Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling long-term condition of unknown cause. The National Institute for Health and Care Excellence (NICE) published a guideline in 2021 that highlighted the seriousness of the condition, but also recommended that graded exercise therapy (GET) should not be used and cognitive-behavioural therapy should only be used to manage symptoms and reduce distress, not to aid recovery. This U-turn in recommendations from the previous 2007 guideline is controversial.We suggest that the controversy stems from anomalies in both processing and interpretation of the evidence by the NICE committee. The committee: (1) created a new definition of CFS/ME, which 'downgraded' the certainty of trial evidence; (2) omitted data from standard trial end points used to assess efficacy; (3) discounted trial data when assessing treatment harm in favour of lower quality surveys and qualitative studies; (4) minimised the importance of fatigue as an outcome; (5) did not use accepted practices to synthesise trial evidence adequately using GRADE (Grading of Recommendations, Assessment, Development and Evaluations trial evidence); (6) interpreted GET as mandating fixed increments of change when trials defined it as collaborative, negotiated and symptom dependent; (7) deviated from NICE recommendations of rehabilitation for related conditions, such as chronic primary pain and (8) recommended an energy management approach in the absence of supportive research evidence.We conclude that the dissonance between this and the previous guideline was the result of deviating from usual scientific standards of the NICE process. The consequences of this are that patients may be denied helpful treatments and therefore risk persistent ill health and disability.

Immunotherapy to reduce frequency of urinary tract infections in people with neurogenic bladder dysfunction; a pilot randomised, placebo-controlled trial.

OBJECTIVE: To establish the feasibility of a randomized, placebo-controlled trial to investigate the effect of a specific immunotherapy bacterial lysate OM-89 (Uro-Vaxom®) in reducing the frequency of urinary tract infections in people with neurogenic bladder dysfunction. DESIGN: A parallel-group, double-blind, randomized, placebo-controlled trial. SETTING: Patients at home, recruited through out-patient contact, social media and patient support groups. SUBJECTS: People with a spinal cord injury, multiple sclerosis, transverse myelitis or cauda equina syndrome who had suffered three or more clinically diagnosed urinary tract infections treated with antibiotics over the preceding 12 months. INTERVENTIONS: All participants took one capsule of oral OM-89 immunotherapy (6 mg) or matching Placebo (randomisation ratio 1:1), once daily in the morning for 3 months. MAIN MEASURES: The primary outcome was occurrence of a symptomatic urinary tract infection treated with an antibiotic, assessed at 3 and 6 months. Feasibility measures included recruitment, retention and practical difficulties. RESULTS: Of 115 patients screened, 49 were recruited, one withdrew before randomization, and 23 were allocated to the control group receiving matching placebo. Six participants, all in the control group, discontinued the intervention; all participants provided full data at both follow-up times. Over 6 months, 18/25 active group patients had 55 infections, and 18/23 control group patients had 47 infections. Most research and clinical procedures were practical, and acceptable to participants. CONCLUSION: It is feasible to undertake a larger trial. We recommend broader inclusion criteria to increase eligibility and generalizability.

How many patients in a prolonged disorder of consciousness might need a best interests meeting about starting or continuing gastrostomy feeding?

OBJECTIVE:: To estimate the number of people in a prolonged disorder of consciousness (PDOC) who may need a formal best interests decision-making process to consider starting and/or continuing life-sustaining treatment each year in the population of a developed country. METHOD:: Identification of studies on people with a PDOC giving information about incidence, and/or prevalence, and/or cause, and/or location of long-term care. Sources included systematic reviews, a new search of MEDLINE (April 2018), and a personal collection of papers. Validating information was sought from existing data on services. RESULTS:: There are few epidemiologically sound studies, most having bias and/or missing information. The best estimate of incidence of PDOC due to acute onset disease is 2.6/100,000/year; the best estimate of prevalence is between 2.0 and 5.0/100,000. There is evidence that prevalence in the Netherlands is about 10% of that in other countries. The commonest documented causes are cerebral hypoxia, stroke, traumatic brain injury, and tumours. There is some evidence suggesting that dementia is a common cause, but PDOC due to progressive disorders has not been studied systematically. Most people receive long-term care in nursing homes, but a significant proportion (10%-15%) may be cared for at home. CONCLUSION:: Each year, about 5/100,000 people will enter a prolonged state of unconsciousness from acute onset and progressive brain damage; and at any one time, there may be 5/100,000 people in that state. However, the evidence is very limited in quality and quantity. The numbers may be greater.

Rehabilitation interventions for foot drop in neuromuscular disease.

BACKGROUND: "Foot drop" or "Floppy foot drop" is the term commonly used to describe weakness or contracture of the muscles around the ankle joint. It may arise from many neuromuscular diseases. OBJECTIVES: To conduct a systematic review of randomised trials for the treatment of foot drop resulting from neuromuscular disease. SEARCH STRATEGY: In this update, we searched the Cochrane Neuromuscular Disease Group Trials Register (April 2009), MEDLINE (January 1966 to April 24 2009), EMBASE January 1980 to April 24 2009), CINAHL (January 1982 to May 6 2009), AMED (January 1985 to April 24 2009), the British Nursing Index (January 1985 to January 2008) and Royal College of Nursing Journal of Databases (January 1985 to January 2008). SELECTION CRITERIA: Randomised and quasi-randomised trials of physical, orthotic and surgical treatments for foot drop resulting from lower motor neuron or muscle disease and related contractures were included. People with primary joint disease were excluded. Interventions included a 'wait and see' approach, physiotherapy, orthoses, surgery and pharmacological therapy. The primary outcome measure was quantified ability to walk whilst secondary outcome measures included range of movement, dorsiflexor torque and strength, measures of activity and participation, quality of life and adverse effects. DATA COLLECTION AND ANALYSIS: Methodological quality was evaluated by two authors using the van Tulder criteria. Four studies with a total of n = 152 participants were included in the update to the original review. Heterogeneity of the studies precluded pooling the data. MAIN RESULTS: Early surgery did not significantly affect walking speed in a trial including 20 children with Duchenne muscular dystrophy. Both groups deteriorated during the 12 months follow-up. After one year, the mean difference (MD) of the 28 feet walking time was 0.00 seconds (95% confidence interval (CI) -0.83 to 0.83) and the MD of the 150 feet walking time was -2.88 seconds, favouring the control group (95% CI -8.18 to 2.42). Night splinting of the ankle did not significantly affect muscle force or range of movement about the ankle in a trial of 26 participants with Charcot-Marie-Tooth disease. Improvements were observed in both the splinting and control groups. In a trial of 26 participants with Charcot-Marie-Tooth disease and 28 participants with myotonic dystrophy, 24 weeks of strength training significantly improved six-metre timed walk in the Charcot-Marie-Tooth group compared to the control group (MD 0.70 seconds, favouring strength training, 95% CI 0.23 to 1.17), but not in the myotonic dystrophy group (MD -0.20 seconds, favouring the control group, 95% CI -0.79 to 0.39). No significant differences were observed for the 50 metre timed walk in the Charcot-Marie-Tooth disease group (MD 1.90 seconds, favouring the training group, 95% CI -0.29 to 4.09) or the myotonic dystrophy group (MD -0.80 seconds, favouring the control group, 95% CI -5.29 to 3.69). In a trial of 65 participants with facioscapulohumeral muscular dystrophy, 26 weeks of strength training did not significantly affect ankle strength. After one year, the mean difference in maximum voluntary isometric contraction was -0.43 kg, favouring the control group (95%CI -2.49 to 1.63) and the mean difference in dynamic strength was 0.44 kg, favouring the training group (95%CI -0.89 to 1.77). AUTHORS' CONCLUSIONS: Only one study, involving people with Charcot-Marie-Tooth disease, demonstrated a statistically significant positive effect of strength training. No effect of strength training was found in people with either myotonic dystrophy or facioscapulohumeral muscular dystrophy. Surgery had no significant effect in children with Duchenne muscular dystrophy and night splinting of the ankle had no significant effect in people with Charcot-Marie-Tooth disease. More evidence generated by methodologically sound trials is required.

The effect of a perceptual cognitive task on exercise performance: the dual-task condition after brain injury.

OBJECTIVE: To examine the effect of additional cognitive demand on cycling performance in individuals with acquired brain injury (ABI). DESIGN: Prospective observational study. SETTING: Rivermead Rehabilitation Centre. PARTICIPANTS: Ten individuals with ABI (7 men, 3 women) (traumatic brain injury 7, tumour 1, stroke 2) and 10 healthy controls (6 men, 4 women). INTERVENTION: Individuals were asked to maintain a set cadence during a three-stage incremental cycling test in both single-task (no additional task) and dual-task (whilst performing an additional cognitive task) conditions. RESULTS: The ABI group showed a slight slowing in cadence in stages 1 and 3 of the graded exercise test from the single- to the dual-task condition, although this was not significant (p < or = 0.05). The control group showed no slowing of cadence at any incremental stage. When directly comparing the ABI with the control group, the change in cadence observed in dual-task conditions was only significantly different in stage 3 (p < or = 0.05). CONCLUSIONS: Clinicians should be aware of the possibility that giving additional cognitive tasks (such as monitoring exercise intensity) while individuals with acquired brain injury are performing exercises may detrimentally affect performance. The effect may be more marked when the individuals are performing exercise at higher intensities.

A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms.

OBJECTIVES: To determine whether plant-derived cannabis medicinal extracts (CME) can alleviate neurogenic symptoms unresponsive to standard treatment, and to quantify adverse effects. DESIGN: A consecutive series of double-blind, randomized, placebo-controlled single-patient cross-over trials with two-week treatment periods. SETTING: Patients attended as outpatients, but took the CME at home. SUBJECTS: Twenty-four patients with multiple sclerosis (18), spinal cord injury (4), brachial plexus damage (1), and limb amputation due to neurofibromatosis (1). INTERVENTION: Whole-plant extracts of delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), 1:1 CBD:THC, or matched placebo were self-administered by sublingual spray at doses determined by titration against symptom relief or unwanted effects within the range of 2.5-120 mg/24 hours. Measures used: Patients recorded symptom, well-being and intoxication scores on a daily basis using visual analogue scales. At the end of each two-week period an observer rated severity and frequency of symptoms on numerical rating scales, administered standard measures of disability (Barthel Index), mood and cognition, and recorded adverse events. RESULTS: Pain relief associated with both THC and CBD was significantly superior to placebo. Impaired bladder control, muscle spasms and spasticity were improved by CME in some patients with these symptoms. Three patients had transient hypotension and intoxication with rapid initial dosing of THC-containing CME. CONCLUSIONS: Cannabis medicinal extracts can improve neurogenic symptoms unresponsive to standard treatments. Unwanted effects are predictable and generally well tolerated. Larger scale studies are warranted to confirm these findings.