Guided graded exercise self-help plus specialist medical care versus specialist medical care alone for chronic fatigue syndrome (GETSET): a pragmatic randomised controlled trial

Background: Graded exercise therapy is an effective and safe treatment for chronic fatigue syndrome, but it is therapist intensive and availability is limited. We aimed to test the efficacy and safety of graded exercise delivered as guided self-help. Methods: In this pragmatic randomised controlled trial, we recruited adult patients (18 years and older) who met the UK National Institute for Health and Care Excellence criteria for chronic fatigue syndrome from two secondary-care clinics in the UK. Patients were randomly assigned to receive specialist medical care (SMC) alone (control group) or SMC with additional guided graded exercise self-help (GES). Block randomisation (randomly varying block sizes) was done at the level of the individual with a computer-generated sequence and was stratified by centre, depression score, and severity of physical disability. Patients and physiotherapists were necessarily unmasked from intervention assignment; the statistician was masked from intervention assignment. SMC was delivered by specialist doctors but was not standardised; GES consisted of a self-help booklet describing a six-step graded exercise programme that would take roughly 12 weeks to complete, and up to four guidance sessions with a physiotherapist over 8 weeks (maximum 90 min in total). Primary outcomes were fatigue (measured by the Chalder Fatigue Questionnaire) and physical function (assessed by the Short Form-36 physical function subscale); both were self-rated by patients at 12 weeks after randomisation and analysed in all randomised patients with outcome data at follow-up (ie, by modified intention to treat). We recorded adverse events, including serious adverse reactions to trial interventions. We used multiple linear regression analysis to compare SMC with GES, adjusting for baseline and stratification factors. This trial is registered at ISRCTN, number ISRCTN22975026. Findings: Between May 15, 2012, and Dec 24, 2014, we recruited 211 eligible patients, of whom 107 were assigned to the GES group and 104 to the control group. At 12 weeks, compared with the control group, mean fatigue score was 19·1 (SD 7·6) in the GES group and 22·9 (6·9) in the control group (adjusted difference −4·2 points, 95% CI −6·1 to −2·3, p<0·0001; effect size 0·53) and mean physical function score was 55·7 (23·3) in the GES group and 50·8 (25·3) in the control group (adjusted difference 6·3 points, 1·8 to 10·8, p=0·006; 0·20). No serious adverse reactions were recorded and other safety measures did not differ between the groups, after allowing for missing data. Interpretation: GES is a safe intervention that might reduce fatigue and, to a lesser extent, physical disability for patients with chronic fatigue syndrome. These findings need confirmation and extension to other health-care settings

Headache Diagnosis in Primary Care

Introduction: Doctors in primary care are responsible for diagnosing and managing patients with headache, but frequently lack confidence in doing so. We aimed to compare Family Practitioners’ (FPs) diagnosis of headaches to classification based on a symptom questionnaire, and to describe how classification links to other important clinical features. Methods: This was an observational study of patients attending primary care doctors for headache. Main outcome measures: Patients completed a questionnaire including the Headache Impact Test, the Migraine Disability Assessment Score, the Hospital Anxiety and Depression Scale, the Illness Perceptions Questionnaire, a satisfaction scale, a service use inventory and a symptom questionnaire rated by two Practitioners with Special Interest (PSIs) in Headache. Results: 255 patients completed questionnaires. There was low agreement between FP diagnosis and classification using the symptom questionnaire. FPs frequently did not use the diagnosis migraine, when patient reported symptoms which justified this. FPs did not classify patients with ≥15 days of headache separately as chronic daily headache (CDH), and this could be because the classification system used does not have that code. Patients classified as CDH using the symptom questionnaire reported more disability, more symptoms of anxiety and depression (HADS), more service use, and less satisfaction with FP care. Conclusion: Patients, who present with headache in primary care, tend to receive non-specific diagnoses. Having a system that would allow separate classification of people with headache of ≥ 15 days a month might help FPs to explore and address associated features with patients in terms of disability, psychological co-morbidity and cost, and improve satisfaction with care

Mental health, well-being and support interventions for UK ambulance services staff: an evidence map 2000 to 2020

Background: Prior to COVID-19 there had been a renewed policy focus in the National Health Service on the health and well-being of the healthcare workforce, with the ambulance sector identified as a priority area. This focus is more important than ever as the sector deals with the acute and longer-term consequences of a pandemic. Aim: To systematically identify, summarise and map the evidence regarding mental health, well-being and support interventions for United Kingdom ambulance services staff and to identify evidence gaps. Method: Evidence mapping methodology of published and grey original research published in English from 1 January 2000 to 23 May 2020 describing the health risk, mental health and/or well-being of UK ambulance services staff including retired staff, volunteers and students. MEDLINE, EMBASE, PsychINFO, CINAHL and AMED databases, plus EThOS, Zetoc, OpenGrey and Google, were searched, alongside hand-searching of grey literature and bibliographies. Information was extracted on study aims, sample, design and methodology, funding source, country and key findings. Included studies were categorised into seven a priori theme areas. Results: Of 1862 identified articles, 45 peer-reviewed studies are included as well as 24 grey literature documents. Peer-reviewed research was largely observational and focused on prevalence studies, post-traumatic stress disorder or organisational and individual social factors related to health and well-being. Most grey literature reported the development and testing of interventions. Across all study types, underpinning theory was often not cited. Conclusion: To date, intervention research has largely been funded by charities and published in the grey literature. Few studies were identified on self-harm, bullying, sleep and fatigue or alcohol and substance use. Theoretically informed intervention development and testing, including adaptation of innovations from other countries and 24-hour workforces, is needed. This evidence map provides important context for planning of staff well-being provision and research as the sector responds to and recovers from the pandemic. PROSPERO registration number: CRD42018104659

Response to the editorial by Dr Geraghty

This article is written in response to the linked editorial by Dr Geraghty about the adaptive Pacing, graded Activity and Cognitive behaviour therapy; a randomised Evaluation (PACE) trial, which we led, implemented and published. The PACE trial compared four treatments for people diagnosed with chronic fatigue syndrome. All participants in the trial received specialist medical care. The trial found that adding cognitive behaviour therapy or graded exercise therapy to specialist medical care was as safe as, and more effective than, adding adaptive pacing therapy or specialist medical care alone. Dr Geraghty has challenged these findings. In this article, we suggest that Dr Geraghty’s views are based on misunderstandings and misrepresentations of the PACE trial; these are corrected

Quality of life and neck pain in nurses

Objectives: To investigate the association between neck pain and psychological stress in nurses. Material and Methods: Nurses from the Avon Orthopaedic Centre completed 2 questionnaires: the Short Form-36 (SF-36) and 1 exploring neck pain and associated psychological stress. Results: Thirty four nurses entered the study (68% response). Twelve (35.3%) had current neck pain, 13 (38.2%) reported neck pain within the past year and 9 (26.5%) had no neck pain. Subjects with current neck pain had significantly lower mental health (47.1 vs. 70.4; p = 0.002), physical health (60.8 vs. 76.8; p = 0.010) and overall SF-36 scores (56.8 vs. 74.9; p = 0.003). Five (41.7%) subjects with current neck pain and 5 (38.5%) subjects with neck pain in the previous year attributed it to psychological stress. Conclusions: Over 1/3 of nurses have symptomatic neck pain and significantly lower mental and physical health scores. Managing psychological stress may reduce neck pain, leading to improved quality of life for nurses, financial benefits for the NHS, and improved patient care

Service use and costs for people with headache: a UK primary care study

This paper aims to estimate the service and social costs of headache presenting in primary care and to identify predictors of headache costs. Patients were recruited from GP practices in England and service use and lost employment recorded. Predictors of cost were identified using regression models. Service and social costs were available on 288 and 282 patients, respectively. Average service costs over 3 months were £117 whilst total costs (including lost production) were £582. Patients referred to neurologists had service costs that were £82 higher than those not referred (90% CI £36–£128). Costs including lost employment were higher by £150, but this was not significant (90% CI -£139–£439). The annual mean service and social costs, weighted to represent population rates of referral, were £468 and £2328, respectively. Higher costs were significantly related to pain. Age was linked to higher service costs and lower social costs. The figures extrapolated to the whole of the UK suggest £956 million due to service use and £4.8 billion including lost employment. These are likely to be underestimates because many people experiencing headaches do not consult their GP

Auditory conflict and congruence in frontotemporal dementia.

Impaired analysis of signal conflict and congruence may contribute to diverse socio-emotional symptoms in frontotemporal dementias, however the underlying mechanisms have not been defined. Here we addressed this issue in patients with behavioural variant frontotemporal dementia (bvFTD; n = 19) and semantic dementia (SD; n = 10) relative to healthy older individuals (n = 20). We created auditory scenes in which semantic and emotional congruity of constituent sounds were independently probed; associated tasks controlled for auditory perceptual similarity, scene parsing and semantic competence. Neuroanatomical correlates of auditory congruity processing were assessed using voxel-based morphometry. Relative to healthy controls, both the bvFTD and SD groups had impaired semantic and emotional congruity processing (after taking auditory control task performance into account) and reduced affective integration of sounds into scenes. Grey matter correlates of auditory semantic congruity processing were identified in distributed regions encompassing prefrontal, parieto-temporal and insular areas and correlates of auditory emotional congruity in partly overlapping temporal, insular and striatal regions. Our findings suggest that decoding of auditory signal relatedness may probe a generic cognitive mechanism and neural architecture underpinning frontotemporal dementia syndromes

Cessation of Smoking Trial in the Emergency Department (COSTED): a multi-centre, randomised controlled trial

Background: Supporting people to quit smoking is one of the most powerful interventions to improve health. The Emergency Department (ED) represents a potentially valuable opportunity to deliver a smoking cessation intervention if it is sufficiently resourced. The objective of this trial was to determine whether an opportunistic ED based smoking cessation intervention can help people to quit smoking.   Methods: In this multi-centre, parallel-group, randomised controlled superiority trial conducted between January and August 2022, adults who smoked daily and attended one of six UK EDs were randomised to intervention (brief advice, e-cigarette starter kit and referral to stop smoking services) or control (written information on stop smoking services). The primary outcome was biochemically validated abstinence at six months.   Results: An intention-to-treat analysis included 972 of 1443 people screened for inclusion (intervention= 484, control= 488). Of 975 participants randomised, 3 were subsequently excluded, 17 withdrew and 287 were lost to follow-up. The six month biochemically verified abstinence rate was 7.2% in the intervention group and 4.1% in the control group (relative risk, 1.76; 95% confidence interval [CI] 1.03 to 3.01; p=0.038]). Self-reported 7-day abstinence at 6 months was 23.3% in the intervention group and 12.9% in the control group (relative risk, 1.80; 95% CI 1.36 to 2.38; p<0.001]). No serious adverse events related to taking part in the trial were reported.   Conclusions: An opportunistic smoking cessation intervention comprising brief advice, an e-cigarette starter kit and referral to stop smoking services is effective for sustained smoking abstinence with few reported adverse events

Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis

National Institutes of Health grants GM-38765 and P50-DE016191 (C.N.S.), Welcome Trust Programme grant 086867/Z/08/Z (R.J.F. and M.P.) and Project grant 085903/Z/08 (R.J.F.) and Arthritis Research Campaign UK fellowships 18445 and 18103 (to L.V.N. and D.C., respectively). M.S. received a National Research Service Award from the NHLBI (HL087526)

The VLT-FLAMES Tarantula survey VIII. Multiplicity properties of the O-type star population

Context. The Tarantula Nebula in the Large Magellanic Cloud is our closest view of a starburst region and is the ideal environment to investigate important questions regarding the formation, evolution and final fate of the most massive stars. Aims. We analyze the multiplicity properties of the massive O-type star population observed through multi-epoch spectroscopy in the framework of the VLT-FLAMES Tarantula Survey. With 360 O-type stars, this is the largest homogeneous sample of massive stars analyzed to date. Methods. We use multi-epoch spectroscopy and variability analysis to identify spectroscopic binaries. We also use a Monte-Carlo method to correct for observational biases. By modeling simultaneously the observed binary fraction, the distributions of the amplitudes of the radial velocity variations and the distribution of the time scales of these variations, we constrain the intrinsic current binary fraction and period and mass-ratio distributions. Results. We observe a spectroscopic binary fraction of 0.35 ± 0.03, which corresponds to the fraction of objects displaying statistically significant radial velocity variations with an amplitude of at least 20 km s-1. We compute the intrinsic binary fraction to be 0.51 ± 0.04. We adopt power-laws to describe the intrinsic period and mass-ratio distributions: f(log 10P/d) ~ (log 10P/d)π (with log 10P/d in the range 0.15−3.5) and f(q) ~ qκ with 0.1 ≤ q = M2/M1 ≤ 1.0. The power-law indexes that best reproduce the observed quantities are π = −0.45 ± 0.30 and κ = −1.0 ± 0.4. The period distribution that we obtain thus favours shorter period systems compared to an Öpik law (π = 0). The mass ratio distribution is slightly skewed towards low mass ratio systems but remains incompatible with a random sampling of a classical mass function (κ = −2.35). The binary fraction seems mostly uniform across the field of view and independent of the spectral types and luminosity classes. The binary fraction in the outer region of the field of view (r > 7.8′, i.e. ≈117 pc) and among the O9.7 I/II objects are however significantly lower than expected from statistical fluctuations. The observed and intrinsic binary fractions are also lower for the faintest objects in our sample (Ks > 15.5 mag), which results from observational effects and the fact that our O star sample is not magnitude-limited but is defined by a spectral-type cutoff. We also conclude that magnitude-limited investigations are biased towards larger binary fractions. Conclusions. Using the multiplicity properties of the O stars in the Tarantula region and simple evolutionary considerations, we estimate that over 50% of the current O star population will exchange mass with its companion within a binary system. This shows that binary interaction is greatly affecting the evolution and fate of massive stars, and must be taken into account to correctly interpret unresolved populations of massive stars