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Fibromyalgia (FM) is a common chronic pain disorder that presents diagnostic challenges for clinicians. Several classification, diagnostic and screening criteria have been developed over the years, but there continues to be a need to develop criteria that reflect the current understanding of FM and are practical for use by clinicians and researchers. The Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks (ACTTION) public-private partnership with the U.S. Food and Drug Administration (FDA) and the American Pain Society (APS) initiated the ACTTION-APS Pain Taxonomy (AAPT) to develop a diagnostic system that would be clinically useful and consistent across chronic pain disorders. The AAPT established an international FM working group consisting of clinicians and researchers with expertise in FM to generate core diagnostic criteria for FM and apply the multidimensional diagnostic framework adopted by AAPT to FM. The process for developing the AAPT criteria and dimensions included literature reviews and synthesis, consensus discussions, and analyses of data from large population-based studies conducted in the United Kingdom. The FM working group established a revised diagnosis of FM and identified risk factors, course, prognosis, and pathophysiology of FM. Future studies will assess the criteria for feasibility, reliability, and validity. Revisions of the dimensions will also be required as research advances our understanding of FM. PERSPECTIVE: The ACTTION-APS FM taxonomy provides an evidence-based diagnostic system for FM. The taxonomy includes diagnostic criteria, common features, comorbidities, consequences, and putative mechanisms. This approach might improve the recognition of FM in clinical practice.

Objective To assess whether two or more functional somatic symptom complexes (SSCs) showed stronger association with psychosocial correlates than single or no SSC after adjustment for depression/anxiety and general medical disorders. Methods In a population-based sample we identified, by standardised questionnaire, participants with chronic widespread pain, chronic fatigue and irritable bowel syndrome, excluding those with a medical cause for pain/fatigue. We compared psychosocial variables in three groups: multiple (>1), single or no FSS, adjusting for depression/anxiety and general medical disorders using ordinal logistic regression. We evaluated whether multiple SSCs predicted health status 1 year later using multiple regression to adjust for confounders. Results Of 1443 participants (58.0% response) medical records were examined in 990: 4.4% (n = 44) had 2 or 3 symptom complexes, 16.2% a single symptom complex. Many psychosocial adversities were significantly associated with number of SSCs in the expected direction but, for many, statistical significance was lost after adjustment for depression/anxiety and medical illness. Somatic symptoms, health anxiety, impairment and number of prior doctor visits remained significantly associated. Impaired health status 1 year later was predicted by multiple somatic symptom complexes even after adjustment for depression, anxiety, medical disorders and number of symptoms. Conclusions Depression, anxiety, medical illness and health anxiety, demonstrated an exposure-response relationship with number of somatic symptom complexes. These may be core features of all Functional Somatic Syndromes and may explain why number of somatic symptom complexes predicted subsequent health status. These features merit inclusion in prospective studies to ascertain causal relationships.

Objective Chronic widespread pain and chronic fatigue share common associated factors but these associations may be explained by the presence of concurrent depression and anxiety. Methods We mailed questionnaires to a randomly selected sample of people in the UK to identify participants with chronic widespread pain (ACR 1990 definition) and those with chronic fatigue. The questionnaire assessed sociodemographic factors, health status, healthcare use, childhood factors, adult attachment, and psychological stress including anxiety and depression. To identify persons with unexplained chronic widespread pain or unexplained chronic fatigue; we examined participant's medical records to exclude medical illness that might cause these symptoms. Results Of 1443 participants (58.0% response rate) medical records of 990 were examined. 9.4% (N = 93) had unexplained chronic widespread pain and 12.6% (N = 125) had unexplained chronic fatigue. Marital status, childhood psychological abuse, recent threatening experiences and other somatic symptoms were commonly associated with both widespread pain and fatigue. No common effect was found for few years of education and current medical illnesses (more strongly associated with chronic widespread pain) or recent illness in a close relative, neuroticism, depression and anxiety scores (more strongly associated with chronic fatigue). Putative associated factors with a common effect were associated with unexplained chronic widespread pain or unexplained chronic fatigue only when there was concurrent anxiety and/or depression. Discussion This study suggests that the associated factors for chronic widespread pain and chronic fatigue need to be studied in conjunction with concurrent depression/anxiety. Clinicians should be aware of the importance of concurrent anxiety or depression., Highlights • Chronic widespread pain and chronic fatigue commonly co-occur, share similar risk factors and are considered by some to be part of the same disorder. • In this study not all putative associated factors were commonly associated with both disorders. • The apparent common association appeared to be explained by the presence of common psychiatric disorders, anxiety and depression.

Objective To examine, separately, in children and adults with autoimmune chronic uveitis (ACU), the evidence regarding the effectiveness and the safety of switching to a non-anti-TNF biologic modifier immunosuppressant treatment (NTT) currently available in clinical practice. Methods A systematic search between January 2000 and April 2014 was conducted using EMBASE, Ovid MEDLINE, Evidence Based Medicine Reviews—ACP Journal Club, Cochrane libraries, and EBM Reviews. Studies investigating the efficacy of NTT as a biologic modifier immunosuppressant medication for ACU, refractory to topical and/or systemic steroid therapy, were eligible for inclusion. The primary outcome measure was the improvement of intraocular inflammation, as defined by the SUN working group criteria. We determined a combined estimate of the proportion of subjects responding to NTT. Results We initially identified 526 articles, of which 89 were potentially eligible. From the selection process, a total of 10 retrospective chart reviews and a randomized single-blind controlled study, providing a total of 12 children and 34 adults, were deemed eligible: 3 articles looked at rituximab, 3 at abatacept, 3 at tocilizumab, and the remaining 1 at alemtuzumab and the other at anakinra. Before the NTT treatment, all the eligible subjects received several combinations of one or more DMARDs and at least one anti-TNF strategy. With the exclusion of 7 adults enrolled in the RCT, 8 of 12 children and 18 of 27 adults responded to NTT treatment: 0.66 was the combined estimate of the proportion of subjects improving on NTT treatment in children (95% CI: 0.46−0.99) and in adults (95% CI: 0.49–0.84). Further statistical comparison between different NTT strategies was not possible due to the small sample size. Conclusion Although randomized controlled trials are needed, the available evidence suggests the clinical use of a NTT strategy in selected categories of ACU, refractory to previous course of immunosuppressive treatment, DMARDs, as well as anti-TNFα, in adults as well as children.

Objective A common population sampling frame in countries with universal health care is health service registers. We have evaluated the use of such a register, in the United Kingdom, against a commercially available database claiming large population coverage, an alternative that offers ease of access and flexibility of use. Study Design and Setting A case–control study of vasculitis, which recruited cases from secondary care clinics in Scotland, compared two alternative sampling frames for population controls, namely the registers of National Health Service (NHS) primary care practices and a commercially available database. The characteristics of controls recruited from both sources were compared in addition to separate case–control comparison using logistic regression. Results A total of 166 of 189 cases participated (88% participation rate), while both the commercial database and NHS Central Register (NHSCR) controls achieved a participation rate of 24% among persons assumed to have received the invitation. On several measures, the NHSCR patients reported poorer health than the commercial database controls: low scores on the physical component score of the Short Form 36 (odds ratio [OR]: 2.3; 95% confidence interval [CI]: 1.3–4.1), chronic widespread pain (OR: 2.3; CI: 1.1–4.7), and high levels of fatigue (OR: 2.0; CI: 1.3–3.1). These had an important influence on the estimates of association with case status with one association (pain) showing a strong and significant association using commercial database controls, which was absent with NHSCR controls. Conclusion There are important differences in self-reported measures of health and quality of life using controls from two alternative population sampling frames. It emphasizes the importance of methodological rigor and prior assessment in choosing sampling frames for case–control studies.

ObjectiveFunctional somatic syndromes commonly occur together, share a genetic component and are associated with numerous somatic symptoms. This study aimed to determine if genetic variation in two neuroendocrine systems, the serotoninergic system and the hypothalamic-pituitary-adrenal (HPA) axis, was associated with the number of reported somatic symptoms.MethodsThis population-based cohort study (Epidemiology of Functional Disorders) recruited participants from three primary care registers in the northwest of England. Somatic symptoms, anxiety, depression, and pain were assessed using the Somatic Symptoms Checklist, Hospital Anxiety and Depression scales, and body manikins, respectively, via a postal questionnaire. Tag Single Nucleotide Polymorphisms (SNPs) (r2>0.8) were selected for serotoninergic system genes (TPH2, SLC6A4 and HTR2A) and HPA axis genes (CRH, CRHR1, CRHBP, MC2R, POMC, NR3C1, and SERPINA6) and genotyped using Sequenom technology. Negative binomial regression was used to test for association between SNPs and the number of somatic symptoms. Stepwise-regression was used to identify independent effects and adjustments were made for anxiety, depression, and pain.ResultsA total of 967 subjects were successfully genotyped for 143 (87%) SNPs. Multiple SNP associations with the number of somatic symptoms were observed in HTR2A and SERPINA6 as well as two SNPs in TPH2. Stepwise regression identified two effects in HTR2A and a single effect in TPH2 which were independent of anxiety, depression, and pain. A single effect was also identified in SERPINA6 but was no longer significant when adjusted for pain.ConclusionThis study finds association of SNPs in HTR2A, SERPINA6, and TPH2 with somatic symptoms implicating them as potentially important in the shared genetic component to functional somatic syndromes, although replication is required.

Summary Objective Name-based classification systems are potentially useful in identifying study samples based on probable ethnic minority group. The aim of the current study was to assess the validity of the Nam Pehchan name classification programme of religion and language against subject self-report. Study design and setting A population-based cross-sectional survey conducted in areas of the North-West and West Midland regions of England with a relatively high density of South Asian ethnic minority groups. The sampling frame was age–sex registers of selected general practices and subjects were classified according to language and religion using the Nam Pehchan programme. These were compared with responses by subjects on a self-complete postal questionnaire. Results One thousand nine hundred and forty-nine subjects who participated, classified themselves as South Asian. Sensitivity in identifying religion was high amongst Muslims (92%) and Sikhs (86%), and somewhat lower in Hindus (62%). Specificity exceeded 95% for all ethnic groups. The vast majority of subjects assigned Punjabi or Gujarati as their main South Asian language indicated that they did in fact speak these languages (97% and 94%, respectively). Subjects assigned Urdu or Bengali, however, were less likely to do so (61% and 35%, respectively). Conclusions The name-based classification system Nam Pehchan has demonstrated high levels of accuracy in some sub-groups of the South Asian population in determining subjects likely language spoken and religion—and is likely to be a useful additional tool when information on ethnicity is not already available.

Purpose To determine whether higher rates of mortality are observed in people reporting psychological distress, to establish the nature of any excess, and to examine the possible existence of a dose response relationship. Methods We conducted a prospective follow-up study of mortality over an eight-year period in the North West of England. A total of 4,501 adults were recruited from two general practices during a population-based survey conducted at the start of 1992. At baseline psychological distress was assessed using the General Health Questionnaire (12-item version, GHQ-12). The relationship between levels of distress and subsequent mortality was examined using Cox proportional hazard models. Results Risk of all-cause mortality was greatest in subjects reporting the highest levels of distress (hazard ratio (HR) 1.71, 95% CI 1.32–2.23) but was also raised in subjects reporting intermediate distress (HR 1.38 95% CI 1.06–1.79) when compared to those reporting no distress. Increased risk of mortality in subjects reporting distress appeared to be due largely to an excess of deaths from ischaemic heart disease (high distress, HR 1.90, 95% CI 1.08–3.35; intermediate distress, HR 1.58, 95% CI 0.90–2.76) and respiratory diseases (high distress, HR 5.39, 95% CI 2.70–10.78; intermediate distress, HR 2.33, 95% CI 1.12–4.22). Conclusions The association between mortality and psychological distress observed in this study seems to arise largely because of premature deaths from ischaemic heart disease and respiratory diseases. The existence of a dose-response effect between distress and mortality provides further evidence to support the existence of a casual relationship.

Allelic imbalance on chromosome arm 8p is common in head and neck squamous cell carcinoma (HNSCC). DLC1, a tumour suppressor gene inactivated in liver carcinogenesis and encoding a Rho GTPase activating protein (RhoGAP) maps to one of the deleted regions (8p21.3-22). In order to determine whether inactivation of DLC1 is involved in HNSCC, we have screened tumour cell lines for DLC1 mutations and expression. Pathological mutations were not identified in any of the 17 cell lines tested. Seven polymorphisms were identified; 13 of the 17 of cell lines were homozygous for all seven polymorphisms compared to only 2 of 17 controls suggesting a loss of heterozygosity in a majority of the cell lines. DLC1 expression was observed in all 11 HNSCC cell lines tested, thus excluding the possibility of transcriptional silencing of DLC1 by promoter hypermethylation. Overall, our data suggest that hemizygous deletions of the DLC1 locus are frequent in HNSCCs but this gene is unlikely to be primary target for inactivation on this chromosomal arm.

As part of a large, nationwide community-based study in France on health and urinary condition, involving 2011 men aged between 50 and 80 years, information was collected on sexual life factors (e.g., frequency of sexual desires and sexual relations, and the frequency of having difficulties with erection and ejaculation) in addition to an assessment of overall sexual life satisfaction. Data on sexual life were obtained by means of a self-administered questionnaire, while information on the frequency of urinary symptoms was obtained by a professional interviewer. The median number of sexual relations decreased with age from “once per week” in those aged 50–59 years to “less than once per week” in those aged 60–69 years to “never” in those aged over 70 years, while the percentage reporting difficulty with erection at least some of the time increased from 20 to 38% between 50–59 and 70–79 years, respectively. The number of sexual relations during the past month was by far the most important factor having an influence on overall sexual life satisfaction, with those men reporting relations less than once per week almost 10 times more likely to be dissatisfied. Severity of overall urinary symptoms (as well as many individual symptoms) was also inversely related to sexual life satisfaction, and the association persisted after taking account of the strong influence of age and the frequency of sexual relations. All other factors being equal (age, number of relations, comorbidities, and previous prostate surgery), the likelihood of men being dissatisfied with sexual life increased twofold in men with moderate symptoms and fourfold in those with severe symptoms. The results obtained in the current study should be considered preliminary, given the complexity of the relationship between these two factors and the lack of previously published evidence. They certainly call for further studies, which should include a detailed assessment of sexual function and a clinical assessment of the urinary condition.

Data over at least 20 years from three large population-based registries in Europe and Australasia have been used to assess the risk of second primary tumours occurring after a cancer of the mouth or pharynx. These patients have previously been shown in clinical series to be at a particularly high risk of subsequent tumours, while data from cancer registries have shown conflicting results on the magnitude of the risk. In this study, patients were found to have between a 2-fold (Scotland and New South Wales) and 4-fold (Slovenia) increase in risk of a subsequent tumour over that in the population, although the actual risk in each centre was similar (between 2.8 and 3.1 per 100 person years). The risk remained for 10 years after diagnosis of the original tumour and was primarily in the upper aero-digestive tract. The most elevated risks (approximately 10-fold) were for tumours in the oral cavity and oesophagus. These data provide higher estimates of risk than previously reported from European cancer registries for second primary tumours and emphasize the need for close follow-up of patients who may represent an appropriate population in which to assess possible new chemopreventive agents.

The reasons for an increasing incidence of oral cancer, particularly amongst younger persons is unclear. It has been hypothesised either to be a result of an increase in exposure to known risk factors amongst certain groups in the community, or to be due to new aetiological agents. Prior to conducting large expensive population-based studies, it seems appropriate to conduct initial smaller-scale surveys to assess evidence for each of these two hypotheses. This survey of young persons with oral cancer suggest that most are exposed to traditional risk factors of tobacco smoking, drinking alcohol and a low consumption of fruit and vegetables.