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.

Risky driving among UK regular armed forces personnel: changes over time.

OBJECTIVES: To compare the prevalence of self-reported risky driving in a sample of UK military personnel at 2 different time points (2004 and 2009), and to identify the incidence of new onset risky driving and possible determinants of becoming a new risky driver. METHODS: Data were used from 2 phases of a military cohort study investigating the health and well-being of UK military personnel between 2004 and 2009. Participants were included if they were undertaking regular (rather than reserve) engagements, had completed both surveys and reported being a driver at both surveys. Univariable and multivariable logistic regression analyses were performed to examine the relationship between risky driving status and sociodemographic and military characteristics. Data analysis was conducted in 2011. RESULTS: The prevalence of risky driving reduced from 18% to 14%, over an average of 3.3 years. The incidence of new onset risky driving was 7%. Predictors for becoming a new risky driver were: younger age, not being in a relationship at phase 2 and harmful alcohol use. Those deployed after 2007 were less likely to become risky drivers following deployment, compared with those deployed before 2007 (adjusted OR 0.62 (95% CI 0.40 to 0.95)). CONCLUSIONS: The prevalence of becoming a risky driver appears to have reduced over time. This paper suggests a number of explanations for this reduction, including changes in the way that the UK military have dealt with road safety with the introduction of the road safety campaign (in 2007).

The role of mentoring in academic career progression: a cross-sectional survey of the Academy of Medical Sciences mentoring scheme.

Summary OBJECTIVES: To describe a successful mentoring scheme designed for mid-career clinician scientists and to examine factors associated with mentee report of positive career impact. DESIGN: Mixed methods study including in-depth interviews and cross-sectional data collection via an online survey. SETTING: Academy of Medical Sciences mentoring scheme set up in 2002 and evaluated in 2010. PARTICIPANTS: One hundred and forty-seven of 227 mentees took part in the study (response rate of 65%). Ten mentees, three mentors and eight stakeholders/scheme staff were selected to participate in in-depth interviews. MAIN OUTCOME MEASURES: Qualitative data: Interviews were transcribed, and free text was analysed to identify themes and subthemes in the narrative. Quantitative data: We examined the associations of reported positive career impact of mentoring by performing simple and multiple logistic regression analysis. RESULTS: Mentoring success was determined by a variety of factors including reasons for selection (e.g. presence of a personal recommendation), mentee characteristics (e.g. younger age), experience and skills of the mentor (e.g. 'mentor helped me to find my own solutions') and the quality of the relationship (e.g. 'my mentor and I set out clear expectations early on'). CONCLUSIONS: Our evaluation demonstrates that both mentor and mentee value mentoring and that careful planning of a scheme including preparation, training and ongoing support of both mentor and mentee addressing expectations, building rapport and logistics are likely to be helpful in ensuring success and benefit from the intervention.

Randomised controlled trial of a brief alcohol intervention in a general hospital setting.

BACKGROUND: The evidence suggests that brief alcohol-focused interventions, directed at hazardous and harmful drinkers in non-specialist settings such as primary care are effective in reducing alcohol consumption. However, there is a need for further research in the hospital setting. This is a randomised controlled trial to investigate the effectiveness of a 10-minute brief intervention amongst 'at risk' drinkers admitted to general hospital wards. Unlike some previous trials, this trial is randomised, used blinded assessors, includes an intention-to-treat analysis, included female subjects and excluded people with alcohol dependence. METHODS: A total of 250 'at risk' drinkers admitted to King's College Hospital were identified using the Alcohol Use Disorders Identification Test (AUDIT). Some 154 subjects entered the study and were randomly allocated to the control and intervention groups. Subjects in the control group received no advice about their drinking whilst subjects in the intervention group received 10 minutes of simple advice on reducing alcohol consumption. Recruitment took place between 1995 and 1997. The primary outcome was the AUDIT questionnaire at 12 months. Secondary outcomes were a previous week's Drinks Diary, questionnaires (General Health Questionnaire, Alcohol Problems Questionnaire and the Severity of Alcohol Dependence Questionnaire) and laboratory blood tests (gamma glutamyl transferase, mean cell volume and haemoglobin). RESULTS: At 3-month and 12-month follow-up, all participants were included in the intention-to-treat analysis. At both time points there was no evidence of an intervention effect that could be attributed to the brief intervention. Both the intervention and control groups had an improved AUDIT score and reduced levels of alcohol consumption as measured by a subjective Drinks Diary at 3 months which was maintained at 12 months. CONCLUSIONS: This study has added further evidence on brief interventions in the hospital setting. In contrast to the recent Cochrane review by McQueen et al., the results of this study do not support the effectiveness of a brief alcohol intervention in general hospital wards. However our study was underpowered and there were flaws in the statistical analyses, and these limitations temper the strength of our conclusions.

Diagnosis and classification of disorders specifically associated with stress: proposals for ICD-11.

The diagnostic concepts of post-traumatic stress disorder (PTSD) and other disorders specifically associated with stress have been intensively discussed among neuro- and social scientists, clinicians, epidemiologists, public health planners and humanitarian aid workers around the world. PTSD and adjustment disorder are among the most widely used diagnoses in mental health care worldwide. This paper describes proposals that aim to maximize clinical utility for the classification and grouping of disorders specifically associated with stress in the forthcoming 11th revision of the International Classification of Diseases (ICD-11). Proposals include a narrower concept for PTSD that does not allow the diagnosis to be made based entirely on non-specific symptoms; a new complex PTSD category that comprises three clusters of intra- and interpersonal symptoms in addition to core PTSD symptoms; a new diagnosis of prolonged grief disorder, used to describe patients that undergo an intensely painful, disabling, and abnormally persistent response to bereavement; a major revision of "adjustment disorder" involving increased specification of symptoms; and a conceptualization of "acute stress reaction" as a normal phenomenon that still may require clinical intervention. These proposals were developed with specific considerations given to clinical utility and global applicability in both low- and high-income countries.

The function of 'functional': a mixed methods investigation.

OBJECTIVE: 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. DESIGN: 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. RESULTS: 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. CONCLUSIONS: '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.

Differential effects of pre and post-payment on neurologists' response rates to a postal survey.

BACKGROUND: Monetary incentives are an effective way of increasing response rates to surveys, though they are generally less effective in physicians, and are more effective when the incentive is paid up-front rather than when made conditional on completion. METHODS: In this study we examine the effectiveness of pre- and post-completion incentives on the response rates of all the neurologists in the UK to a survey about conversion disorder, using a cluster randomised controlled design. A postal survey was sent to all practicing consultant neurologists, in two rounds, including either a book token, the promise of a book token, or nothing at all. RESULTS: Three hundred and fifty-one of 591 eligible neurologists completed the survey, for a response rate of 59%. While the post-completion incentive exerted no discernible influence on response rates, a pre-completion incentive did, with an odds-ratio of 2.1 (95% confidence interval 1.5-3.0). CONCLUSIONS: We conclude that neurologists, in the UK at least, may be influenced to respond to a postal survey by a pre-payment incentive but are unaffected by a promised reward.

What's so special about conversion disorder? A problem and a proposal for diagnostic classification.

Conversion disorder presents a problem for the revisions of DSM-IV and ICD-10, for reasons that are informative about the difficulties of psychiatric classification more generally. Giving up criteria based on psychological aetiology may be a painful sacrifice but it is still the right thing to do.

The origins of factitious disorder.

Factitious disorder is the deliberate simulation of illness for the purpose of seeking the sick role. It is a 20th-century diagnosis, though the grounds for its introduction are uncertain. While previous authors have considered the social changes contributing to growth in the disorder, this article looks at some of the pressures on doctors that may have created the diagnostic need for a disorder between hysteria and malingering. The recent history of those disorders suggests that malingering would no longer be acceptable when applied to the potentially larger numbers involved in workers' compensation or in mass conscription. Equally, the absolution given to hysteria on the basis of the Freudian subconscious would survive only as long as that model retained credibility. Growing egalitarianism and changing doctor-patient relationships in the 20th century would no longer tolerate a sharp division between culpable malingering and exculpated hysteria, which may previously have been made on grounds of class or gender. They would contribute to the need for a mediating diagnosis, such as factitious disorder.

Factitious disorders in neurology: an analysis of reported cases.

BACKGROUND: Factitious disorder (FD) is the deliberate production or simulation of symptoms in order to adopt the sick role. OBJECTIVE: The authors look at FD in the neurology setting. METHOD: The authors examined documented, published cases. RESULTS: FD cases in neurology are strikingly different from those in other specialties in terms of their demographics. Whereas the paradigm of FD in medicine as a whole is of the socially stable female healthcare worker, neurology continues to report largely the classic itinerant "Munchausen's" type. DISCUSSION: The authors explore two possible explanations for this: either that female healthcare workers with FD do not present neurologically, or that, if they do, they are diagnosed with conversion disorder.

The association or otherwise of the functional somatic syndromes.

OBJECTIVE: To review the evidence for overlap in the phenomenology of the Functional Somatic Syndromes (FSS). The FSS show considerable comorbidity, leading some to suggest they may be aspects of the same disorder. METHODS: We conducted a selective review of peer-reviewed articles on the co-occurrence of FSS symptoms and diagnoses. RESULTS: Considerable evidence of overlap was found at the level of symptoms, diagnostic criteria, and clinical diagnoses made. CONCLUSIONS: Phenomenological commonalities support a close relationship between the FSS, although differences remain in other domains. Whether the FSS may best be considered the same or different will depend on the pragmatics of diagnosis.

Imaging repressed memories in motor conversion disorder.

OBJECTIVES: Conversion disorders comprise neurologically unexplained symptoms with a presumed psychiatric cause, though a neuroscientific basis for this is lacking. The standard psychiatric model of conversion holds that events and processes that might explain the symptoms are, by hypothesis, either repressed or subconscious. This makes assessments based on subjective reports unreliable. We circumvent this by using a standardized method to quantify stressful life events and by assessing objectively the neural correlates of emotion processing. METHODS: Single case study of a 37-year-old woman with clinically repressed recall and unexplained right-sided paralysis. We describe the application of the Life Events and Difficulties Schedule (LEDS) to her history, and a novel functional magnetic resonance imaging (fMRI) procedure exploring emotion processing of traumatic and control memories. RESULTS: While in the scanner, cued recall of the clinically repressed event was associated with regional brain activations characteristic of emotional arousal, including the amygdala and right inferior frontal lobe, when compared with an equally severe event from the patient's past, as rated by the LEDS. Such recall was also associated with decreased motor activity in the area corresponding to the subjectively paralyzed limb. CONCLUSION: This case study provides neuroimaging evidence for a connection between traumatic events and ongoing neurological symptoms.

Psychosocial responses to environmental incidents: a review and a proposed typology.

OBJECTIVE: The objective of this review was to propose a typology for understanding the diversity of psychosocial reactions to environmental incidents. METHODOLOGY: The first section provides an introduction and background to the topic; we then attempt to provide a typology of psychosocial responses to environmental incidents. RESULTS: Response to an environmental incident can be usefully considered in terms of the exposure, the response of the individual, the action of professionals, the response of the community, and the influence of the society in which the incident occurs. We reviewed each of these factors. CONCLUSIONS: By examining incidents in an ordered framework, we suggest that a more comprehensive understanding is possible. We also suggest some basic ways in which the psychosocial management of such difficult and diverse incidents could be improved.

Analysis of anthrax and plague biowarfare vaccine interactions with human monocyte-derived dendritic cells.

The anti-biowarfare anthrax and plague vaccines require repeated dosing to achieve adequate protection. To test the hypothesis that this limited immunogenicity results from the nature of vaccine interactions with the host innate immune system, we investigated molecular and cellular interactions between vaccines, dendritic cells (DCs), and T cells and explored the potential for adjuvants (pertussis) to boost induction of host immunity. Human monocyte-derived DCs were matured in the presence of vaccines and analyzed for their ability to induce Th1/Th2 development from naive T cells, expression of cell surface maturation/costimulation molecules, and cytokine production. The vaccines showed different behavior patterns. Although the plague vaccine is equivalent to control maturation factors in maturation and stimulation of DCs and induces strong MLR and Th outgrowth, the anthrax vaccine is a poor inducer of DC maturation, as indicated by low levels of HLA-DR, CD86, and CD83 induction and minimal proinflammatory cytokine production. Interestingly, however, anthrax vaccine-treated DCs stimulate Th1 and Th2 outgrowth and a limited MLR response. There was no sustained negative modulatory effects of the anthrax vaccine on DCs, and its limited stimulatory effects could be overridden by coculture with pertussis. These results were supported by analysis of anthrax vaccine recall responses in subjects vaccinated using pertussis as an adjuvant, who demonstrate anthrax-specific effector T cell responses. These data show that the anthrax vaccine is a suboptimal DC stimulus that may in part explain the observation that it requires repeated administration in vivo and offer a rational basis for the use of complementary DC-maturing adjuvants in combined immunotherapy.

Cellular immune activation in Gulf War veterans.

The etiology and pathology of illnesses related to the first Persian Gulf War are unclear. Among the constellation of symptoms noted in sick veterans, some, such as skin rashes, musculoskeletal pains, and neuropsychiatric problems, have been proposed to reflect an underlying immune dysfunction. In this study we explored the hypothesis that sickness following deployment to the Gulf in 1991 is associated with altered immune function, and we examine possible associated exposures. In particular, we focused on peripheral blood Th1/Th2 balance by measuring intracellular production of IFN-gamma, IL-2 (Th1), IL-4 (Th2), and IL-10 by CD4 T cells, using a nested case control study design within a large epidemiological survey. We compared symptomatic Gulf War veterans (sGWV) with well GWVs (wGWV), and a second control group of symptomatic veterans who served in Bosnia or were nondeployed military personnel of the same era. We found evidence for an altered immune status in sGWV in comparison to the other study groups. In particular, ongoing Th1-type immune activation was associated with multisymptom illness in GWVs, with sick veterans having significantly elevated levels of IFN-gamma and IL-2 producing CD4+ cells in the absence of in vitro stimulation compared with wGWVs (P = 0.01 and P =0.001). In vitro polyclonal activation revealed significantly elevated levels of IL-10 producing memory CD4 cells in sGWVs (P <0.001), but other cytokines were normal. In terms of possible exposures that might influence immune function, we found a trend for reduced levels of IFN-gamma producing cells after polyclonal activation with increasing numbers of vaccines administered (P <0.05) but no changes in other cytokines. These data show that multisymptom illness in Gulf War veterans is characterized by ongoing Th1-type immune activation and a biased generation of memory cells secreting the suppressor cytokine, IL-10.

Self-reported health of Persian Gulf War veterans: a comparison of help-seeking and randomly ascertained cases.

The objective of this study was to compare self-selected Persian Gulf War veterans attending a health assessment program with veterans ascertained in an epidemiological study to determine why Gulf War veterans do, or do not, present for clinical assessment. A postal survey was sent to randomly selected United Kingdom Armed Forces personnel who served in the Persian Gulf conflict. Outcome measures included a symptom checklist, health perception, physical functioning, psychological distress, post-traumatic stress symptoms, and health attributions. A total of 173 survey respondents had also attended the Medical Assessment Program (MAP). MAP attendees were more likely to be female, older, and working part time or not working at all. They had poorer health perception and reported higher levels of illness, and they differed in terms of their health attributions. The belief that one had Gulf War syndrome and attributing health problems to Gulf War service were the most powerful predictors of MAP attendance, even when controlling for the level of physical functioning. The findings suggest that health beliefs rather than symptoms are more important predictors of attendance of an assessment program and that Gulf War veterans who attended the MAP have different characteristics than those who did not. This suggests that MAP patients are unrepresentative of the wider deployment to the Persian Gulf.