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\begin{document}

\title{Evidence for the BUAS test ability to diagnose Lumbar Radicular-Pain in
Low Back Pain patients.}



\author[1]{Boaz Samolsky-Dekel}%
\author[2]{Maria Sorella}%
\author[2]{Alessio Vasarri}%
\author[1]{Rita Melotti}%
\affil[1]{University of Bologna}%
\affil[2]{Azienda Ospedaliera-Universitaria di Bologna Policlinico S. Orsola-Malpighi, Anesthesia and Pain Therapy Unit, Via Massarenti n. 9, 40138, Bologna, Italy}%


\vspace{-1em}



  
  \date{June 13, 2024}


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\selectlanguage{english}
\begin{abstract}
Background. Differential diagnosis of Low-back pain (LBP) is complex and
a prominent health care issue at all Health-care levels; guidance may
come from patients' history cues and clinical examination signs. Human
and animal studies report that lumbar radicular pain (LRP) may be
diagnosed, at all care settings, by the evaluation of subjective
responses of injured lumbar nerves to a strain applied at the buttock.
The Buttock Applied Strain (BUAS-test) may guide the differential
diagnosis of LBP. Following an ex-adiuvantibus criterion, clinical
improvement of LRP, diagnosed with the BUAS-test and congruently
treated, may support this test diagnostic ability. Methods. Among 258
LRP patients, positive at V1, to the BUAS-test (with/without positive
Straight-Leg-Raising-Test, SLRT), the effect of gabapentin on painDETECT
(PD) questionnaire and BPI outcomes was quantified in the follow-up
visit (V2). We hypothesized that, at V2, \textgreater{}50\% of the
sample would present negative PD-outcome, significant (t-Test), and ?2
points V2-V1 differences for each the BPI-item's score.
Multinomial-Logistic-Regression (MLR) and \selectlanguage{greek}χ\selectlanguage{english}2 analyses were used to
evaluate the PD-V2-outcomes' dependence upon independent variables.
Results. Of the sample, 77\% reported Negative PD-V2-outcome. V2-V1
differences of all BPI-items were significant and \textgreater{}2
points. PD-V2-outcomes showed significant associations with SLRT-V1 and
PD-V1, respectively, but not with gender, age group, or pain-site. MLR
showed a significant relationship between SLRT-V1 and PD-V2 outcomes.
Conclusions. Among LRP patients, diagnosed by the BUAS-test and treated
with gabapentin, all prespecified endpoints were reached. These results
may be considered a piece of ex-adiuvantibus evidence for the BUAS-test
ability to diagnose LRP. While positive BUAS-test implies potential LRP,
the co-presence with positive SLRT may imply a severer LRP condition.
Further prospective research, in different settings and direct clinical
measures, is needed.%
\end{abstract}%



\sloppy


\textbf{}

\section*{Introduction}

{\label{introduction}}

Low-back pain (LBP) is complex and a prominent health care issue at all
Health-care levels.\textsuperscript{1} Pathophysiology of lower-back and
limb pain may include nociceptive back pain, somatic referred pain,
radicular pain (RP), and radiculopathy \textsuperscript{2}. The latter
two are considered neuropathic-pain (NeP) conditions\textsuperscript{3}.
Radiculopathy is the result of a conduction block along a spinal nerve
or its roots while RP is the expression of abnormal neuronal singling
arising from an injured dorsal root, its ganglion\textsuperscript{3}, or
inflamed nerve \textsuperscript{4--6}. Nociceptive back pain is due to
lumbar-spine nociceptors activation. In contrast, the convergence of
activated nociceptive afferents on the spinal-cord second-order neurons
which subtend regions of the lower limb cause somatic referred pain.

Clinically, RP and radiculopathy show neurological signs and
symptoms\textsuperscript{3}. RP may show dysesthesias, whereas
radiculopathy may show paresthesias and negative signs like compromised
reflexes, numbness, and weakness depending on whether sensory or motor
fibers are involved, respectively.

Differential diagnosis of LBP pain, and hence congruent therapeutic
approach, are challenging as clinical presentation patterns are variable
and different pathophysiological elements may coexist. A focused
history, thorough clinical and neurological examination may guide
differential diagnosis and treatment \textsuperscript{1}.
Anticonvulsants, such as gabapentin or pregabalin, along with
antidepressants, are considered the first choice or bridge therapy for
non-invasive treatment of RP \textsuperscript{7--9}.

We have previously reported the description and reliability features of
a clinical adjunctive test, namely, the Buttock Applied Strain (BUAS)
test, that may facilitate the differential diagnosis of LBP and may
uncover the presence of RP in LBP patients \textsuperscript{10}. This
test showed high sensitivity, specificity and, linear correlation with
the PainDETECT (PD) questionnaire and thus implying the ability to
detect the presence of NeP (ie, lumbar-RP) in LBP patients.

To further support the BUAS-test diagnostic ability, we sought to verify
the influence of an anticonvulsant (namely, gabapentin) on PD outcomes
and pain scores of patients who were positive to the BUAS test and hence
diagnosed with potential lumbar-RP. The latter patients are routinely
treated in our practice with the gabapentin protocol. We have
hypothesized that, given the properties of gabapentin to modulate NeP
(and hence lumbar-RP), a subsequent significant clinical improvement in
PD outcomes and pain scores, might be considered a piece
of\emph{ex-adiuvantibus} evidence for the ability of the BUAS test to
detect lumbar-RP.

\section*{Methods}

{\label{methods}}

\subsection*{Settings and patients}

{\label{settings-and-patients}}

This retrospective and observational study was held at the acute and CP
center of Bologna's Teaching Hospital, Italy. This is an
anesthesiology-based pain program that provides outpatient consultation
to primary care physicians and specialty services for inpatients. The
sample for the present study, according to the inclusion/exclusion
criteria (see below), includes n=258 consecutive non-cancer LBP
outpatients.

\subsection*{Proceedings and
instruments}

{\label{proceedings-and-instruments}}

Routinely, upon first visit (V1) and before the clinical examination,
patients complete three questionnaires: Short Portable Mental Status
Questionnaire (SPMSQ), the Brief Pain Inventory (BPI), and the
painDETECT (PD) questionnaire; BPI and PD are administered to patients
also upon follow-ups. Focused clinical history and physical examination
for LBP patients include Straight Leg Raising Test (SLRT) and the BUAS
test. The rationale, description, and reliability of the BUAS test for
detecting lumbar-RP in LBP patients were earlier
reported\textsuperscript{10}. Briefly, ``it consists of identifying,
with the patient in the prone position, the Posterior Superior Iliac
Spine (PSIS) with the examiner's index or middle finger. Hence, with a
full extended hand, the examiner's thumb reaches the greater trochanter;
keeping the index or middle finger on the PSIS, the thumb is moved
towards halfway between the greater trochanter and the sacrococcygeal
symphysis. The thumb thus exerts pressure (ie, the strain) against the
underlying bony structures hitting the sciatic nerve. The test is
considered positive if the patient reports pain exacerbation different
from that of the mere pressure, or reproduction of his/her pain''
\textsuperscript{10}.

In our practice, all patients, positive to the BUAS test or the SLRT,
are prescribed (if no counterindications exist) with gabapentin 300 mg
tablets. Our inhouse gabapentin-prescription protocol foresees one
tablet at bedtime for three days, hence, one tablet bid (in the morning
and at bedtime) for three days, and afterwards one tablet tid. Therapy
outcomes are evaluated in the follow-up visits where gabapentin dose may
be tapered or increased according to the patients' clinical responses.
All retrieved clinical and therapy information is stored in the
patients' chart and at the clinic's database.

Inclusion criteria for this study were: outpatients with at least one
follow-up visit after V1, [?]18 years of age, with chronic LBP ([?]3
months), positive, at V1, for the BUAS test with or without positive
SLRT, having had, at the end of V1, gabapentin-protocol prescription,
and no pain procedures before the first follow-up visit (V2), and who
signed informed consent. Exclusion criteria were: SPMSQ score
\textless{}8, history or diagnosis of cancer or diabetes upon V1 or
later, positive clinical signs for the piriformis syndrome, ongoing
therapy, at V1, with anticonvulsants (gabapentin or pregabalin) or
antidepressants, and finally, withdrawal from the gabapentin protocol,
before V2, for severe side effects.

\subsection*{Demographic and clinical
predictors}

{\label{demographic-and-clinical-predictors}}

Demographic predictors are: (I) gender: male/female; (II) age groups
{[}in order to avoid unbalanced over representation in wider age
interval groups, patients over 35 years of age are divided into 15-year
interval subsets: 36--50; 51--65; 66--80 and [?]81 years (classes B- E,
respectively); the only subset having a 17-year interval is that of
young adults ie 18--35 years of age (class A){]}.

Pain-related predictors were retrieved from the BPI. In the latter, a
human body image allows the topographical location of the pain site.
Pain site categories were: lumbar spine, lumbar spine and sciatica,
lumbar spine associated with diffused pain, and lumbar spine associated
with other specific pain sites (cervix, groin, dorsal spine, shoulder,
and headache). The following five items assess, using a 0--10 numerical
rating scale (NRS), the highest, lowest, and mean pain intensity in the
past 24 hours, and the actual pain both under static and dynamic
conditions. Item-6, estimates the percentage of pain relief with the
ongoing pain therapy (0\%, no relief -- 100\%, optimal relief). Finally,
items 7-13 assess how much, in the past 24 hours, pain interferes with
the patient's QoL (activity in general, mood, ability to walk, work
activity, social interaction, sleep, and the enjoyment of life;
estimation is made using a 0--10 NRS (0 = no interference to 10 =
maximum interference).

The PD is a clinician-administered and patient-reported screening
questionnaire to reveal the likelihood of a neuropathic pain component
in LBP patients; it consists of seven items that address
neuropathic-pain symptoms' quality with a final score between --1 and 38
(a score of [?]12 implies no neuropathic component, a score of [?]19 implies
the presence of neuropathic component, while a score of 13-18 implies
that the result is uncertain \textsuperscript{11--13}.

Finally, based on the results of the SLRT and BUAS test, the sample
includes two subsets of patients: those who, at V1, were positive for
the BUAS test and negative for the SLRT (BUAS+/SLART-), and those who
were positive to both tests (BUAS+/SLART+).

\subsection*{Ethics}

{\label{ethics}}

This study was approved and authorized by the Hospital Ethics Committee
(235/2013/O/Oss). The study was conducted according to the Helsinki
Declaration and the International Association for the study of Pain
(IASP)'s guidelines for pain research in animals and humans. All
participants were personally and thoroughly informed by the
investigators on the aims of the study. Patients were informed that
participation was voluntary, anonymous and would not affect their care;
hence, an informed consent was obtained.

\subsection*{Study questions, data presentation and statistical
analysis}

{\label{study-questions-data-presentation-and-statistical-analysis}}

Fig. 1 describes the flowchart of the study. We sought to quantify, at
V2, the changes in PD outcomes and BPI scores, in patients who were, at
V1, positive for the BUAS test, with or without being positive for the
SLRT, and thus were prescribed with the gabapentin protocol to treat
their potential lumbar-RP condition. We have hypothesized that, at V2,
positive BUAS-test patients will report significant improvement in PD
outcomes and BPI scores. We have established that significant
improvement should include the following elements: over 50\% of the
sample will present, at V2, negative PD outcome, statistically
significant differences of BPI mean-scores between V2 and V1, and that
such differences will be [?]2 points for each BPI item. We have
established these elements following literature recommendations for
achieving a prespecified Minimal Clinically Important Change (MCIC) in
pain research \textsuperscript{14,15}. We assumed that in case of
affirmative results, these might be considered a piece
of\emph{ex-adiuvantibus} evidence for the capacity of the BUAS test to
detect lumbar-RP in LBP patients. Finally, we planned to look for
associations between patients' independent variables and PD outcomes at
V2 (PD-V2) in order to uncover variables that may undermine the capacity
of the BUAS test to detect lumbar-RP.

Continuous data are reported as the mean (\selectlanguage{ngerman}± SD, standard deviation);
category data are expressed as absolute numbers and percentages. The
dependence of PD-V2 outcomes upon independent variable categories was
determined using \selectlanguage{greek}χ\selectlanguage{english}\textsuperscript{2} analysis. Independent variables
were gender, age group, pain localization, SLRT-V1, and BUAS-test-V1;
when significant, a post-hoc cell contribution analysis was performed,
and major contributions for the association were reported. Multinomial
Logistic Regression (MLR) was used to classify subjects based on a set
of predictor variables. Dependent variables for MLR were the PD-V2
outcome classes and the `negative' class (the most numerous) was the
reference outcome class. Independent variables were those used for the
above mentioned \selectlanguage{greek}χ\selectlanguage{english}\textsuperscript{2} analysis. Differences of BPI-items'
mean scores between V2 and V1 are reported as absolute difference (\selectlanguage{greek}Δ\selectlanguage{english})
and 95\% upper and lower confidential intervals (CI); \emph{t} -test was
used to compare the BPI-items' scores between V1 and V2. Statistical
significance was defined as p\textless{}0.05. When appropriate, p values
were rounded to three decimals.

\section*{Results}

{\label{results}}

Table 1 reports the sample and its subsets' demographic and clinical
features. The sample included n=258 consecutive cases with mean age of
67.4 (\selectlanguage{ngerman}±15.0; range 27-93) years; 67.4\% (n=174) were females. The most
frequent pain localizations, 67.3\% (n=175), was `lumbar spine and
sciatica'. The Median of V1-V2 visit-interval was 82 days. The sample
subsets were similar for all demographic and clinical features except
for mean age and PD-V1 outcomes. Indeed, the mean age in the
BUAS+/SLART+ subset (64.5 ±15.7) was slightly lower than that of the
BUAS+/SLART- subset (69.3 ±14.3); uncertain PD-V1-outcome was reported
by 79\% and 19\% of the BUAS+/SLART- and BUAS+/SLART+ subsets,
respectively; inverted percentages were reported for the positive
PD-V1-outcome. Thirty patients (1.2\%) reported initial dizziness and
somnolence during the gabapentin titration period; however, no patient
stopped the therapy as these side effects decreased over time.

\subsection*{PD outcomes}

{\label{pd-outcomes}}

Table 2 shows the frequency distribution of PD-V1 and PD-V2 outcomes,
and the mean (± SD) of the PD final scores, split by the two subsets of
patients: the BUAS+/SLART-, and the BUAS+/SLART+ one. At V2, 77\%
(n=199) of the entire sample showed negative PD-outcome. In particular,
at V2, all patients (100.0\%) of the BUAS+/SLART- subset showed negative
PD-outcome. Of the BUAS+/SLART+ subset, 43\% showed negative PD-outcome
at V2. In this subset, positive PD-outcome at V1 decreased at V2 by
60\%, and uncertain PD-outcome increased roughly two folds. Finally, in
the BUAS+/SLART+ subset, among patients who showed positive PD-outcome
at V1, 37\% and 23\%, respectively, shifted at V2, to uncertain or
negative PD-outcomes; 20\% remained, at V2, with positive PD-outcome.

To note, we have compared, both in the sample and the study's subsets,
the mean of PD-V1 and PD-V2 \emph{final scores} (Table 2) and found
significant differences between them (t-test, p\textless{}0.001,
respectively)\emph{.} At V2, there were no PD `positive' or `uncertain'
outcomes in the BUAS+/SLART- subset. By contrast, in the BUAS+/SLART+
subset, mean PD-V1 final scores (vs PD-V2) decreased, respectively, from
23.8 to 19.0 for the `positive' PD outcome, and from 18.0 to 15.9 for
the `uncertain' PD outcome. In both subsets, the mean of the `negative'
PD-outcome at V2 was 4.3 (BUAS+/SLART-), and 6.7 (BUAS+/SLART+),
respectively. Interestingly, in the BUAS+/SLART+ subset, PD-V1
`positive' and `uncertain' final scores were roughly 5 and 3 points
higher.

\subsection*{BPI outcomes}

{\label{bpi-outcomes}}

Fig. 2 shows, for the entire sample, the mean scores of the BPI items,
at V1 and V2, and their V2-V1 absolute differences (solid line; V2-V1
values are anchored by a dashed line). For all BPI items, the V2-V1
differences of the BPI item mean scores were of \textgreater{}2 points,
implying a clinically significant improvement in both pain control and
the pain-interference with daily activities. All BPI items showed
statistically significant differences between V2 and V1 (\emph{t-test} ,
p\textless{}0.001, respectively). The same results were also found
within the study's subsets, respectively. For details view table 3,
which shows the mean scores of the BPI items spilt by the BUAS+/SLART-
and the BUAS+/SLART+ subsets, their V2-V1 differences (\selectlanguage{greek}Δ \selectlanguage{english}and 95\% CI),
and the results of the \emph{t-test} analyses. To note, the relief
obtained with the therapy improved by roughly 40\% in both subsets. All
BPI items in both subsets showed statistically significant differences
between V2 and V1 (t-test, p\textless{}0.001, respectively).

\subsection*{Associations and MLR}

{\label{associations-and-mlr}}

Table 4 reports the results of the association analyses (\selectlanguage{greek}χ\selectlanguage{english}2-analysis)
between the PD-V2 outcomes and the independent predictors. It also
reports the post hoc analyses results as cell contribution for the
reported association (the two most influential contributions). No
significant associations were found between the PD-V2 outcomes and the
independent predictors gender, age groups, and pain sites (\selectlanguage{greek}χ\selectlanguage{english}2-analysis,
p \textgreater{} 0.05). Statistically significant associations
(\selectlanguage{greek}χ\selectlanguage{english}2-analysis, p \textless{} 0.0001, respectively) were found between the
PD-V2 outcomes and the independent predictors SLRT-V1 and PD-V1,
respectively. In particular, post hoc analysis showed that the
`positive' and `negative' SLRT-V1 outcomes were associated,
respectively, with `uncertain' and `negative' PD-V2 outcomes. Finally,
`positive' and `uncertain' PD-V1 outcomes were associated, respectively,
with `uncertain' and `negative' PD-V2 outcomes.

For the MLR analysis, PD-V2 outcomes were the dependent variable
(reference outcome class, `negative') while SLRT-V1 and BUAS-test-V1
outcomes were the predictors. Other predictors were excluded, given the
lack of associations observed with the \selectlanguage{greek}χ\selectlanguage{english}\textsuperscript{2}-analysis. As
reported in table 5, The model was found to fit the data significantly
(p=0.000), and the predictor SLRT-V1 had a significant overall effect on
the outcome (Likelihood Ratio Tests, p=0.000). In particular, for the
`positive' and the `uncertain' PD-V2 outcomes, the predictor `negative'
SLRT had adjusted odds-ratios (p-values, 95\% CI) of 0.038, respectively
(p=0.000, 0.012-0.115 and 0.016-0.090, respectively). Thus, for
`negative' SLRT cases, the risks for `positive' or `uncertain' PD-V2
outcomes to occur decrease versus the Reference outcome class PD-V2
`negative'.

\section*{Discussion}

{\label{discussion}}

We report the changes in PD and BPI outcomes of n=258 LBP patients who
were positive to the BUAS test and hence were treated with gabapentin
for their potential lumbar-RP condition. After the treatment, all
prespecified endpoints of the study were reached. We argue that these
results may be considered a piece of \emph{ex-adiuvantibus} evidence for
the ability of the BUAS test to detect lumbar-RP in LBP patients.

In a medical context, the term \emph{ex adiuvantibus} (from Latin,
meaning ''from that which helps'') refers to the method of making an
inference about the presence/cause of a \emph{pathological
condition}from the \emph{observed responses} of the condition to a
given\emph{treatment} . In our case, the potential \emph{pathological
condition} was lumbar-RP, as the BUAS test potentially diagnosed it.

We have recently proposed the BUAS-test as an adjunctive clinical sign
for lumbar-RP \textsuperscript{10}. We have argued that positive BUAS
test implies potential lumbar-RP, and vice-versa. Lumbar-RP, a known NeP
condition, can be indirectly quantified by measures like the PD
questionnaire and the BPI, which we here used to quantify the observed
responses to the given treatment. We hypothesized that a congruent
treatment for potential lumbar-RP (in our case, gabapentin) might lead
to its clinical improvement. Such improvement is measurable with the
tools mentioned above. Thus, subsequent significant improvement in PD
and BPI outcomes may imply, \emph{ex adiuvantibus} , that the underlying
pathological condition was indeed lumbar-RP as the BUAS test initially
implied it. Accordingly, we argued that should a significant improvement
in the lumbar-RP condition occur, it would be reasonable to infer that
the BUAS-test did detect the lumbar-RP. To further support this
inference, we assumed that, after treatment, the observed responses
might be considered 'significant improvement' only should these
responses fulfill restricted prespecified statistical and clinical
endpoints, following the recommendations for achieving MCIC in pain
research \textsuperscript{14,15}. These endpoints were: over 50\% of the
sample should show negative PD-V2 outcome, significant V2-V1 differences
of the BPI-items' mean-score, and that these differences should be of at
least 2 points for each BPI item.

Lumbar-RP is considered the result of abnormal discharges arising from
afferents of an injured dorsal root, ganglion, or inflamed
nerve\textsuperscript{3}. These abnormal discharges are the expression
of nerve roots' sensitization to mechanical stimulation after sustained
and protracted compression (i.e., Mass Effect), or their response to the
perineural-spread of inflammogenic material arising from the nucleus
polposus (i.e., Chemical Radiculitis) \textsuperscript{16}. These
mechanisms induce maladaptive neuronal responses that thus have the
potential to generate abnormal responses from the affected
nerve\textsuperscript{17}. The differential diagnosis of LBP is
complicated by the variability and possible coexistence of multiple
pathophysiological and presentation patterns. A thorough history and
clinical examination, also in primary care settings, are essential in
establishing diagnosis and treatment in LBP patients. In particular,
symptoms, an accurate neurological examination, imaging, and specific
signs (e.g., SLRT and recently, the BUAS test) for lumbar-RP may guide
differential diagnosis \textsuperscript{1}.

The rationale for the application of the BUAS test is explained
elsewhere \textsuperscript{10}. Briefly, animal and human research
assert that applying a strain on an injured nerve, sensitized or
inflamed, may elicit heterospecific discharges, and hence subjective
responses in multiple somatosensory afferents. Such elicited responses
to the applied strain can confirm the presence of RP in various clinical
conditions, including injured/inflamed lumbar dorsal roots and
ganglion\textsuperscript{2,3,5,6,18--25}.

With the BUAS test, we proposed to apply the strain on the sciatic nerve
along its course in the buttock. Several reasons support the feasibility
and efficacy of the BUAS test. First, the sciatic nerve, which contains
axons from the L4-S3 levels, often involved in lumbar RP, is easily
identifiable in the buttock. Second, applying the strain at this
proximal sciatic-nerve course, the abnormal responses can be directly
associated with proximal nerve injuries. Third, in the buttock, the
sciatic nerve lies above stable anatomical structures allowing the
strain to be effectively applied. Finally, the BUAS test showed, among
LBP patients, satisfactory sensitivity (92\%), specificity (100\%),
prior probability, and interrater reliability (Cohen's Kappa,
0.911)\textsuperscript{10}. It showed no associations with predictors
like gender and age groups while it showed significant associations with
predictors like the pain site (lumbar pain and sciatica), and the PD
questionnaire. These findings imply that the BUAS test is not
compromised by patients' demographic features and supports its content
validity. By contrast, the SLRT, widely used for the diagnosis of
lumbar-RP, should be considered with caution as it shows crucial
limitations \textsuperscript{26}. These limitations include the lack of
standard procedure for carrying out and interpreting the SLRT, unclear
underlying mode-of-action, compromised diagnostic reliability related to
specific predictors (the patient's age, gender, psychosocial factors,
and diurnal variability), and lack of direct correlation with MRI
findings, in case of a herniated disc. Finally, ``the diagnostic value
of the SLRT in detecting the presence of lumbar disc herniation may lie
primarily in ruling out its presence because the test sensitivity (0.8)
is far higher than its specificity (0.4)'' \textsuperscript{26} .

Treating lumbar-RP implies a step-wise approach from diagnosis to
treatment (conservative, invasive, or potential surgery) to ameliorate
or resolve the lumbar-RP condition and to permit patients to achieve a
better functional status and quality of life \textsuperscript{27}. Based
on moderate or high quality of evidence and efficacy, antidepressants
and anticonvulsants (e.g., pregabalin and gabapentin) have strong GRADE
recommendations for use in all NeP conditions and are thus proposed as
first-line treatment for NeP \textsuperscript{7,28,29}. Several
controlled studies have found gabapentinoids to be effective for NeP and
lumbar-RP \textsuperscript{10,30--34}. We chose gababapentin both
because of our positive experience with this drug, its known
pharmacodynamic properties in lumbar-RP, and local favorable economic
characteristics \textsuperscript{9}. Gabapentin is prescribed with a
starting dose of 300 mg and may be titrated up to 1800-3600 mg/day with
a ``low and slow'' incremental fashion \textsuperscript{8,9,35}. For
optimal clinical efficacy gabapentin should be prescribed
\emph{tid}because of its short elimination half-life, and saturable
absorption system.

Our inhouse protocol for first-line treatment of potential lumbar-RP
(i.e., patients positive to the BUAS test and/or the SLRT), is a 7 days
titration to 900 mg of gabapentin daily (300 mg tablets tid). Therapy
outcomes and side effects are evaluated in the follow-up visits where
doses may be tapered or increased according to the patients' clinical
responses. In our sample no patient stopped the therapy because of side
effects even though 1.2\% patients reported initial dizziness and
somnolence during the gabapentin titration period, which diminished over
time.

The \emph{observed responses} to the gabapentin treatment in this paper
were retrieved from the PD and BPI questionnaires. The PD explores the
likelihood of the NeP component in LBP patients. The final score of the
questionnaire yields the three PD outcomes: negative, uncertain, and
positive \textsuperscript{11--13}. In our sample, PD-V1 outcomes were
positive (45\%) or uncertain (55\%), while PD-V2 outcomes were mostly
negative (77\%). These results imply that over 50\% of the sample had a
negative PD-V2 outcome and hence fulfilling the first endpoint of the
study. Interestingly, while the BUAS+/SLART- subset showed only negative
PD-V2 outcome, in the BUAS+/SLART+ subset, several PD-V2 outcomes were
positive (20\%) or uncertain (37\%). A possible explanation to these
results may be that in the BUAS+/SLART+ subset, the underlying lumbar-RP
condition was somehow severer. Indeed, unlike the BUAS+/SLART- subset,
patients in the BUAS+/SLART+ subset were positive to both SLRT and BUAS
tests. Further, it is possible that in these patients, the gabapentin
dose (300 mg \emph{tid} ) was not sufficient to manage the severer
lumbar-RP condition. Indeed, recommended daily dose of gabapentin is
higher (1800-3600 mg daily) \textsuperscript{8,9,35}. Interestingly, we
found that in the BUAS+/SLART+ subset, and compared to PD-V1, the mean
of the positive PD-V2 final-scores decreased from 23.8 to 19.0 (the
lower cutoff of the negative PD outcome) in all patients, and from 18.0
to 15.9 for the uncertain outcome. These results indirectly show that
the treatment did affect the severer lumbar-RP condition but yet, it was
not clinically sufficient. Congruently, it is reasonable to speculate
that the BUAS test may diagnose the presence of potential lumbar-RP also
in the absence of positive SLRT. The presence of both signs may imply a
severer lumbar-RP condition and possibly the necessity of higher doses
of gabapentin or more invasive approach for its treatment. Indeed, in
most patients who did not achieve a negative PD-V2 outcome, gabapentin
dose was increased, or epidural steroid injections were programmed.

We used the BPI to evaluate changes in patients' pain intensity and its
interference with quality of life, given the clinical importance of pain
as a primary patient-reported outcome in pain
research\textsuperscript{14}. This tool permits to follow the key
recommendations for reporting pain research outcomes given its
established content validity, reliability, and the ability to detect
MCIC. In this study, we retrieved information about MCIC from the
comparison between V2 and V1 of the BPI items' mean score and their
absolute difference. Following literature recommendations for achieving
a prespecified MCIC in pain research \textsuperscript{14,15}, we have
established that for this study the MCIC should include statistically
significant differences of BPI mean-scores between V2 and V1 and that
such differences will be [?]2 points for each BPI item.

BPI outcomes showed, both in the sample and in the study's subsets,
significant V2-V1 differences of the BPI-items' mean-score, and these
differences were of [?]2 points for each of the BPI item. These results
thus fulfill the second and the third endpoints of the study.

Interestingly, although not significant, V2-V1 absolute differences of
the BPI-items' mean-score in the BUAS+/SLART+ subset were slightly
higher than in the BUAS+/SLART- subset. In particular, in the
BUAS+/SLART+, the BPI pain items (item 1 to 5) showed absolute
differences of roughly 3 points or higher; for the QoL items the trend
of higher absolute difference was less pronounce but still present.
These results indirectly show that the treatment did affect the pain
outcomes of the severer lumbar-RP condition, and thus confirming its
presence as yielded by the BUAS test.

Finally, no significant associations were found between the PD-V2
outcomes and the independent predictors gender, age groups, and pain
sites. These findings imply that the BUAS test was not compromised by
patients' demographic or clinical features and thus supports its
reliability and content validity. Significant associations were found
between the PD-V2 outcomes and the predictors SLRT-V1 and PD-V1,
respectively. In particular, the presence of positive SLRT at V1 was
associated with the uncertain PD-V2 outcome while its absence with the
negative PD-V2 outcome. These findings imply that, as mentioned above,
the co-presence of both signs may denote a severer lumbar-RP condition.
In such a condition, the treatment was able to shift part of the
positive PD-V1 outcome cases to the uncertain PD-V2 outcome, but not to
a negative one like it could in the absence of positive SLRT. Similarly,
positive and uncertain PD-V1 outcomes were associated, respectively,
with uncertain and negative PD-V2 outcomes. Also, the MLR analysis
confirms that for `negative' SLRT-V1 cases, the risks for `positive' or
`uncertain' PD-V2 outcomes to occur decrease versus the Reference
outcome class PD-V2 `negative'. Albeit, the results mentioned above
imply that in the presence of positive BUAS test, with or without
positive SLRT, the given treatment (i.e., gabapentin) did affect the
lumbar-RP condition.

Study limitations. The main limitation of the study is its observational
and retrospective nature. The study's ecological and external validity
may be questioned as to the study design of the indirect assessment of
the BUAS-test diagnostic ability. Indeed, using the effect of gabapentin
on PD and BPI outcomes modifies the direct evaluation method. A direct
evaluation would have implied, for example, a comparison of the BUAS
test outcomes with invasive neurological tests or imaging studies whose
outcomes are not always reliable and conclusive for lumbar-RP diagnosis
and often yield~\emph{ex-adiuvantibus} ~treatments. In this study, data
were collected within a setting of routine work. The external validity
of such observational study comes from its strong relevance to practice
and the ability to highlight meaningful pain assessment solutions.

\section*{Conclusions.}

{\label{conclusions.}}

In a sample of LBP patients who were treated with gabapentin because
they were diagnosed with potential LRP by the BUAS test, all of the
study's prespecified endpoints of MICC in PD and BPI outcome changes
were reached. These results may be considered a piece \emph{of
ex-adiuvantibus} evidence for the ability of the BUAS test to detect
lumbar-RP. While positive BUAS test implies potential lumbar-RP, the
co-presence of positive SLRT, may imply a severer lumbar-RP condition.
To generalize findings, more prospective research in different clinical
settings and direct clinical measures is needed.

\textbf{Conflicts of interest}

The Authors declare that there were no funding sources that supported
the work and there are no conflicts of interest.

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\textbf{Table 1. Demographic and clinical variables of the sample and
its subsets.}\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
& Sample & Subsets &\tabularnewline
\midrule
\endhead
& & BUAS+/SLRT- & BUAS+/SLRT+\tabularnewline
Variable & n (\%) & n (\%) & n (\%)\tabularnewline
Total & 258 (100.0) & 155 (100.0) & 103 (100.0)\tabularnewline
Gender & & &\tabularnewline
Male & 84 (32.3) & 48 (31.0) & 36 (35)\tabularnewline
Female & 174 (67.4) & 107 (69.0) & 67 (65)\tabularnewline
Age \textsuperscript{+} & 67.4 (15.0) & 69.3 (14.3) & 64.5
(15.7)\tabularnewline
Age group (years) & & &\tabularnewline
A (18--35) & 10 (3.8) & 6 (3.9) & 4.0 (3.9)\tabularnewline
B (36--50) & 28 (10.8) & 12 (7.7) & 16.0 (15.5)\tabularnewline
C (51--65) & 58 (22.3) & 32 (20.6) & 26.0 (25.2)\tabularnewline
D (66--80) & 112 (43.1) & 70 (45.2) & 42.0 (40.8)\tabularnewline
E (\textgreater{}80) & 50 (19.2) & 35 (22.6) & 15.0
(14.6)\tabularnewline
Pain site & & &\tabularnewline
Lumbar spine & 26 (10.0) & 16 (10.3) & 10.0 (9.7)\tabularnewline
Lumbar spine and Sciatica & 175 (67.3) & 102 (65.8) & 73.0
(70.9)\tabularnewline
Lumbar spine and diffused pain & 39 (14.6) & 24 (8.4) & 6.0
(5.8)\tabularnewline
Lumbar spine and other specific pain sites & 19 (7.3) & 13 (15.5) & 14.0
(13.6)\tabularnewline
\bottomrule
\end{longtable}

\textsuperscript{+}\emph{, mean (SD) years.}

\emph{Abbreviations: SLRT, Straight Leg Raising Test (SLRT-, negative
SLRT; SLART+, positive SLRT); BUAS, Buttock Applied Strain test (BUAS+,
positive BUAS test).}

\textbf{Table 2. Frequency distribution of PD-V1 and PD-V2 outcomes,
split by subsets of patients positive for the BUAS test with or without
positive SLRT.}\selectlanguage{english}
\begin{longtable}[]{@{}lllllllll@{}}
\toprule
Test Group & & & PD- V1 outcome & PD- V1 outcome & PD- V1 outcome & PD-
V2 outcome & PD- V2 outcome & PD- V2 outcome\tabularnewline
\midrule
\endhead
& & Total n & Positive n (\%) & Uncertain n (\%) & Negative n (\%) &
Positive n (\%) & Uncertain n (\%) & Negative n (\%)\tabularnewline
BUAS + / SLRT - & BUAS + / SLRT - & 155 & 33 (21.3) & 122 (78.7) & 0
(0.0) & 0 (0.0) & 0 (0.0) & 155 (100.0)\tabularnewline
BUAS + / SLRT + & BUAS + / SLRT + & 103 & 83 (80.6) & 20 (19.4) & 0
(0.0) & 21 (20.4) & 38 (36.9) & 44 (42,7)\tabularnewline
Total & Total & 258 & 116 (45,0) & 142 (55.0) & 0 (0.0) & 21 (8.1) & 38
(14.7) & 199 (77.1)\tabularnewline
PD Final score \textsuperscript{+} & PD Final score \textsuperscript{+}
& & & & & & &\tabularnewline
BUAS + / SLRT - & BUAS + / SLRT - & 155 & 19.0 (0.0) & 14.6 (2.0) & 0
(0.0) & 0 (0.0) & 0 (0.0) & 4.3 (2.0)\tabularnewline
BUAS + / SLRT + & BUAS + / SLRT + & 103 & 23.8 (2.5) & 18.0 (0.0) & 0
(0.0) & 19.0 (0.0) & 15.9 (0.9) & 6.7 (0.5)\tabularnewline
Total & Total & 258 & 22.4 (3.6) & 15.1 (2.2) & 0 (0.0) & 19.0 (0.0) &
15.9 (0.9) & 4.9 (2.0)\tabularnewline
\bottomrule
\end{longtable}

\textsuperscript{+}\selectlanguage{ngerman}\emph{, Mean (± SD)}

\emph{Abbreviations: SLRT, Straight Leg Raising Test (SLRT-, negative
SLRT; SLART+, positive SLRT); BUAS, Buttock Applied Strain test (BUAS+,
positive BUAS test).}

\textbf{Table 3. Mean scores of BPI items, at V1 and V2, split by
subsets of positive BUAS Test with or without positive SLRT.}\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
& BUAS + / SLRT - & BUAS + / SLRT - & BUAS + / SLRT - & BUAS + / SLRT +
& BUAS + / SLRT + & BUAS + / SLRT +\tabularnewline
\midrule
\endhead
BPI & V1 & V2 & V2-V1 & V1 & V2 & V2-V1\tabularnewline
Pain intensity & Mean (\selectlanguage{ngerman}± SD) & Mean (\selectlanguage{ngerman}± SD) & \selectlanguage{greek}Δ \selectlanguage{english}(95\% CI)
\textsuperscript{+} & Mean (\selectlanguage{ngerman}± SD) & Mean (\selectlanguage{ngerman}± SD) & \selectlanguage{greek}Δ \selectlanguage{english}(95\% CI)
\textsuperscript{+}\tabularnewline
1. Worst Pain & 8.4 (1.8) & 5.7 (1.7) & 2.7 (2.4-3.1) & 8.8 (1.4) & 5.8
(1.8) & 3.0 (2.6-3.4)\tabularnewline
2. Least Pain & 4.2 (2.5) & 1.9 (1.8) & 2.2 (1.8-2.6) & 4.5 (2.6) & 1.9
(1.8) & 2.7 (2.1-3-2)\tabularnewline
3. Mean Pain & 6.6 (2.0) & 3.5 (1.7) & 3.1 (2.7-3.4) & 7.0 (1.8) & 3.5
(1.7) & 3.4 (3.0-3.9)\tabularnewline
4. Actual Pain & 5.5 (2.6) & 3.1 (2.0) & 2.4 (2.0-2.8) & 6.0 (2.5) & 3.0
(2.1) & 3.1 (3.5-3.6)\tabularnewline
5. Dynamic Pain & 7.9 (1.9) & 5.1 (2.2) & 2.9 (2.5-3.3) & 8.1 (2.2) &
5.0 (2.2) & 3.2 (2.6-3.6)\tabularnewline
6. Relief with therapy (\%) & 21.0 (21) & 57.0 (23) & 36.0 (31-40) &
20.0 (17) & 59.0 (23) & 39.0 (34-44)\tabularnewline
Pain interference with & & & & & &\tabularnewline
7. General Activity & 6.3 (2.4) & 3.7 (1.8) & 2.6 (2.2-3.0) & 6.7 (2.3)
& 3.9 (2.0) & 2.9 (2.3-3.4)\tabularnewline
8. Mood & 5.5 (2.6) & 3.1 (2.0) & 2.5 (2.0-2.9) & 6.1 (2.7) & 3.2 (1.9)
& 2.9 (2.4-3.4)\tabularnewline
9. Ambulation & 6.0 (2.8) & 3.5 (2.1) & 2.5 (2.1-3.0) & 6.2 (2.9) & 3.6
(2.2) & 2.6 (2.1-3.2)\tabularnewline
10. Work & 6.2 (2.3) & 3.4 (1.9) & 2.8 (2.4-3.2) & 6.7 (2.4) & 3.7 (2.1)
& 3.0 (2.5-3.5)\tabularnewline
11. Social interactions & 4.3 (2.9) & 2.0 (2.0) & 2.2 (1.8-2.7) & 4.6
(3.0) & 2.2 (1.9) & 2.5 (1.9-3.1)\tabularnewline
12. Sleep & 4.5 (3.2) & 1.9 (2.3) & 2.6 (2.1-3.1) & 4.8 (3.0) & 2.2
(2.1) & 2.7 (2.1-3.2)\tabularnewline
13. Enjoyment of Life & 4.1 (2.7) & 2.0 (2.0) & 2.0 (1.6-2.5) & 4.6
(3.0) & 2.0 (1.7) & 2.6 (2.0-3-2)\tabularnewline
\bottomrule
\end{longtable}

\emph{\textsuperscript{+}, For all BPI Items, and in both} BUAS + /
SLRT- and BUAS + / SLRT + \emph{subsets, V2-V1 differences were
significant (t-Test, p\textless{}0.000).}

\emph{Abbreviations: SLRT, Straight Leg Raising Test (SLRT-, negative
SLRT; SLART+, positive SLRT); BUAS, Buttock Applied Strain test (BUAS+,
positive BUAS test); SD, Standard Deviation; CI, Upper and lower 95\%
Confidence Interval.}

\textbf{Table 4. Association analyses between PD-V2 outcomes and
independent predictors.}\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
\begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
predictor\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
Post hoc cell contribution \textsuperscript{+}\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
Post hoc cell contribution \textsuperscript{+}\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
Post hoc cell contribution \textsuperscript{+}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
PD-V2\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\selectlanguage{greek}χ\selectlanguage{english}2\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
p Value\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Negative\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Uncertain\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Positive\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Gender\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
1.012\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\textgreater{}0.05\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Age group\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
6.433\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textgreater{}0.05\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Pain site\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2.162\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textgreater{}0.05\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
SLRT-V1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
115.110\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textless{}0.0001\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Positive\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
8.189\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Negative\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
10.729\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
PD-V1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
93.637\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textless{}0.0001\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Positive\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
7.386\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Uncertain\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
9.677\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textsuperscript{+}\selectlanguage{greek}\emph{, χ2 -- post hoc analysis results are reported
as cell contribution for the reported association (the most influent
two).}\selectlanguage{english}

\emph{Abbreviations: SLRT, Straight Leg Raising Test;} PD, painDetect
questionnaire; V1, first visit; V2, follow up visit.

\textbf{Table 5. Multinomial logistic regression, significant results.}\selectlanguage{english}
\begin{longtable}[]{@{}lllllllll@{}}
\toprule
& Effect / Predictor & \selectlanguage{greek}χ\selectlanguage{english}\textsuperscript{2} & DF & p & Adjusted Odds
Ratio & Adjusted Odds Ratio & Adjusted Odds Ratio & Risk
\textsuperscript{++}\tabularnewline
\midrule
\endhead
& & & & & n & 95\% CI & 95\% CI &\tabularnewline
& & & & & & Lower & Upper &\tabularnewline
Model fitting (final) & Model fitting (final) & 130.097 & 6 & 0.000 & &
& &\tabularnewline
Likelihood ratio & Likelihood ratio & & & & & & &\tabularnewline
& SLRT-V1 outcomes & 147.826 & 3 & 0.000 & & & &\tabularnewline
Parameter estimates \textsuperscript{+} & Parameter estimates
\textsuperscript{+} & & & & & & &\tabularnewline
\emph{SLRT Negative} & PD-V2 Positive & & & 0.000 & 0.038 & 0.012 &
0.115 & decrease\tabularnewline
& PD-V2 Uncertain & & & 0.000 & 0.038 & 0.016 & 0.090 &
decrease\tabularnewline
\bottomrule
\end{longtable}

\emph{CI, 95\% confidential intervals of the Adjusted Odds Ratio.}

\textsuperscript{+}\emph{, Comparison outcomes (V1-SLRT, positive and
negative outcomes) versus reference outcome (V2-PD, negative outcome) as
yielded by the multinomial logistic regression model.}

\textsuperscript{\textbf{++}} \emph{, with regard to the predictor, the
risk of the considered comparison outcomes to occur versus the reference
outcome (PD, negative) decreases when the adjusted odds ratio (and 95\%
CI lower and upper values) are \textless{}1 and increases when the
adjusted odds ratio (and 95\% CI lower and upper values) values are
\textgreater{}1, respectively.}

Figures legends.

Fig. 1. Flowchart of the study.

Foot notes:

\emph{LBP, Low Back Pain,}

\emph{RP, Radicular Pain,}

\emph{BUAS-test, Buttock Applied Strain test,}

\emph{SLRT, Straight Leg Raising Test,}

\emph{V1, first visit.}

\emph{V2, follow-up visit.}

\emph{BPI, Brief Pain Inventory,}

\emph{PD, PainDETECT questionnaire.}

Fig. 2. Mean scores of the BPI items in the sample, at V1 and V2, and
their V2-V1 absolute differences.

Foot notes:

\emph{For BPI items 1-13 names, see table 3.Solid line, absolute
differences of BPI items' mean score between V1 and V2; values are
anchored by a dashed line.For all BPI-items, the V2-V1 differences were
statistically significant, (t-test, p\textless{}0.001, respectively).}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Fig-1-flowchart-2/Fig-1-flowchart-2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Fig-2/Fig-2}

\end{center}
\end{figure}

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\selectlanguage{english}
\FloatBarrier
\end{document}

