From the Journal of Internal Medicine, provisional text e-published January 2013 before print.
Postural orthostatic tachycardia syndrome as a clinically important subgroup of chronic fatigue syndrome: further evidence for central nervous system dysfunctioning
(1) Pain in Motion Research Group, Departments of Human Physiology and Rehabilitation Sciences, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Belgium
(2) Department of Physical Medicine and Physiotherapy, University Hospital Brussels, Belgium
In this issue of the Journal of Internal Medicine, Lewis and colleagues  provide compelling data for a novel subgroup within the chronic fatigue syndrome (CFS) population. They show that approximately 13% (24/179) of CFS patients have postural orthostatic tachycardia syndrome (POTS), a form of dysautonomia implying that when patients change their body position from supine to upright, their heart rate will increase abnormally (tachycardia).
POTS is associated with several symptoms often seen in CFS patients: fatigue, lightheadedness, dizziness, neurocognitive deficits and exercise intolerance.
Importantly, this was a confirmatory study of a previously published pilot study that found a prevalence rate for POTS of 29% in a smaller sample (n=63) of CFS patients .
Another significant finding is the differences in fatigue severity, depressive thoughts, and daytime hypersomnolence between CFS patients with and without POTS, providing evidence for the clinical importance of POTS in CFS.
From the Journal of Neurology, Neurosurgery and Psychiatry (with Practical Neurology), e-published 16 January 2013 (open access article).
Neuropsychiatry – short report
The function of ‘functional’: a mixed methods investigation
Richard A Kanaan(1). David Armstrong(2), Simon C Wessely(1)
(1) King’s College London, Department of Psychological Medicine, Institute of Psychiatry, Weston Education Centre, London, UK
(2) King’s College London, Department of General Practice, London, UK
The term ‘functional’ has a distinguished history, embodying a number of physiological concepts, but has increasingly come to mean ‘hysterical’. The DSM- V working group proposes to use ‘functional’ as the official diagnostic term for medically unexplained neurological symptoms (currently known as ‘conversion disorder’). This study aimed to explore the current neurological meanings of the term and to understand its resilience.
Mixed methods were used, first interviewing the neurologists in a large UK region and then surveying all neurologists in the UK on their use of the term.
The interviews revealed four dominant uses – ‘not organic’, a physical disability, a brain disorder and a psychiatric problem – as well as considerable ambiguity. Although there was much dissatisfaction with the term, the ambiguity was also seen as useful when engaging with patients. The survey confirmed these findings, with a majority adhering to a strict interpretation of ‘functional’ to mean only ‘not organic’, but a minority employing it to mean different things in different contexts – and endorsing the view that ‘functional’ would one day be a neurological construct again.
‘Functional’ embodies real divisions in neurologists’ conceptualisation of unexplained symptoms and, perhaps, between those of patients and neurologists: its diversity of meanings allows it to be a common term while meaning different things to different people, or at different times, and thus conceal some of the conflict in a particularly contentious area. This flexibility may help explain the term’s longevity.
From BMC Family Practice 2013 (open access journal), 18 January 2013.
Cost-effectiveness of supported self-management for CFS/ME patients in primary care
Gerry Richardson(1), David Epstein(1), Carolyn Chew-Graham(2), Christopher Dowrick(3), Richard P Bentall(4), Richard K Morriss(5), Sarah Peters(6), Lisa Riste(6), Karina Lovell(7), Graham Dunn(2) and Alison J Wearden(6)
the FINE Trial Writing group on behalf of the FINE Trial group
(1) Centre for Health Economics, University of York, Hull/York Medical School, York YO10 5DD, United Kingdom
(2) School of Community Based Medicine, University of Manchester, Manchester M13 9PL, United Kingdom
(3) School of Population, Community and Behavioural Sciences, University of Liverpool, Liverpool L69 3GB, United Kingdom
(4) School of Psychology, University of Bangor, Adeilad Brigantia, Penrallt Road, Bangor, Gwynedd LL57 2AS, United Kingdom
(5) School of Community Health Sciences, Institute of Mental Health, University of Nottingham, Nottingham NG7 2TU, United Kingdom
(6) School of Psychological Sciences, University of Manchester, Manchester M13 9PL, United Kingdom
(7) School of Nursing, Midwifery and Social Work, University of Manchester, Manchester M13 9PL, United Kingdom
Nurse led self-help treatments for people with chronic fatigue syndrome/myalgic encephalitis (CFS/ME) have been shown to be effective in reducing fatigue but their cost-effectiveness is unknown.
Cost-effectiveness analysis conducted alongside a single blind randomised controlled trial comparing pragmatic rehabilitation (PR) and supportive listening (SL) delivered by primary care nurses, and treatment as usual (TAU) delivered by the general practitioner (GP) in North West England. A within trial analysis was conducted comparing the costs and quality adjusted life years (QALYs) measured within the time frame of the trial. 296 patients aged 18 and over with CFS/ME diagnosed using the Oxford criteria were included in the cost-effectiveness analysis.
Treatment as usual is less expensive and leads to better patient outcomes compared with Supportive Listening. Treatment as usual is also less expensive than Pragmatic Rehabilitation. PR was effective at reducing fatigue in the short term, but the impact of the intervention on QALYs was uncertain. However, based on the results of this trial, PR is unlikely to be cost-effective in this patient population.
This analysis does not support the introduction of SL. Any benefits generated by PR are unlikely to be of sufficient magnitude to warrant recommending PR for this patient group on cost-effectiveness grounds alone. However, dissatisfaction with current treatment options means simply continuing with ‘treatment as usual’ in primary care is unlikely to be acceptable to patients and practitioners.
Trial registration: The trial registration number is IRCTN74156610
The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.
From Arthritis and Rheumatism, 17 January 2013[Epub ahead of print].
Rituximab therapy for primary Sjögren’s syndrome: An open-label clinical trial and mechanistic analysis.
St Clair EW, Levesque MC, Luning Prak ET, Vivino FB, Alappatt CJ, Spychala ME, Wedgwood J, McNamara J, Moser Sivils KL, Fisher L, Cohen P; for the Autoimmunity Centers of Excellence.
Department of Medicine, Duke University Medical Center, Durham, NC. firstname.lastname@example.org.
To study the safety and clinical efficacy of rituximab therapy for primary Sjögren’s syndrome, as well as investigate its mechanisms.
METHODS Patients with primary Sjögren’s syndrome were enrolled in an open-label trial and received rituximab (1 g) on days 1 and 15 and followed through week 52. The primary endpoint was safety, with secondary endpoints evaluating clinical and biologic efficacy. Blood was obtained for enumeration of lymphocyte subsets, measurement of serum autoantibodies and BAFF levels, and analysis of gene expression.
Twelve female subjects with primary Sjögren’s syndrome were administered rituximab. They had a median (range) age of 51 (34-69) years and a median (range) disease duration of 8.0 (2-18) years. We observed no unexpected toxicities from rituximab therapy. Modest improvements were observed at week 26 in patient-reported symptoms of fatigue and oral dryness, with no significant improvement in the objective measures of lacrimal and salivary gland function. The recovery of blood B cells following the nadir from rituximab therapy was characterized by a predominance of transitional B cells and a lack of memory B cells. While blood B cell depletion was associated with an increase in serum BAFF levels, no significant changes were observed in the levels of serum anti-Ro/SSA, anti-La/SSB, and anti-muscarinic receptor 3 autoantibodies or in the blood IFN signature.
In primary Sjögren’s syndrome, a single treatment course of rituximab was not associated with any unexpected toxicities and led to only modest clinical benefits despite effective depletion of blood B cells.
MEA note: Our medical adviser, Dr Charles Shepherd, comments: Some preliminary results re efficacy and safety on the use of rituximab in Sjögren’s syndrome – an autoimmune multisystem rheumatic condition with some interesting clinical (eg debilitating central fatigue) and pathological (eg dorsal root ganglionitis) overlaps with ME/CFS.
It will be interesting to see how long it took for any improvement to occur, and whether there was a long time lag as occurred in the ME/CFS trial. But I don’t yet have the full paper.