symptom burden hindered the patients oral self-care during
the nadir (T3). In fact, patients used the right kind of oral care
(e.g., rinses, materials) but the frequency was reduced. Two
patients discontinued their oral care but found the protocol
useful to return to it as recommended. In general, intervention
patients found the protocol beneficial to their health behavior.
Further, compared to nonstudy patients, the study nurses observed higher motivation levels in both the IG and the UCG
regarding performance of their oral care.

Primary outcome: incidence, severity, and duration of OM

OM incidence was 100 % in both groups. The IG showed a
median OMmax of 2 (interquartile range [IQR]=2) compared
to 3 (IQR=2) in the UCG (effect size: r=0.1; Fig. 3).

Enrollment

Assessed for eligibility

(n = 31)

Randomized (N = 18)

Excluded (n = 13)
Not meeting inclusion criteria (n = 5)
language barriers (n = 3)
not able to perform oral care due to
a poor health condition (n = 2)
Declined to participate (n = 2)
Other reasons (n = 6)
no preparatory visit (n = 3)
no interventionist (n = 3)

Allocation
Received usual care (n = 10)

Received OrCaSS intervention (n = 8)

Follow-Up
Lost to follow-up (death = 1)

Lost to follow-up (n = 0)

Analysis
T1 + T2 Analysed (n = 8)

T1 + T2 Analysed (n = 10)

T3 Analysed (n = 8)

T 3 Analysed (n = 9)

Daily Assessment of OM (n = 8)

Daily Assessment of OM (n = 9)

OrCaSS = oral care self-management protocol

T1 = one week before admission
T2 = at day of admission
T3 = at days 8, 9 or 10 after aHSCT
OM = oral mucositis

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Fig. 3 Severity of oral mucositis
(OM)

mild/moderate
OM

mild/moderate
OM

severe OM

severe OM

Usual Care Group

Grade 1 = soreness and or erythema

Grade 2 = erythema, ulcers, ability to eat
Grade 3 = ulcers, requiring liquid diet
Grade 4 = oral alimentation impossible

The IGs median OM duration was 12.0 days (IQR=5.5),

compared to 14.0 days (IQR=9.5) in the UCG (r=0.1). In
accordance with the literature, OM grades of 12 were defined
as mild/moderate OM and grades 34 as severe [3]. For severe
OM, the median duration was 0 days (IQR=5.8) for the IG
and 1.0 day in the UCG (IQR=4.0; r=0.1). The median
duration of mild/moderate OM was 11.0 days (IQR=4.3) in
the IG and 10.0 days (IQR=8.0) in the UCG (r=0.1). The
median OM onset was day 8 (IQR=3) in the IG and day 6
(IQR=8) in the UCG (r=0.3, Fig. 4).

Intervention Group

mild/moderate OM
severe OM

Secondary outcome: patient adherence

According to the BAASIS data, at T2, adherence to oral care
recommendations was 50.0 % (n=4) in the IG and 40 % in the
UCG (n=4). In the IG, three patients had difficulty with taking
(n=1) or timing (n=2) implementation, while one reduced the
frequency. In the UCG, nonadherent patients had the most
implementation difficulties (taking n=4; timing n=4). Two
patients reduced the frequency. The median VAS scores for
self-rated adherence to oral care were 80.0 % (IQR=20; IG)
and 70.0 % (IQR=20; UCG). At T3, adherence had decreased
to 25.0 % (n=2) in the IG and 33.3 % (n=3) in the UCG, with
equal difficulties per group in implementing oral care (IG
taking n=3 (37.5 %); UCG taking n=2 (20.0 %); IG timing
n=4 (50.0 %); UCG timing n=4 (40.0 %)). Four patients
(50 %) in the IG and two (22.2 %) in the UCG had reduced
the frequency of their oral care. The median self-assessed
adherence at T3 was 75 % (IG IQR 30) and 80.0 % (UCG
IQR 17.5), respectively.
Change scores of the QPI over all three measurement
points improved in the IG (0.69 at T2 and 0.04 at T3). In the
UCG, QPI change scores were constant (mean=1.05).

Discussion

Fig. 4 Kaplan-Meier curve of onset of oral mucositis

We tested the OrCaSS oral care intervention using a randomized controlled pilot study. Crucially, research and intervention procedures proved feasible. In addition, compared to the
usual care group, patients receiving the newly developed oral

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care protocol experienced later OM onset and shorter severe

OM period. Observed effects ranged from small to medium
(r=0.1 to r=0.3).
This studys high incidence of OM (100 %) is congruent
with previous research [6, 35] and underscores the importance
of developing and testing oral care protocols in clinical practice. Judging by previous studies reported median OM durations of 9 to 20 days [18, 19, 36], our groups median durations14 days for the UCG and 12 for the IGwere quite
short. This might be explained by the high level of usual care
(i.e., nursing guideline implementation) provided in the study
setting. However, even under these conditions, our findings
indicate that onset and severity of OM can be improved by a
systematically and consistently applied oral care protocol such
as OrCaSS.
Regarding our selection criteria, because the two patients
receiving chemotherapy for the second time strongly influenced the studys effect sizes, we would recommend adding
previous cytotoxic therapy exposure to future studies exclusion criteria. However, the small sample size certainly amplified these patients proportional impact. In a much larger sample, rather than excluding second-time aHSCT recipients, researchers could ensure representative distributions by stratifying patients according to conditioning therapy and health
condition.
With post-aHSCT symptom burden increases, some of the
intervention group had difficulty adhering to their oral care
timing and taking schedules. A previous nonexperimental
study in patients with leukemia and aHSCT reported 58 %
oral care adherence, i.e., only slightly higher than found here
[37]. However, as adherence is clearly essential to any oral
care protocol, OrCaSS should be adapted by increasing the
frequency of intervention sessions and giving practical support when patients symptom load is highest in the nadir. Feasible ways to deliver higher doses may include a team approach, whereby several intervention nurses apply the oral
care protocol. Furthermore, an adapted timing of the intervention should be considered due to the crucial time from the day
of transplantation to the nadir when OM is in the upswing.
Adherence rates at T3 were most probably related to high
symptom load during the nadir. An increased adherence
follow-up measurement should be planned for future studies
to examine whether adherence to oral care after the nadir is
ascending.
Focusing on patient experiences, as oral hygiene researchers including Michie et al. have suggested, techniques
to foster patient adherence could integrate additional selfmonitoring techniques, e.g., daily diaries, use of new media
(e.g., putting reminders and using smartphone apps as assessment tools) or emotional support, e.g., motivational interviews
[27, 3840]. Such techniques should be incorporated into
standard practice as well as future research. However, to our
knowledge, no studies in the aHSCT population have yet

examined nonadherence or other hindrances to oral care protocols. Developing effective strategies to foster patient adherence would also be a promising topic for qualitative research.
In addition, recent research clearly indicates that professional dental care prior to aHSCT can reduce OMs incidence
and severity and delay its onset [17, 18]. Considering that only
2 of this studys 18 patients received professional dental
cleaning prior to their aHSCT, hemato-oncology departments
would be well advised to intensify their collaboration with
dental experts.
A big limitation is this studys small sample size. However,
the results provide a solid basis to plan a larger RCT. Another
major limitation was that contamination was observed between patients and nurses. For example, as the nurses on the
wards were blinded to the patients allocation, several advised
IG patients in ways that might have negatively influenced
their adherence (i.e., diffusion of treatment). As this kind of
contamination cannot be avoided in a multilevel intervention,
a cluster randomized controlled trial would be advisable in
which all nurses within one cluster would be trained to deliver
congruent information about oral care. Furthermore, blinding
patients was not possible. As a result, we observed a Hawthorne effect (i.e., the study setting itself motivated patients in
both groups to apply oral care).
In spite of the limitations listed above, this preliminary
study yields promising results of the systematic implementation of patients oral self-care in a clinical setting. Moreover, it
suggests the possibility that OrCaSS may add to the improvements of aHSCT patients oral health outcomes and that it
might be worthwhile to test OrCaSS in a larger multicenter
cluster randomized clinical trial.
Acknowledgments The authors wish to thank Dr. med. dent Sebastjan
Varljen for the support in dental questions, as well as Chris Shultis and
Anne Rebafka for their assistance with language and formatting revision.
Further, we wish to express our gratitude to Gila Sellam, Matthias
Naegele, Therese Hirsbrunner, Sandra Schnfeld, Barbara Gresch, and
Sulin Bnzinger of the Institute of Nursing Science, Basel, for reviewing
this paper.
Conflict of interest The authors declare that they have no conflicts of
interest, have full control of all primary data, and allow the journal to
review their data if requested.

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