Abstract
Objectives
Feline osteoarthritis causes pain and disability. Detection and measurement is challenging, relying heavily on owner report. This study describes refinement of the Montreal Instrument for Cat Arthritis Testing, for Use by Veterinarians.
Methods
A video analysis of osteoarthritic (n = 6) and non-osteoarthritic (n = 4) cats facilitated expansion of scale items. Three successive therapeutic trials (using gabapentin, tramadol and oral transmucosal meloxicam spray) in laboratory cats with and without natural osteoarthritis (n = 12–20) permitted construct validation (assessments of disease status sensitivity and therapeutic responsiveness) and further scale refinements based on performance.
Results
Scale osteoarthritic sensitivity improved from phase I to phase III; phase III scale total score (P = 0.0001) and 4/5 subcategories – body posture (P = 0.0006), gait (P = 0.0031), jumping (0.0824) and global distance examination (P = 0.0001) – detected osteoarthritic cats. Total score inter-rater (intra-class correlation coefficients [ICC] = 0.64–0.75), intra-rater (ICC = 0.90–0.91) and overall internal consistency (Cronbach’s alpha = 0.85) reliability were good to excellent. von Frey anesthesiometer-induced paw withdrawal threshold increased with gabapentin in phase I, in osteoarthritic cats (P <0.001) but not in non-osteoarthritic cats (P = 0.075). Night-time activity increased during gabapentin treatment. Objective measures also detected tramadol and/or meloxicam treatment effects in osteoarthritic cats in phases II and III. There was some treatment responsiveness: in phase I, 3/10 subcategory scores improved (P <0.09) in treated osteoarthritic cats; in phase II, 3/8 subcategories improved; and in phase III, 1/5 subcategories improved (P <0.096).
Conclusions and relevance
The revised scale detected naturally occurring osteoarthritis, but not treatment effects, in laboratory cats, suggesting future potential for screening of at-risk cats. Further study is needed to confirm reliability, validity (disease sensitivity and treatment responsiveness) and clinical feasibility, as well as cut-off scores for osteoarthritic vs non-osteoarthritic status, in client-owned cats.
Introduction
Osteoarthritis (OA) is common in cats; the radiographic prevalence of degenerative changes of the joints, including those associated with OA specifically, increases with age and is associated with pain and disability.1–4 Clinical trials of non-steroidal anti-inflammatory drugs (NSAIDs), meloxicam and robenacoxib, an anti-nerve growth factor (NGF) antibody, a therapeutic diet and dietary supplementation with long-chain omega-3 fatty acids have yielded improvements in mobility (eg, jumping) and activity (telemetric activity monitoring [AM] or subjective assessment), lameness/stiffness, mood and grooming.4–14
Subtle and non-specific osteoarthritic (OA) signs in this species may be incorrectly attributed to mere aging, contributing to under-diagnosis of feline OA.1,3 Clinical OA detection relies heavily on owner-reported historical abnormalities.1,15 Lameness has been reported,15,16 but appears less prominent,1,3 for example, than in canine OA. 17 In addition, joint pain upon manipulation and palpable abnormalities may be poorly reliable, 18 and do not correlate highly either with radiographic or historical OA signs.2,11,12,15,18–20
Difficulty detecting OA pain in cats impedes clinical case management, and novel drug testing. Recent studies describe objective and subjective (ie, pain scales) measures of feline OA pain and functional impairment. The former include AM,12,13,21 peak vertical ground reaction force (PVF),12,21–25 thermographic imaging, 20 functional bioimaging, 26 kinematics 27 and measures of central sensitization, eg, von Frey punctate tactile withdrawal threshold (VF),21,25 response to mechanical temporal summation (RMTS)24,28,29 and thermal sensitivity. 25 These measures show promise but have practical limitations for clinical use, although a recent report supports the repeatability, ability to detect OA status and feasibility of VF in naïve, client-owned cats. 25
Pain scales improve objectivity and facilitate comparisons within and between individuals. 30 They must be shown to measure the phenomenon of interest (eg, feline OA pain) reliably (ie, minimizing error), in the context of interest (eg, by the veterinarian, in the clinic). 31 Aspects of reliability include inter-rater (agreement between raters), intra-rater (repeatability over time given unchanged subject status) and internal consistency reliability (interrelatedness of scale components).31,32 Validation may include face (target user acceptability) and content (completeness/representativeness) validation, as well as criterion validation (ie, gold-standard comparison). 31 Construct validation for phenomena that are not directly measurable (eg, pain) comprises hypothesis testing (eg, therapeutic response, known group distinction such as OA/non-OA), and convergence with or divergence from, respectively, measures of related (eg, activity or weight-bearing) or unrelated (eg, temperament, sedation) phenomena.31,32 Reported feline OA owner scales include two standardized scales and a client-specific outcome measures questionnaire,5,13,33–36 but distinction between treatment and placebo effects remains challenging.9,35,36 It is not known to what extent owner characteristics (eg, attentiveness) influence owner scale outcomes, and no other veterinary feline OA scales have been reported.
Development and preliminary validation for the Montreal Instrument for Cat Arthritis Testing, for use by Veterinarians (MI-CAT[V]), have been described. 18 This study’s broad goal was refinement to improve scale OA sensitivity, and re-evaluation of validity and reliability in laboratory cats. Specific objectives included comparison of OA and non-OA cats to facilitate expansion of scale criteria, and subsequent comparisons of scale outcomes for: (1) OA vs non-OA cats; (2) OA cats before vs after treatment; (3) treatment-associated changes in OA vs non-OA cats; and (4) variation within and between veterinarians. Refinement of the standardized MI-CAT(V) assessment was hypothesized to improve sensitivity to clinical OA in cats, while maintaining reliability.
Materials and methods
Ethics
The Institutional Animal Care and Use Committee approved the study (#Rech-1482, #Rech-1757). Cat care and handling adhered to the Canadian Council on Animal Care’s guidelines.
Animals
Cats were group-housed in temperature- and humidity-controlled rooms containing environmental enrichment (access to windows, perches, covered and uncovered beds, scratching posts and toys). Lights were turned on at 7 AM and turned off at 7 PM. A standard, certified, commercial diet (Hill’s Prescription Diet w/d Feline; Hill’s Pet Nutrition) was fed according to the manufacturer’s directions; water was supplied ad libitum. Cats had no clinically significant abnormalities on complete blood count (CBC), serum chemistry (SC; including T4), and urinalysis, nor changes on general, neurologic and orthopedic physical examinations other than those compatible with OA. Neither NSAID nor glucocorticoid administration was permitted for 4 or 8 weeks, respectively, preceding any study phase.
A board-certified veterinary radiologist analyzed digital radiographs of the appendicular joints, taken under sedation with intramuscular medetomidine (0.02 mg/kg Domitor 1 mg/ml; Zoetis Canada) and morphine (0.1–0.2 mg/kg Morphine Sulfate Injection 10 mg/ml; Sandoz). 12 Joints (views) assessed included the stifle (mediolateral and caudocranial), coxofemoral (ventrodorsal and lateral), carpal (dorsopalmar), tarsal (dorsoplantar), shoulders and elbows (mediolateral). Non-OA cats had neither radiographic nor orthopedic examination signs of OA at screening. OA cats had radiographic OA in at least one appendicular joint, and orthopedic examination abnormalities consistent with OA in the video analysis and phase I validation study (see below).
Subjective assessments were performed either in a 4.9 × 3.2 m (video analysis and phase I), a 4.1 × 4.0 m (phase II) or a 3.0 × 3.0 m (phase III) room, containing either a two-level (38 cm and 90 cm) examination table and/or a chair with a seat height of 44 cm. Cats were encouraged to move about and to jump up and down by calling, tossing treats or toys, petting or brushing. All evaluators were blinded to cat OA and treatment status.
Video analysis
Six OA and four non-OA cats were videotaped individually while moving about an examination room. Four evaluators (one board-certified veterinary surgeon, two board-certified veterinary behaviorists, one veterinary student) reviewed the videos under blinded conditions. Evaluators were simply asked in an open-ended manner to identify criteria, particularly pertaining to posture, gait and willingness to move about, which varied between cats. These were used to formulate new items and detailed evaluation procedure instructions, and to reformat response options. The MI-CAT(V)-v3 (Appendix A, supplementary material) included 67 ordinal scale items in 10 subcategories: body posture – back (BP-B); body posture – forelimbs (BP-F); body posture – hindlimbs (BP-H); gait – general; gait – forelimbs (G-F); gait – hindlimbs (G-H); willingness and ease of horizontal movements (WEHM); standing up on hindfeet to investigate a higher surface (SUHF); jumping; other behaviors (OB).
Validation phase I
Sensitivity to OA and responsiveness to treatment were assessed via a therapeutic trial. A power calculation based on mean VF anesthesiometer-induced paw withdrawal threshold (PWT; power = 0.80, alpha = 0.05, one-sided PWT increase from 60 g to 80 g) yielded a minimum sample size of six OA cats. Gabapentin (gabapentin 100 mg/ml oral suspension; Gentès & Bolduc Pharmaciens) was administered to seven OA and five non-OA cats, at a dose of 10 mg/kg orally three times daily, for 30 days. Additional inclusion criteria were the presence (OA) or absence (non-OA) of allodynia, as described below. See Figure 1 for study design.
Figure 1.
Validation phase I trial design. OA = osteoarthritic; D = day; W = week; AM = locomotor activity monitoring; SOE = surgeon’s orthopedic evaluation; PWT = von Frey anesthesiometer-induced paw withdrawal threshold; MI-CAT(V) = Montreal Instrument for Cat Arthritis Testing, for Use by Veterinarians
The MI-CAT(V), a surgeon’s orthopedic evaluation (SOE) (Appendix B, supplementary material) and PWT assessments were completed once at baseline (day [D] –7/–6) and twice during the treatment period (D15/16 and D29/30). Cats wore AM sensors from D –12 to D30; night-time AM (NAM) data (6 PM to 5.58 AM) collected from Friday to Monday were considered for analysis,12,21 for D –12 to D –9 (baseline), D3–D6 (week [W] 1), D10–D13 (W2), D17–D20 (W3) and D24–D27 (W4).
PWT
Allodynic status was determined based on measurements of perpendicular pressure on the palmar/plantar aspect of the paw in standing cats, using a mechanical VF polypropylene probe (Rigid Tip 0.7 mm2 28 G; IITC Life Science). 12 Peak force was measured twice per paw, 60 s apart, with stimulus cessation upon paw withdrawal/behavioral signs of pain. Data under 2 g were discarded, and a maximal cut-off of 200 g was applied. The allodynia threshold was 50 g for front- and hindpaws, based on the data distribution. All OA cats had at least one paw with a mean threshold <50 g and duplicate measurements <60 g. Non-OA cats had single paw mean thresholds ⩾60 g, and no duplicate measurements for any paw <80 g. The PWT was calculated by averaging available measurements (n = 8) for each cat, at each time point.
AM
Collar-mounted accelerometer-based activity sensors (ActiWatch-mini; Minimitter, Bio-Lynx Scientific Equipment) made counts every 2 mins; numeric amplitude (0 to infinite, no unit) was based on intensity. 12
Subjective measures
A board-certified veterinary behaviorist (MK) completed the MI-CAT(V)-v3. A board-certified veterinary surgeon (BL) performed the SOE (Appendix B, supplementary material), consisting of palpation/manipulation of each axial segment and appendicular joint for pain (numerical rating scale [NRS], 0–10) or physical abnormalities (heat, edema, thickening, effusion, instability, crepitus, reduced range of motion; scored as present/absent) and distance observation for lameness (NRS, 0–10; based on evaluation of gait, posture and ease of movements, such as when rising from a recumbent position).
Scale revisions
Subsection and individual item (data not shown) performance guided scale modifications. A global distance examination (GDE; lameness) was added. Next, a veterinarian naïve to the scale (BM) evaluated the MI-CAT(V) for clarity and ease of use. Altered scoring, minor rewording, reordering and removal of several items, and condensing of the gait subcategories into one, and the jumping and SUHF subcategories into one, produced the MI-CAT(V)-v4 (Appendix C, supplementary material), with 44 items in eight subcategories.
Validation phase II
Scale internal consistency and inter- and intra-rater reliability, and detection of OA status and response to treatment (construct validity), were assessed via a therapeutic trial, details of which have been previously described in the context of a study assessing treatment effects via objective measures (PVF, NAM, RMTS).24,29 See Figure 2 for the trial design. A power calculation based on phase I MI-CAT(V) data (power = 0.80, α = 0.05, MI-CAT[V] one-sided total score decrease from 0.25 to 0.18) yielded a minimum sample size of 13 OA cats. Fifteen OA and five non-OA cats participated at baseline (D –7 to –1). OA cats were then randomly assigned to two treatment groups, with observers blinded to treatments and OA status. In period 1 (D1–D33), group A (n = 7) received placebo (15 mg corn starch) and group B (n = 8) received identically appearing tramadol (3 mg/kg Tramadol HCl; Gentès & Bolduc Pharmaciens), orally twice daily. 24 In period 2 (D33–D54), meloxicam oral transmucosal spray (OTMS; approximately 0.05 mg/kg OroCAM Oral TransMucosal Spray, 0.25 mg/spray [Abbott Animal Health]) was also given (group A: placebo and OTMS; group B: tramadol and OTMS). 29
Figure 2.
Validation phase II trial design. OA = osteoarthritic; D = day; W = week; MI-CAT(V) = Montreal Instrument for Cat Arthritis Testing, for Use by Veterinarians; OTMS = meloxicam oral transmucosal spray
Two evaluators, one familiar with (MK) and one new to the MI-CAT(V)-v4 (BM), completed it at D –7, D –3 (baseline), D17, D19 (W3), D29, D33 (W5), D52 and D54 (W8). Naïve evaluator training involved reviewing video examples (n = 3 cats) of scale criteria at different score levels and practicing the MI-CAT(V)-v4 evaluation procedure with two of her own cats.
Scale revisions
Subsection and individual item (data not shown) performance-guided scale modifications, comprising minor changes to instructions, removal of several items (including the OB subcategory), condensing of body posture subcategories into one and scoring changes. The MI-CAT(V)-v5 had 25 items in five subcategories (Appendix D, supplementary material).
Validation phase III
Scale internal consistency and inter- and intra-rater reliability, and detection of OA status and response to treatment, were assessed via a therapeutic trial, details of which have been previously described in the context of a study assessing treatment effects via objective measures (PVF, NAM, RMTS). 24 See Figure 3 for trial design. Cats (n = 13 OA, n = 6 non-OA) had participated in phase II with the following changes: two OA cats were unavailable, 24 and an additional non-OA cat was included. OA and non-OA cats participated at baseline (D –13 to D –1). OA cats received tramadol or placebo (as described above), based on a their phase II – period 1 treatment group assignment (crossover). Those having received placebo in phase II – period 1 received tramadol in phase III, as described above, and vice versa; group A (n = 6) received tramadol and group B (n = 7) received placebo, from D1 to D19. MI-CAT(V)-v5 assessments were performed at D –13, D –1, D17 and D19, by two veterinarians (MK and BM), with observers blinded to treatments and OA status.
Figure 3.
Validation phase III trial design. OA = osteoarthritic; D = day; MI-CAT(V) = Montreal Instrument for Cat Arthritis Testing, for Use by Veterinarians
Statistical methods
All analyses were conducted with statistical software (SAS system, version 9.3 [SAS Institute], and SPSS Statistics for Macintosh, version 20 or 24 [IBM]). Data were assessed for normality using the Shapiro–Wilk test. Model covariance structures were based on information criteria. An exploratory α level was set at 0.10 for subjective measures, with no corrections for multiple comparisons, to maximize the chances of significant results in a comparative pilot study setting of MI-CAT(V) and SOE with such small sample size. It is acceptable to set a higher α value, when the goal of the study is to find an effect that could lead to a promising scientific discovery. This allows us not only to increase the power and consequently decrease the risk of type II error, but also increases the chances of making a type I error (ie, saying there is a difference when there is not); α = 0.05 in all other instances. Analyses were two-tailed, except as noted below.
Phase I
Analyses were one-tailed for treatment effects in OA cats (H0 = treatment does not improve outcomes; H1 = treatment improves outcomes). 37 Treatment effect on PWT was analyzed via a linear mixed model for repeated measures (fixed effects: day, OA group and their interaction; compound symmetry covariance structure). For each NAM evaluation period (3 days × 12 h), every 10 successive NAM recordings (ie, over 20 mins) were averaged from 6 PM to 5.58 AM, yielding 108 average NAM values for each period (baseline, W1, W2, W3, W4) for each cat. Log-plus-one-transformed means were analyzed via a generalized estimating equation model (fixed effects: time, OA status and their interaction; repeated measurements: time, day [Friday– Monday] and recordings; exchangeable covariance structure). Total MI-CAT(V) and subsection 1–10 scores were sums of individual item scores. Total SOE score was the sum of all pain and other physical abnormality scores (maximum possible = 334); this was also subdivided into total axial score (maximum possible = 52) and total individual limb scores (maximum possible for each = 68). Total pain score was the sum of axial segment and appendicular joint pain scores (maximum possible = 210); total palpation score was the sum of pain and physical abnormalities scores for all axial and appendicular joints (maximum possible = 324). Long bone scores were used only to rule out orthopedic abnormalities unassociated with the joints. Non-parametric Wilcoxon rank sum tests (baseline; OA vs non-OA) and Wilcoxon signed rank tests (pre- vs post-treatment) were used for MI-CAT(V) and SOE score analyses.
Phases II and III
The MI-CAT(V)-v4/v5 total score was a percentage of the maximum possible score (Appendices B and C, supplementary material). Exact Wilcoxon–Mann–Whitney tests evaluated sensitivity to OA status (phase II D –7; phase III D –13). Treatment effect was analyzed via a generalized linear mixed model (fixed effects: treatment group, week and their interaction; random effect: cat; compound symmetry covariance structure; phase II – period 1: baseline vs W3 and W5) or paired t-tests (phase II – period 2: baseline vs W8; phase III: baseline vs D19). Internal consistency was assessed using Cronbach’s α (phase II: D –7, D –3; phase III: D –1), based on the experienced evaluator’s (MK) scores. Average measures for two-way random intra-class correlation coefficients assessing for consistency are reported for inter-rater (phase II: D –7, D52; phase III: D –13, D17) and intra-rater (phase II: D –7 and D –3, D52 and D54; phase III: D –13 and D –1, D17 and D19) reliability. Interpretation was as follows: <0.40 = poor; 0.40–0.59 = fair; 0.60–0.74 = good; 0.75–1.00 = excellent. 38
Results
Phase I
Mean age was 5.98 years (range 2.3–12.4 years) for non-OA cats and 8.27 years (range 4.3–12.4 years) for OA cats. No serious adverse events attributable to gabapentin were noted on clinical, CBC and SC analyses. No long-bone abnormalities were detected on the SOE. See Table 1 for OA vs non-OA MI-CAT(V) results. Only WEHM detected OA status (P = 0.048); no aspect of the SOE did so (P ⩾0.537). Table 2 presents MI-CAT(V)-v3 results for OA cats at baseline vs D29. Following treatment, OA cat scores decreased significantly (improved) for BP-B (P = 0.09), G-F (P = 0.055) and SUHF (P = 0.0785); G-H scores increased (P = 0.09). For the SOE, only the distance score improved (P = 0.055). Treatment did not affect MI-CAT(V) and SOE scores for non-OA cats.
Table 1.
Phase I baseline comparison of Montreal Instrument for Cat Arthritis Testing, for Use by Veterinarians version 3 (MI-CAT[V]-v3) scores, expressed as median (range), for osteoarthritic (OA) and non-OA cats
| Scale component assessed | OA cats (n = 7) |
Non-OA cats (n = 5) |
P value |
|---|---|---|---|
| 1 Body posture – back | 0 (0–3) | 1 (0–3) | 0.530 |
| 2 Body posture – forelimbs | 1 (0–3) | 1 (0–1) | 1.000 |
| 3 Body posture – hindlimbs | 3 (0–8) | 1 (1–3) | 0.268 |
| 4 Gait – general | 1 (0–4) | 2 (0–5) | 0.432 |
| 5 Gait – forelimbs | 0 (0–3) | 1 (0–5) | 0.343 |
| 6 Gait – hindlimbs | 1 (0–2) | 0 (0–4) | 0.639 |
| 7 Willingness and ease of horizontal movements | 4 (0–8) | 0 (0–3) | 0.048* |
| 8 Standing up on hind feet to investigate a higher surface | 0 (0–4) | 0 (0–0) | 0.432 |
| 9 Jumping | 5 (1–7) | 6 (2–7) | 0.202 |
| 10 Other behaviors | 0 (0–1) | 0 (0–2) | 0.876 |
| Total MI-CAT(V)-v3 score | 13 (6–28) | 16 (7–26) | 0.755 |
P <0.10
Table 2.
Phase I Montreal Instrument for Cat Arthritis Testing, for Use by Veterinarians version 3 (MI-CAT[V]-v3) scores, expressed as median (range), over time in osteoarthritic cats (n = 7)
| Scale component assessed | Baseline | Day 29 | P value |
|---|---|---|---|
| 1 Body posture – back | 0.5 (0–3) | 0 (0–2) | 0.090* |
| 2 Body posture – forelimbs | 1 (0–3) | 1 (0–2) | 0.3537 |
| 3 Body posture – hindlimbs | 2.5 (0–8) | 2.5 (0–7) | 0.200 |
| 4 Gait – general | 1 (0–5) | 1 (0–3) | 0.340 |
| 5 Gait – forelimbs | 1 (0–5) | 0 (0–3) | 0.055* |
| 6 Gait – hindlimbs | 1 (0–4) | 1 (1–5) | 0.090* |
| 7 Willingness and ease of horizontal movements | 2.5 (0–8) | 2.5 (0–8) | 0.4331 |
| 8 Standing up on hind feet to investigate a higher surface | 0 (0–4) | 0 (0–2) | 0.0785* |
| 9 Jumping | 5 (1–7) | 4 (2–6) | 0.399 |
| 10 Other behaviors | 0 (0–2) | 0 (0–1) | 0.1593 |
| Total MI-CAT(V)-v3 score | 14.5 (6–28) | 15 (10–25) | 0.3687 |
Gabapentin was administered three times daily from days 1–30
P <0.10
OA status (P = 0.012), time (P = 0.001) and their interaction (P = 0.041) significantly affected PWT. Figure 4 shows OA and non-OA mean PWT over time; the univariate effect of time was significant for OA (P <0.001) but not non-OA cats (P = 0.075).
Figure 4.
Validation phase I osteoarthritic (OA) vs non-OA group mean (confidence intervals [CIs]) values for paw withdrawal threshold (PWT) over time. All cats received gabapentin three times daily from days 1 to 30. Error bars represent 95% CIs. The univariate effect of day was significant in OA (P <0.001) but not in non-OA (P = 0.075) cats. *Statistically significant (P <0.05) difference between groups
Baseline NAM was higher for non-OA than OA cats (P = 0.01). OA cats’ NAM increased from baseline during gabapentin treatment (P <0.0001), beginning at W1 (P <0.0001) (Table 3). Non-OA cats’ NAM also increased during treatment (P <0.0001), and remained higher than OA cats’ NAM (P = 0.027).
Table 3.
Night-time locomotor activity monitoring (NAM) for osteoarthritic (OA) and non-OA cats over time, expressed as mean (SE) of the log-plus-one-transformed mean nightly (6 PM to 5.58 AM) activity for the period (n = 108 averaged recordings over each period for each cat). All cats received gabapentin three times daily from weeks 1–4
| Group | Baseline | Week 1 | Week 2 | Week 3 | Week 4 |
|---|---|---|---|---|---|
| Non-OA (n = 5) | 0.519 (0.037)* | 0.584 (0.387) † | 0.615 (0.044) † | 0.600 (0.022) † | 0.559 (0.042) |
| OA (n = 7) | 0.350 (0.054)* | 0.455 (0.035) † | 0.465 (0.054) † | 0.521 (0.072) † | 0.453 (0.063) |
Significant between-group difference (P = 0.01)
Significantly different from baseline (P <0.05)
Phase II
Mean age was 3.25 years (range 2.75–4 years) for non-OA and 10.64 years (range 9.75–11.75 years) for OA cats. One OA cat was withdrawn for allergic dermatitis, as described elsewhere. 24 Table 4 shows baseline MI-CAT(V) results for OA vs non-OA cats; BP-H (P = 0.0074) and jumping (P = 0.085) detected OA status. Total scale inter-rater (⩾0.85), intra-rater (⩾0.88) and internal consistency (⩾0.84) reliability were excellent (Tables 5, 6 and 7).
Table 4.
Phase II baseline comparison of Montreal Instrument for Cat Arthritis Testing, for Use by Veterinarians version 4 (MI-CAT[V]-v4) scores (based on percentage of maximum possible score; range 0–1), expressed as mean (SD), for osteoarthritic (OA) and non-OA cats
| Scale component assessed | OA cats (n = 15) |
Non-OA cats (n = 5) |
P value |
|---|---|---|---|
| 1 Body posture – back | 0.23 (0.15) | 0.18 (0.11) | 0.5853 |
| 2 Body posture – forelimbs | 0.08 (0.05) | 0.08 (0.03) | 0.8785 |
| 3 Body posture – hindlimbs | 0.15 (0.09) | 0.04 (0.04) | 0.0074* |
| 4 Gait | 0.26 (0.19) | 0.12 (0.06) | 0.1705 |
| 5 Willingness and ease of horizontal movements | 0.34 (0.15) | 0.43 (0.08) | 0.1406 |
| 6 Jumping | 0.25 (0.14) | 0.14 (0.06) | 0.0895* |
| 7 Other behaviors | 0.08 (0.17) | 0.00 (0.00) | 0.5395 |
| 8 Global distance examination (lameness) | 0.35 (0.28) | 0.12 (0.13) | 0.1471 |
| MI-CAT(V)-v4 final score | 0.22 (0.09) | 0.15 (0.05) | 0.1035 |
P <0.10
Table 5.
Phase II Montreal Instrument for Cat Arthritis Testing, for Use by Veterinarians version 4 (MI-CAT[V]-v4) inter-rater reliabilities
| Scale component assessed | Day –7 (n = 20) |
Day 52 (n = 14) |
||
|---|---|---|---|---|
| ICC | 95% CI | ICC | 95% CI | |
| 1 Body posture – back | 0.833 | 0.578–0.934 | 0.864 | 0.576–0.956 |
| 2 Body posture – forelimbs | 0.458 | −0.370 to 0.785 | 0.464 | −0.669 to 0.828 |
| 3 Body posture – hindlimbs | 0.686 | 0.207–0.876 | 0.833 | 0.479–0.946 |
| 4 Gait | 0.676 | 0.182–0.872 | 0.687 | 0.026–0.900 |
| 5 Willingness and ease of horizontal movements | 0.778 | 0.438–0.912 | 0.964 | 0.888–0.988 |
| 6 Jumping | 0.883 | 0.704–0.954 | 0.930 | 0.781–0.977 |
| 7 Other behaviors | 0.636 | 0.079–0.856 | 0.952 | 0.851–0.985 |
| 8 Global distance examination (lameness) | 0.767 | 0.411–0.908 | 0.775 | 0.261–0.931 |
| MI-CAT(V)-v4 final score | 0.850 | 0.620–0.940 | 0.896 | 0.675–0.967 |
Bold indicates excellent reliability coefficients
ICC = intra-class correlation coefficient; CI = confidence interval
Table 6.
Phase II Montreal Instrument for Cat Arthritis Testing, for Use by Veterinarians version 4 (MI-CAT[V]-v4) intra-rater reliabilities
| Scale component assessed | Days –7 and –3 (n = 20) |
Days 52 and 54 (n = 14) |
||
|---|---|---|---|---|
| ICC | 95% CI | ICC | 95% CI | |
| 1 Body posture – back | 0.770 | 0.420–0.909 | 0.745 | 0.204–0.918 |
| 2 Body posture – forelimbs | 0.433 | −0.432 to 0.776 | 0.850 | 0.532–0.952 |
| 3 Body posture – hindlimbs | 0.797 | 0.487–0.920 | 0.794 | 0.360–0.934 |
| 4 Gait | 0.917 | 0.791–0.967 | 0.918 | 0.744–0.974 |
| 5 Willingness and ease of horizontal movements | 0.466 | −0.349 to 0.789 | 0.857 | 0.556–0.954 |
| 6 Jumping | 0.837 | 0.588–0.935 | 0.546 | −0.415 to 0.854 |
| 7 Other behaviors | 0.689 | 0.215–0.877 | 0.864 | 0.575–0.956 |
| 8 Global distance examination (lameness) | 0.962 | 0.903–0.985 | 0.978 | 0.927–0.993 |
| MI-CAT(V)-v4 final score | 0.885 | 0.709–0.954 | 0.897 | 0.679–0.967 |
Bold indicates excellent reliability coefficients
ICC = intra-class correlation coefficient; CI = confidence interval
Table 7.
Phase II Montreal Instrument for Cat Arthritis Testing, for Use by Veterinarians version 4 internal consistency reliabilities based on experienced evaluator’s assessments, expressed as Cronbach’s alpha (95% confidence interval)
| Assessment time | OA cats (n = 15) |
Non-OA cats (n = 5) |
All cats (n = 20) |
|---|---|---|---|
| Day –7 | 0.847 (0.69–0.95) | 0.743 (0.25–0.97) | 0.842 (0.71–0.93) |
| Day –3 | 0.858 (0.72–0.95) | 0.810 (0.35–0.99) | 0.880 (0.78–0.95) |
OA = osteoarthritic
Neither tramadol treatment, week nor their interaction significantly affected total MI-CAT(V) score (P >0.26), despite positive responses of objective outcomes (PVF, NAM and RMTS), such as described elsewhere. 24 Gait (P = 0.0199) and GDE (P = 0.0682) decreased with week (period 1, tramadol group). Gait improved with OTMS (P = 0.096) and BP-H with tramadol + OTMS (P = 0.042), but total MI-CAT(V)-v4 score did not (P >0.79) (period 2); objective outcomes responded to treatment (PVF in both groups, NAM in OTMS and RMTS in tramadol + OTMS), such as described elsewhere. 29
Phase III
Mean age was 3.38 years (range 2.75–4 years) for non-OA and 10.78 years (range 9.75–11.75 years) for OA cats. Scale completion took approximately 10 mins per cat. Total MI-CAT(V)-v5 score, and all subcategories except WEHM, detected OA status (Table 8). Total score reliability was good to excellent for inter-rater (0.64–0.75) and excellent for intra-rater (0.79–0.91) reliability; internal consistency was acceptable (overall α = 0.85) (Tables 9, 10 and 11). Only jumping improved (P = 0.064) with tramadol treatment; total MI-CAT(V)-v5 score did not (P = 0.9347), nor did treatment and placebo effects on scores differ (P = 0.4244), despite positive responses of objective outcomes (PVF, NAM and RMTS), such as described elsewhere. 24 Worsening of WEHM (P =0.028) occurred with tramadol treatment.
Table 8.
Phase III baseline comparison of Montreal Instrument for Cat Arthritis Testing, for Use by Veterinarians version 5 (MI-CAT[V]-v5) scores (based on percentage of maximum possible score; range 0–1), expressed as mean (SD) for osteoarthritic (OA) and non-OA cats
| Scale component assessed | OA cats (n = 13) |
Non-OA cats (n = 6) |
P value |
|---|---|---|---|
| 1 Body posture | 0.30 (0.10) | 0.11 (0.03) | 0.0006* |
| 2 Gait | 0.28 (0.20) | 0.04 (0.05) | 0.0031* |
| 3 Willingness and ease of horizontal movements | 0.24 (0.15) | 0.15 (0.05) | 0.2020 |
| 4 Jumping | 0.30 (0.19) | 0.13 (0.14) | 0.0824* |
| 5 Global distance examination (lameness) | 0.37 (0.23) | 0.05 (0.05) | 0.0001* |
| Total MI-CAT(V)-v5 score | 0.30 (0.12) | 0.09 (0.04) | 0.0001* |
P <0.10
Table 9.
Phase III Montreal Instrument for Cat Arthritis Testing, for Use by Veterinarians version 5 (MI-CAT[V]-v5) inter-rater reliabilities
| Scale component assessed | Day –13 (n = 19) |
Day 17 (n = 13) |
||
|---|---|---|---|---|
| ICC | 95% CI | ICC | 95% CI | |
| 1 Body posture | 0.70 | 0.37–0.87 | 0.24 | 0.00–0.69 |
| 2 Gait | 0.59 | 0.20–0.82 | 0.47 | 0.00–0.80 |
| 3 Willingness and ease of horizontal movements | 0.61 | 0.23–0.83 | 0.70 | 0.26–0.90 |
| 4 Jumping | 0.50 | 0.07–0.77 | 0.40 | 0.00–0.77 |
| 5 Global distance examination (lameness) | 0.72 | 0.41–0.88 | 0.66 | 0.20–0.88 |
| Total MI-CAT(V)-v5 score | 0.75 | 0.46–0.90 | 0.64 | 0.17–0.88 |
Bold indicates excellent reliability coefficients
ICC = intra-class correlation coefficient; CI = confidence interval
Table 10.
Phase III Montreal Instrument for Cat Arthritis Testing, for Use by Veterinarians version 5 (MI-CAT[V]-v5) intra-rater reliabilities
| Scale component assessed | Days –13 and -1 (n = 19) |
Days 17 and 19 (n = 13) |
||
|---|---|---|---|---|
| ICC | 95% CI | ICC | 95% CI | |
| 1 Body posture | 0.79 | 0.54–0.91 | 0.66 | 0.20–0.88 |
| 2 Gait | 0.85 | 0.65–0.94 | 0.86 | 0.60–0.95 |
| 3 Willingness and ease of horizontal movements | 0.45 | 0.01–0.74 | 0.31 | 0.00–0.72 |
| 4 Jumping | 0.50 | 0.08–0.77 | 0.66 | 0.18–0.89 |
| 5 Global distance examination (lameness) | 0.97 | 0.92–0.99 | 0.92 | 0.77–0.98 |
| Total MI-CAT(V)-v5 score | 0.91 | 0.79–0.97 | 0.90 | 0.72–0.97 |
Bold indicates excellent reliability coefficients
ICC = intra-class correlation coefficient; CI = confidence interval
Table 11.
Phase III Montreal Instrument for Cat Arthritis Testing, for Use by Veterinarians version 5 internal consistency reliabilities based on experienced evaluator’s assessments, expressed as Cronbach’s alpha (95% confidence interval)
| Assessment time | OA cats (n = 13) | Non-OA cats (n = 6) | All cats (n = 19) |
|---|---|---|---|
| Day –1 | 0.73 (0.41–0.92) | 0.12 (–1.67 to 0.86) | 0.85 (0.72–0.94) |
OA = osteoarthritic
Discussion
The MI-CAT(V) was designed to complement veterinary examination of cats at risk for OA, but it previously lacked sensitivity. 18 This report describes scale refinement and validation. Phases I–III assessed various versions of the revised scale for ability to detect OA status and treatment effects, with modifications (eg, item removal, wording/scoring changes), based on item/subcategory performance. The resulting MI-CAT(V)-v5 distinguished OA from non-OA cats and was reliable. It did not detect OA treatment effects, despite apparent treatment responsiveness of some subcategories in each phase, and despite responses of objective measures (PVF, NAM, RMTS; reported elsewhere) to treatments.24,29
In phase I, it was expected that several new scale items would contribute ‘noise’ to the total score or might be miscoded; indeed, only one MI-CAT(V)-v3 subcategory, WEHM, detected OA. The SOE did not discriminate OA status, aligning with previous findings.18,19 Detection of a gabapentin treatment effect in OA but not in non-OA cats by three scale subcategories, BP-B, G-F, and SUHF, and SOE distance score was cautiously interpreted (owing to the lack of a placebo group for comparison, and results of objective assessments described above and discussed below) as promising. The distance score subsequently included in the MI-CAT(V)-v4 is comparable to lameness scores used in other species (eg, dog, horse, cow, sow) but not reported in cats.39–42 Prior reports conflict regarding lameness as a feature of feline OA.1,3,15
In phases II and III, OA detection improved, with the MI-CAT(V)-v5 total score and most scale subcategories detecting OA. This was despite a reduction in the number of items, and it supports the scale refinements made between study phases, particularly with respect to the selection of items for retention vs removal. Disappointingly, total MI-CAT(V) score detected no treatment effects in the placebo-controlled trials of phases II and III, though objective measures24,29 and individual subcategories (BP-H, gait, jumping), did. Difficulty detecting therapeutic responses with the MI-CAT(V) and SOE underscores the challenges facing veterinarians when evaluating OA pain in cats.
Scale internal consistency between 0.70 and 0.90 (for OA cats, or all cats) indicated item relatedness, without redundancy. 31 Lower internal consistency in non-OA cats (phase III) is of little concern (the scale targets cats with/at risk for OA), and was likely due to fewer scale items and sample homogeneity.31,43 However, it should be noted that the large number of scale items likely inflated the Cronbach α results; future, larger-scale studies should assess relationships between scale components via factor analysis. Total score inter- and intra-rater reliability were good to excellent. Inter-rater and intra-rater reliability for most scale subcategories was good to excellent in phase II, with mild inter-rater reliability improvements between assessments. Detailed evaluation instructions and training prior to scale use minimized the impact of inexperience with the scale (naïve evaluator). Weaker subcategory inter- and intra-rater reliabilities in phase III may have resulted from the reduced number of scale items. The GDE subcategory performed generally well. Gait had lower inter- than intra-rater reliability, suggesting a systematic difference between evaluators; more user training may be needed. The same was the case for jumping in phase III. Subcategories BP-B and BP-H performed well, but BP-F performed similarly to gait (phase II), and body posture (phase III) had inconsistent inter-rater reliability, again suggesting a need for more user training. Better WEHM inter- than intra-rater reliability could indicate day-to-day instability, which, combined with poorer OA detection and therapeutic responsiveness in phase III, may warrant item revisions or removal. However, tramadol may have behavioral effects (eg, sedation, agitation, dysphoria); such effects could have contributed to WEHM’s poor response to treatment.44,45 Elimination of several jumping and WEHM items after phase II may have decreased reliability.
Gabapentin has been recommended for feline neuropathic and OA pain.46,47 To our knowledge, this is the first reported therapeutic trial of gabapentin in feline OA, 48 although one case report described a positive response. 49 Improvements in PWT and NAM are promising, despite the small number of cats and lack of a placebo group; however, OA cats without central sensitization may respond differently to gabapentin. Therapeutic responsiveness of AM in feline OA is well established for meloxicam (oral suspension or OTMS), tramadol, a therapeutic diet and anti-NGF monoclonal antibody,9,10,12,13,24,29 but high inter-individual variability generally limits comparisons between individuals. 50 Baseline NAM in phase I distinguished non-OA from OA cats. Greater age in OA than in non-OA cats could have contributed to this, but previous studies having similar sample sizes and greater OA vs non-OA group age disparities have not reported distinction of OA status.12,21,24,26 All participating OA cats had evidence of central sensitization (allodynia), which affects a subset of humans and cats with OA;12,51 this may have contributed to activity differences between OA and non-OA cats. OA cats had decreased allodynia on gabapentin (beginning D16); non-OA cats’ PWT also tended to increase, later in treatment. Based on the latter and the small sample size, further research is needed to confirm effects of gabapentin on central sensitization, as measured by PWT. OA and non-OA cats’ NAM both increased (beginning W1). Undetected causes of neuropathic pain, other than OA, could have influenced non-OA cat activity, and responded to gabapentin. Alternatively, gabapentin or other study influences may have had non-analgesic effects on both groups’ NAM. Different aspects of OA pain are measured by PWT and NAM; PWT appears less susceptible to non-specific effects of gabapentin. The combination of ability to detect feline OA-associated central sensitization, 12 its apparent response to treatment with gabapentin and tramadol, 24 and the recent finding that it is moderately reliable, valid and clinically feasible in naïve, client-owned cats 25 suggest further investigation of PWT as a diagnostic modality for feline clinical practice would be worthwhile.
There is a lack of consensus on the determination of sample sizes in scale validation studies, but our samples were small compared with those typically recommended for human health measurement scale validation. 52 This, and the use of the same cats in phases II and III, could have favored selection of OA characteristics particular to the sample. Results also may not translate from the laboratory colony to the clinical setting (eg, owing to poorer compliance of client-owned cats, variability in the time cats have to acclimate to the examination room and examiner, or the influences of unrelated procedures on cat behavior). We would argue that many cats can be persuaded, using treats, vocal encouragement, petting, brushing, etc, to move about an examination room, 53 giving the MI-CAT(V) potential for clinical application.
Feline OA evaluation relies heavily on owner report; 15 some owner pain scales distinguish OA from non-OA cats and detect treatment effects.5,13,33,35,36 However, in the absence of accurate owner report (eg, research or homeless cats, or inattentive or medically/cognitively impaired owners), a valid OA scale for veterinarians could be particularly useful. Future, larger-scale studies, with different classes of analgesics, is needed to confirm MI-CAT(V) reliability and ability to detect OA, particularly in client-owned cats in a clinical setting, and to determine its feasibility. Thresholds must also be established for determination of OA status. Finally, responsiveness to treatment requires improvement if the MI-CAT(V) is to be used for more than OA screening.
Conclusions
The MI-CAT(V) was reliable and distinguished OA from non-OA cats, giving it potential for the screening of at-risk cats. Owing to study limitations, further assessment is needed to confirm this potential. Although individual subcategories showed promise, total MI-CAT(V) score did not detect treatment effects, limiting its current utility in veterinary case management.
Supplemental Material
Version 3 of the Montreal Instrument for Cat Arthritis Testing for use by Veterinarians (MI-CAT[V]) with 67 ordinal scale items distributed in 10 subcategories
Surgeon’s orthopedic evaluation scale
Version 4 of the Montreal Instrument for Cat Arthritis Testing for use by Veterinarians (MI-CAT[V]) with 44 ordinal scale items distributed in eight subcategories
Version 5 of the Montreal Instrument for Cat Arthritis Testing for use by Veterinarians (MI-CAT[V]) with 25 ordinal scale items distributed in five subcategories
Acknowledgments
The authors would like to thank all the participating cats, and all staff members of ArthroLab (Montreal, QC, Canada) and the Ferme et Animaleries of the Université de Montréal (Saint-Hyacinthe, QC, Canada) for their valuable assistance in data collection and animal care, as well as Ms Dominique Gauvin and Myriam Charest for their contribution to this work. The authors also thank TopCat Metrology personnel (Dr Polly Taylor and Dr Michael Dixon) for their scientific collaboration.
Footnotes
Accepted: 2 August 2017
Supplementary material: The following files are available:
Appendix A: Version 3 of the Montreal Instrument for Cat Arthritis Testing for use by Veterinarians (MI-CAT[V]) with 67 ordinal scale items distributed in 10 subcategories.
Appendix B: Surgeon’s orthopedic evaluation scale.
Appendix C: Version 4 of the Montreal Instrument for Cat Arthritis Testing for use by Veterinarians (MI-CAT[V]) with 44 ordinal scale items distributed in eight subcategories.
Appendix D: Version 5 of the Montreal Instrument for Cat Arthritis Testing for use by Veterinarians (MI-CAT[V]) with 25 ordinal scale items distributed in five subcategories.
This study was partly supported by a Collaborative Research and Development grant (#RDCPJ 418399–2011, #RDCPJ 491953–2016, supporting operations and salaries) in partnership with ArthroLab, from the Natural Sciences and Engineering Research Council of Canada. Dr Johanne Martel-Pelletier and Dr Jean-Pierre Pelletier are shareholders in ArthroLab. Dr Mary Klinck and Dr Beatriz Monteiro have received fees as consultants for Zoetis Canada. Prof Eric Troncy was a consultant for Zoetis Canada, Boehringer-Ingelheim Vetmedica and Abbott Animal Health. Funding for the therapeutic trial studies was provided by grants from ArthroLab, Montreal (QC, Canada), Elanco Animal Health, a division of Eli Lilly and company, Greenfield (IA, USA) and by Abbott Animal Health. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. There are no patents, products in development or marketed products to declare.
Funding: This study was funded (Prof Eric Troncy), in part, by a Morris Animal Foundation Grant (#D09FE-803A), ‘TOP-CAT: Tracking Osteoarthritis Pain in the CAT’, by a Discovery grant (#441651–2013 supporting salaries) and a Collaborative Research and Development grant (#RDCPJ 418399–2011, #RDCPJ 491953–2016 supporting operations and salaries in partnership with ArthroLab) from the Natural Sciences and Engineering Research Council (NSERC) of Canada, as well as by an ongoing New Opportunities Fund grant (#9483) and a Leader Opportunity Fund grant (#24601), supporting pain/function equipment, from the Canada Foundation for Innovation. Dr Mary Klinck was the recipient of an Alexander Graham Bell NSERC Canada Graduate Scholarship for Master’s research, and of a Zoetis – Morris Animal Foundation (#D10-901) Doctoral Fellowship, ‘Creating validated pain scales for feline osteoarthritis pain identification and quantification’. Dr Beatriz Monteiro is the recipient of a Vanier Canada Graduate Scholarship. Dr Maxim Moreau received a Doctoral Scholarship from the Fonds de recherche du Québec-Santé, and a Doctoral Scholarship from the Canadian Institutes of Health Research – MENTOR Strategic Training Initiative in Health Research Program. Dr Martin Guillot was the recipient of an Alexander Graham Bell NSERC Canada Graduate Scholarship for Doctorate research, and a Doctoral Scholarship from the Canadian Institutes of Health Research – MENTOR Strategic Training Initiative in Health Research Program.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Version 3 of the Montreal Instrument for Cat Arthritis Testing for use by Veterinarians (MI-CAT[V]) with 67 ordinal scale items distributed in 10 subcategories
Surgeon’s orthopedic evaluation scale
Version 4 of the Montreal Instrument for Cat Arthritis Testing for use by Veterinarians (MI-CAT[V]) with 44 ordinal scale items distributed in eight subcategories
Version 5 of the Montreal Instrument for Cat Arthritis Testing for use by Veterinarians (MI-CAT[V]) with 25 ordinal scale items distributed in five subcategories