Reliability and minimal detectable change of a modified passive neck flexion test in patients with chronic nonspecific neck pain and asymptomatic subjects

Musculoskeletal Science and Practice 28 (2017) 10e17

Contents lists available at ScienceDirect

Musculoskeletal Science and Practice journal homepage: https://www.journals.elsevier.com/musculoskeletalscience-and-practice

Original article

Reliability and minimal detectable change of a modified passive neck flexion test in patients with chronic nonspecific neck pain and asymptomatic subjects
pez-de-Uralde-Villanueva a, b, c, d, e, *, Mario Acuyo-Osorio a, María Prieto-Aldana b, Ibai Lo Roy La Touche a, b, c, d
noma de Madrid, Aravaca, Department of Physiotherapy, Faculty of Health Science, Centro Superior de Estudios Universitarios La Salle, Universidad Auto Madrid, Spain
noma de Madrid, Aravaca, Madrid, Spain Motion in Brains Research Group, Centro Superior de Estudios Universitarios La Salle, Universidad Auto c Institute of Neuroscience and Craniofacial Pain (INDCRAN), Madrid, Spain d Hospital La Paz Institute for Health Research, IdiPAZ, Madrid, Spain e
n, Madrid, Spain Faculty of Health Science, Escuela Internacional de Doctorado, Universidad Rey Juan Carlos, Alcorco a

b

a r t i c l e i n f o

a b s t r a c t

Article history: Received 12 May 2016 Received in revised form 17 December 2016 Accepted 8 January 2017

Background: The Passive Neck Flexion Test (PNFT) can diagnose meningitis and potential spinal disorders. Little evidence is available concerning the use of a modified version of the PNFT (mPNFT) in patients with chronic nonspecific neck pain (CNSNP). Objectives: To assess the reliability of the mPNFT in subjects with and without CNSNP. The secondary objective was to assess the differences in the symptoms provoked by the mPNFT between these two populations. Design: We used repeated measures concordance design for the main objective and cross-sectional design for the secondary objective. Method: A total of 30 asymptomatic subjects and 34 patients with CNSNP were recruited. The following measures were recorded: the range of motion at the onset of symptoms (OS-mPNFT), the range of motion at the submaximal pain (SP-mPNFT), and evoked pain intensity on the mPNFT (VAS-mPNFT). Results: Good to excellent reliability was observed for OS-mPNFT and SP-mPNFT in the asymptomatic group (intra-examiner reliability: 0.95e0.97; inter-examiner reliability: 0.86e0.90; intra-examiner testretest reliability: 0.84e0.87). In the CNSNP group, a good to excellent reliability was obtained for the OSmPNFT (intra-examiner reliability: 0.89e0.96; inter-examiner reliability: 0.83e0.86; intra-examiner testretest reliability: 0.83e0.85) and the SP-PNFT (intra-examiner reliability: 0.94e0.98; inter-examiner reliability: 0.80e0.82; intra-examiner test-retest reliability: 0.88e0.91). The CNSNP group showed statistically significant differences in OS-mPNFT (t ¼ 4.92; P < 0.001), SP-mPNFT (t ¼ 2.79; P ¼ 0.007) and in VAS-mPNFT (t ¼ 10.39; P < 0.001) versus the asymptomatic group. Conclusion: The mPNFT is a reliable tool regardless of the examiner and the time factor. Patients with CNSNP have a decrease range of motion and more pain than asymptomatic subjects in the mPNFT. This exceeds the minimal detectable changes for OS-mPNFT and VAS-mPNFT. © 2017 Elsevier Ltd. All rights reserved.

Keywords: Neck pain Neural provocation test Repeatability Smallest detectable change

1. Introduction Neck pain is a common condition that affects approximately 30e50% of the world's population annually(Manchikanti et al.,

* Corresponding author. Faculty of Health Science, Physiotherapy Department,
noma de Centro Superior de Estudios Universitarios La Salle, Universidad Auto Madrid, Calle La Salle, 10, 28023, Madrid, Spain.
pez-de-Uralde-Villanueva). E-mail address: [email protected] (I. Lo http://dx.doi.org/10.1016/j.msksp.2017.01.004 2468-7812/© 2017 Elsevier Ltd. All rights reserved.

2009). Neck pain reduces the abilities and quality of life of affected individuals and results in high costs for society(Guzman et al., 2008; Hogg-Johnson et al., 2009; Haldeman et al., 2010). Most chronic neck pain is classified as nonspecific(Binder, 2007b). This condition has a multifactorial nature, and its symptoms usually have a postural or mechanical basis(Binder, 2007a). Inflammatory processes in the zygapophysial joints and/or intervertebral discs, which are difficult to identify with radiological tests (Riley and Long, 1995), can irritate nerve tissue(Taylor and Taylor, 1996; Eliav et al., 1999).


pez-de-Uralde-Villanueva et al. / Musculoskeletal Science and Practice 28 (2017) 10e17 I. Lo

Mechanical stimulation in sensitized nerve tissue may causes hyperalgesic responses(Hall and Quintner, 1996). The alternatives that can be used to assess increases in the mechanosensitivity (sensitivity to mechanical stimuli) of the nervous system include the neural provocation/neurodynamic test(Elvey, 1997; Butler 2000). The neural provocation test consists of a sequence of movements that are designed to assess both the mechanics and physiology of a part of the nervous system by increasing the length and pressure of the peripheral nerve (mechanical tension) (Coppieters et al., 2002). Previous studies evaluated the reliability of some neural provocation/neurodynamic tests in different regions, such as in the upper and lower extremities(Coppieters et al., 2002; Vanti et al., 2010; Oliver and Rushton, 2011; Trainor and Pinnington, 2011; Boyd, 2012; Talebi et al., 2012). However, little evidence is available concerning the reliability of the neural provocation test in assessing the neuromeningeal mechanosensitivity of the cervical region. In the available literature, the term neuromeningeal mechanosensitivity is used to describe the mechanosensitivity of the neuromeningeal structures within the vertebral canal(Tucker et al., 2007). To achieve this objective, therapists could use the Passive Neck Flexion Test (PNFT), which was described by Butler(Butler and Jones, 1991). The PNFT consists of passively flexing the participant's neck and drawing the “chin to the chest” while the participant is supine. However, it is important to mention that there is currently no gold standard for determining if the symptoms provoked by the mPNFT are caused by neural components or musculoskeletal components. The PNFT (also known as Brudzinski's sign) assesses the consequences of sliding in the cranial direction of the neuroaxis and is an indicated test for diagnosing meningitis (sensitivity: 66%; specificity: 74%) (Curtis et al., 2010) and hypothesized to provoke neurological tissue that may be responsible for clinical symptoms such as headaches, or pain in the arms and legs of spinal origin(Butler and Jones, 1991). To our knowledge, only one study has employed a modified
pez-de-Uralde-Villanueva et al., version of the PNFT (mPNFT)(Lo 2016). The only change with respect to the original version of the test is the addition of a craniocervical flexion to the passive flexion of the participant's neck to increase neuromeningeal tension; this addition could increase the specificity of the test(Tencer et al., 1985). This craniocervical flexion is performed before passive neck flexion and is applied through two grasps: one grasp on the occipital region and the other grasp on the superior maxilla immediately below the participant's nose. The study conducted by
pez-de-Uralde-Villanueva et al. (2016) found differences in the Lo symptoms provoked by the mPNFT between patients with chronic nonspecific neck pain and healthy subjects. Nevertheless, the measurement error of the mPNFT is not yet known. This uncertainty makes it difficult to determine whether or not a difference observed in this test is real. In addition, little evidence is available concerning the reliability of the mPNFT. Thus, the authors believe that it necessary to improve our understanding of this topic. For the cervical region, there is limited evidence concerning the ability to detect differences in neural mechanosensitivity between patients with cervical pain and asymptomatic subjects using neural provocation tests(Sterling et al., 2002; Petersen et al., 2009; Smith
pez-de-Uralde-Villanueva et al., et al., 2013; Ng et al., 2014; Lo 2016). According to the available literature, patients with cervical pain have increased neural mechanosensitivity in comparison to asymptomatic subjects when the Upper Limb Neural Test (ULNT) is applied(Sterling et al., 2002; Petersen et al., 2009; Smith et al., 2013;
pez-de-Uralde-Villanueva et al., 2016). The ULNT Ng et al., 2014; Lo was selected to assess neural mechanosensitivity due to the fact that the brachial plexus consists almost entirely of cervical nerve roots. However, despite the fact that the ULNT produces displacement and strain of the cervical nerve roots (Lohman et al., 2015), the test does

11

not assess possible overall neuromeningeal mechanosensitivity. Thus, it could be interesting to use the mPNFT to evaluate the presence of possible neuromeningeal mechanosensitivity. However, to our knowledge, only one study has shown that patients with chronic nonspecific neck pain experience symptoms at a lower
pez-derange of motion than healthy subjects via the mPNFT (Lo Uralde-Villanueva et al., 2016). This finding might suggest the existence of a greater neural mechanosensitivity in the cervical region. Thus, studies that assess differences between patients with chronic nonspecific neck pain and healthy subjects are needed. The objective of this study was to assess the reliability (intraexaminer, inter-examiner and intra-examiner test-retest) and other measures of the mPNFT both in asymptomatic subjects and in patients with chronic nonspecific neck pain. The secondary objective was to assess the differences in the symptoms provoked by the mPNFT (range of motion at the onset of symptoms, range of motion when provoking submaximal pain and perceived pain intensity) between patients with chronic nonspecific neck pain and asymptomatic subjects. 2. Methods 2.1. Study design This research study consists of two well-differentiated designs that satisfy the two proposed objectives. We used a repeated measures concordance design according to the directives of the Guidelines for Reporting Reliability and Agreement Studies (GRRAS)(Kottner et al., 2011). To assess differences in the symptoms provoked by the mPNFT between patients with chronic nonspecific neck pain and asymptomatic subjects, we used a cross-sectional design, according to the “Strengthening the Reporting of Observational Studies in Epidemiology” (STROBE) statement(von Elm et al., 2008). The Ethics Committee of the Centro Superior de Estudios Universitarios La Salle (Madrid, Spain) approved the implementation of this study (registration number: PI-089/2015). 3. Participants The study population consisted of two groups: patients with chronic nonspecific neck pain and asymptomatic subjects. The patients with chronic nonspecific neck pain were recruited at the Primary Care Centre Miraflores de Alcobendas (Madrid, Spain) using consecutive sampling. The patients were required meet the following criteria to be included in the study: 1) age between 18 and 65 years; 2) nonspecific neck pain for more than three months; and 3) a pain intensity of 30e60 mm on the Visual Analogue Scale (VAS). Patients were excluded if they presented “red flags” (rheumatological disease, cancer, cervical radiculopathy, myelopathy, previous cervical surgery or whiplash) (Greenhalgh and Selfe, 2009), if they had any type of symptom in the arm/craniofacial region, or if they had undergone any type of treatment for their pain (physical therapy, medication, etc.) in the past three months. The asymptomatic subjects were recruited through a snowball sampling process with the help of the enrolled patients (their relatives, friends, etc.). The subjects were required to be 18e65 years of age and to have not experienced any type of pain during the past three months. In addition, all subjects received a physical assessment to confirm their pain-free state. The exclusion criteria of the asymptomatic group included the following criteria: 1) previous cervical surgery and/or whiplash; 2) taking any medication during the past three months that could affect the test outcomes; 3) the presence of systemic disease such as cancer, rheumatoid arthritis, or fibromyalgia; and 4) any type of cognitive impairment that could limit communication or the comprehension of the tests.

12


pez-de-Uralde-Villanueva et al. / Musculoskeletal Science and Practice 28 (2017) 10e17 I. Lo

All participants were required to read and sign the informed consent form to be included in the study. Any participant who presented any of the exclusion criteria over the course of the study was excluded from the study and was considered to be a loss. 3.1. Examiners Two physiotherapists with MSc degrees in manual therapy, and having more than nine years of clinical experience, performed the test. To standardize the process, both examiners received training for 120 min concerning how to apply the mPNFT and how to perform the related measurement. The examiners were blinded to the participants’ symptoms or lack of symptoms. The external individual who randomized the participants asked each participant not to comment on his or her condition (symptomatic or asymptomatic) to the final examiner. 3.2. Outcome measures 3.2.1. Range of motion An Acumar single digital inclinometer (Model ACU 001 from Lafayette Instrument Company; Lafayette, Indiana, USA) was used to measure the range of motion at the onset of symptoms (defined as the moment when the least experience of pain was perceived) and that was achieved when reaching the submaximal pain (defined as the moment when pain increased and the participant wanted the test to cease) (van der Heide et al., 2001) when performing the mPNFT. This instrument uses a simple mechanism (pushing a button to show the data on a digital screen) to measure a joint's angle. According to the manufacturer's specifications, this instrument is capable of measuring (þ180 to 180 ) with an accuracy of ±1. In the sagittal plane, the digital inclinometer is a reliable tool for assessing the cervical range of motion in patients with chronic nonspecific neck pain (Intraclass Correlation Coefficient [ICC] ¼ 0.96 to 0.97) and asymptomatic subjects (ICC ¼ 0.77 to 0.83)(de Koning et al., 2008). 3.3. Pain intensity The VAS was used to measure the submaximal pain intensity caused by the mPNFT. This scale consists of a 100-mm horizontal line with pain descriptors marked “no pain” on the left side and “the worst pain imaginable” on the right side. The VAS has been shown to be a valid and reliable tool(Jensen et al., 1999; Katz and Melzack, 1999).

3.4. Procedures After ensuring that all participants met the study inclusion criteria, an individual external to the study determined which examiner should assess the participant first by a simple random distribution generated by the GraphPad software. All participants attended two sessions separated by a period of 48 h. To minimize any external factor that could affect the measurement, the participants were asked not to change their daily routines; both sessions were performed at the same time of day. During each session, the corresponding examiner applied the mPNFT five times, with each test separated by 30 s. Once the first examiner had finished five measurements, the participant was required to wait 10 min before evaluation by the second examiner. This procedure ensured that the second assessment was not influenced by the first assessment. The examiner was not assisted during the measurements. The measurement process for each repetition was as follows (Fig. 1): 1) the Acumar single digital inclinometer was attached to the participant's forehead using a Velcro strap, which was placed around the participant's head; 2) the participant was placed in supine decubitus with the arms along the body and the legs stretched; 3) a manoeuver was performed manually on the occipital region and the superior maxilla immediately below the participant's nose; 4) a double chin movement was used to increase the mechanical tension in the craniocervical area dthis movement was performed by the examiner without help from the participantd; 5) the participant was passively brought to neck flexion; 6) at the onset of symptoms (pain), the participants were asked to raise their hand, and the range of motion was recorded (OS-mPNFT); 7) the examiner continued increasing the neck flexion until provoking the participant's submaximal pain (this moment was indicated when the participants raised their hand a second time). The examiner recorded the achieved range of motion (SP-mPNFT); and 8) the participant indicated his or her perceived pain intensity during the neural test using the VAS (VAS-mPNFT). Following a model reported in a previous research study (Oliver and Rushton, 2011), the authors performed a pilot study with 15 subjects to assess the possible influence of repeating the mPNFT on several occasions due to the tissue's viscoelastic properties. After analysing the results of this pilot study, the decision was made to discard the first two measurements of each examiner because they showed greater variability. Thus, of the five measurements performed by each examiner, only the last three were analysed.

Fig. 1. Modified Passive Neck Flexion Test. A, initial position. B, final position.


pez-de-Uralde-Villanueva et al. / Musculoskeletal Science and Practice 28 (2017) 10e17 I. Lo

3.5. Sample-size determination The sample size was calculated using the statistical software G  Power 3.1.7. (G  Power©, University of Dusseldorf, Germany)(Faul et al., 2007). To detect differences in the symptoms provoked by the mPNFT between groups (patients and asymptomatic subjects), the authors chose a power of 80% (1-b error) and a sig
pez-denificance level of 5% (a error). Based on a previous study, (Lo Uralde-Villanueva et al., 2016) a large effect size was used (d ¼ 0.80). Hence, at least 52 participants were required. Ultimately, a sample size of 60 participants was established to account for the possibility of a 15% loss due to the study's longitudinal nature. 3.6. Data analysis The Statistical Package for Social Sciences (SPSS 21, SPSS Inc, Chicago, IL, USA) software was used for statistical analysis. The normal distribution of the variables was assessed using the Kolmogorov-Smirnov test. For all of the analyses, statistical significance was set at P < 0.05. The ICC was used to evaluate reliability (intra-examiner, interexaminer, and intra-examiner test-retest). The intra-examiner reliability was obtained using the three measurements performed by an examiner in the same trial. The inter-examiner reliability was calculated by employing the mean of the three measurements performed by each examiner. The influence of time on the intra-examiner reliability (intra-examiner test-retest reliability) was analysed by using the means of the three measurements performed by the same examiner in trial 1 and trial 2. Reliability levels were defined based on the following classification: excellent reliability (ICC  0.90); good reliability (0.90 > ICC  0.70); fair reliability (0.70 > ICC  0.40); and poor reliability, ICC < 0.40(Shrout and Fleiss, 1979).

13

The measurement error (expressed as the standard error of measurement, SEM) is the systematic and random error of a participant's score that is not attributable to the true changes in the construct being measured(Mokkink et al., 2010).pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi The SEM was calculated using the following formula: SD  1  ICC (Weir, 2005). Responsiveness was assessed by using the minimal detectable change (MDC). The MDC90 expresses the minimal change required to be 90% confident that the observed change between the two measures reflects real change and is not measurement error(Haley and Fragala-Pinkham, 2006). We used a 90% confidence interval because such an interval is appropriate for decisions regarding the effectiveness of an intervention(Haley and Fragala-Pinkham, 2006; Portney and Watkins, 2009). The MDC90 was calculated using the pffiffiffi following formula: SEM  2  1:65 (Wyrwich, 2004; Haley and Fragala-Pinkham, 2006). An independent t-test was used to detect differences between symptomatic and asymptomatic subjects. Specifically, the differences between these two populations (symptomatic and asymptomatic) in the outcomes OS-mPNFT, SP-mPNFT and VAS-mPNFT were analysed using the mean values of trials 1 and 2. Effect sizes were calculated according to Cohen's method (Cohen's d), and the magnitude of the effect was classified as small (0.20e0.49), medium (0.50e0.79), or large (0.8)(Cohen, 1988). 4. Results This research study was conducted from September 2015 to December 2015. The flow of participants for this study is demonstrated in Fig. 2. The final sample consisted of 30 asymptomatic subjects (23 females and 7 males) and 34 patients with chronic nonspecific neck pain (30 females and 4 males). The demographic

Fig. 2. Flow diagram for experimental procedures.


pez-de-Uralde-Villanueva et al. / Musculoskeletal Science and Practice 28 (2017) 10e17 I. Lo

14

pain when the mPNFT was applied. Thus, it was impossible to calculate any type of reliability for the VAS-mPNFT. The ICC values of the inter-examiner reliability for OS-mPNFT and SP-mPNFT were 0.86e0.90; 7.73 was the highest value for the MDC90 for both variables (Table 3). To measure the impact of time, the OS-mPNFT and SP-mPNFT were found to have intra-examiner test-retest reliability values (48 h) of 0.84e0.87. The largest MDC90 was 8.51 for both variables (Table 4).

Table 1 Demographic characteristics for asymptomatic subjects and patients with chronic nonspecific neck pain. Values are mean ± SD and n (%).

Age (years) Gender (female) Height (cm) Weight (kg)

Asymptomatic subjects (n ¼ 30)

Patients with CNSNP (n ¼ 34)

P value

47.30 ± 13.45 23 (76.7) 162.30 ± 8.59 68.48 ± 12.94

46.06 ± 11.84 30 (88.2) 162.18 ± 8.59 66.92 ± 12.13

0.70a 0.22b 0.95a 0.62a

Abbreviations: CNSNP, chronic nonspecific neck pain. a Independent t-test. b c2 tests.

4.2. Reliability in patients with chronic nonspecific neck pain

characteristics of the two groups were similar, and no statistically significant differences were observed (Table 1). The symptomatic group had a mean duration of neck pain of 44.53 ± 42.25 months (mean ± SD). The participants had similar clinical characteristics both days, with no statistically significant intragroup differences (P > 0.05) in the variables OS-mPNFT and SP-mPNFT between trials 1 and 2 (separated by 48 h).

The highest ICC values for intra-examiner reliability were found for SP-mPNFT (0.94e0.98). The intra-examiner reliability values were 0.89e0.96 for OS-mPNFT and 0.88e0.97 for VAS-mPNFT. The highest MDC90 scores for the variables evaluated using the range of motion were 9.64 for onset of symptoms and 18.99 mm for VASmPNFT. The descriptive statistics, ICCs, and associated 95% CIs, SEMs, and MDC90 values are presented in Table 5. The inter-examiner reliability evaluation revealed ICC values of 0.83e0.86, 0.80e0.82 and 0.81e0.85 for OS-mPNFT, SP-mPNFT and VAS-mPNFT, respectively (Table 3). With respect to the range of motion, the highest MDC90 value was observed for OS-mPNFT (12.13 ). The MDC90 for VAS-mPNFT varied between 20.15 mm and 24.41 mm. With respect to the intra-examiner test-retest reliability, OSmPNFT and SP-mPNFT had ICC values that ranged from 0.83 to

4.1. Reliability in asymptomatic subjects The intra-examiner reliability for OS-mPNFT and SP-mPNFT varied from 0.95 to 0.97 (Table 2). The greatest MDC90 for these variables was 4.62 . The range of motion achieved at the onset of symptoms was identical to the range of motion at the moment of submaximal pain because none of the asymptomatic subjects felt Table 2 Intra-examiner reliability in asymptomatic subjects. Trial

Examiner A

Examiner B

Measurements (mean ± SD) 3 1 OS-mPNFT ( ) SP-mPNFT ( ) VAS-mPNFT (mm) 2 OS-mPNFT ( ) SP-mPNFT ( ) VAS-mPNFT (mm)

4

ICC

95% CI

SEM MDC90 Measurements (mean ± SD)

5

3

4

ICC

95% CI

SEM MDC90

5

93.33 ± 9.42 93.20 ± 10.15 93.33 ± 10.34 0.96 0.93 to 0.98 1.98 4.62 93.33 ± 9.42 93.20 ± 10.15 93.33 ± 10.34 0.96 0.93 to 0.98 1.98 4.62 0 0 0 e e e e

90.73 ± 10.07 91.47 ± 9.48 92.03 ± 9.51 0.97 0.95 to 0.99 1.61 3.76 90.73 ± 10.07 91.47 ± 9.48 92.03 ± 9.51 0.97 0.95 to 0.99 1.61 3.76 0 0 0 e e e e

92.10 ± 8.07 92.43 ± 8.38 92.10 ± 8.07 92.43 ± 8.38 0 0

92.70 ± 9.77 92.70 ± 9.77 0

92.60 ± 8.31 92.60 ± 8.31 0

0.95 0.91 to 0.97 1.87 4.36 0.95 0.91 to 0.97 1.87 4.36 e e e e

93.10 ± 9.75 93.50 ± 9.41 0.97 0.95 to 0.99 1.66 3.88 93.10 ± 9.75 93.50 ± 9.41 0.97 0.95 to 0.99 1.66 3.88 0 0 e e e e

Abbreviations: OS-mPNFT, range of motion at Onset of Symptom in the modified version of the Passive Neck Flexion Test; SP-mPNFT, range of motion at Submaximal Pain in the mPNFT; VAS-mPNFT, pain intensity caused by mPNFT; ICC, intraclass correlation coefficient; CI, confidence interval; SEM, standard error of the measurement; MDC90, minimal detectable change at the 90% confidence level.

Table 3 Inter-examiner reliability in asymptomatic subjects and patients with chronic nonspecific neck pain. Trial

Mean ± SD Examiner A

Asymptomatic subjects 93.29 1 OS-mPNFT ( ) SP-mPNFT ( ) 93.29 VAS-mPNFT (mm) 0 2 OS-mPNFT ( ) 92.38 SP-mPNFT ( ) 92.38 VAS-mPNFT (mm) 0 Patients with chronic nonspecific neck pain 1 OS-mPNFT ( ) 82.30 SP-mPNFT ( ) 88.16 VAS-mPNFT (mm) 37.37 2 OS-mPNFT ( ) 80.95 SP-mPNFT ( ) 88.11 VAS-mPNFT (mm) 34.11

± 9.85 ± 9.85 ± 8.11 ± 8.11

± ± ± ± ± ±

11.78 11.00 22.77 14.19 11.06 22.08

ICC

95% CI

SEM

MDC90

0.90 0.90 e 0.86 0.86 e

0.79 0.79 e 0.73 0.73 e

to 0.95 to 0.95

3.14 3.14 e 3.31 3.31 e

7.33 7.33 e 7.73 7.73 e

0.83 0.80 0.81 0.86 0.82 0.85

0.68 0.64 0.65 0.74 0.68 0.71

to to to to to to

5.20 5.17 10.46 5.07 4.66 8.64

12.13 12.06 24.41 11.83 10.87 20.15

Examiner B 91.41 91.41 0 93.10 93.10 0

± 9.60 ± 9.60

77.70 82.71 41.51 76.18 83.81 40.55

± ± ± ± ± ±

± 9.55 ± 9.55

13.32 12.23 25.00 12.97 11.12 21.85

to 0.93 to 0.93

0.91 0.90 0.90 0.93 0.91 0.92

Abbreviations: OS-mPNFT, range of motion at Onset of Symptom in the modified version of the Passive Neck Flexion Test; SP-mPNFT, range of motion at Submaximal Pain in the mPNFT; VAS-mPNFT, pain intensity caused by mPNFT; ICC, intraclass correlation coefficient; CI, confidence interval; SEM, standard error of the measurement; MDC90, minimal detectable change at the 90% confidence level.


pez-de-Uralde-Villanueva et al. / Musculoskeletal Science and Practice 28 (2017) 10e17 I. Lo

15

Table 4 Intra-examiner test-retest reliability in asymptomatic subjects and patients with chronic nonspecific neck pain. Mean ± SD

Examiner

Trial 1 Asymptomatic subjects 93.29 A OS-mPNFT ( ) SP-mPNFT ( ) 93.29 VAS-mPNFT (mm) 0 B OS-mPNFT ( ) 91.41 SP-mPNFT ( ) 91.41 VAS-mPNFT (mm) 0 Patients with chronic nonspecific neck pain A OS-mPNFT ( ) 82.30 SP-mPNFT ( ) 88.16 VAS-mPNFT (mm) 37.37 77.70 B OS-mPNFT ( ) 82.71 SP-mPNFT ( ) VAS-mPNFT (mm) 41.51

± 9 0.85 ± 9.85 ± 9.60 ± 9.60

± ± ± ± ± ±

ICC

95% CI

SEM

MDC90

0.84 0.84 e 0.87 0.87 e

0.69 0.69 e 0.74 0.74 e

to 0.92 to 0.92

3.65 3.65 e 3.49 3.49 e

8.51 8.51 e 8.14 8.14 e

0.85 0.91 0.84 0.83 0.88 0.85

0.73 0.83 0.71 0.68 0.77 0.71

to to to to to to

5.00 3.31 8.85 5.44 4.08 9.25

11.66 7.73 20.65 12.69 9.53 21.59

Trial 2

11.78 11.00 22.77 13.32 12.23 25.00

92.38 92.38 0 93.10 93.10 0

± 8.11 ± 8.11

80.95 88.11 34.11 76.18 83.81 40.55

± ± ± ± ± ±

± 9.55 ± 9.55

14.19 11.06 22.08 12.97 11.12 21.85

to 0.94 to 0.94

0.92 0.95 0.92 0.91 0.94 0.92

Abbreviations: OS-mPNFT, range of motion at Onset of Symptom in the modified version of the Passive Neck Flexion Test; SP-mPNFT, range of motion at Submaximal Pain in the mPNFT; VAS-mPNFT, pain intensity caused by mPNFT; ICC, intraclass correlation coefficient; CI, confidence interval; SEM, standard error of the measurement; MDC90, minimal detectable change at the 90% confidence level.

Table 5 Intra-examiner reliability in patients with chronic nonspecific neck pain. Trial

Examiner A

Examiner B

Measurement (mean ± SD) 3 1 OS-mPNFT ( ) SP-mPNFT ( ) VAS-mPNFT (mm) 2 OS-mPNFT ( ) SP-mPNFT ( ) VAS-mPNFT (mm)

4

ICC 95% CI

SEM MDC90 Measurement (mean ± SD)

5

3

4

ICC 95% CI

SEM MDC90

5

82.38 ± 11.55 82.65 ± 12.85 81.88 ± 12.31 0.89 0.81 to 0.94 4.13 9.64 87.97 ± 11.03 88.74 ± 10.83 87.77 ± 11.74 0.95 0.91 to 0.97 2.61 6.09 36.62 ± 22.39 37.74 ± 23.50 37.74 ± 25.21 0.88 0.80 to 0.94 8.14 18.99

76.65 ± 13.62 77.94 ± 13.74 78.50 ± 13.17 0.96 0.93 to 0.98 2.77 6.46 82.27 ± 12.38 82.85 ± 12.15 83.00 ± 12.39 0.98 0.97 to 0.99 1.73 4.04 42.71 ± 25.91 41.50 ± 25.01 40.32 ± 25.85 0.93 0.88 to 0.96 6.71 15.66

80.94 ± 14.46 81.68 ± 14.72 80.24 ± 14.53 0.92 0.87 to 0.96 4.04 9.43 88.00 ± 11.25 88.35 ± 11.53 87.97 ± 11.09 0.94 0.89 to 0.97 2.75 6.42 34.29 ± 21.85 32.62 ± 22.85 35.41 ± 23.30 0.92 0.87 to 0.96 6.37 14.86

75.68 ± 13.71 77.15 ± 13.29 75.71 ± 12.98 0.92 0.86 to 0.96 3.81 8.88 83.88 ± 10.71 83.97 ± 11.49 83.59 ± 11.43 0.98 0.96 to 0.99 1.74 4.06 39.94 ± 21.29 40.18 ± 21.17 41.53 ± 23.69 0.97 0.95 to 0.98 3.84 8.96

Abbreviations: OS-mPNFT, range of motion at Onset of Symptom in the modified version of the Passive Neck Flexion Test; SP-mPNFT, range of motion at Submaximal Pain in the mPNFT; VAS-mPNFT, pain intensity caused by mPNFT; ICC, intraclass correlation coefficient; CI, confidence interval; SEM, standard error of the measurement; MDC90, minimal detectable change at the 90% confidence level.

0.85 and 0.88e0.91, respectively. The onset of symptoms again showed the highest MDC90 value with a value of 12.69 . The ICC values for VAS-mPNFT were between 0.84 and 0.85, and the highest MDC90 value was 21.59 mm. The descriptive statistics, ICCs, and associated 95% CIs, SEMs, and MDC90 are presented in Table 4. 4.3. Asymptomatic subjects versus patients with chronic nonspecific neck pain The patient group with chronic nonspecific neck pain showed statistically significant differences in the mPNFT for variables Table 6 Comparison between asymptomatic subjects and patients with chronic nonspecific neck pain for the modified version of the passive neck flexion test. Outcomes

Asymptomatic subjects (Mean ± SD)

Patients with CNSNP (Mean ± SD)

Mean differences (95% CI)

Cohen's d

OS-mPNFT ( )

92.54 ± 8.79

79.28 ± 12.24

1.24

SP-mPNFT ( )

92.54 ± 8.79

85.69 ± 10.61

VAS-mPNFT (mm)

0

38.38 ± 21.51

13.26 (7.87e18.65)* 6.85 (1.94e11.76)* 38.38 (45.89 to 30.89)*

0.70 2.52

Abbreviations: CNSNP, chronic nonspecific neck pain; OS-mPNFT, range of motion at Onset of Symptom in the modified version of the Passive Neck Flexion Test; SPmPNFT, range of motion at Submaximal Pain in the mPNFT; VAS-mPNFT, pain intensity caused by mPNFT. *P < 0.01.

related to the range of motion [OS-mPNFT (t ¼ 4.92; P < 0.001); SPmPNFT (t ¼ 2.79; P ¼ 0.007)] and for the intensity of pain evoked by the test [VAS-mPNFT (t ¼ 10.39; P < 0.001)] in comparison to the asymptomatic group. None of the healthy participants felt pain; the healthy participants experienced only tightness. The OS-mPNFT had a larger effect size in the range of motion variables (d ¼ 1.24). The descriptive statistics, mean differences (95% confidence intervals, CIs), and effect sizes between the two samples are presented in Table 6. 5. Discussion This study contributes to the scarce available evidence concerning the mPNFT. To our knowledge, this report is the first study to assess the reliability and other measures supplementing the contrasts in statistical significance of mPNFT both in patients with chronic nonspecific neck pain and in asymptomatic subjects. The results of this study show that the mPNFT is a reliable tool regardless of the examiner, the time between tests and whether the test is applied to patients with chronic nonspecific neck pain or to asymptomatic subjects. In fact, the ICCs of the two groups were similar, and all values were greater than 0.80. Thus, the reliability varied between good and excellent(Shrout and Fleiss, 1979). As reported for other research studies that assessed the reliability of neural tests, the best results were found for the intra-examiner assessment(Coppieters et al., 2002; Vanti et al., 2010; Oliver and Rushton, 2011). This result was predictable because the study

16


pez-de-Uralde-Villanueva et al. / Musculoskeletal Science and Practice 28 (2017) 10e17 I. Lo

conditions varied the least for the intra-examiner assessment; this design minimized any possible change caused by external factors. The ICC values observed for the intra-examiner reliability were
pez-de-Uralde-Villanueva et al. higher than those reported by Lo (2016) However, this difference could be due to the larger number of repetitions that were performed in our study in order to satisfy the secondary objective. In addition, it is worth noting that the standard error of the mean for all intra-examiner assessments was less than 5 . Hence, this type of assessment dwith this measurement errord is applicable in a clinical context according to the model established by the American Medical Association Guides for assessing range of motion of the spine(Nitschke et al., 1999). The variability produced by the examiner factor and the variability produced by the time factor were nearly the same because the inter-examiner reliability and the intra-examiner test-retest reliability were similar. Moreover, this study suggests that patients with chronic nonspecific neck pain could have greater neuromeningeal mechanosensitivity than asymptomatic subjects. This statement is supported by the lower range of motion at the onset of symptoms and by the more intense pain caused when applying the mPNFT in the symptomatic group versus the asymptomatic group. However, this hypothesis must be considered with caution because it is not possible to determine if the provocation of symptoms with the mPNFT is only due to the neural component or if the musculoskeletal component could affect the outcomes. The differences observed between the pathological group and the asymptomatic group exceeded the highest MDCs90 found in this study for the variables OS-mPNFT and VAS-mPNFT but not for the variable SPmPNFT. Thus, we can be 90% confident that these values exceed the minimal detectable change and are not measurement errors(Haley and Fragala-Pinkham, 2006). To our knowledge, only one study assessed mechanosensitivity
pez-de-Uralde-Villanueva using the mPNFT in this population.(Lo et al., 2016) Consistent with our study, the results of that study suggest the existence of a change in mechanosensitivity in patients with chronic nonspecific neck pain. It is worth noting that in the
pez-de-Uralde-Villanueva et al. (2016), study performed by Lo symptom onset occurred at a smaller range of motion than observed in our study. Nevertheless, the absolute values of the difference between the symptomatic and asymptomatic populations were similar in the two studies. This similarity could be due to the viscoelastic properties of the tissue (De Deyne, 2001; Jin et al., 2015) because the number of repetitions of the neural test was greater in
pez-de-Uralde-Villanueva et al. (2016) performed the our study. Lo mPNFT on three occasions, and our study applied the test on five occasions (discarding the first two occasions). As a counter to this theory, some evidence demonstrates that the viscoelastic deformation is practically unchanged with only 30 s of rest between stretches(Magnusson et al., 2000; McNair et al., 2001). This period of time coincides with the remainder of our study. Hence, the observed increase in the range of motion could be caused by a change in the participant's sensation due to repeated application(Weppler and Magnusson, 2010). This hypothesis fits our model because the range of motion was recorded when the participants began to feel symptoms. In addition, several other studies have also found increased neural mechanosensitivity of the upper quadrant in patients with cervical pain (whiplash and chronic nonspecific neck pain) in comparison to asymptomatic subjects(Sterling et al., 2002;
pez-dePetersen et al., 2009; Smith et al., 2013; Ng et al., 2014; Lo Uralde-Villanueva et al., 2016). These results reinforce our study because a displacement (intraforaminal and extraforaminal) of the C5-C8 nerve roots occurs when strain is placed on the median nerve. Therefore, meningeal involvement occurs when strain is placed on the nerve(Lohman et al., 2015).

5.1. Limitations The main limitation of the study is the fact that the first two mPNFT measurements were discarded to increase the reliability of the measurements and identify authentic differences between the two study populations. This feature decreased the variability of the measurements but could also represent an obstacle to the clinical impact of these results because several repetitions (two or more) of a test are not usually performed in clinical practice. Thus, based on our results, the authors recommend performing the mPNFT at least five times and discarding the results of the first two. Another limitation was the lack of structural differentiation at the onset of symptomsdthis limitation makes it unclear whether the onset of symptoms was due to the neural component or the musculoskeletal component. Although structural differentiation is important for interpreting neural tests (Breig and Troup, 1979; Butler, 2000), very few studies have performed this differentiation(Wainner et al., 2003; Schmid et al., 2009; Lohkamp and Small, 2011). Additional studies are needed to evaluate the sensitivity and specificity of the mPNFT for detecting alterations in neuromeningeal mechanosensitivity. 6. Conclusion Regardless of the examiner and the time factor, the mPNFT is a reliable tool when it is applied to patients with chronic nonspecific neck pain or to asymptomatic subjects. Patients with chronic nonspecific neck pain experience symptoms at a lower range of motion and experience a stronger pain intensity than asymptomatic subjects when applying the mPNFT. This findings could suggest the presence of greater neuromeningeal mechanosensitivity in patients with chronic nonspecific neck pain. The differences observed in the range of motion at the onset of symptoms and in the pain perceived when applying the mPNFT between the two populations exceed the MDC90 established in this study. Future studies are needed to increase the available evidence concerning increases in neuromeningeal mechanosensitivity and rectify the limitations of this research. Author disclosures No presentation of this material before. No financial support. No conflicts of interest. References Binder, A., 2007a. Cervical spondylosis and neck pain. BMJ 334 (7592), 527e531. Binder, A., 2007b. The diagnosis and treatment of nonspecific neck pain and whiplash. Eura Medicophys 43 (1), 79e89. Boyd, B.S., 2012. Measurement properties of a hand-held inclinometer during straight leg raise neurodynamic testing. Physiotherapy 98 (2), 174e179. Breig, A., Troup, J.D., 1979. Biomechanical considerations in the straight-leg-raising test. Cadaveric and clinical studies of the effects of medial hip rotation. Spine (Phila Pa 1976) 4 (3), 242e250. Butler, D.S., Jones, M.A., 1991. Mobilisation of the Nervous System, first ed. Churchill Livingstone, Melbourne. Butler, D.S., 2000. The Sensitive Nervous System. Noigroup Publications, Adelaide. Cohen, J., 1988. Statistical Power Analysis for the Behavioral Sciences, second ed. Lawrence Earlbaum Associates, Hillsdale: New Jersey. Coppieters, M., Stappaerts, K., Janssens, K., Jull, G., 2002. Reliability of detecting “onset of pain” and “submaximal pain” during neural provocation testing of the upper quadrant. Physiother. Res. Int. 7 (3), 146e156. Curtis, S., Stobart, K., Vandermeer, B., Simel, D.L., Klassen, T., 2010. Clinical features suggestive of meningitis in children: a systematic review of prospective data. Pediatrics 126 (5), 952e960. De Deyne, P.G., 2001. Application of passive stretch and its implications for muscle fibers. Phys. Ther. 81 (2), 819e827. Eliav, E., Herzberg, U., Ruda, M.A., Bennett, G.J., 1999. Neuropathic pain from an experimental neuritis of the rat sciatic nerve. Pain 83 (2), 169e182.


pez-de-Uralde-Villanueva et al. / Musculoskeletal Science and Practice 28 (2017) 10e17 I. Lo von Elm, E., Altman, D.G., Egger, M., Pocock, S.J., Gøtzsche, P.C., Vandenbroucke, J.P., 2008. The Strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Rev. Esp. Salud Publica 82 (3), 251e259. Elvey, R.L., 1997. Physical evaluation of the peripheral nervous system in disorders of pain and dysfunction. J. Hand Ther. 10 (2), 122e129. Faul, F., Erdfelder, E., Lang, A.G., Buchner, A., 2007. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav. Res. Methods 39 (2), 175e191. Greenhalgh, S., Selfe, J., 2009. A qualitative investigation of Red Flags for serious spinal pathology. Physiotherapy 95 (3), 224e227. ^ te
, P., Carragee, E.J., et al., Guzman, J., Hurwitz, E.L., Carroll, L.J., Haldeman, S., Co 2008. A new conceptual model of neck pain: linking onset, course, and care: the bone and joint decade 2000-2010 task force on neck pain and its associated disorders. Spine (Phila Pa 1976) 33 (4 Suppl. l). S14-23. Haldeman, S., Carroll, L., Cassidy, J.D., 2010. Findings from the bone and joint decade 2000 to 2010 task force on neck pain and its associated disorders. J. Occup. Environ. Med. 52 (4), 424e427. Haley, S.M., Fragala-Pinkham, M.A., 2006. Interpreting change scores of tests and measures used in physical therapy. Phys. Ther. 86 (5), 735e743. Hall, T., Quintner, J., 1996. Responses to mechanical stimulation of the upper limb in painful cervical radiculopathy. Aust. J. Physiother. 42 (4), 277e285. van der Heide, B., Allison, G.T., Zusman, M., 2001. Pain and muscular responses to a neural tissue provocation test in the upper limb. Man. Ther. 6 (3), 154e162. Hogg-Johnson, S., van der Velde, G., Carroll, L.J., Holm, L.W., Cassidy, J.D., Guzman, J., et al., 2009. The burden and determinants of neck pain in the general population: results of the bone and joint decade 2000-2010 task force on neck pain and its associated disorders. J. Manip. Physiol. Ther. 32 (2 Suppl. l). S46-60. Jensen, M.P., Turner, J.A., Romano, J.M., Fisher, L.D., 1999. Comparative reliability and validity of chronic pain intensity measures. Pain 83 (2), 157e162. Jin, H., Yang, Q., Ji, F., Zhang, Y.-J., Zhao, Y., Luo, M., 2015. Human amniotic epithelial cell transplantation for the repair of injured brachial plexus nerve: evaluation of nerve viscoelastic properties. Neural Regen. Res. 10 (2), 260e265. Katz, J., Melzack, R., 1999. Measurement of pain. Surg. Clin. North Am. 79 (2), 231e252. de Koning, C.H.P., van den Heuvel, S.P., Staal, J.B., Smits-Engelsman, B.C.M., Hendriks, E.J.M., 2008. Clinimetric evaluation of active range of motion measures in patients with non-specific neck pain: a systematic review. Eur. Spine J. 17 (7), 905e921.
bjartsson, A., et al., Kottner, J., Audige, L., Brorson, S., Donner, A., Gajewski, B.J., Hro 2011. Guidelines for reporting reliability and agreement studies (GRRAS) were proposed. Int. J. Nurs. Stud. 48 (6), 661e671. Lohkamp, M., Small, K., 2011. Normal response to upper limb neurodynamic test 1 and 2A. Man. Ther. 16 (2), 125e130.
e, J.-M., James, C.R., Day, M., et al., Lohman, C.M., Gilbert, K.K., Sobczak, S., Brisme 2015. 2015 young investigator award winner: cervical nerve root displacement and strain during upper limb neural tension testing: Part 1: a minimally invasive assessment in unembalmed cadavers. Spine (Phila Pa 1976) 40 (11), 793e800.
pez-de-Uralde-Villanueva, I., Beltran-Alacreu, H., Ferna
ndez-Carnero, J., GilLo Martínez, A., La Touche, R., 2016. Differences in neural mechanosensitivity between patients with chronic nonspecific neck pain with and without neuropathic features. A descriptive cross-sectional study. Pain Med. 17 (1), 136e148. Magnusson, S.P., Aagaard, P., Nielson, J.J., 2000. Passive energy return after repeated stretches of the hamstring muscle-tendon unit. Med. Sci. Sports Exerc. 32 (6), 1160e1164. Manchikanti, L., Singh, V., Datta, S., Cohen, S.P., Hirsch, J.A., 2009. Comprehensive review of epidemiology, scope, and impact of spinal pain. Pain Physician 12 (4), E35eE70. McNair, P.J., Dombroski, E.W., Hewson, D.J., Stanley, S.N., 2001. Stretching at the ankle joint: viscoelastic responses to holds and continuous passive motion. Med. Sci. Sports Exerc. 33 (3), 354e358.

17

Mokkink, L.B., Terwee, C.B., Patrick, D.L., Alonso, J., Stratford, P.W., Knol, D.L., et al., 2010. The cosmin study reached international consensus on taxonomy, terminology, and definitions of measurement properties for health-related patientreported outcomes. J. Clin. Epidemiol. 63 (7), 737e745. Ng, T.S., Pedler, A., Vicenzino, B., Sterling, M., 2014. Less efficacious conditioned pain modulation and sensory hypersensitivity in chronic whiplash-associated disorders in Singapore. Clin. J. Pain 30 (5), 436e442. Nitschke, J.E., Nattrass, C.L., Disler, P.B., Chou, M.J., Ooi, K.T., 1999. Reliability of the American medical association guides' model for measuring spinal range of motion. Its implication for whole-person impairment rating. Spine (Phila Pa 1976) 24 (3), 262e268. Oliver, G.S., Rushton, A., 2011. A study to explore the reliability and precision of intra and inter-rater measures of ULNT1 on an asymptomatic population. Man. Ther. 16 (2), 203e206. Petersen, C.M., Zimmermann, C.L., Hall, K.D., Przechera, S.J., Julian, J.V., Coderre, N.N., 2009. Upper limb neurodynamic test of the radial nerve: a study of responses in symptomatic and asymptomatic subjects. J. Hand Ther. 22 (4), 344e353. Portney, L.G., Watkins, M.P., 2009. Foundations of Clinical Research; Applications to Practice, third ed. Prentice Hall Health, Upper Saddle River, New Jersey. Riley, L.H., Long, D., 1995. The science of whiplash. Med. Baltim. 74 (5), 298e299. Schmid, A.B., Brunner, F., Luomajoki, H., Held, U., Bachmann, L.M., Künzer, S., et al., 2009. Reliability of clinical tests to evaluate nerve function and mechanosensitivity of the upper limb peripheral nervous system. BMC Musculoskelet. Disord. 10, 11. Shrout, P.E., Fleiss, J.L., 1979. Intraclass correlations: uses in assessing rater reliability. Psychol. Bull. 86 (2), 420e428. Smith, A.D., Jull, G., Schneider, G., Frizzell, B., Hooper, R.A., Sterling, M., 2013. A comparison of physical and psychological features of responders and nonresponders to cervical facet blocks in chronic whiplash. BMC Musculoskelet. Disord. 14, 313. Sterling, M., Treleaven, J., Jull, G., 2002. Responses to a clinical test of mechanical provocation of nerve tissue in whiplash associated disorder. Man. Ther. 7, 89e94. Talebi, G.A., Oskouei, A.E., Shakori, S.K., 2012. Reliability of upper limb tension test 1 in normal subjects and patients with carpal tunnel syndrome. J. Back Musculoskelet. Rehabil. 25 (3), 209e214. Taylor, J., Taylor, M., 1996. Cervical spinal injuries: an autopsy study of 109 blunt injuries. J. Musculoskelet. Pain 4 (4), 61e79. Tencer, A.F., Allen, B.L., Ferguson, R.L., 1985. A biomechanical study of thoracolumbar spine fractures with bone in the canal. Part III. Mechanical properties of the dura and its tethering ligaments. Spine (Phila Pa 1976) 10 (8), 741e747. Trainor, K., Pinnington, M.A., 2011. Reliability and diagnostic validity of the slump knee bend neurodynamic test for upper/mid lumbar nerve root compression: a pilot study. Physiotherapy 97 (1), 59e64. Tucker, N., Reid, D., McNair, P., 2007. Reliability and measurement error of active knee extension range of motion in a modified slump test position: a pilot study. J. Man. Manip. Ther. 15 (4), E85eE91. Vanti, C., Conteddu, L., Guccione, A., Morsillo, F., Parazza, S., Viti, C., et al., 2010. The upper limb neurodynamic test 1: intra- and intertester reliability and the effect of several repetitions on pain and resistance. J. Manip. Physiol. Ther. 33 (4), 292e299. Wainner, R.S., Fritz, J.M., Irrgang, J.J., Boninger, M.L., Delitto, A., Allison, S., 2003. Reliability and diagnostic accuracy of the clinical examination and patient selfreport measures for cervical radiculopathy. Spine (Phila Pa 1976) 28 (1), 52e62. Weir, J.P., 2005. Quantifying test-retest reliability using the intraclass correlation coefficient and the SEM. J. Strength Cond. Res. 19 (1), 231e240. Weppler, C.H., Magnusson, S.P., 2010. Increasing muscle extensibility: a matter of increasing length or modifying sensation? Phys. Ther. 90 (3), 438e449. Wyrwich, K.W., 2004. Minimal important difference thresholds and the standard error of measurement: is there a connection? J. Biopharm. Stat. 14 (1), 97e110.