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Hong Kong Physiother. J. 2018.38:41-51. Downloaded from www.worldscientific.com techniques on low back pain patients. IOSR J E®ect of MET with and without SCS technique 51 by Horizon College Physiotherapy on 05/28/22. Re-use and distribution is strictly not permitted, except for Open Access articles. Sports Phys Educ 2013;1(2):9–15. 33. Patil PN, Basavaraj C, Metgud S, Khatri S. 42. Nambi GS, Sharma R, Inbasekaran D, Vaghesiya E®ectiveness of muscle energy technique on quad- A, Bhatt U. Di®erence in e®ect between ischemic rates lumborum in acute low back pain — ran- compression and muscle energy technique on upper domized controlled trial. Indian J Physiother trepezius myofascial trigger points: Comparative Occup Ther 2010;4(1):54–8. study. Int J Health Allied Sci 2013;2:17–22. 34. Franke H, Fryer G, Ostelo RWJG, Kamper SJ. Muscle energy technique for non-speci¯c low-back 43. Lewis C, Souvlis T, Sterling M. Strain-counter- pain. The Cochrane Database Syst Rev 2015;27(2): strain therapy combined with exercise is not more CD009852. e®ective than exercise alone on pain and disability 35. Ellythy MA. E±cacy of muscle energy technique in people with acute LBP: A randomised trial. versus strain counter strain on low back dysfunc- J Physiother 2011;57:91–8. tion. Bull Fac Phys Ther 2012;17(2):29–35. 36. Sharma D, Sen S. E®ects of muscle energy tech- 44. Brose SW, Jennings DC, Kwok J, et al. Sham nique on pain and disability in patients with SI manual medicine protocol for cervical strain– joint dysfunction. Int J Physiother Res 2014; counterstrain research. PM & R 2013;5(5):400–7. 2(1):305–11. 37. Mullai D, Sareen A, Arora T. Comparative analysis 45. Okhovatian F, Mehdikhani R, Naimi SS. Compar- of muscle energy technique and conventional ison between the immediate e®ect of manual pres- physiotherapy in treatment of sacroiliac joint sure release and strain–counterstrain techniques on dysfunction. Indian J Physiother Occup Ther 2011; latent trigger point of upper trapezius muscle. Clin 5(4):127–30. Chiropr 2012;15(2):55–61. 38. Moore SD, Laudner KG, McLoda TA, Sha®er MA. The immediate e®ects of muscle energy technique 46. Ibañez-García J, Alburquerque-Sendín F, Rodríguez- on posterior shoulder tightness: A randomized Blanco C, et al. Changes in masseter muscle trig- controlled trial. J Orthop Sports Phys Ther 2011; ger points following strain–counterstrain or neuro- 6(4):400–7. muscular technique. J Bodyw Mov Ther 2009;13 39. Narayan A, Jagga V. E±cacy of muscle energy (1):2–10. technique on functional ability of shoulder in ad- hesive capsulitis. J Exerc Sci Physiother 2014; 47. Küçükşen S, Yilmaz H, Sallı A, Uğurlu H. Muscle 10(2):72–6. energy technique versus corticosteroid injection for 40. Smith M, Fryer G. A comparison of two muscle management of chronic lateral epicondylitis: Ran- energy techniques for increasing °exibility of the domized controlled trial with 1-year follow-up. hamstring muscle group. J Bodyw Mov Ther Arch Phys Med Rehabil 2013;94(11):2068–74. 2008;12(4):312–7. 41. Rajadurai V. The e®ect of muscle energy technique 48. Wong CK, Straincounter strain: Current con- on temporo mandibular joint dysfunction: A ran- cepts and clinical evidence. Man Ther 2012; domized clinical trial. Asian J Sci Res 2011;4:71–7. 17(1):2–8. 49. Lenehan KL, Fryer G, McLaughlin P. The e®ect of muscle energy technique on gross trunk range of motion. J Osteopath Med 2003;6(1):13–8. 50. Vela LI, Haladay DE, Denegar C. Clinical assess- ment of low-back-pain treatment outcomes in athletes. J Sport Rehabil 2011;20(1):74–88.

Research Paper Hong Kong Physiotherapy Journal Vol. 38, No. 1 (2018) 53–61 DOI: 10.1142/S1013702518500063 Hong Kong Physiother. J. 2018.38:53-61. Downloaded from www.worldscientific.com Hong Kong Physiotherapy Journal by Horizon College Physiotherapy on 05/28/22. Re-use and distribution is strictly not permitted, except for Open Access articles. http://www.worldscientific.com/worldscinet/hkpj Clinical assessment of balance using BBS and SARAbal in cerebellar ataxia: Synthesis of ¯ndings of a psychometric property analysis Stanley John Winser1,*, Catherine M Smith2, Leigh A Hale2, Leica S Claydon3 and Susan L Whitney4,5 1Department of Rehabilitation Sciences, Hong Kong Polytechnic University, Hong Kong 2School of Physiotherapy, University of Otago, New Zealand 3Department of Allied and Public Health, Anglia Ruskin University, UK 4School of Health and Rehabilitation Sciences, Department of Physical Therapy University of Pittsburgh, USA 5Rehabilitation Research Chair at King Saud University, Saudi Arabia *[email protected] Received 24 August 2016; Accepted 19 July 2017; Published 4 April 2018 Background: In the previous psychometric analysis paper in our series for identifying the core set of balance measures for the assessment of balance, we recommended the Berg Balance Scale (BBS) and balance sub- components of the Scale for the assessment and rating of ataxia (SARAbal) as psychometrically sound measures of balance for people with cerebellar ataxia (CA) secondary to multiple sclerosis. Objective: The present study further examined the suitability of BBS and SARAbal for the assessment of balance in CA with regard to psychometric property strength, appropriateness, interpretability, precision, acceptability and feasibility. Methods: Criteria to ful¯ll each factor was de¯ned according to the framework of Fitzpatrick et al. (1998). Based on the ¯ndings of our previous psychometric analysis, each criterion was further analyzed. *Corresponding author. Copyright@2018, Hong Kong Physiotherapy Association. Published by World Scienti¯c Publishing Pte Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 53

54 S.J. Winser et al. Results: The psychometric analysis reported good reliability and validity estimates for the BBS and SARAbal recommending them as psychometrically sound measures; they ful¯lled both criteria for appro- priateness and interpretability, the measures showed evidence for precision and acceptability, and they were found to be feasible in terms of the time and cost involved for the balance assessment. Conclusion: We have provided evidence for the use of the BBS and SARAbal for the assessment of balance among people with CA. Keywords: Balance; cerebellar ataxia; multiple sclerosis; psychometric analysis. Hong Kong Physiother. J. 2018.38:53-61. Downloaded from www.worldscientific.com Introduction outcome measure for clinical trials and clinical by Horizon College Physiotherapy on 05/28/22. Re-use and distribution is strictly not permitted, except for Open Access articles. practice.5 The ¯ndings of the present study were Poor balance and gait di±culties are hallmarks of based on the outcomes of a psychometric property health conditions that result in cerebellar ataxia analysis of four outcome measures of balance tested (CA).1 Assessment of balance and gait in CA is in people with CA secondary to multiple sclerosis.4 challenging as there are no standardized measures For the present study, we grouped reliability, va- of balance available. Previously, a series of studies lidity and responsiveness as psychometric proper- by our research group recommended a set of core ties.4 The factors are analyzed and their de¯nitions measures. A systematic review2 and a Delphi sur- are listed in Table 1. vey3 reported the Berg Balance scale (BBS), the Timed Up and Go (TUG) test, posture and gait Each factor was analyzed based on the set sub-component of the International Co-operative criteria outlined as follows. Ataxia Rating Scale (PG-ICARS) and the gait, stance and sit sub-components of the Scale for the Key ¯ndings of the psychometric analysis of the Assessment and Rating of Ataxia (SARAbal) as BBS and SARAbal were summarized to report the appropriate measures of balance in CA.2,3 Further, a reliability and validity of these measures in people psychometric property analysis was done to estimate with CA. The detailed methodology and results of constructs of reliability and validity of these four this psychometric property analyses are published measures among people with CA secondary to mul- elsewhere.4,6 The other reported factors including tiple sclerosis in New Zealand and the United States appropriateness, interpretability, precision, ac- of America. The study aimed at proposing the best ceptability and feasibility we based on the experi- outcome measures based on the ¯ndings of the psy- ence gained during the data collection and chometric analysis. The BBS and SARAbal were interpretation of results of our previous psycho- recommended as the optimal measures of balance in metric analysis study. To summarize, 60 partici- people with CA secondary to multiple sclerosis.4 pants aged 18–65 years with CA secondary to multiple sclerosis were recruited. Data were collect- Fitzpatrick et al. reported eight factors to be ed at four outpatient units in New Zealand and the addressed while selecting an outcome measure for United States of America. All included participants clinical trials.5 In the process of choosing a stan- underwent balance assessment using the BBS, TUG, dardized set of measures for balance in people with SARAbal and PG-ICARS. The participants were CA, these eight factors were considered. The present assessed on a single occasion and during the assess- study therefore aimed to examine the psychometric ment, a video recording was done. The video re- properties, appropriateness, interpretability, preci- cording was later used to estimate the intra-rater sion, acceptability and feasibility of the BBS and and inter-rater reliabilities. The Barthel Index, the SARAbal for people with CA based on the ¯ndings Expanded Disability Status Scale (EDSS), the full of the psychometric property analysis done by our scales of the ICARS and the SARA were also research team earlier.4 assessed and disease duration was recorded. The EDSS was completed by a neurologist. To investi- Methods gate the intra-rater and inter-rater reliabilities, a repeat assessment was performed by the same This paper examined eight factors in light with physiotherapist (intra-rater) or a second physio- Fitzpatrick's framework of evaluating a suitable therapist (inter-rater) from the video recording.

Clinical assessment of balance using BBS and SARAbal in CA 55 Table 1. Descriptors of the factors analyzed. were discussed. A third reviewer (LC) was involved for unresolved discrepancies in the ¯ndings be- Factor Descriptor tween the ¯rst two reviewers or if the reviewers marked \\unclear\" for the criteria. Psychometric Common term that includes reliability, Balance measures properties validity and responsiveness of the The BBS is a performance-based measure of bal- outcome measures ance7 and has been reported to be the most com- monly used balance tool by physiotherapists.8 The Appropriateness Described as how suitable the contents of the BBS is a ¯ve-point ordinal scale scored between 0 instrument are for use in people with CA5 and 4 for each task and has 14 tasks in total. The highest total score a participant may obtain is 56. Interpretability Indicates how meaningful are the scores This measure is interpreted as better balance with obtained from the outcome measures5 higher scores. Normative scores for the BBS have been established among community dwelling older Precision De¯ned as the accuracy of the instrument in adults.9 This measure has good inter-rater (ICC ¼ 0:96) and test retest (ICC ¼ 0:94) reli- Hong Kong Physiother. J. 2018.38:53-61. Downloaded from www.worldscientific.com categorizing sub-groups and distribution abilities and low standard error of measurement by Horizon College Physiotherapy on 05/28/22. Re-use and distribution is strictly not permitted, except for Open Access articles. (SEM).10 The BBS is found to have acceptable of numerical value concurrent validity in assessing balance and poor in discriminating between fallers and non-fallers in Acceptability De¯ned as the level to which the outcome people with multiple sclerosis.11 measure is tolerable for its use in people The SARA is an ataxia severity rating mea- with CA5 sure.12 It consists of eight items among which gait, sitting and the standing sub-components are re- Feasibility Described as the ease of use of the outcome lated to balance. The full scale is scored out of 40. The three sub-components of balance are scored measure in terms of administering it, and out of 18 (SARAbal). Scoring of the eight sub- the associated ¯nancial cost5 components do not have equal weighting, with scores ranging between eight for the \\gait\" sub- In this study, appropriateness was analyzed component and four for the \\heel-shin glide\". The based on two criteria: (i) to judge whether the higher the score obtained, the worse the condition. contents of the outcome measure suit the target The SARA has high test re-test reliability (ICC ¼ population and (ii) if the recommended set of 0.90), inter-rater reliability (ICC ¼ 0.97) and in- outcome measures has a combination of a condition- ternal consistency ( ¼ 0:93).12 Structural validity speci¯c tool and a generic tool for the assessment of has been reported,13 satisfactory convergent va- balance. Interpretability was analyzed based on lidity when correlated with other ataxia rating two criteria: (i) to determine how meaningful the scales12 and adequate responsiveness has been obtained scores were, using the BBS and the demonstrated.14 The testing has been done and SARAbal and (ii) to determine if the outcome conducted with both genetic and acquired forms of measures have established normative data. Preci- cerebellar disorders. sion was analyzed based on two criteria: (i) to de- termine if the instrument is able to discriminate Results between two known sub-groups within the col- lected samples and (ii) the accuracy of distribution The review of criteria for each factor resulted in of numerical values assessed using Rasch analysis 100% agreement between the reviewers and or estimation of unidimensionality of the testing therefore the third reviewer was not approached. items using factorial analysis. Acceptability was The reliability and validity of the measures were determined by estimating the response rate of the found to be strong and the responsiveness was not participants to the items of the outcome measures. estimated. A summary of the ¯ndings on the In general, the lesser the missing items, the better the acceptability.5 Feasibility was assessed by observing the ease of use, cost involved for the assessment, time taken to complete and training required for the assessor to complete the balance assessment using the two outcome measures. The criteria were organized into a tabular column and the reviewer marked either \\yes\" if the criteria were met or \\no\" if the criteria were not met or \\unclear\" if the answer was ambiguous. Each of the criterion was independently reviewed by two authors (SW and CS) and discrepancies in ¯ndings

Hong Kong Physiother. J. 2018.38:53-61. Downloaded from www.worldscientific.com 56 S.J. Winser et al. validity and responsiveness of the measures of by Horizon College Physiotherapy on 05/28/22. Re-use and distribution is strictly not permitted, except for Open Access articles. balance were not determined. psychometric properties of the BBS and the SAR- Abal are highlighted in Table 2. For appropriate- Appropriateness of the measures ness, the measures met both the criteria. With of balance regards to interpretability, o® the two required criteria, both the measures met the ¯rst criteria A straightforward method to determine if the whereas the BBS met the second criteria and contents of the outcome measure suit the target SARAbal did not. The ¯rst criteria for precision population is to obtain feedback from end users, were met by both the measures however, the sec- the clinicians. The psychometric analysis involved ond criteria were not established as Rasch analysis testing four balance measures of which three were and factor analysis were outside the scope of the endorsed by experts through the Delphi survey psychometric analysis. Both the measures met the done earlier by our research team.3 In the Delphi criteria for acceptability and in addition, they were survey, neurologists and physiotherapists involved found to be feasible. in research and clinical practice of CA were inter- viewed. They were asked to indicate the most ap- Discussion propriate measure of balance they might use to quantify balance de¯cits relating to CA. The This study aimed at identifying the suitability of internet-based survey went on for two rounds and using the BBS and SARAbal for the clinical as- the participants came to a consensus on the use of sessment of balance in people with CA. The the BBS, TUG and SARAbal as the most appro- framework of Fitzpatrick et al.5 was used to ad- priate choice of assessment tool. Two of the mea- dress eight independent factors for this recom- sures recommended as the core set were those mendation. We have provided evidence for most of endorsed by the clinical experts in the Delphi study the factors and in addition, recommendations for providing evidence for appropriateness.3 future research for strengthening the present ¯nd- ings have been provided. Secondly, it is recommended that an appropri- ate set of patient outcome measures should have Psychometric properties of the one condition-speci¯c measure and a generic mea- measures of balance sure.5 A condition-speci¯c measure identi¯es chan- ges that are in close relation or \\proximal\" to the The BBS and SARAbal reported good intra-rater, disease such as di±culty in performing tandem inter-rater reliabilities and internal consistency.4 walking in CA and the generic measure identi¯es The criterion validity was found to be good for changes that are slightly less proximal or \\distal\" to both the measures (S > 0:80). The measures were the health condition,18 such as altered stepping sec- correlated against disease duration, disease severi- ondary to coordination de¯cits in CA. Among the core ty and functional independence to determine con- set of measures, the SARAbal is condition-speci¯c struct validity and correlation was moderate and the BBS is a generic measure of balance.2 (S > 0:55). The measures were correlated against ataxia severity rating scales to estimate convergent Interpretability of the measures validity which was found to be good. The study of balance participants were sub-divided into assistive walk- ing device users and non-users. The ability of the In order to identify a meaningful score, the most measures of balance to di®erentiate between users signi¯cant approach may be to relate the scores and non-users of assistive devices was studied to achieved to the minimal clinically important dif- determine the discriminant validity. The balance ference (MCID).5 The MCID is described as the scores showed a statistically signi¯cant di®erence smallest di®erence in the score following an inter- between the scores of assistive device users and vention that the patient perceives as bene¯cial.19 non-users showing evidence for discriminant va- Since the psychometric analysis did not involve a lidity. In summary, both the BBS and SARAbal repeat assessment, where arguably a change in have good reliability and acceptable validity for score could be expected, determining the MCID the assessment of balance among people with CA score was not possible. However, we established the secondary to multiple sclerosis. The structural

Hong Kong Physiother. J. 2018.38:53-61. Downloaded from www.worldscientific.com by Horizon College Physiotherapy on 05/28/22. Re-use and distribution is strictly not permitted, except for Open Access articles. Table 2. De¯nition, accepted statistical analysis, interpretation and ¯ndings of the psychometric properties considered. Psychometric Description Statistical analysis Interpretation Results property Reliability De¯ned as the degree of interrelatedness Cronbach alpha There are no universal  ¼ 0:94 (BBS)  ¼ 0:72 Internal between the test items within each guidelines for interpreting (SARAbal) consistency outcome measures considered.15 reliability, in general, higher Inter-rater reliability the value towards 1, greater Intra-rater the reliability. We reliability interpreted as follows: Validity Criterion  > 0:80: good,  between validity 0.5 and 0.79: moderate, Hypothesis  < 0:50: poor testing De¯ned as the proportion of variation in Continuous scores: ICC Dichotomous/ ICC > 0:80: good, ICC ICC ¼ 0.97 (BBS) Convergent validity the scores of the participant done by nominal/ordinal scores: kappa () between 0.5 and 0.79: ICC ¼ 0.96 (SARAbal) two di®erent investigators.16 or weighted kappa moderate, A < 0:50: poor De¯ned as the proportion of variation in Same as inter-rater reliability ICC ¼ 0.99 (BBS) the scores of the participant done by ICC ¼0.98 (SARAbal) the same investigator with an interval Clinical assessment of balance using BBS and SARAbal in CA 57 of 7–10 days.15 De¯ned as the degree to which the scores Spearman or Pearson correlation co-e±cient. S > 0:80: good, S between BBS versus TUG: À0.88 PGICARS: À0.80 of the measure under investigation are Since the outcome measures considered 0.5 and 0.79: moderate, SARAbal: À0.92 SARAbal an adequate re°ection of a \\gold were ordinal, we used the Spearman S < 0:50: poor versus BBS: À0.92 standard\".16 correlation co-e±cient (S). Since \\`gold TUG: 0.72 PGICARS: 0.92 standard\" was not available for balance BBS versus ICARS: À0.76 assessment, we correlated the measures SARA: À0.82 SARAbal versus ICARS: of balance (BBS, TUG, PGICARS and 0.79 SARA: 0.85 SARAbal) against each other. De¯ned as the degree to which the scores Spearman correlation co-e±cient (SÞ. Same as above of the measures under investigation are consistent with the hypotheses.16 Convergent, divergent, external and construct validity are grouped under hypothesis testing. Indicates that two measures examining Spearman correlation co-e±cient (SÞ. Same as above similar underlying phenomenon will The measures of balance were correlated provide similar results. For example, with two ataxia rating scales (ICARS high correlation can be anticipated and SARA) between the results of two outcome measures assessing balance.

Hong Kong Physiother. J. 2018.38:53-61. Downloaded from www.worldscientific.com by Horizon College Physiotherapy on 05/28/22. Re-use and distribution is strictly not permitted, except for Open Access articles. Table 2. (Continued ) 58 S.J. Winser et al. Psychometric Description Statistical analysis Interpretation Results property External validity De¯ned as the degree to which the Spearman correlation co-e±cient (SÞ. The Same as above BBS versus EDSS: À0.78 outcome measure under investigation measures of balance were correlated with BI: 0.55 Disease correlates with other instruments or ADL status, disease duration and disease duration: À0.61 other constructs, for example ADL, severity. ADL was assessed using BI and SARAbal versus disease severity or disease duration. disease severity using the EDSS. EDSS: 0.76 BI: À0.44 Disease duration: 0.58 Discriminant De¯ned as the ability of the outcome Group di®erences of scores between users and Statistically signi¯cant Mean, SD and p value validity measures to di®erentiate between non-users of assistive walking devices were di®erence (p < 0:05) in the BBS ADU: 34.6 (11.8) two-known groups within the study considered for establishing discriminant scores between groups was ADNU: 52.19 (4.43) p < population. validity. We used Mann–Whitney U test. considered evidence for 0:01 SARAbal ADU:7.0(2.8) discriminant validity. ADNU: 1.71 (1.37) p < 0:01 Cut-o® score, Sensitivity is an indication that the Receiver operating characteristics (ROC) The examiner makes a logical BBS: cut-o® < 44 out sensitivity and outcome measure is capable of curve was constructed to determine the decision based on the needs of 56 sensitivity 90% speci¯city for identifying certain trait that is really cut-o® score, sensitivity and speci¯city of for the cut-o® score. In this speci¯city 94% assistive present in the given population. the measures to predict the users of an case, the score needs to SARAbal: cut-o® walking Speci¯city is an indication that the assistive walking device. In addition, to precisely identify an > 5 out of 18 device use outcome measure is capable of determine and quantify which measure assistive device user more sensitivity 90% identifying the lack of certain trait had a better predictive ability, the \\Area than identifying a non-user. speci¯city 100% that is really absent in the given Under the Curve\" (AUC) was used. Thereof, the sensitivity was population. kept high and constant at 90% and the corresponding cut-o® score and the highest speci¯city at 90% of sensitivity were derived. Responsiveness Responsiveness Described as the ability of the outcome Can be determined using di®erent Responsiveness was not measure to detect changes over approaches. Some commonly adopted estimated. time.16 analysis include ROC (distribution-based approach) or relating the change of score to \\Global Rating of Change\" score (anchor- based approach).17 Notes:  — Cronbach's alpha, ICC — intra class correlation co-e±cient, S — Spearman's Rho, BBS — Berg Balance Scale, SARAbal, gait, sit and stance sub-component of the SARA, PGICARS — Posture and gait sub-component of the ICARS, SARA — Scale for the Assessment and Rating of Ataxia, ICARS — International Co-operative Ataxia Rating Scale, ADl — activities of daily living, BI — Barthel Index, EDSS — Expanded Disability Status Scale, ADU — assistive device user, ADNU — assistive device non-user SD — standard deviation, p — level of signi¯cance.

Clinical assessment of balance using BBS and SARAbal in CA 59 Hong Kong Physiother. J. 2018.38:53-61. Downloaded from www.worldscientific.com minimal detectable change (MDC) for the BBS ¯ve (8%) for the SARAbal. However, we hesitate to by Horizon College Physiotherapy on 05/28/22. Re-use and distribution is strictly not permitted, except for Open Access articles. and the SARAbal. comment on the question \\were the contents too easy to complete?\" Future studies are recommended to The MDC is described as the smallest change estimate the °oor and ceiling e®ect for these measures that an outcome measure detects due to a notable of balance. change in the participants' performance. The established MDC is a re°ection of the SEM for the Precision of the measures of balance measures of balance and could be considered as a \\proxy\" for the MDC. The term \\proxy\" in sta- The psychometric property analysis estimated tistics refers to a value that is probably not in itself discriminant validity by sub-dividing the partici- of any great interest, but from which a variable of pants into assistive device users and non-users. interest can be obtained. The MDC was estimated Mann–Whitney U test was used to determine the using a data-driven method proposed by Wyrwich group di®erences between the two known groups et al.20 The Cronbach alpha of the measures of (assistive device users and non-users). The ¯ndings balance was used to estimate the SEM that of this analysis revealed a statistically signi¯cant re°ected the MDC. Therefore, the derived MDC (p < 0:01) di®erence between the two groups for provides meaningful information on the expected both the measures of balance providing evidence change in score that may be perceived to be clini- for precision.4 Secondly, it is recommended that cally meaningful for the patient following inter- the precision could be derived by estimating the vention. Future studies may use the obtained unidimensionality of the measures under consider- MDC as reference scores for reporting their results. ation. However, unidimensionality estimation was outside the scope of the psychometric analysis. The second method of assessing interpretability Therefore, we recommend future studies to con- is to compare the scores with normative data in a duct Rasch analysis or factorial analysis to provide way that the di®erence in the score re°ects the evidence for unidimensionality for these measures magnitude of di®erence between the tested sample in future. and an age-matched healthy peer. The BBS has established normative data among community Feasibility of the measures of balance dwelling healthy older adults.9 Being condition- speci¯c and relatively new, the SARA does not Based on the experience gained during data col- have established normative data. Future studies lection, the two measures of balance took 15–20 are recommended to establish the normative scores min to complete. They did not require the use of for the SARAbal among healthy older adults. sophisticated equipment and are available at free of cost. In addition, formal training is not needed Acceptability of the measures to perform these tests (the measures include instruction). However, the examiners who con- of balance ducted these tests were quali¯ed physiotherapists and therefore, the feasibility of administration is The response rate to the outcome measures was limited to quali¯ed physiotherapists. With regard high for the psychometric analysis and there were to patient safety, it is recommended that the as- no missing items in our data providing evidence for sessment room is well-lighted, surface is non-slippery, acceptability.5 Acceptability can also be demonstrated and adequate rest breaks are given between the by determining the °oor and ceiling e®ect of the tool. assessment sessions. There were no adverse events These estimates report on the level of ease to complete documented during data collection providing evidence the items i.e., were the contents of the tool too easy or for feasibility of the measures. too di±cult or tolerable for the tested population? Determining the acceptability was outside the scope of Generalizability of the ¯ndings the psychometric analysis; however, based on the ¯ndings of the psychometric analysis, the answer to The ¯ndings of the present study are based on the this question may be partially resolved. Of the 60 outcomes of a psychometric analysis conducted participants, only one (2%) had di±culty in com- earlier. As reported, the psychometric property pleting all four assessments due to fatigue providing some evidence for acceptable °oor e®ect. The parti- cipants were able to complete all four tests. Eight (13%) participants obtained full score for BBS and

Hong Kong Physiother. J. 2018.38:53-61. Downloaded from www.worldscientific.com 60 S.J. Winser et al. the manuscript and revising the manuscript. Dr. by Horizon College Physiotherapy on 05/28/22. Re-use and distribution is strictly not permitted, except for Open Access articles. Catherine Smith contributed to write up for funding, analysis recruited people with CA secondary to data review, data interpretation, project manage- multiple sclerosis. The recruited sample was het- ment and writing the manuscript. Prof. Leigh A Hale erogeneous in terms of disease course of multiple contributed to write up for funding, data interpre- sclerosis which enables the generalizability of tation, project management and writing the manu- ¯ndings to all types of multiple sclerosis. In addi- script. Dr. Leica S Claydon contributed to write up tion, the sample was homogenous in terms of the for funding, data review, data interpretation, project type of lesion. The included participants with management and writing the manuscript. Prof. multiple sclerosis were restricted to primary cere- Susan L Whitney contributed to data interpretation, bellar impairment. Therefore, these recommenda- project management and writing the manuscript. tions may be considered for people with other types of cerebellar ataxic lesions. Conclusion References The ¯ndings of this study suggests that the BBS 1. Palliyath S, Hallett M, Thomas SL, Lebiedowska and SARAbal are psychometrically sound, appro- MK. Gait in patients with cerebellar ataxia. Mov priate, interpretable, precise, acceptable and fea- Disord 1998;13(6):958–64. sible for the assessment of balance in people with CA and multiple sclerosis. Future studies are 2. Winser SJ, Smith CM, Hale LA, Claydon LS, warranted to estimate the structural validity, Whitney SL, Mehta P. Systematic review of the responsiveness, MCID, plus °oor and ceiling e®ect psychometric properties of balance measures for for these measures to strengthen the present ¯ndings. cerebellar ataxia. Clin Rehabil 2015;29:69–79. Con°ict of Interest 3. Winser SJ, Smith C, Hale LA, Claydon LS, Whitney SL. Balance outcome measures in cerebellar ataxia: The authors declare that there is no con°ict of A Delphi survey. Disabil Rehabil 2015;37:165–70. interest relevant to the study. 4. Winser SJ, Smith C, Hale LH, et al., Psychometric Funding/Support properties of a core set of measures of balance for people with cerebellar ataxia secondary to multiple This research was funded by the University of sclerosis. Arch Phys Med Rehabil 2016; in press. Otago, New Zealand Doctoral Scholarship, School of Health and Rehabilitation Research, University 5. Fitzpatrick R, Davey C, Buxton MJ, Jones DR. of Pittsburgh, USA and Division of Health Science, Evaluating patient-based outcome measures for use University of Otago, New Zealand, travel grants, in clinical trials. Health Technol Assess 1998;2:1–74. Maurice and Phyllis Paykel Trust (MPPT) fund Physiotherapy New Zealand, Otago Branch Edu- 6. Winser SJ, Smith C, Hale LH, et al., Balance as- cational Fund, Physiotherapy New Zealand's sessment in multiple sclerosis and cerebellar ataxia: Neurology Special Interest Group Grant, School of Rationale, protocol and demographic data. Phys Physiotherapy, Research fund, and was partially Med Rehabil Int 2014;1(5):6. and ¯nancially supported by King Saud Universi- ty, through Vice Deanship of Research Chairs, 7. Berg K, Wood-Dauphinee S, Williams JI. The Rehabilitation Research Chair. balance scale: Reliability assessment with elderly residents and patients with an acute stroke. Scand Author Contributions J Rehabil Med 1995;27(1):27–36. Dr. Stanley John Winser contributed to structuring 8. Korner-Bitensky N, Wood-Dauphinee S, Teasell study design, write up for funding, subject recruit- R, et al., Best versus actual practices in stroke ment, data collection, data review, data analysis, rehabilitation: Results of the Canadian national data interpretation, project management, writing survey. Stroke 2006;37:631. 9. Ste®en TM, Hacker TA, Mollinger L. Age-and gender-related test performance in community- dwelling elderly people: Six-minute walk test, Berg balance scale, timed up & go Test, and gait speeds. Phys Ther 2002;82(2):128–37. 10. Cattaneo D, Jonsdottir J, Repetti S. Reliability of four scales on balance disorders in persons with multiple sclerosis. Disabil Rehabil 2007;29:1920–5. 11. Cattaneo D, Regola A, Meotti M. Validity of six balance disorders scales in persons with multiple sclerosis. Disabil Rehabil 2006;28(12):789–95.

Clinical assessment of balance using BBS and SARAbal in CA 61 Hong Kong Physiother. J. 2018.38:53-61. Downloaded from www.worldscientific.com 12. Schmitz-Hübsch T, du Montcel ST, Baliko L, et al., 17. Portney LG, Watkins MP. Statistical measures of by Horizon College Physiotherapy on 05/28/22. Re-use and distribution is strictly not permitted, except for Open Access articles. Scale for the assessment and rating of ataxia: validity. In: Foundations of Clinical Research Development of a new clinical scale. Neurology Application to Practice. 3rd ed. New Jersey, USA: 2006;66(11):1717–20. Julie Levin Alexander, 2009:620–25. 13. Bürk K, Mälzig U, Wolf S, et al., Comparison of 18. Brenner MH, Curbow B, Legro MW. The proximal– three clinical rating scales in Friedreich ataxia distal continuum of multiple health outcome (FRDA). Mov Disord 2009;24(12):1779–84. measures: The case of cataract surgery. Med Care 1995:AS236–44. 14. Lee YC, Liao YC, Wang PS, Lee IH, Lin KP, Soong BW. Comparison of cerebellar ataxias: A 19. Jaeschke R, Singer J, Guyatt GH. Measurement of three-year prospective longitudinal assessment. health status: Ascertaining the minimal clinically Mov Disord 2011;26(11):2081–7. important di®erence. Control Clin Trials 1989;10 (4):407–15. 15. Portney LG, Watkins MP. Reliability of mea- surements. In: Foundations of Clinical Research 20. Wyrwich KW, Tierney WM, Wolinsky FD. Fur- Application to Practice. 3rd ed. New Jersey, ther evidence supporting an SEM-based criterion USA: Julie Levin Alexander, 2009:77–96. for identifying meaningful intra-individual changes in health-related quality of life. J Clin Epidemiol 16. Mokkink LB, Terwee CB, Patrick DL, et al., The 1999;52(9):861–73. COSMIN study reached international consensus on taxonomy, terminology, and de¯nitions of measurement properties for health-related patient- reported outcomes. J Clin Epidemiol 2010;63 (7):737–45.

Research Paper Hong Kong Physiotherapy Journal Vol. 38, No. 1 (2018) 63–75 DOI: 10.1142/S1013702518500075 Hong Kong Physiother. J. 2018.38:63-75. Downloaded from www.worldscientific.com Hong Kong Physiotherapy Journal by Horizon College Physiotherapy on 05/28/22. Re-use and distribution is strictly not permitted, except for Open Access articles. http://www.worldscientific.com/worldscinet/hkpj Symptoms-modifying e®ects of electromotive administration of glucosamine sulphate among patients with knee osteoarthritis Ayodele Teslim Onigbinde1,*, Adegbenga Rotimi Owolabi2, Kamil Lasisi3, Sarah Oghenekewe Isaac1 and Adeoye Folorunsho Ibikunle1 1Department of Medical Rehabilitation, Faculty of Basic Medical Sciences College of Health Sciences, Obafemi Awolowo University Ile-Ife, Osun State, Nigeria 2Department of Medical Pharmacology and Therapeutics Faculty of Basic Medical Sciences, College of Health Sciences Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria 3Department of Physiotherapy, Ladoke Akintola University Teaching Hospital Osogbo, Osun State, Nigeria *[email protected] Received 22 August 2016; Accepted 19 July 2017; Published 27 April 2018 Background: Most trials on symptom-modifying e®ects of glucosamine are limited to administration through oral route with dearth of empirical data on the use of electromotive force. Objective: The study determined the e®ects of glucosamine sulphate (GS) iontophoresis (IoT) on radio- graphic parameters of patients with knee osteoarthritis (OA). Methods: Fifty-three patients were randomly assigned to three groups. About 1 g each of GS was admin- istered using IoT and cross-friction massage (CFM) for participants in groups 1 (IoT) and 2 (CFM), re- spectively. Group 3 ((Combined therapy) CoT) received 1 g of GS using both IoT and CFM. Interventions were twice a week for 12 weeks. Analysis of variance (ANOVA) was used to analyze the data (p < 0:05). Results: After 12 weeks, the medial joint space width (JSW) of the CFM group was signi¯cantly higher than that of IoT and CoT groups (p ¼ 0:005 and p ¼ 0:004). Lateral JSW of IoT group was signi¯cantly higher than both CFM (p ¼ 0:001) and CoT groups (p ¼ 0:01). There were signi¯cant decreases in pain intensities; *Corresponding author. Copyright@2018, Hong Kong Physiotherapy Association. Published by World Scienti¯c Publishing Pte Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 63

64 A. T. Onigbinde et al. increase in knee °exion and physical functions across the groups (F ¼ 9:33; p ¼ 0:01; F ¼ 3:23; p ¼ 0:01; H ¼ 4:97; p ¼ 0:01, respectively). Conclusion: It was concluded that there were signi¯cant decreases in the degenerative changes at the knee joint. Keywords: Osteoarthritis; glucosamine; electromotive administration; degenerative changes. Hong Kong Physiother. J. 2018.38:63-75. Downloaded from www.worldscientific.com Introduction the ¯ndings are clinical indications in which the by Horizon College Physiotherapy on 05/28/22. Re-use and distribution is strictly not permitted, except for Open Access articles. medications are delivered in su±cient amount to Osteoarthritis (OA) is the most common arthritis the targeted tissues.4,10,11 In IoT, there is percu- with about 3.8% a®ecting the knee and hip joints.1 taneous absorption through three main pathways: Approximately 10% and 18% of men and women, the intercellular (paracellular) pathway between respectively, present with multifarious symptoms the conneocytes along the lamellar lipids, the in- and radiological evidence in more than 50% of tracellular (transcellular) pathway through the people over 65 years of age.2,3 There is an in- cells or the appendageal (shunt) pathway via hair creasing prevalence of OA with resultant decrease follicles, sweat ducts and secretary glands.12 in functional capacities of patients.4 The earliest Patients with OA should receive a combination signs of knee OA are narrowing of the medial of non-pharmacologic and pharmacologic treat- compartment of the joint, sub-chondral sclerosis, ment.13 Amongst drugs which have been specu- cystic changes in the articular surfaces, and spur lated to be disease-modifying are glucosamine and formation on the tibia spine.5 The measurement of chondroitin, but the magnitude of their e®ects the distance between the distal femur and the remains unclear and controversial. The e®ective- proximal tibia is the joint space width (JSW) and ness of administration of glucosamine on slowing it is an indirect way of measuring cartilage thick- progression of OA is still shrewd with specula- ness. The JSW is reproducible for the assessment of tion.14 The evidence that it can modify the struc- progressive knee cartilage degenerations, and ture of joints is still early and inconclusive. Some evaluation of disease-modifying e®ects of thera- clinical trials have shown that glucosamine may pies.6,7 The diagnosis of OA is based on the com- prevent or slow down the loss of cartilage rather bination of typical mechanical pain symptoms and than re-growing it.15,16 Speculation still surrounds physical ¯ndings in the joints. OA has traditionally the e®ectiveness of topical application of glucos- been diagnosed with radiographs that demonstrate amine sulphate (GS) cream using massage to al- JSW and osteophytes.8 leviate pain and slow down degenerative changes in patients with OA and it appears that there is The main goal of managing OA includes alle- inadequate data on the electromotive administra- viation of pain and improving functional abilities tion of glucosamine. However, it is unknown if and main drugs of choice are non-steroidal anti- electromotive force will drive in more GS to hasten in°ammatory drugs (NSAIDs), but the oral and pain relief and also reduce joint degenerative injectables are not without potential hazards. The changes faster than massage, hence, this study is adverse e®ects include gastrointestinal disorders needed. and reduction in body immunity, particularly in the elderly.9 In view of this, there is an increasing The primary aim of the study was to investigate quest in medical technology towards establishing the e®ect of GS IoT on selected radiographic safer and e®ective means of delivering medications parameters (JSW, inter-condylar thickening (ICT) beside these common methods. Hence, drug tibia width, pain intensity, range of motion (ROM) administration using electromotive forces (ionto- and physical function in patients with knee OA. phoresis (IoT) and phonophoresis) are being con- It was hypothesized that there would be no sig- sidered as alternatives in clinical physiotherapy ni¯cant di®erence in the selected radiographic practice. Although, pharmacokinetic parameters of parameters, pain intensity, ROM and physical ac- most of these drugs have not been analytically tivity of patients with knee OA among patients established after administration through the use of who received GS through cross-friction massage electromotive forces, the successes attached to

Symptoms-modifying e®ects of electromotive administration of GS 65 Hong Kong Physiother. J. 2018.38:63-75. Downloaded from www.worldscientific.com (CFM) only, IoT only; and a combination of both Instruments by Horizon College Physiotherapy on 05/28/22. Re-use and distribution is strictly not permitted, except for Open Access articles. CFM and IoT in administering GS. The instruments and test items included bathroom Methods weighing scale, a modi¯ed height meter, an elec- trical stimulator (Model: Endomed 582, India), Participants 70% alcohol and GS cream (glucosamine 8% w/w), (Urah). Amongst the test items are the following: a The 53 participants were patients with knee osteo- 10-point visual analogue scale (VAS), a plastic arthritis, receiving treatment at the Out-Patient semi-circle Goniometer (Model E-Z ReadTM), Physiotherapy Clinic of a Nigerian University Western Ontario and Mcmaster University — Teaching Hospital in South West Nigeria. WOMAC OA index Questionnaire, X-ray ¯lm report, pointing divider, Vernier caliper and Research design magnifying lens (Roger Bacon, Model No AC099). This study was a randomized controlled trial Procedure for data collection (pre-test and post-test) experimental design. Ethical approval was obtained from the Health Inclusion and exclusion criteria Research and Ethics Committee, Institute of Public Health, Obafemi Awolowo University, Ile The major inclusion criteria were that the partici- Ife. All the patients consented to participate in the pants must have knee OA with history not less study. Participants in group 1 (IoT) received only than three months. There must also be radiological 1 g (2 Finger-Tip Unit (FTU)) of GS cream which evidences of grade III on Kellegren classi¯cation. was administered via IoT. Group 2 (CFM) parti- Excluded from the study were patients with his- cipants also received 1 g (2 FTU) of GS only, but it tory of knee surgery or replacement, patient with was administered using CFM while group 3 (com- neuromuscular and musculoskeletal diseases; car- bined therapy (CoT)) participants had interven- diac disorder, those using cardiac pacemaker, tions using 1 g of GS cream through both IoT on intra articular steroid therapy within two and CFM. months before the commencement of this study and participants with impaired skin sensation. A 10-point VAS was used to rate the pain. The VAS had been established to be reliable and Sampling techniques e®ective in assessing knee pain arising from OA.17 Pain intensities were rated on three occasions: on A total of 60 participants were recruited for the active and passive knee °exions, and on patellar study with 20 in each group using purposive sam- grinding. The active knee °exion was measured in pling technique. The sample size for this study was prone lying position using a standard procedure. predetermined considering standard normal devi- Physical function was assessed using the WOMAC ation to be 1.96, 0.02 of accuracy, power estimate OS Questionnaire.18 The physical function sub- of 80% and knee OA prevalence of 60% in adults. scale was used to assess functional abilities of The probability of Type I error is considered as patients in this study. There are 17 items on the level of signi¯cance. The sample size was computed physical function sub-scale, it was rated on a to be 18 participants per group but to give room for 5-point Likert scale, ranging from 0 to 4 whereby attrition, 20 participants were recruited for each \\0 ¼ none and \\4 ¼ extreme\". The minimum group totaling 60 participants for the study. They obtainable score was \\0\" indicating best physical were randomly assigned to three groups using ¯sh function while the maximum obtainable was \\68\" bowl technique. Sixty separate slips, labeled groups indicating poor physical function. The obtained 1, 2 and 3 with 20 for each group were mixed and score for physical function was divided by total pooled into a box. Each patient was instructed to possible score and multiplied by 100 and reported pick a slip without looking into the box. Whatever in percentage. Lower value depicts better physical group was picked would be the group that the function performance. patient was allotted. The °ow chart is presented in Fig. 1. The JSW and inter-condylar thickening (ICT) were measured using standard procedures adopted by Deep et al.19 and Lequesne.20 The JSW was also measured manually using the method described by

66 A. T. Onigbinde et al. 78 ParƟcipants invited 18 did not meet inclusion criteria 60 ParƟcipants Hong Kong Physiother. J. 2018.38:63-75. Downloaded from www.worldscientific.com Group 1 n=20 Group 1 n=20 Group 1 n=20 by Horizon College Physiotherapy on 05/28/22. Re-use and distribution is strictly not permitted, except for Open Access articles. 17 18 18 AƩriƟon Transfer from office 1 Personal reason 1 Office work pressure 1 Office work Pressure 1 RelocaƟon from residence 3 53 completed the study and uƟlized for data analysis Fig. 1. Flowchart for recruitment. Lequesne.20 Using the anteroposterior view of the divider and vernier caliper with the aid of magni- X-ray ¯lm of each patient, the horizontal distance fying lens. Prior to this, the reliability of the between the superior tip of the lateral and medial method was determined by using ¯ve X-ray ¯lms of condyles of the tibial was divided into two while patients with knee OA. The test–re-test interval the lateral JSW was measured at the mid point of was one week. The Pearson's product moment the ¯rst half and the medial JSW was measured at correlation reliability coe±ciency obtained for the the mid point of the second half. The dividing method of measuring the tibial width was found to pointer was used to prick the two inter-bone dis- be 0.87. tances on the radiograph with the aid of a magni- fying lens and then pricked a sheet of paper. The About 1 g of GS was placed on positive electrode caliper was used to measure the inter-bone distance (being positively charged) for patients in the between the pricks.20 The ICT on the X-ray ¯lm IoT group.21,22 An electrical stimulator machine was measured manually as the distance between (Model: Endomed 582, India) was used to deliver the tip of the anterior and posterior margins of the GS through the skin with the aid of electrodes. The inter-condylar eminence used the method described Galvanic current mode in the Electrical Stimulator by Lequesne, and the points of the caliper were (Endomed 582) was used. The dose applied was used to measure inter-margin distance with the aid 2 mA-min (2 mA Â 20 min) for each subject in of a magnifying lens. The tibia width was measured groups 1 and 3.23 The active (positive) electrode from the superior tip of the lateral tibia condyle was placed on the side where the participants ex- to that of the medial horizontally using pointing perienced higher pain intensity (that is medial or lateral side of the knee joint). The pain intensity

Symptoms-modifying e®ects of electromotive administration of GS 67 was ascertained using valgus and varus ligamen- Table 1. Gender and distribution of a®ected sides tous stress tests; and appley's compression tests. of patients in the three groups. The skin areas where electrodes were fastened were cleansed with methylated spirit (70% alcohol) Groups N% to minimize the risk of burns.24 Transarthral elec- trode placement technique was used. The indi®er- IoT Gender Male 2 11.8 ent electrode was placed on the opposite side for CFM subject in groups 1 and 3. Both electrodes were CoT Female 15 88.2 held in place by an adhesive strap. Each subject had intervention(s) twice a week for 12 weeks. A®ected knee Right 8 47.1 The intention-to-treat (ITT) principle was Left 9 59.9 adopted in this study but last data measured were not carried forward for the seven patients that Gender Male 4 22.2 dropped out because the attrition happened in the ¯rst and second weeks of the protocols. We ob- Female 14 77.8 served that the recorded data at the time of ter- Hong Kong Physiother. J. 2018.38:63-75. Downloaded from www.worldscientific.com mination did not di®er from the values obtained at A®ected knee Right 10 55.6 by Horizon College Physiotherapy on 05/28/22. Re-use and distribution is strictly not permitted, except for Open Access articles. baseline, hence, they were excluded from data analysis. The rate of attrition was almost uniform Left 8 44.4 in three groups and the drop-out was not due to increase in severity, symptoms, group assign- Gender Male 4 22.2 ment or drug side e®ects. However, all the patients were followed up for another six weeks after the Female 14 77.8 end of the study. A®ected knee Right 7 38.9 Data analysis Left 11 61.1 Descriptive statistics were used to summarize the data obtained. Levene's test was used to compare Note: 1 ¼ IoT group, 2 ¼ CFM group and 3 ¼ CoT the homogeneity of age, weight, height and body group. mass index (BMI) across the groups. Repeated Analysis of Variance (ANOVA) was used to selected anthropometric parameters of patients in compare pain intensity, knee ROM, and selected IoT, CFM and CoT are presented in Table 2. The radiographic parameters across the groups. It was Levene's test for homogeneity showed that there also used to compare within group values at was no signi¯cant di®erence in the selected baseline, 6 weeks and 12 weeks. Where between anthropometric parameters. groups, variance was observed at baseline, Analy- sis of co-variance was used to compare the di®er- Comparison of radiographic ences. Post-hoc analysis (LSD) was used to parameters of participants determine the trend of di®erences in the groups. across the groups at baseline, Kruska–Wallis test was used to compare physical 6th and 12th weeks functions across the three groups. Alpha level was set at p ¼ 0:05. The means of JSW on medial side of the knee in the IoT group were 0:54 Æ 0:08, 0:55 Æ 0:07 and 0:59 Æ Results 0:09 at baseline, 6th and 12th weeks, respectively. There was no signi¯cant di®erence in the medial The result showed that eight (47.1%) of the par- JSW across the three groups at baseline and 6th ticipants who received GS IoT only have right knee week, but there was signi¯cant di®erence at the OA and two (11.8%) are male. The a®ected sides 12th week. (F ¼ 6:00; p ¼ 0:01). There was signif- for other groups are in Table 1. The age and icant di®erence in lateral JSW and ICT across the three groups at baseline (F ¼ 4:34; p ¼ 0:02). Other mean values are presented in Table 3. There was signi¯cant di®erence in lateral JSW across the three groups at baseline (F ¼ 4:34; p ¼ 0:02). At the 6th week, there were no signi¯cant di®erences in all the selected parameters. However, at the 12th week, there were signi¯cant di®erences in the medial and lateral JSW compared to baseline and 6th week (F ¼ 6:00; P ¼ 0:01 and F ¼ 12:32; p ¼ 0:001, respectively) (Table 3).

68 A. T. Onigbinde et al. Table 2. Comparison of anthropometric parameters and onset duration of participants across the three groups. IoT CFM CoT Levene (p) Mean SD Mean SD Mean SD sig Age 63.53 11.35 49.78 13.19 58.11 9.91 0.35 Weight 80.47 9.49 75.78 8.47 76.00 9.08 0.62 Height 1.52 1.61 0.96 0.49 1.63 0.86 0.73 BMI 35.57 4.13 29.55 4.01 28.39 4.76 0.93 Duration 11.47 7.80 8.72 6.17 11.11 7.28 0.26 Hong Kong Physiother. J. 2018.38:63-75. Downloaded from www.worldscientific.com Note: 1 ¼ IoT group, 2 ¼ CFM group and 3 ¼ CoT group. by Horizon College Physiotherapy on 05/28/22. Re-use and distribution is strictly not permitted, except for Open Access articles. *Levene Test for Equality of Variances. Table 3. Comparison of radiographic parameters of all the participants at baseline, 6th and 12th weeks in the three groups. Group 1 Group 2 Group 3 Mean SD Mean SD Mean SD F P Medial JSW Baseline 0.54 0.08 0.49 0.15 0.51 0.11 0.72 0.49 6th week 0.55 0.72 0.52 0.17 0.51 0.10 0.49 0.62 12th week 0.59 0.09 0.79 0.30 0.58 0.15 6.00 0.01 Lateral JSW Baseline 0.82 0.14 0.73 0.17 0.68 0.11 4.34 0.02* 6th week 0.81 0.17 0.82 0.26 0.11 0.68 2.73 0.08* 12th week 0.84 0.16 0.57 0.18 0.68 0.13 12.32 0.001* ICT Baseline 1.05 0.39 0.94 0.19 1.08 0.36 3.97 0.03* 6th week 1.19 0.39 0.94 0.19 1.02 0.31 2.99 0.06* 12th week 1.24 0.42 0.94 0.19 1.13 0.35 3.60 0.04* Tibia width Baseline 6.71 1.38 7.47 0.62 6.84 1.09 2.54 0.09 6th week 6.76 1.33 7.41 0.62 6.83 1.12 1.83 0.17 12th week 6.66 1.34 7.42 0.61 6.78 1.13 2.57 0.09 *Analysis of co-variance. The result of the post-hoc analysis (LSD) at Comparison of pain intensity baseline showed that there were no signi¯cant di®erences in the baseline parameters excluding the and ROM of participants at lateral JSW between CoT and IoT; and between ICT of participants in IoT and CFM groups baseline, 6th and 12th weeks (Table 4). The medial JSW of participants in CFM group was signi¯cantly higher than that of parti- The mean of pain intensity on active knee °exion cipants in IoT and CoT groups (p ¼ 0:005 and was 4:94 Æ 1:30 on a 10-point rating scale (VAS) p ¼ 0:004, respectively) at the 12th week, for participants in IoT group (GS IoT) at baseline. (Table 5). The lateral JSW of IoT group was sig- The mean pain intensities on active knee °exion ni¯cantly higher than that of CFM group at 6th and 12th weeks are also presented in (p ¼ 0:001) and that of CoT group (p ¼ 0:01), but Table 6. The result of ANOVA showed that there that of later was higher than that of the former were signi¯cant di®erences in pain intensities on (p ¼ 0:04) (Table 5). active and passive knee °exion; and patellar grinding within the IoT group participants (F ¼ 43:00; p ¼ 0:001; F ¼ 53:54; p ¼ 0:001; and

Symptoms-modifying e®ects of electromotive administration of GS 69 Table 4. Result of post hoc (LSD) analysis of baseline trends were observed on passive knee °exion and radiographic parameters of all the participants across patellar grinding at 6th and 12th weeks, the three groups. (p ¼ 0:001) (Table 7). The mean ROM (active knee °exion) was 107:35 Æ 12:18 at onset for I J Mean di®erence (I À J) P participants in the IoT group while at the 6th and 12th weeks, the mean of ROMs was 114:06 Æ 10:80 Medial JSW 1 2 0.05 0.24 and 122:94 Æ 0:81, respectively. The result of 3 0.03 0.45 ANOVA showed that there was signi¯cant di®er- 0.02 0.67 ence in ROM within IoT group participants 23 (F ¼ 9:11; p ¼ 0:001) (Table 6). 0.84 0.08 Hong Kong Physiother. J. 2018.38:63-75. Downloaded from www.worldscientific.com Lateral JSW 1 2 0.14 0.05 For participants in the CFM group, the mean by Horizon College Physiotherapy on 05/28/22. Re-use and distribution is strictly not permitted, except for Open Access articles. 3 0.06 0.24 pain intensities on active and passive knee °exions were 4:72 Æ 2:22; 3:39 Æ 1:65 and 1:83 Æ 1:15, re- 23 0.31 0.01 spectively, on a 10-point rating scale (VAS) at 0.17 0.13 baseline, 6th and 12th weeks. The result of ICT 1 2 À0.14 0.20 ANOVA showed that there were signi¯cant dif- 3 ferences in pain intensities on active and passive À0.76 0.08 knee °exions at baseline, 6th and 12th weeks 23 À0.14 0.70 within the CFM group participants (F ¼ 12:59; 0.09 p ¼ 0:001; F ¼ 15:55; p ¼ 0:001, respectively) Tibia width 12 0.62 (Table 6). The post hoc analysis (LSD) showed 3 that the pain intensity on active knee °exion at 6th week for CFM group participants was signi¯cantly 23 lower than that of baseline (p ¼ 0:025) while at the 12th week, it was also signi¯cantly lower than at Note: 1 ¼ IoT group, 2 ¼ CFM group and 3 ¼ CoT group. baseline (p ¼ 0:001). Similarly, the pain intensity on active knee °exion at 12th week for the CFM F ¼ 12:81; p ¼ 0:001, respectively). The mean pain group was signi¯cantly lower than at 6th week intensities on active and passive knee °exion; and (p ¼ 0:009). The result of post hoc analysis (LSD) patellar grinding for CFM and CoT groups are showed that the ROM at 12th week of CFM group presented in Table 6. The post-hoc analysis (LSD) was signi¯cantly higher than that of baseline showed that the pain intensity on active knee (p ¼ 0:001) (Table 8). °exion on a 10-point rating scale (VAS) at the 6th week of IoT group participants was signi¯cantly The result showing comparison of mean of pain lower than that of baseline (p ¼ 0:001), with fur- intensities and ROMs for other groups are pre- ther decrease at 12th week (p ¼ 0:001). Similarly, sented in Table 6. The result of the post hoc the pain intensity on active knee °exion at 12th analysis (LSD) showed that the pain intensity on week for IoT participants was signi¯cantly lower active knee °exion on a 10-point rating scale than that of 6th week (p ¼ 0:001). The same (VAS) at 6th week of CoT group participants was signi¯cantly lower than that of baseline Table 5. Result of post hoc (LSD) analysis of radio- (p ¼ 0:001) and also the pain intensity on active graphic parameters of all the participants across the knee °exion on a 10-point rating scale (VAS) at three groups after 12th week. 12th week in CoT group was signi¯cantly lower than that of baseline (p ¼ 0:001). Similarly, the I J Mean di®erence (I À J) P pain intensity on active knee °exion on a 10-point rating scale (VAS) at 12th week in CoT group was Medial JSW 1 2 À0.20 0.005 signi¯cantly lower than that of 6th week 3 0.01 0.94 (p ¼ 0:01). Other post hoc analysis (LSD) results 0.21 0.004 are shown in Table 9. 23 0.27 0.001 There was signi¯cant di®erence in pain intensity Lateral JSW 1 2 0.15 0.01 on active knee °exion on a 10-point pain rating 3 À0.11 0.04 scale across the three groups (VAS) (F ¼ 9:33; p ¼ 0:01) and same trend was found for passive 23 0.30 0.01 0.11 0.32 ICT 1 2 À0.18 0.10 3 À0.75 0.14 23 À0.12 0.73 0.08 Tibia width 12 0.63 3 23 Note: 1 ¼ IoT group, 2 ¼ CFM group and 3 ¼ CoT group.

70 A. T. Onigbinde et al. Table 6. Comparison of pain intensity and ROM of participants at baseline, 6th and 12th weeks within the groups. Baseline 6th week 12th week F P Mean SD Mean SD Mean SD Hong Kong Physiother. J. 2018.38:63-75. Downloaded from www.worldscientific.com IoT Pain intensity OAKF 4.94 1.30 2.94 0.97 1.77 0.66 43.00 0.001* by Horizon College Physiotherapy on 05/28/22. Re-use and distribution is strictly not permitted, except for Open Access articles. CFM OPKF 6.41 1.33 3.77 0.97 2.94 0.66 53.54 0.001* CoT ROM OPG 3.88 1.50 1.88 1.32 2.24 0.75 12.81 0.001* Pain intensity OAKF 107.35 12.18 114.06 10.80 122.94 8.81 9.11 0.001* ROM OAKF 4.72 2.22 3.39 1.65 1.83 1.83 12.59 0.001* Pain intensity OPKF 5.83 1.98 4.00 1.65 2.83 1.15 15.55 0.001* OPG 3.83 1.58 3.33 1.09 3.00 0.91 2.11 0.130 ROM OAKF 104.22 17.25 113.89 14.24 121.61 10.18 6.78 0.002* OAKF 6.83 1.02 3.39 1.04 2.50 0.92 93.79 0.001* OPKF 7.33 1.37 4.12 1.15 3.06 1.06 61.58 0.001* OPG 5.67 1.65 3.39 1.38 2.56 0.78 26.84 0.001* OAKF 97.33 14.38 102.28 10.25 116.00 11.69 11.27 0.001* Notes: ÃSigni¯cant at p < 0:05. OAKF: On Active Knee Flexion, OPKF: On Passive Knee Flexion, OPG: On Patellar Grinding, 1 ¼ IoT, 2 ¼ CFM and 3 ¼ CoT. Table 7. Post hoc analysis (LSD) of pain intensity and Table 8. Post hoc analysis (LSD) of pain intensity and ROM of all the participants at baseline, 6th and 12th weeks ROM of all the participants at baseline, 6th and 12th weeks within IoT group. within CFM group. Mean Mean P changes changes I J (I À J) P -value I J (I À J) Pain intensity OAKF 1 2 2.00 0.001* Pain intensity OAKF 1 2 1.33 0.030* 0.001* 3 2.89 0.001* 3 3.18 0.001* 1.56 0.001* 0.001* 23 1.83 0.001* 23 1.18 0.001* OPKF 1 2 3.00 0.001* 0.020* 1.17 0.040* OPKF 1 2 2.65 0.001* 3 0.50 0.230 0.001* 23 0.83 0.050* 3 3.47 0.410 OPG 1 2 0.33 0.420 0.070 23 0.82 0.001* 3 0.020* 23 OPG 1 2 2.00 3 1.65 2 3 À0.35 ROM OAKF 1 2 À6.71 ROM OAKF 1 3 À9.67 0.050* 3 À17.34 0.001* 3 À15.59 2 3 À7.72 0.110 2 3 À8.88 Notes: *Signi¯cant at p < 0:05. Notes: *Signi¯cant at p < 0:05. 1 ¼ Baseline, 2 ¼ 6th week and 3 ¼ 12th week, OAKF: On 1 ¼ Baseline, 2 ¼ 6th week and 3 ¼ 12th week, OAKF: On Active Knee Flexion, OPKF: On Passive Knee Flexion, Active Knee Flexion, OPKF: On Passive Knee Flexion, OPG: On Patellar Grinding. OPG: On Patellar Grinding. knee °exion and patellar grinding at baseline for Comparison of physical function participants in the three groups (Table 10). The of participants across the three post hoc analysis (LSD) showed that the pain in- groups at baseline, 6th and tensity on active knee °exion for IoT group parti- 12th weeks cipants was signi¯cantly lower than that of CoT group (p ¼ 0:001) and CFM group (p ¼ 0:001). The physical function of participant in IoT group Similar trends were also observed for passive knee at baseline was 28:31 Æ 6:19 on a WOMAC scale. °exion and on patellar grinding (Table 11).

Symptoms-modifying e®ects of electromotive administration of GS 71 Table 9. Post hoc (LSD) analysis of pain intensity and week are presented in Table 12. There were also ROM of all the participants at baseline, 6th and 12th weeks signi¯cant di®erences in physical functions among within CoT group. the participants across the three groups at 6th and 12th weeks (H ¼ 9:19; p ¼ 0:01; H ¼ 3:23; p ¼ Mean 0:01, respectively) (Table 12). changes I J (I À J) P Hong Kong Physiother. J. 2018.38:63-75. Downloaded from www.worldscientific.com Pain intensity OAKF 1 2 3.44 0.001* Discussion by Horizon College Physiotherapy on 05/28/22. Re-use and distribution is strictly not permitted, except for Open Access articles. 3 4.33 0.001* 0.89 0.010* Topical delivery of medication permits the avoid- 23 3.17 0.001* ance of ¯rst pass metabolism by the liver and it OPKF 1 2 4.28 0.001* also by-passes the gastric system providing higher 1.11 0.008* levels and quicker tissue saturation.11,25 It is widely 3 2.28 0.001* acknowledged that transdermal delivery improves 23 3.11 0.001* patient compliance.25 Levene's test was used to OPG 1 2 0.83 0.060 determine if the three groups have equal variances. Comparability across samples is called homogene- 3 ity of variance. The result of Levene test in this 23 study con¯rmed that the anthropometric para- meters of patients in the three groups were com- ROM OAKF 1 2 À4.94 0.230 parable in age, weight, height and (BMI), hence 3 À18.67 0.001* di®erences observed in this study could not be À13.72 0.001* attributed to the parameters. Chronicity of dis- 23 eases could also a®ect the outcome of interven- tions, however, there was no signi¯cant di®erence Notes: *Signi¯cant at p < 0:05. in the duration of onset of knee OA of patients in 1 ¼ Baseline, 2 ¼ 6th week and 3 ¼ 12th week, OAKF: On the three groups. Active Knee Flexion, OPKF: On Passive Knee Flexion, OPG: On Patellar Grinding. Measurement of changes in JSW is currently the gold standard in evaluation of structured modify- The physical functions of participants in the CFM ing drugs in OA.26 This current study evaluated and CoT groups are presented in Table 12. The both medial and lateral JSWs because OA may result of Kruskal–Wallis showed that there were signi¯cant di®erences in physical function among the participants across the three groups at baseline (H ¼ 4:97; p ¼ 0:01). The physical functions of participants in IoT, CFM, CoT groups at the 6th Table 10. Comparison of pain intensity and ROM of all the participants across the three groups after 12th week. IoT CFM CoT Mean SD Mean SD Mean SD F P Pain intensity OAKF: Base 4.94 1.30 4.72 2.22 6.83 1.04 9.34 0.001* 6th 2.94 0.97 3.39 1.65 3.35 1.06 0.66 0.520 1.76 0.66 1.83 1.15 2.50 0.92 3.33 0.040* 12th 6.41 1.33 5.83 1.98 7.33 1.37 4.07 0.020* OPKF: Base 3.77 0.97 4.00 1.65 4.12 1.17 0.33 0.720 2.94 0.66 2.83 1.15 3.06 1.06 0.23 0.780 6th 3.88 1.50 3.83 1.58 5.67 1.65 7.84 0.001* 12th 1.88 1.32 3.33 1.09 3.35 1.41 7.51 0.001* OPG: Base 2.23 0.75 3.00 0.91 2.56 0.78 3.86 0.030* 6th 12th ROM AKF: Base 107.35 12.18 104.22 17.25 97.33 14.38 2.12 0.130 6th 114.06 10.80 113.89 14.24 01.53 10.04 6.27 0.004* 122.94 8.81 121.61 10.18 116.00 11.69 2.26 0.120 12th Notes: *Signi¯cant at p < 0:05. OAKF: On Active Knee Flexion, OPKF: On Passive Knee Flexion, OPG: On Patellar Grinding, Base: Baseline.

72 A. T. Onigbinde et al. Table 11. Post hoc (LSD) analysis of pain intensity and joint space that makes use of CFM technique only. ROM of all the participants across the three groups at In knee OA, tight muscle increases the compression baseline. of joint while tightening of quadriceps, hamstring and calf muscle results in poor coordination and Mean p slower reaction time.28 The tightening of quadri- changes ceps, hamstring, calf muscle and poor °exibility I J (I À J) associated with knee OA may likely have a com- bined closing e®ect on the 1knee joint space. The Pain intensity OAKF 1 2 2.19 0.690 administration of GS cream through massage À1.89 0.001* might have loosened and relaxed soft tissues at the 3 À2.11 0.001* knee joint; and these might be the reason for the 0.290 increased medial joint space at the knee joint. The 23 0.58 0.090 use of massage is an age-old process that involves À0.92 0.010* stimulations of tissues by rhythmically applying OPKF 1 2 À1.5 0.930 both stretching and pressure.29 0.002* Hong Kong Physiother. J. 2018.38:63-75. Downloaded from www.worldscientific.com 3 0.05 0.001* CFM had been reported to stimulate blood °ow by Horizon College Physiotherapy on 05/28/22. Re-use and distribution is strictly not permitted, except for Open Access articles. À1.78 0.530 and also breaks down cross-bridge; and the fric- 23 À1.83 0.050* tional pressure is applied at right angle thereby 0.170 stretching apart the musculo-tendinous tissues.30 OPG 1 2 3.13 The stretching and pressure at the knee joint might improve the °exibility of the quadriceps and ham- 3 10.01 string muscles which subsequently open up the 6.89 joint space of the knee in patients with OA. Flexi- 23 bility is related to the extensibility of musculo- tendinous units that cross a joint. Onigbinde et al.31 ROM OAKF 1 2 reported that transdermal massage of glucosamine was very e®ective in improving hamstring °exibil- 3 ity and increasing knee °exion ROM among patients with knee OA. The reported improvement 23 in medial joint space might be attributed to the contributions of the manipulative e®ects of CFM Notes: *Signi¯cant at p < 0:05. and transdermal application of GS cream which 1 ¼ IoT, 2 ¼ CFM, 3 ¼ CoT, OAKF: On Active Knee both improve °exibility. This study corroborated Flexion, OPKF: On Passive Knee Flexion, OPG: On that of Reginster et al.32 who also observed an in- Patellar Grinding. crease in the JSW in patients with OA. Also, Dahmers and Schiller33 reported the increase in involve either medial and lateral tibiofemoral or medial compartment of tibia femoral joint space patellafemoral compartments according to the lo- following the administration of GS after 12 weeks of calization of cartilage deterioration.27 At baseline, the three groups were comparable in medial joint space and tibial widths. At the 6th week, there were no signi¯cant changes in all the radiographic parameters. However, at the 12th week (after three months), there were di®used e®ects of di®erent interventions on JSWs. There was signi¯cant in- crease in the medial joint space when massage was used to administer GS cream while there was a signi¯cant increase in lateral joint space when GS cream was administered through the process of IoT. The combined therapies improved the lateral Table 12. Comparison of physical function of participant across the three groups at baseline, 6th and 12th weeks. Physical function IoT CFM CoT Mean Æ SD Mean Æ SD Mean Æ SD H P Baseline 28.31 6.19 34.08 10.82 37.96 9.50 4.97 0.010* At 6th week 17.85 4.98 22.70 5.83 23.37 6.64 9.19 0.010* At 12th week 11.27 2.64 16.61 6.63 14.82 8.23 3.23 0.010* Notes: *Signi¯cant at p < 0:05. IoT: iontophoresis, CFM: cross-friction massage, CoT: combined therapy.

Symptoms-modifying e®ects of electromotive administration of GS 73 Hong Kong Physiother. J. 2018.38:63-75. Downloaded from www.worldscientific.com intervention. Also, in a recent study, Durmus Reginster et al.32 Furthermore, Onigbinde et al.11 by Horizon College Physiotherapy on 05/28/22. Re-use and distribution is strictly not permitted, except for Open Access articles. et al.34 evaluated the e®ect of GS on the cartilage reported that the administration of 1 g of GS cream repair, and found an increase in the medial JSW. was e®ective in alleviating pain experienced by knee OA patients. GS IoT has been severally ob- This study observed that at baseline, the ICT of served to modulate and signi¯cantly reduce pain patients who had intervention using CFM was immediately after use.11,35 signi¯cantly lower than that of those who received GS IoT only at baseline, however, after 12 weeks of There was signi¯cant increment in knee °exion intervention, the ICT remained lower for the for- at six weeks of interventions across the groups. mer. There was no signi¯cant di®erence in the tibia However, after 12 weeks of intervention, there was width across the three groups at baseline, 6th and no signi¯cant di®erence in the ROMs. This implied 12th weeks. This implied that there was no pro- that patients who had CoT might have reached a gression in the degeneration of bone margins of the plateau in ROM at the 12th week. This current tibia condyle after three months. The within ¯nding supported the report of Onigbinde et al. groups assessment showed that knee OA patients who observed that patients who had GS IoT had who received GS via CFM only had increased lat- signi¯cantly better active knee °exion compared eral JSW at 12th week than at baseline. Also, the with those who had the topical medication through lateral JSW at 12th week was signi¯cantly higher massage because the duration of their intervention than that at baseline and 6th week. The signi¯cant was also within six weeks.11 However, within the increase in the medial and lateral JSW of the knee groups, there was signi¯cant increase in active knee joints corroborated the ¯ndings of Reginster et al.32 °exion. This is in consistent with ¯ndings of This study observed no signi¯cant di®erence in the Onigbinde et al. who also reported that there was medial JSW, lateral JSW, ICT and tibia width of an increase in the ROM of patient with knee OA patient who received GS IoT only and similar trend following the administration of GS.22 was observed for patients who had both glucos- amine through IoT and massage. The clinical im- OA of the knee is the most common cause of plication of this is that there was neither regression chronic disability among the elderly worldwide.36 nor progression in degenerative changes in the ra- The degree of °exibility of the quadriceps and diographic features of patients who received either hamstring group of muscles contributes to smooth IoT only or combined interventions. Besides, it is and precise ambulatory functions. Most subjects also suggestive of the importance of using plain with OA usually experience functional limitations radiograph to monitor progress made in the man- in activities of daily living.37 The current ¯ndings on agement of knee OA using JSW, ICT and tibia physical functions showed that after 12 weeks of width as indices for outcome measures. intervention, there was signi¯cant improvement across the groups, but participants in the IoT group This study rated pain intensities on active and showed improved physical function compared to passive movements; and during patellar grinding. the other groups. This corroborated the previous It was observed that after 12 weeks of interven- study that showed that GS alleviates pain and tions, the administration of glucosamine via IoT subsequently improves the physical functions of signi¯cantly reduced the pain intensity on active patients.22 Also, Braham et al. reported that glu- knee °exion and patellar grinding. The pain in- cosamine supplementation provides degree of pain tensity experienced by patients who had CoT was relief and further improved the function in persons signi¯cantly higher at baseline compared to that of who experience regular knee pain, which may be those who received massage only. However, after caused by prior cartilage injury and/or OA.22,38 12 weeks, there was no signi¯cant di®erence be- tween levels of intensities between the groups. This Conclusion implied that combination of GS IoT and massage was more e®ective in managing pain associated We concluded that at the 12th week, there were with knee OA. This corroborated the reported de- signi¯cant decreases in the degenerative changes at crease in pain intensity of patient with knee OA the knee joints of patients with knee OA. The ad- after administration of GS.22,26 This current study ministration of GS using IoT alone signi¯cantly further lent credence to the e®ectiveness of ad- increases the lateral JSW than other interventions ministration of GS in alleviating pain in patient 6 while CFM only signi¯cantly increases the medial with knee OA as reported by Graig.26 and JSW. However, none of the three interventions was

Hong Kong Physiother. J. 2018.38:63-75. Downloaded from www.worldscientific.com 74 A. T. Onigbinde et al. °exibility of subjects with knee osteoarthritis by Horizon College Physiotherapy on 05/28/22. Re-use and distribution is strictly not permitted, except for Open Access articles. and their age matched control. Clin Med Res superior in their e®ects on ICT and degeneration 2013;2(6):121–5. of tibia bone margin after 12 weeks. Also, GS 5. Sellam J, Berenbaum F. The role of synovitis in administration through CFM alleviated pains, in- pathophysiology and clinical symptoms of osteo- creased active and passive knee °exion better than arthritis. Nat Rev Rheumatol 2010;6(11):625–35. the use of IoT alone or combination of both inter- 6. Beattie K, Duryea J, Pui M, O'Neill J, Boulos P, ventions. Furthermore, the administration of GS Webber CE. Minimum joint space width and tibial using IoT only increased the physical functions cartilage morphology in the knees of healthy indi- than CFM or combination of both interventions. viduals: A cross-sectional study. BMC Muscu- loskelet Disord 2008;9:119–26. Con°ict of Interest 7. Hilliquinb P, Pessisc E, Costed J, Maugetc D, Azriab A, Chevrotc A. Quantitative assessment of There was no con°ict of interest in this study. joint space width with an electronic caliper. Osteoarthr Cartil 2002;10(7):542–6. Funding/Support 8. Braun HJ, Gold GE. Diagnosis of osteoarthritis: Imaging. Bone 2011;51(2):278–88. There was no external ¯nancial support for the 9. Writer Sta®. Acupuncture treatment specialist. study. The cost of clinical trial was met by the 2007. Available at: http//acupuncture-treatment- investigators. specialists.com articles acupuncture-articles-id 501. htm/acupuncture-articles1d502.htm. Author Contributions 10. Onigbinde AT, Adedoyin RA, Johnson O. E®ect of physical therapy intervention on pharmacokinetic Onigbinde Ayodele Teslim contributed in devel- variables. Niger J Med Rehabil 2006;2(19):1–5. oping the concept, data collection and analysis, 11. Onigbinde AT, Adedoyin RA, Olaugun MOB, script preparation, revising the manuscript and Ojoawo OA, Akinpelu AO, Onibokun A. E±cacy of editing. Owolabi Adegbenga Rotimi contributed to glucosamine iontophoresis in the management data collection, analysis, script preparation, revis- of knee osteoarthritis. Niger Med Pract 2008;54(3): ing the manuscript and editing. Lasisi Kamil con- 66–9. tributed to data collection, analysis, script 12. Uitto O, White S. Electrosmotic pore transport in preparation, revising the manuscript and editing. human skin. Pharmacol Res 2003;20:646–52. Sarah Oghenekewe Isaac contributed to data col- 13. Lozada CJ, Pace SSC. Osteoarthritis Treatment lection, script preparation and editing. Ibikunle and Management. 2015. Available at: emedicine. Adeoye Folorunso contributed to data collection, medscape.com/article330487-treatment. script preparation and editing. 14. Reginister J, Bruyere O, Lecart M, Henroitin Y. Glucosamine and chondroitin sulphate. Am Coll References Rheumatol 2009;25:1160–5. 15. The Glucosamine Osteoarthritis Resource Centre. 1. Bridges SL. National institute of arthritis and Glucosamine and Osteoarthritis. 2005. Available musculoskeletal and skin diseases. Arthritis Res at: http://www.glucosamine osteoarthritis.org/ Ther 2000;2(1):0003. Available at:www.niams.nih. glucosamine/Glucosamine for-arthritis.html. gov/health info/osteoarthritis/default.asp.ref- 16. McAlindon E, LaValley P, Guhlin J. Glucosamine NIH2015 2-6. and chondroitin for treatment of osteoarthritis: A systematic quality assessment and meta-analysis, 2. Woolf AD, P°eger B. Burden of major musculo- Jama 2000;283(11):1483–4. skeletal conditions. Bull World Health Organ 17. Adedoyin RA, Olaogun MOB, Fagbeja OO. E®ect 2003;81:646–56. of interferential current stimulation in the man- agement of osteoarthritis knee pain. Physiotherapy 3. Royal Australian College of General Practitioners 2002;88(8):493–9. RACGP. Guideline for the non-surgical manage- 18. Sala± F, Leardini G, Canesi B, et al. Reliability ment of hip and knee osteoarthritis. 2009. Available and validity of the Western Ontario and McMaster at:www.racgp.org.au/download/documents/guide- Universities [WOMAC] osteoarthritis index in lines/musculoskeletal. Italian patients with osteoarthritis of the knee. Osteoarthr Cartil 2003;11:551–60. 4. Onigbinde AT, Oluukola AF, Adenike F, Oniyangi 19. Deep K, Norris M, Smart C. Radiographic mea- S, Olaitan OL. An assessment of hamstring surement of joint space height in non-osteoarthritic

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