physiological and clinical effects of radiofrequency- based therapy

378 Pages·2017·7.47 MB·English

PHYSIOLOGICAL AND CLINICAL
EFFECTS OF RADIOFREQUENCY-
BASED THERAPY

Binoy Radha Kumaran

Submitted to the University of Hertfordshire in partial fulfilment of
the requirements of the degree of Doctor of Philosophy

PhD
February 2017
2
Abstract
Electrophysical agents (EPA) are a fundamental element of therapy practice and are vital for
the treatment of a variety of conditions. Many of these agents employ some form of
electromagnetic fields (EMF), in which radiofrequency (RF) is a major component. The
therapeutic effects of RF are mainly linked to their effects on pain relief and potential effects
on tissue repair. Although RF across various frequency ranges has been in use, reviews
have shown that the frequency ranges currently used in therapy practice have narrowed to
within 30 kHz–30,000 kHz (30 MHz). The most commonly used and hence the most
commonly researched are shortwave therapies (SWT) that operate at 27.12 MHz, which is
presently used predominantly in its pulsed form (PSWT).
In addition to SWT, devices employing significantly lower RF ranges have also been used
widely despite their lack of evidence. Capacitive Resistive Monopolar Radiofrequency
(CRMRF) that operates at 448 kHz is one such RF. This programme of research was
designed to investigate the physiological and clinical efficacy of CRMRF delivered using the
‘Indiba Activ 902’ device. The project also evaluated the scope and evidence for RF-based
EPAs in therapy, through a comprehensive review of literature. A total of 120 relevant
clinical studies on either acute (30 studies) or chronic (90 studies) conditions were reviewed.
Notable evidence was identified for chronic OA knee and acute postoperative pain and
wound healing. Some evidence also exists for chronic low back pain and healing of chronic
wounds. Only eight studies reported devices that employed RF outside the shortwave
frequency band.
In a randomised crossover laboratory study on asymptomatic adults, the effects of
contrasting doses of CRMRF on skin temperature (SKT), skin blood flow (SBF), nerve
conduction velocity (NCV), deep blood flow and the extensibility of tissues were examined
against a placebo dose and a control condition with no treatment. The study further
compared CRMRF results with that of PSWT. The results showed that high (moderately
thermal) and low (sub/minimally thermal) doses of CRMRF significantly enhanced and
sustained SKT (p<0.001), while only the high dose meaningfully increased SBF (p<0.001).
High dose PSWT increased SKT marginally (p<0.001) but did not sustain it. Further, the high
and low dose CRMRF significantly enhanced blood flow volume at depth (p=0.003), while
PSWT failed to show any significant impact. None of the treatments significantly affected
deep blood flow velocity, tissue extensibility or NCV.
These results were reproduced on a cohort of patients affected by OA knee in a randomised
controlled trial (RCT), and the effects appeared more pronounced in the patients than in the
asymptomatic people. More importantly, the RCT showed that a four-week high dose
CRMRF treatment (eight sessions) produced statistically and clinically significant gains in
3
pain and function associated with OA knee in the short to medium term (p<0.001), which
was also significantly more pronounced than the gains produced by a placebo, or standard
care (p=0.001for pain; p=0.031 for function). The findings of this study were considered
promising. It is therefore suggested that CRMRF-based treatment can potentially be used as
an adjunct to current therapeutic methods to enhance the clinical outcomes. However,
further studies are needed to substantiate this, and the current results will provide credible
baseline data for future research.
4
Acknowledgements
My sincere thanks to the following people without whom this work would
have fallen short...

To Professor Tim Watson who has been inspirational and critical in the right measure, for
being my perfect guide and best friend in this job for the last five years!
To Mr Roy Smith (CEO, Indiba S. A.), Dr Sebastia Sendros, Mr Xavier Rami and other
colleagues at Indiba S. A., Barcelona for all their support and continued funding throughout
the project.
To Dr Karen Beeton for her support on the provision of extended funding from the
department.
To Mr Jon Woollard for being extremely helpful on the laboratory matters throughout, and for
being the most prolific participant in my experiments.
To Mrs Diana Davis and other former and current colleagues at the University of
Hertfordshire for their kind support and participation in the project.
To Dr Anthony Herbland for his invaluable expertise and help with the ultrasound image
analysis.
To Dr Jane Simmonds for all her help, and for introducing me to this project in the first place.
To all the colleagues at the Safari Therapy Unit, Hemel Hempstead Hospital for their help
and support for the clinical trial.
To all those patients at the Hemel Hempstead Hospital who kindly volunteered to participate
in the clinical trial.
…and finally
To my parents who kept asking every other week that when was I going to finish this work!
To my seven-year-old son Sidharth for appreciating that I was working on ‘something big’!
To my wife Byju for all her patience and support (…and sometimes the lack of it)!

Thank God.
5
List of contents
Title page 1
Abstract 2
Acknowledgements 4
List of contents 5
Table of contents 6
List of tables 14
List of figures 16
List of publications 21
6
Table of Contents
Table of Contents .................................................................................................................. 6
1 Chapter 1 – Electromagnetism, radiofrequency and radiofrequency-based
electrophysical agents: key concepts and project overview. ................................................ 23
Research context .................................................................................................. 23
Electromagnetic fields ........................................................................................... 23
Radiofrequency ..................................................................................................... 24
Radiofrequency and biological systems ................................................................ 25
1.4.1 RF-tissue interaction ...................................................................................... 25
1.4.2 Thermal versus nonthermal effects of RF ....................................................... 26
1.4.3 RF tissue absorption ...................................................................................... 28
1.4.4 Biological effects of RF .................................................................................. 28
Overview of the project ......................................................................................... 29
1.5.1 Development and sequencing ........................................................................ 29
1.5.2 RF-based treatment in therapy-related clinical practice .................................. 30
1.5.3 Rationale ........................................................................................................ 31
1.5.4 Key aims and research questions .................................................................. 31
Conclusions .......................................................................................................... 32
2 Chapter 2 – Literature review on the biological effects of radiofrequency: methodology
and main results. ................................................................................................................. 34
Introduction ........................................................................................................... 34
Methods ................................................................................................................ 35
2.2.1 Search strategy and reference management ................................................. 35
2.2.2 Narrative review ............................................................................................. 36
2.2.3 Quality assessment of studies ........................................................................ 37
Main results........................................................................................................... 38
Radiofrequency-based treatment: the non-clinical literature .................................. 41
2.4.1 Human studies in vivo on asymptomatic people ............................................. 41
2.4.2 Animal studies, in vitro studies on cell and tissue models .............................. 42
2.4.3 Experimental animal studies simulating acute clinical conditions.................... 43
2.4.4 Experimental animal studies simulating chronic clinical conditions ................. 44
Conclusions .......................................................................................................... 44
7
3 Chapter 3 – Radiofrequency-based treatment in therapy-related clinical practice. ........ 45
Studies on acute conditions .................................................................................. 45
3.1.1 Studies on pain and inflammation .................................................................. 49
3.1.2 Studies on tissue healing ............................................................................... 53
3.1.3 Studies on other applications ......................................................................... 54
3.1.4 Conclusions ................................................................................................... 54
Studies on chronic conditions ................................................................................ 55
3.2.1 Non-shortwave studies ................................................................................... 55
3.2.2 Shortwave studies .......................................................................................... 59
3.2.3 Conclusions ................................................................................................... 79
Section II summary ............................................................................................... 80
4 Chapter 4 – Materials and methods, measurement principles and pilot experiments. ... 84
Introduction ........................................................................................................... 84
The RF treatment devices ..................................................................................... 84
4.2.1 The CRMRF device........................................................................................ 84
4.2.2 The PSWT device .......................................................................................... 86
Selection of physiological parameters to investigate ............................................. 87
Selection of a body area to treat ............................................................................ 87
Superficial physiological measurements ................................................................ 88
4.5.1 Skin temperature ............................................................................................ 88
4.5.2 Skin blood flow ............................................................................................... 89
4.5.3 Nerve conduction velocity .............................................................................. 90
4.5.4 The skin physiological measurement devices................................................. 91
Deep physiological measurements ........................................................................ 93
4.6.1 Deep blood flow ............................................................................................. 93
4.6.2 Tissue extensibility ......................................................................................... 94
4.6.3 Ultrasound scanning devices ......................................................................... 94
Other outcome measures ...................................................................................... 95
Other devices used in the project .......................................................................... 95
Processing of physiological data ........................................................................... 95
4.9.1 Processing of Biopac data.............................................................................. 95
8
4.9.2 Processing of ultrasound data ........................................................................ 96
4.9.3 Processing of FlexComp Infiniti data .............................................................. 99
Methodological considerations and pilot experiments ............................................ 99
4.10.1 The CRMRF device: familiarisation, operating principles and identifying the key
issues (addressed aim 1)........................................................................................... 100
4.10.2 Calibration of equipment (addressed aim 2) ................................................. 102
4.10.3 Investigating signal interference (addressed aim 3) ..................................... 103
4.10.4 Issues surrounding probe attachment and signal noise (addressed aims 4 & 5).
……….... ................................................................................................................... 106
4.10.5 Baselining of the data streams and electrode acclimatisation (addressed aims
6 & 10). ……………………………………………………………………………………….109
4.10.6 Sampling rate for the Biopac system (addressed aim 7) .............................. 109
4.10.7 Validation of temperature readings using different measurement techniques
(addressed aim 8)...................................................................................................... 109
4.10.8 Electrode stability tests for NCV (addressed aim 9)...................................... 111
4.10.9 Intra-rater reliability of ultrasound measurements (addressed aim 11) ......... 112
Conclusions ........................................................................................................ 114
5 Chapter 5 – Basic considerations on CRMRF therapy: Skin thermal onset, thermal
decay and thermal retention responses to the CAP and RES modes – a randomised
crossover study ................................................................................................................. 115
Introduction ......................................................................................................... 115
Physiological effects of heat ................................................................................ 115
Key aims ............................................................................................................. 116
Materials and methods ........................................................................................ 116
5.4.1 Apparatus .................................................................................................... 116
5.4.2 Sample and groups ...................................................................................... 118
5.4.3 Pretesting and pilot work .............................................................................. 118
5.4.4 Experimental procedure ............................................................................... 119
Electrode temperature testing ............................................................................. 120
Data analysis ...................................................................................................... 121
Results ................................................................................................................ 121
Discussion .......................................................................................................... 133
Conclusions ........................................................................................................ 137
9
6 Chapter 6 – Skin and deep tissue physiological effects of CRMRF treatment: single-
blind randomised crossover study with a comparison to PSWT ......................................... 138
Introduction ......................................................................................................... 138
Aims .................................................................................................................... 138
Materials and methods ........................................................................................ 139
6.3.1 Apparatus .................................................................................................... 139
6.3.2 Sample and groups ...................................................................................... 139
6.3.3 Experimental procedure ............................................................................... 141
6.3.4 Data acquisition ........................................................................................... 141
6.3.5 The CRMRF intervention ............................................................................. 144
6.3.6 PSWT treatment .......................................................................................... 148
6.3.7 Data analysis ............................................................................................... 148
Results ................................................................................................................ 149
6.4.1 Skin temperature results .............................................................................. 151
6.4.2 Skin blood flow results ................................................................................. 156
6.4.3 Nerve Conduction Velocity results ................................................................ 161
6.4.4 Blood flow volume ........................................................................................ 162
6.4.5 Blood flow intensity ...................................................................................... 166
6.4.6 Blood flow velocity ....................................................................................... 170
6.4.7 Tissue extensibility ....................................................................................... 170
6.4.8 Results from the control leg .......................................................................... 172
6.4.9 Other results ................................................................................................ 173
Discussion .......................................................................................................... 174
Conclusions ........................................................................................................ 181
7 Chapter 7 – Section III conclusions: key findings, limitations of the studies and
implications for clinical practice and research .................................................................... 183
Key findings ........................................................................................................ 183
Methodological considerations and potential limitations of the studies ................ 184
Implications for practice and future research ....................................................... 186
8 Chapter 8 – The effect of CRMRF on pain and function in patients with OA of the knee
joint: a randomised controlled trial ..................................................................................... 188
Introduction to osteoarthritis ................................................................................ 188
10
8.1.1 Epidemiology ............................................................................................... 188
8.1.2 Global costs ................................................................................................. 188
8.1.3 Classification of OA ...................................................................................... 189
8.1.4 Pathophysiology and symptoms of OA knee ................................................ 189
8.1.5 Current best treatment for OA knee ............................................................. 190
8.1.6 Physiotherapy interventions for OA knee ..................................................... 190
Rationale for the study ........................................................................................ 192
Key aims of the study .......................................................................................... 192
The study design ................................................................................................. 192
Materials and methods ........................................................................................ 193
8.5.1 The CRMRF device...................................................................................... 193
8.5.2 Outcome measures ...................................................................................... 194
8.5.3 The study setting, Ethics approval, trial registration and key dates ............... 196
8.5.4 The study population and sample recruitment .............................................. 197
8.5.5 Sample size and power calculation .............................................................. 198
8.5.6 The study groups ......................................................................................... 198
8.5.7 Interventions ................................................................................................ 199
8.5.8 Procedure .................................................................................................... 200
8.5.9 Analysis of data ............................................................................................ 201
Results ................................................................................................................ 201
8.6.1 Self-reported pain ........................................................................................ 204
8.6.2 WOMAC osteoarthritis index ........................................................................ 207
8.6.3 Walking ability .............................................................................................. 209
8.6.4 Knee joint ROM ............................................................................................ 211
8.6.5 Subgroup analyses and correlations ............................................................ 213
8.6.6 Post-hoc power and sample size calculation ................................................ 215
Discussion .......................................................................................................... 216
Conclusions ........................................................................................................ 222
9 Chapter 9 – Skin and deep physiological effects of CRMRF treatment in patients with
OA of the knee joint: a single-blind randomised controlled trial .......................................... 223
Introduction ......................................................................................................... 223