`Current Medical Research and Opinion (cid:9)Current Medical Research and Opinion (cid:9)
`Current Medical Research and Opinion
`
`Vol. 3, Suppl. 4.1975
`
`Vol. 3, Suppl. 4, 1975 Vol. 3, Suppl. 4, 1975
`
`Thermographic assessment
`
`Thermographic assessment Thermographic assessment
`of the anti-inflammatory
`
`of the anti-inflammatory of the anti-inflammatory
`effect of flurbiprofen
`
`effect of flurbiprofen effect of flurbiprofen
`in rheumatoid arthritis
`
`in rheumatoid arthritis in rheumatoid arthritis
`
`P. A. Bacon,*M.B.,Ch.B.,M.R.C.P.,
`
`P. A. Bacon,*M.B.,Ch.B.,M.R.C.P., P. A. Bacon,*M.B.,Ch.B.,M.R.C.P.,
`A. J. Collins, Ph.D.,
`
`A. J. Collins, Ph.D., A. J. Collins, Ph.D.,
`and
`
`and and
`J. A. Cosh, M.D.,F.R.C.P.
`
`J. A. Cosh, M.D., F.R.C.P. J. A. Cosh, M.D., F.R.C.P.
`Royal National Hospital
`
`Royal National Hospital Royal National Hospital
`for Rheumatic Daeases,
`
`for Rheumatic Diseases, for Rheumatic Diseases,
`Bath, England
`
`Bath, England Bath, England
`
`Paper read: 6th June 1975
`
`Paper read: 6th June 1975 Paper read: 6th June 1975
`
`Curr. med. Res. Opin., (1975), 3, Suppl. 4,20.
`
`Curr. med. Res. Opin., (1975), 3, Suppl. 4, 20. (cid:9)Curr. med. Res. Opin., (1975), 3, Suppl. 4, 20. (cid:9)
`Summary
`
`Summary Summary
`Fifteen hospitalisedpatients with active rheumatoid arthritis were studied to assess the
`
`Fifteen hospitalised patients with active rheumatoid arthritis were studied to assess the Fifteen hospitalised patients with active rheumatoid arthritis were studied to assess the
`anti-inflammatory and analgesic action of flurbiprofen (200 mg. daily). Quantitative
`
`anti-inflammatory and analgesic action of flurbiprofen (200 mg. daily). Quantitative anti-inflammatory and analgesic action of flurbiprofen (200 mg. daily). Quantitative
`thermographic and clinical assessments were made during the pre-trial week whilst
`
`thermographic and clinical assessments were made during the pre-trial week whilst thermographic and clinical assessments were made during the pre-trial week whilst
`patients received 1.0 g. paracetamol6-hourly, at the end of each week offlurbiprofen
`
`patients received 1.0 g. paracetamol 6-hourly, at the end of each week of flurbiprofen patients received 1.0 g. paracetamol 6-hourly, at the end of each week of flurbiprofen
`therapy (2 or 3 weeks), and 2 days afterwards when patients again received para-
`
`therapy (2 or 3 weeks), and 2 days afterwards when patients again received para-therapy (2 or 3 weeks), and 2 days afterwards when patients again received para-
`cetamol.
`
`cetamol. cetamol.
`Improvement in the thermographic index continued steadily during the flurbiprofen
`
`Improvement in the thermographic index continued steadily during the flurbiprofen Improvement in the thermographic index continued steadily during the flurbiprofen
`period but not whilst patients were on paracetamol. The results suggest that flurbi-
`
`period but not whilst patients were on paracetamol. The results suggest that flurbi-period but not whilst patients were on paracetamol. The results suggest that flurbi-
`profen has an anti-inflammatory as well as an analgesic action in patients with rheu-
`
`profen has an anti-inflammatory as well as an analgesic action in patients with rheu-profen has an anti-inflammatory as well as an analgesic action in patients with rheu-
`matoid arthritis. The magnitude of the improvement was similar to that seen with
`
`matoid arthritis. The magnitude of the improvement was similar to that seen with matoid arthritis. The magnitude of the improvement was similar to that seen with
`aspirin and after a single injection of a steroid into an inflamed rheumatoidjoint.
`
`aspirin and after a single injection of a steroid into an inflamed rheumatoid joint. aspirin and after a single injection of a steroid into an inflamed rheumatoid joint.
`Key words: Flurbiprofen - anti-inflammatory agents - arthritis, rheumatoid - thermo-
`
`Key words: Flurbiprofen — anti-inflammatory agents — arthritis, rheumatoid — thermo-Key words: Flurbiprofen — anti-inflammatory agents — arthritis, rheumatoid — thermo-
`WPhY
`
`graphy graphy
`
`Introduction
`
`Introduction Introduction
`Flurbiprofen, 2-(2-fluoro-4-biphenylyl)propionic acid, is a new non-steroidal drug
`
`Flurbiprofen, 2-(2-fluoro-4-biphenylyl)propionic acid, is a new non-steroidal drug Flurbiprofen, 2-(2-fluoro-4-biphenylyl)propionic acid, is a new non-steroidal drug
`and a member of a series of alkanoic acids which have been shown to have anti-
`
`and a member of a series of alkanoic acids which have been shown to have anti-and a member of a series of alkanoic acids which have been shown to have anti-
`inflammatory and analgesic activity in a range of animal modelsl.2 and to be active
`
`inflammatory and analgesic activity in a range of animal models1 , 2 and to be active inflammatory and analgesic activity in a range of animal models1 , 2 and to be active
`clinically in the treatment of rheumatoid disease.3 Clinical assessment of drug action
`
`clinically in the treatment of rheumatoid disease.3 Clinical assessment of drug action clinically in the treatment of rheumatoid disease.3 Clinical assessment of drug action
`in rheumatoid arthritis has many problems since most of the indices used depend, at
`
`in rheumatoid arthritis has many problems since most of the indices used depend, at in rheumatoid arthritis has many problems since most of the indices used depend, at
`least in part, on the subjective appreciation of pain. The anti-inflammatory aspect of
`
`least in part, on the subjective appreciation of pain. The anti-inflammatory aspect of least in part, on the subjective appreciation of pain. The anti-inflammatory aspect of
`drug action is particularly difficult to assess clinically. There are two objective methods
`
`drug action is particularly difficult to assess clinically. There are two objective methods drug action is particularly difficult to assess clinically. There are two objective methods
`of assessing the anti-inflammatory effect of drugs in arthritis, namely technetium
`
`of assessing the anti-inflammatory effect of drugs in arthritis, namely technetium of assessing the anti-inflammatory effect of drugs in arthritis, namely technetium
`scanning* and thermography.6 In this study, thermographic assessment was made
`
`scannings and thermography.6 In this study, thermographic assessment was made scannings and thermography.6 In this study, thermographic assessment was made
`in patients with active rheumatoid disease treated with flurbiprofen.
`
`in patients with active rheumatoid disease treated with flurbiprofen. in patients with active rheumatoid disease treated with flurbiprofen.
`
`Method and materials
`
`Method and materials Method and materials
`Fifteen patients with classical or definite rheumatoid arthritis in an active inflamm-
`
`Fifteen patients with classical or definite rheumatoid arthritis in an active inflamm-Fifteen patients with classical or definite rheumatoid arthritis in an active inflamm-
`atory stage, sufficiently severe to require admission to hospital, were selected for
`
`atory stage, sufficiently severe to require admission to hospital, were selected for atory stage, sufficiently severe to require admission to hospital, were selected for
`
`*Presenting author
`
`*Presenting author *Presenting author
`
`20
`
`20 20
`
`Ex. 1063 - Page 1
`
`

`

`P. A. Bacon, A. J. Collins and J. A. Cosh
`
`P. A. Bacon, A. J. Collins and J. A. Cosh P. A. Bacon, A. J. Collins and J. A. Cosh
`
`study. Patients with a history of peptic ulcer, renal or hepatic disease, and women
`
`study. Patients with a history of peptic ulcer, renal or hepatic disease, and women study. Patients with a history of peptic ulcer, renal or hepatic disease, and women
`during pregnancy were excluded. Patients on steroid therapy, gold therapy or
`
`during pregnancy were excluded. Patients on steroid therapy, gold therapy or during pregnancy were excluded. Patients on steroid therapy, gold therapy or
`cytotoxic drugs were also excluded. In addition, a further 3 patients fulfilling the
`
`cytotoxic drugs were also excluded. In addition, a further 3 patients fulfilling the cytotoxic drugs were also excluded. In addition, a further 3 patients fulfilling the
`same criteria were studied serially for the response to a single large dose.
`
`same criteria were studied serially for the response to a single large dose. same criteria were studied serially for the response to a single large dose.
`The drug regime was standardised. In the week prior to the study all anti-
`
`The drug regime was standardised. In the week prior to the study all anti-The drug regime was standardised. In the week prior to the study all anti-
`rheumatic treatment was stopped and the patients were given 1.0 g. paracetamol
`
`rheumatic treatment was stopped and the patients were given 1.0 g. paracetamol rheumatic treatment was stopped and the patients were given 1.0 g. paracetamol
`6-hourly. During the first 2, or more often, 3 weeks of the study, patients received
`
`6-hourly. During the first 2, or more often, 3 weeks of the study, patients received 6-hourly. During the first 2, or more often, 3 weeks of the study, patients received
`50 mg. flurbiprofen 6-hourly. Assessments were made at the end of the paracetamol
`
`50 mg. flurbiprofen 6-hourly. Assessments were made at the end of the paracetamol 50 mg. flurbiprofen 6-hourly. Assessments were made at the end of the paracetamol
`week and at the end of each week of flurbiprofen therapy. In the majority of patients
`
`week and at the end of each week of flurbiprofen therapy. In the majority of patients week and at the end of each week of flurbiprofen therapy. In the majority of patients
`a further assessment was made 2 days after the end of the flurbiprofen period when
`
`a further assessment was made 2 days after the end of the flurbiprofen period when a further assessment was made 2 days after the end of the flurbiprofen period when
`the patients had been receiving paracetamol for 48 hours.
`
`the patients had been receiving paracetamol for 48 hours. the patients had been receiving paracetamol for 48 hours.
`Assessments were made at the same time of the morning on each occasion.
`
`Assessments were made at the same time of the morning on each occasion. Assessments were made at the same time of the morning on each occasion.
`Thermographic assessment was carried out using quantitative thermography taking
`
`Thermographic assessment was carried out using quantitative thermography taking Thermographic assessment was carried out using quantitative thermography taking
`the mean index of at least 4 joint areas, normally including both hands and both
`
`the mean index of at least 4 joint areas, normally including both hands and both the mean index of at least 4 joint areas, normally including both hands and both
`knees or both feet, according to previously described methods.5 Clinical assessment
`
`knees or both feet, according to previously described methods.5 Clinical assessment knees or both feet, according to previously described methods.5 Clinical assessment
`was made by a single observer in a routine drug assessment clinic. This included
`
`was made by a single observer in a routine drug assessment clinic. This included was made by a single observer in a routine drug assessment clinic. This included
`assessment of articular index, morning stiffness, grip strength and pain score on a
`
`assessment of articular index, morning stiffness, grip strength and pain score on a assessment of articular index, morning stiffness, grip strength and pain score on a
`visual analogue scale. Routine blood counts and assessment of side-effects weremade
`
`visual analogue scale. Routine blood counts and assessment of side-effects were made visual analogue scale. Routine blood counts and assessment of side-effects were made
`at the same time. The blood levels of flurbiprofen were measured by gas chromato-
`
`at the same time. The blood levels of flurbiprofen were measured by gas chromato-at the same time. The blood levels of flurbiprofen were measured by gas chromato-
`graphyg from samples collected at the time of clinical assessment in half the patients.
`
`graphy9 from samples collected at the time of clinical assessment in half the patients. graphy9 from samples collected at the time of clinical assessment in half the patients.
`
`Results
`
`Results Results
`The thermographic results from the entire group are plotted in Figure 1. A very
`
`The thermographic results from the entire group are plotted in Figure 1. A very The thermographic results from the entire group are plotted in Figure 1. A very
`good result, with a fall in the thermographic index of between 0.75 and 1.50 over
`
`good result, with a fall in the thermographic index of between 0.75 and 1.50 over good result, with a fall in the thermographic index of between 0.75 and 1.50 over
`2 weeks, was seen in 9 patients. This contrasts with the deterioration noted in most
`
`2 weeks, was seen in 9 patients. This contrasts with the deterioration noted in most 2 weeks, was seen in 9 patients. This contrasts with the deterioration noted in most
`patients during the initial paracetamol week and also in the 48-hour paracetamol
`
`patients during the initial paracetamol week and also in the 48-hour paracetamol patients during the initial paracetamol week and also in the 48-hour paracetamol
`wash-out period at the end of the study. A further 3 patients showed a less marked
`
`wash-out period at the end of the study. A further 3 patients showed a less marked wash-out period at the end of the study. A further 3 patients showed a less marked
`response over 2 weeks, and were classed as poor responders. Finally, 3 patients
`
`response over 2 weeks, and were classed as poor responders. Finally, 3 patients response over 2 weeks, and were classed as poor responders. Finally, 3 patients
`showed no improvement or deterioration in thermographic index during the study
`
`showed no improvement or deterioration in thermographic index during the study showed no improvement or deterioration in thermographic index during the study
`period. It is notable that in those patients who did improve, the improvement
`
`period. It is notable that in those patients who did improve, the improvement period. It is notable that in those patients who did improve, the improvement
`continued for the 2 or 3 weeks of the study.
`
`continued for the 2 or 3 weeks of the study. continued for the 2 or 3 weeks of the study.
`The overall change in grip strength, morning stiffness and articular index can be
`
`The overall change in grip strength, morning stiffness and articular index can be The overall change in grip strength, morning stiffness and articular index can be
`seen in Figure 2. Morning stiffness showed a steady improvement throughout the
`
`seen in Figure 2. Morning stiffness showed a steady improvement throughout the seen in Figure 2. Morning stiffness showed a steady improvement throughout the
`treatment period with a mean of 27 minutes at the end of 2 weeks compared to the
`
`treatment period with a mean of 27 minutes at the end of 2 weeks compared to the treatment period with a mean of 27 minutes at the end of 2 weeks compared to the
`75 minutes at the beginning of the flurbiprofen period. The articular index and the
`
`75 minutes at the beginning of the flurbiprofen period. The articular index and the 75 minutes at the beginning of the flurbiprofen period. The articular index and the
`grip strength showed an improvement, most marked during the first week of the
`
`grip strength showed an improvement, most marked during the first week of the grip strength showed an improvement, most marked during the first week of the
`study but showing little change in the second week.
`
`study but showing little change in the second week. study but showing little change in the second week.
`Blood levels of flurbiprofen showed a wide range from patient to patient with
`
`Blood levels of flurbiprofen showed a wide range from patient to patient with Blood levels of flurbiprofen showed a wide range from patient to patient with
`levels varying between 3.1 and 11.0 pg./ml. However, in most patients the levels
`
`levels varying between 3.1 and 11.0 (cid:9)levels varying between 3.1 and 11.0 (cid:9)
`
`However, in most patients the levels However, in most patients the levels
`were remarkably consistent from week to week. This was not true for 1 patient in
`
`were remarkably consistent from week to week. This was not true for 1 patient in were remarkably consistent from week to week. This was not true for 1 patient in
`whom the level for the third week of the study was only one-third of that for the
`
`whom the level for the third week of the study was only one-third of that for the whom the level for the third week of the study was only one-third of that for the
`first week. It is interesting that this was the one patient who showed a striking
`
`first week. It is interesting that this was the one patient who showed a striking first week. It is interesting that this was the one patient who showed a striking
`deterioration in her thermographic index in the third week after having made a
`
`deterioration in her thermographic index in the third week after having made a deterioration in her thermographic index in the third week after having made a
`
`21
`
`21 21
`
`Ex. 1063 - Page 2
`
`

`

`Thermographic assessment of the anti-inflammatory effect of flurbiprofen in rheumatoid arthritis
`
`Thermographic assessment of the anti-inflammatory effect of flurbiprofen in rheumatoid arthritis Thermographic assessment of the anti-inflammatory effect of flurbiprofen in rheumatoid arthritis
`
`Figure 1. Thermographic results in 15 patients studied. Top graph shows poor responders and those
`
`Figure 1. Thermographic results in 15 patients studied. Top graph shows poor responders and those Figure 1. Thermographic results in 15 patients studied. Top graph shows poor responders and those
`with no response or deterioration. Bottom graph shows those with good d t s
`
`with no response or deterioration. Bottom graph shows those with good results with no response or deterioration. Bottom graph shows those with good results
`5 1
`
`5 5
`
`
`
`4 4
`
`
`
`2 2
`
`1
`
`1 1
`
`5
`
`5 5
`
`4
`
`4 4
`
`Y 4
`.-
`.-
`U c
`n 3
`E
`
`3 3
`2
`i$
`
`Thermogra ph ic index
`Thermogra ph ic index
`
`M
`
`2
`
`2 2
`
`1
`
`1 1
`
`22
`
`22 22
`
`Paracetamol
`
`Paracetamol (cid:9)Paracetamol (cid:9)
`
`-1
`
`-1 (cid:9)-1 (cid:9)
`
`
`I (cid:9)I (cid:9)
`I
`0
`
`0 (cid:9)0 (cid:9)
`
`2
`
`2 2
`
`Flurbiprofen
`
`Flurbiprofen (cid:9)Flurbiprofen (cid:9)
`I
`
`1 (cid:9)1 (cid:9)
`Time (weeks)
`
`Time (weeks) Time (weeks)
`Note: arrow indicates patient with lowered blood level of flurbiprofen
`
`Note: arrow indicates patient with lowered blood level of flurbiprofen Note: arrow indicates patient with lowered blood level of flurbiprofen
`
`Paracetamol
`
`Paracetamol Paracetamol
`-1
`
`1
`
`t t
`0
`
`0 0
`
`
`Flurbiprofen (cid:9)Flurbiprofen (cid:9)
`Flurbiprofen
`1
`
`1 1
`Time (weeks)
`
`Time (weeks) Time (weeks)
`
`2
`
`2 2
`
`Paracetamol
`
`Paracetamol Paracetamol
`1
`
`I I
`3
`
`3 3
`
`/
`
`
`I I
`
`I I
`
`I I
`
`I I
`
`
`• •
`
`.0.-41 .0.-41
`
`41... ,a 41... ,a
`
`,• ,•
`
`Paracetamol
`
`Paracetamol Paracetamol
`I
`
`I I
`3
`
`3 3
`
`Ex. 1063 - Page 3
`
`(cid:9)
`(cid:9)
`(cid:9)
`(cid:9)
`(cid:9)
`(cid:9)
`(cid:9)
`(cid:9)
`(cid:9)
`(cid:9)
`(cid:9)
`(cid:9)
`

`

`P. A. Bacon, A. J. Collins and J. A. Cosh
`
`P. A. Bacon, A. J. Collins and J. A. Cosh P. A. Bacon, A. J. Collins and J. A. Cosh
`
`Figure 2. Mean changes in thennographic index and clinical assessments over period of trial io
`
`Figure 2. Mean changes in thermographic index and clinical assessments over period of trial in Figure 2. Mean changes in thermographic index and clinical assessments over period of trial in
`15 patients studied
`
`15 patients studied 15 patients studied
`
`I60
`
`160 160
`
`-.
`M % 140
`
`en en
`
`140 140
`E
`E
`
`E E
`v
`5
`M
`
`or) or)
`e
`
`C 0.) C 0.)
`;I 120
`.-
`
`c. 120 c. 120
`n
`6
`
`0 0
`
`100
`
`100 100
`
`5
`
`5 5
`
`4
`
`4 4
`
`x
`8
`.- .-
`C
`0 r
`n 3
`g J E
`8
`b
`
`2
`
`
`
`Grip strength.6-....ss"----....... Grip strength.6-....ss"----.......
`
`
`
`• •
`
`
`
`Articular index Articular index
`
`Paracetamol
`
`Paracetamol Paracetamol
`-1
`
`—1 —1
`
`0
`
`0 (cid:9)0 (cid:9)
`
`Flurbiprofen
`
`Flurbiprofen Flurbiprofen
`1
`
`1 (cid:9)1 (cid:9)
`Time (weeks)
`
`Time (weeks) Time (weeks)
`
`2
`
`2 (cid:9)2 (cid:9)
`
`Paracetarnol
`
`Paracetamol Paracetamol
`3
`
`3 3
`
`.#I))
`
`
`
`Thermographic index Thermographic index
`
`
`
`30 30
`
`
`
`20 20
`
`
`
`5' 5'
`
`
`
`10 10
`
`
`
`0 0
`
`
`
`200 200
`
`
`
`150 150
`
`
`
`0 0
`
`
`
`1004°4 1004°4
`
`
`
`50 g, 50 g,
`
`
`
`Morning stiffness Morning stiffness
`
`Flurbiprofen
`
`Flurbiprofen (cid:9)Flurbiprofen (cid:9)
`
`1
`
`1 (cid:9)1 (cid:9)
`Time (weeks)
`
`Time (weeks) Time (weeks)
`
`2
`
`2 (cid:9)2 (cid:9)
`
`1
`
`1 1
`
`Paracetamol
`
`Paracetamol (cid:9)Paracetamol (cid:9)
`-1
`
`—1 (cid:9)—1 (cid:9)
`
`I
`
`1 (cid:9)1 (cid:9)
`0
`
`0 (cid:9)0 (cid:9)
`
`Paracetamol
`
`Paracetamol Paracetamol
`I
`
`1 1
`3
`
`3 3
`
`
`
`0 0
`
`marked improvement during the first 2 weeks, (see Figure 1). This suggests that her
`
`marked improvement during the first 2 weeks, (see Figure 1). This suggests that her marked improvement during the first 2 weeks, (see Figure 1). This suggests that her
`deterioration was related to inadequate blood levels of the drug at that stage.
`
`deterioration was related to inadequate blood levels of the drug at that stage. deterioration was related to inadequate blood levels of the drug at that stage.
`No major side-effects were detected in this group during the period of study.
`
`No major side-effects were detected in this group during the period of study. No major side-effects were detected in this group during the period of study.
`The effects of a single dose of flurbiprofen were studied in 3 patients who were
`
`The effects of a single dose of flurbiprofen were studied in 3 patients who were The effects of a single dose of flurbiprofen were studied in 3 patients who were
`given 150 mg. at 9.30 a.m. The thermographic index was then followed at hourly
`
`given 150 mg. at 9.30 a.m. The thermographic index was then followed at hourly given 150 mg. at 9.30 a.m. The thermographic index was then followed at hourly
`intervals throughout the day. This was compared with the same patients on another
`
`intervals throughout the day. This was compared with the same patients on another intervals throughout the day. This was compared with the same patients on another
`
`23
`
`23 23
`
`Ex. 1063 - Page 4
`
`

`

`Thermographic assessment of the anti-inflammatory effect of flurbiprofen in rheumatoid arthritis
`Thermographic assessment of the anti-inflammatory effect of flurbiprofen in rheumatoid arthritis
`Thermographic assessment of the anti-inflammatory effect of flurbiprofen in rheumatoid arthritis
`
`day when they were taking paracetamol only. This latter day, in effect, measures the
`day when they were taking paracetamol only. This latter day, in effect, measures the
`day when they were taking paracetamol only. This latter day, in effect, measures the
`intrinsic diurnal variation of thermographic index in these patients. There was less
`intrinsic diurnal variation of thermographic index in these patients. There was less
`intrinsic diurnal variation of thermographic index in these patients. There was less
`increase in the thermographic index after mid-day on the treated day than might
`increase in the thermographic index after mid-day on the treated day than might
`increase in the thermographic index after mid-day on the treated day than might
`have been expected from comparison with the control day. However, the response
`have been expected from comparison with the control day. However, the response
`have been expected from comparison with the control day. However, the response
`to a single dose was not very dramatic.
`to a single dose was not very dramatic.
`to a single dose was not very dramatic.
`
`Discussion
`Discussion
`Discussion
`These studies suggest that flurbiprofen has an anti-inflammatory as well as an
`These studies suggest that flurbiprofen has an anti-inflammatory as well as an
`These studies suggest that flurbiprofen has an anti-inflammatory as well as an
`analgesic action in rheumatoid arthritis. The design of the study was as a non-blind
`analgesic action in rheumatoid arthritis. The design of the study was as a non-blind
`analgesic action in rheumatoid arthritis. The design of the study was as a non-blind
`trial. Clinical assessments were made by a single observer looking at several drugs
`trial. Clinical assessments were made by a single observer looking at several drugs
`trial. Clinical assessments were made by a single observer looking at several drugs
`in a special drug clinic but, of course, aware of the drug being given. The thermo-
`in a special drug clinic but, of course, aware of the drug being given. The thermo-
`in a special drug clinic but, of course, aware of the drug being given. The thermo-
`graphicassessment is an entirely objective one with the thermographic index calculated
`graphic assessment is an entirely objective one with the thermographic index calculated
`graphic assessment is an entirely objective one with the thermographic index calculated
`by a computer on-line thermographic camera. There is no bias whether the study is
`by a computer on-line thermographic camera. There is no bias whether the study is
`by a computer on-line thermographic camera. There is no bias whether the study is
`blind or not. The assessment was made on in-patients, who might be expected to be
`blind or not. The assessment was made on in-patients, who might be expected to be
`blind or not. The assessment was made on in-patients, who might be expected to be
`gaining some benefit from their treatment, even during the paracetamol week. It is
`gaining some benefit from their treatment, even during the paracetamol week. It is
`gaining some benefit from their treatment, even during the paracetamol week. It is
`notable that overall there was not a great deal of change in the thermographic index
`notable that overall there was not a great deal of change in the thermographic index
`notable that overall there was not a great deal of change in the thermographic index
`during this week. In most of our out-patient studies, using the same protocol as the
`during this week. In most of our out-patient studies, using the same protocol as the
`during this week. In most of our out-patient studies, using the same protocol as the
`weeks of paracetamol wash-out, there was a sharp deterioration in thermographic
`weeks of paracetamol wash-out, there was a sharp deterioration in thermographic
`weeks of paracetamol wash-out, there was a sharp deterioration in thermographic
`index during this period.
`index during this period.
`index during this period.
`Most observers agree that maximum non-specific in-patient benefit is derived
`Most observers agree that maximum non-specific in-patient benefit is derived
`Most observers agree that maximum non-specific in-patient benefit is derived
`during the first week. In this study, the fall in the thermographic index did not
`during the first week. In this study, the fall in the thermographic index did not
`during the first week. In this study, the fall in the thermographic index did not
`occur during the first week while the patients were on paracetamol but in the next
`occur during the first week while the patients were on paracetamol but in the next
`occur during the first week while the patients were on paracetamol but in the next
`2 weeks while they were on the active drug. The fact that this improvement was due
`2 weeks while they were on the active drug. The fact that this improvement was due
`2 weeks while they were on the active drug. The fact that this improvement was due
`to the drug and not to the in-patient hospitalisation is reinforced by a further
`to the drug and not to the in-patient hospitalisation is reinforced by a further
`to the drug and not to the in-patient hospitalisation is reinforced by a further
`deterioration in the thermographic index when patients were put back on para-
`deterioration in the thermographic index when patients were put back on para-
`deterioration in the thermographic index when patients were put back on para-
`cetamol for a further 48 hours.
`cetamol for a further 48 hours.
`cetamol for a further 48 hours.
`The rate of action of the drug, in comparison to the different assessment indices,
`The rate of action of the drug, in comparison to the different assessment indices,
`The rate of action of the drug, in comparison to the different assessment indices,
`is of interest. The improvement in thermographic index continued steadily during
`is of interest. The improvement in thermographic index continued steadily during
`is of interest. The improvement in thermographic index continued steadily during
`the first 2 weeks and was usually carried on into the third week in those patients
`the first 2 weeks and was usually carried on into the third week in those patients
`the first 2 weeks and was usually carried on into the third week in those patients
`who responded to the drug. This is in accord with our previous observations that
`who responded to the drug. This is in accord with our previous observations that
`who responded to the drug. This is in accord with our previous observations that
`improvement in the thermographic index takes at least 2 weeks and usually longer
`improvement in the thermographic index takes at least 2 weeks and usually longer
`improvement in the thermographic index takes at least 2 weeks and usually longer
`with an oral drug. The magnitude of the improvement in thermographic index in
`with an oral drug. The magnitude of the improvement in thermographic index in
`with an oral drug. The magnitude of the improvement in thermographic index in
`those patients who made a good response is similar to that seen with aspirin, and is
`those patients who made a good response is similar to that seen with aspirin, and is
`those patients who made a good response is similar to that seen with aspirin, and is
`of the same order of magnitude as that seen after a single injection of steroid into
`of the same order of magnitude as that seen after a single injection of steroid into
`of the same order of magnitude as that seen after a single injection of steroid into
`an inflamed rheumatoid joint.l0
`an inflamed rheumatoid joint.1 0
`an inflamed rheumatoid joint.1 0
`The rate of change in the clinical indices also accords with our previous observ-
`The rate of change in the clinical indices also accords with our previous observ-
`The rate of change in the clinical indices also accords with our previous observ-
`ations. Morning stiffness, like the thermographic index, continued to improve
`ations. Morning stiffness, like the thermographic index, continued to improve
`ations. Morning stiffness, like the thermographic index, continued to improve
`during the 3 study weeks. However, the maximal change in the articular index
`during the 3 study weeks. However, the maximal change in the articular index
`during the 3 study weeks. However, the maximal change in the articular index
`occurred in the first week on active drugs and this was also true with the change in
`occurred in the first week on active drugs and this was also true with the change in
`occurred in the first week on active drugs and this was also true with the change in
`grip strength. Both these factors are affected by the patient’s state of well-being and
`grip strength. Both these factors are affected by the patient's state of well-being and
`grip strength. Both these factors are affected by the patient's state of well-being and
`by appreciation of pain, rather than being indicators of inflammation. Morning
`by appreciation of pain, rather than being indicators of inflammation. Morning
`by appreciation of pain, rather than being indicators of inflammation. Morning
`stiffness appears to correlate better with inflammation as shown by thermographic
`stiffness appears to correlate better with inflammation as shown by thermographic
`stiffness appears to correlate better with inflammation as shown by thermographic
`index. The latter has been shown to reflect the changes in synovial volume and
`index. The latter has been shown to reflect the changes in synovial volume and
`index. The latter has been shown to reflect the changes in synovial volume and
`protein and cell content as well as to correlate with technetium scanning.4
`protein and cell content as well as to correlate with technetium scanning.4
`protein and cell content as well as to correlate with technetium scanning.4
`
`24
`24
`24
`
`Ex. 1063 - Page 5
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`

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`P. A. Bacon, A. J. Coll