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Background: Fatigue is commonly reported in population surveys and has been identified in patients with health conditions as a key co-morbidity which makes remaining in work challenging. Such patients, however, rarely have access to programmes to help them manage their fatigue., Aims: To quantify the relationship between fatigue, work impairment and health-related job loss., Methods: We use data from the Health and Employment After Fifty study, a longitudinal study of people aged 50-64 years when recruited through general practices in England in 2013-14. During follow-up, fatigue was measured using the Fatigue Assessment Scale, work impairment was assessed using the Work Productivity and Activity Impairment scale, and changes in employment status were recorded., Results: A total of 2743 participants were eligible for the current analysis; 23% satisfied criteria for being fatigued. People who were fatigued were less likely to have a partner, university degree, be physically active and were more likely to be obese. Their job was more likely to involve shifts, be perceived as insecure, have reported difficulties coping with job demands, and be unsatisfying. After adjustment for socio-economic, lifestyle and work-related factors, they were almost twice as likely to report both work impairment (relative risk 1.8; 95% confidence interval [CI] 1.6, 2.1) and future health-related job loss, although the latter effect was only in those with other morbidities (incidence rate ratio 1.96; 95% CI 1.03-3.72)., Conclusions: Providing evidence-based support for workers with health conditions who experience fatigue may have an important impact at a population level in terms of extending working lives., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Occupational Medicine.)

Objectives: To estimate the cost-effectiveness of a cognitive behavioural approach (CBA) or a personalized exercise programme (PEP), alongside usual care (UC), in patients with inflammatory rheumatic diseases who report chronic, moderate to severe fatigue., Methods: A within-trial cost-utility analysis was conducted using individual patient data collected within a multicentre, three-arm randomized controlled trial over a 56-week period. The primary economic analysis was conducted from the UK National Health Service (NHS) perspective. Uncertainty was explored using cost-effectiveness acceptability curves and sensitivity analysis., Results: Complete-case analysis showed that, compared with UC, both PEP and CBA were more expensive [adjusted mean cost difference: PEP £569 (95% CI: £464, £665); CBA £845 (95% CI: £717, £993)] and, in the case of PEP, significantly more effective [adjusted mean quality-adjusted life year (QALY) difference: PEP 0.043 (95% CI: 0.019, 0.068); CBA 0.001 (95% CI: -0.022, 0.022)]. These led to an incremental cost-effectiveness ratio (ICER) of £13 159 for PEP vs UC, and £793 777 for CBA vs UC. Non-parametric bootstrapping showed that, at a threshold value of £20 000 per QALY gained, PEP had a probability of 88% of being cost-effective. In multiple imputation analysis, PEP was associated with significant incremental costs of £428 (95% CI: £324, £511) and a non-significant QALY gain of 0.016 (95% CI: -0.003, 0.035), leading to an ICER of £26 822 vs UC. The estimates from sensitivity analyses were consistent with these results., Conclusion: The addition of a PEP alongside UC is likely to provide a cost-effective use of health care resources., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Arm pain is common amongst working-aged adults and causes substantial work disability. The results of a population-based randomized controlled trial (the ARM trial) suggested that advice to remain active reduced disability after 6 months., Aims: To verify ARM trial results amongst people in paid employment., Methods: The ARM trial recruited adults with distal arm pain referred for physiotherapy and randomized equally to three groups: wait-listed for physiotherapy (advised to rest); wait-listed for physiotherapy (advised to remain active) or early physiotherapy. The primary outcome was absence of disability at 26 weeks. Secondary analyses were undertaken amongst participants in paid employment., Results: Amongst 538 trial participants, 347 (64%) were in paid employment, mean age 46.1 years and 47% in manual work. Employed participants were randomized equally to the three arms. Amongst the 271 (78% workers with 26-week data), 43% of those advised to remain active were free from disability, as compared with 37% of those advised to rest. Forty per cent of those who waited for physiotherapy were disability-free as compared with 35% of those treated rapidly. Advice to rest was associated with lower chances of recovery amongst workers who lift/carry weights and those who believed work had caused their symptoms (P = 0.023)., Conclusions: Although not powered as a trial for workers only, our findings suggest that advising activity was as beneficial for people currently in paid work and may be superior to advice to rest in reducing disability. Addressing harmful beliefs about causation of symptoms has the potential to reduce disability., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Low back pain (LBP) is one of the most prevalent occupational health problems in industrialized countries. Little is known about the epidemiology of LBP in developing countries., Aims: To determine the prevalence of LBP among Nepalese textile workers and to investigate the influence of exposure to mechanical and other factors on LBP reporting., Methods: Interviewers completed questionnaires with study subjects, and work-related mechanical exposures were measured by self-completed questionnaires. Associations of LBP with mechanical factors and somatic symptoms were determined by logistic regression and reported as odds ratios (ORs) with 95% confidence intervals (CI)., Results: Nine hundred and thirty-eight workers took part, a participation rate of 92%. The 1 month period prevalence of LBP was 35% (n = 324), being higher in females than males (45% versus 28%; P < 0.001). Several work-related mechanical factors were associated with increased odds of reporting LBP: lifting heavy weights with one hand (OR 1.7; 95% CI 1.1-2.8), pushing weights (OR 1.6; 95% CI 1.2-2.3 and pulling weights (OR 1.6; 95% CI 1.1-2.1). No association was found with working posture. Strong associations were found for reporting one (OR 2.4; 95% CI 1.7-3.4) or two somatic symptoms (OR 2.7; 95% CI 1.4-5.1). On multivariable analysis, reporting of somatic symptoms (OR 2.8; 95% CI 1.5-5.4), female gender (OR 2.2; 95% CI 1.5-3.1) and increasing age were significantly associated with increased risk of reporting LBP (OR 1.7; 95% CI 1.2-2.5), but no associations were found with mechanical factors., Conclusions: This study suggests that mechanical load may not be the leading cause of LBP and adds to evidence that psychological factors play an important role in LBP in non-industrialized countries.

Aims: To investigate the effects of human gut micro-organisms on cytokine production by human intestinal cell lines., Methods and Results: Quantitative real-time PCR assays were developed to measure the production of pro-inflammatory (IL-1α, IL-6, IL-18 and TNFα) and anti-inflammatory (TGF-β1, TGF-β2, TGF-β3, IL-4 and IL-10) cytokines in HT-29 and Caco-2 cell lines. They were co-cultured with a range of mucosal bacteria isolated from ulcerative colitis patients, together with lactobacilli and bifidobacteria obtained from healthy people. HT-29 cells were also co-cultured with Campylobacter jejuni, enterotoxigenic Escherichia coli (ETEC), enteropathogenic E. coli and Salmonella typhimurium. The majority of commensal bacteria tested suppressed the expression of anti-inflammatory cytokine mRNA, increased IL-18, reduced IL-1α, and with the exception of nonpathogenic E. coli, reduced TNF-α. All overtly pathogenic species increased both pro-inflammatory and anti-inflammatory cytokine mRNA., Conclusion:   Commensal and pathogenic species induced fundamentally different cytokine responses in human intestinal epithelial cell lines., Significance and Impact of the Study: Interactions between commensal bacteria tested in this study and the innate immune system were shown to be anti-inflammatory in nature, in contrast to the pathogenic organisms investigated. These data contribute towards our understanding of how potential probiotic species can be used to suppress the pro-inflammatory response in inflammatory bowel disease., (© 2010 The Authors. Journal of Applied Microbiology © 2010 The Society for Applied Microbiology.)

Objectives: To test the hypothesis that individuals with regional and widespread pain disorders have an increased risk of mortality., Methods: We conducted a prospective cohort study of 4515 adults. Subjects were an age- and sex-stratified sample who had participated in a population study of pain occurrence during 1996. Based on those reports subjects were classified as having no pain, regional pain or widespread pain. All subjects were identified on the National Health Service Central Register and followed up until April 2005, a total of 8.2 yrs, at which time information was obtained on vital status, and if applicable, date and cause of death. The relationship between pain status and subsequent death is expressed as mortality rate ratios with 95% CIs, adjusted for age, gender, ethnicity and practice., Results: A total of 35.2% reported regional pain and 16.9% satisfied criteria for widespread pain. In comparison with those without pain, there was a 20% and 30% increased risk of dying over the follow-up period among subjects with regional and widespread pain, respectively. The specific causes of death in excess were cancer and cardiovascular disease. In addition, the mortality risk from both cancer and cardiovascular deaths was found to increase as the number of pain sites that subjects reported increased., Conclusions: This study supports a previous observation that persons with regional and widespread pain are at an increased risk of cancer death. Possible mechanisms should be explored.

Objectives: Poor sleep is associated with chronic widespread pain (CWP). Conversely, good-quality sleep may play a role in the resolution of pain symptoms. Sleep is a multidimensional construct, comprising a number of diverse components. The aims of the current study were to examine the hypotheses that: (i) good sleep quality would predict the resolution of CWP, (ii) restorative sleep would predict the resolution of CWP and (iii) that these relationships would be independent of confounding psychological factors., Methods: Subjects in a population-based prospective study completed a pain questionnaire at baseline from which subjects with CWP were identified. Baseline sleep was measured using the Estimation of Sleep Problems Scale which measures sleep onset, maintenance, early wakening and restorative sleep. The questionnaire also contained scales examining psychosocial status. Subjects were followed up 15 months later and pain status was assessed., Results: A total of 1061 subjects reported CWP at baseline of whom 679 (75% of eligible subjects) responded at follow-up. Of those, a total of 300 (44%) no longer satisfied criteria for CWP. Univariate analysis revealed that three of the four sleep components were associated with the resolution of CWP: rapid sleep onset, odds ratio (OR) = 1.7, 95% CI 1.2, 2.5; absence of early wakening, OR = 1.6, 95% CI 1.1, 2.4; and restorative sleep, OR = 2.7, 95% CI 1.5, 4.8. After adjusting for the effect of psychosocial factors, which may have confounded the relationship, only restorative sleep (OR = 2.0, 95% CI 1.02, 3.8) was associated., Conclusions: Self-reported restorative sleep was independently associated with the resolution of CWP and return to musculoskeletal health.

Most studies involving prebiotic oligosaccharides have been carried out using inulin and its fructo-oligosaccharide (FOS) derivatives, together with various forms of galacto-oligosaccharides (GOS). Although many intestinal bacteria are able to grow on these carbohydrates, most investigations have demonstrated that the growth of bifidobacteria, and to a lesser degree lactobacilli, is particularly favoured. Because of their safety, stability, organoleptic properties, resistance to digestion in the upper bowel and fermentability in the colon, as well as their abilities to promote the growth of beneficial bacteria in the gut, these prebiotics are being increasingly incorporated into the Western diet. Inulin-derived oligosaccharides and GOS are mildly laxative, but can result in flatulence and osmotic diarrhoea if taken in large amounts. However, their effects on large bowel habit are relatively minor. Although the literature dealing with the health significance of prebiotics is not as extensive as that concerning probiotics, considerable evidence has accrued showing that consumption of GOS and FOS can have significant health benefits, particularly in relation to their putative anti-cancer properties, influence on mineral absorption, lipid metabolism, and anti-inflammatory and other immune effects such as atopic disease. In many instances, prebiotics seem to be more effective when used as part of a synbiotic combination.

Background: Musculoskeletal pain is reported more commonly by South Asians in the UK than by white Europeans. This may result from a variety of factors, including cultural differences, and thus we investigated the extent to which differences in the prevalence of pain within the South Asian population could be explained by differences in acculturation (the extent to which immigrants take on the culture of their host population)., Methods: Nine hundred and thirty-three Europeans and 1914 South Asian (1165 Indian, 401 Pakistani and 348 Bangladeshi) subjects were recruited from the age-sex registers of 13 general practices in areas with high densities of South Asian populations (Bolton, Oldham, Ashton-under-Lyne and Birmingham). A 28-item acculturation scale was developed, based, on aspects including use of language, clothing style, and use of own-culture media. Principle component analysis generated a score (range 0-100), which was validated against constructs expected to relate to acculturation, such as years of full time education and time spent in the UK. The presence of widespread pain was assessed by the answer to the question 'Have you suffered from pain all over the body in the past month?', Results: Widespread pain was more common in all three South Asian ethnic groups than in the white Europeans [odds ratio (OR) = 3.7, 95% confidence interval (CI) 2.9-4.9], with this increase ranging from 2.7 to 5.8 in the different South Asian subgroups. There was a similar increase in consultation rates for pain. Within the South Asians, pooling all three groups, there was a strong negative association between acculturation score and widespread pain, which remained after adjusting for age and sex: [OR (95% CI) per standard deviation decrease in acculturation score -1.2 (1.0-1.3)]. Adjusting for acculturation accounted for some, but not all, of the differences between the ethnic groups in the prevalence of widespread pain: OR 2.0 (95% CI 1.4-3.0)., Conclusions: Widespread pain is more commonly reported in South Asians though there are interesting differences within the South Asian community. Lower acculturation has a strong influence on the reporting of pain, but cannot explain all of the difference between South Asian and European populations.

Objective: To determine whether an observation in a UK study, that persons with chronic widespread pain are at long-term increased risk of cancer mortality, can be replicated in a different setting., Methods: Subjects were participants aged >or=30 yrs in the Mini-Finland Health Survey conducted between 1979 and 1980. Information collected included prevalent pains at different joints throughout the body, demographic, anthropometric, lifestyle and occupational factors. During follow-up, until 1994, information on vital status and cause of death was obtained., Results: 7182 persons participated (89.8%). The prevalence of widespread body pain (pain at four or more sites) was 20% in females and 12% in males, and during follow-up there were a total of 1647 deaths. The risk of death was not elevated amongst those with widespread pain [relative risk (RR): 0.86; 95% confidence interval (CI): 0.74-1.00], and in particular, those with widespread pain were at a slightly lower risk of several disease-specific causes of death and cancer death (RR: 0.64; 95% CI: 0.46-0.91)., Conclusions: This study of multiple pains has not confirmed a previous observation of an association between the reporting of widespread pain and subsequent increased risk of cancer death. Differences in the definitions used or, more probably, the population studied, in particular, a larger rural population with more multiple pains related to physical activity may account for the differences.

Objective: Chronic widespread pain (CWP) is strongly associated with psychosocial distress both in a clinical setting and in the community. The aim of this study was to determine the contribution of measures of psychosocial distress, health-seeking behaviour, sleep problems and traumatic life events to the development of new cases of CWP in the community., Methods: In a population-based prospective study, 3171 adults aged 25-65 yrs free of CWP were followed-up 15 months later to identify those with new CWP. Baseline data were available on their scores from a number of psychological scales including Illness Attitude Scales (IAS), Somatic Symptom Checklist (SSC), Hospital Anxiety & Depression Scale, Sleep Problems Scale, and Life Events Inventory., Results: 324 subjects [10%, 95% confidence interval (CI) 9.2, 11.3] developed new CWP at follow-up. After adjustment for age and sex, three factors independently predicted the development of CWP: scoring three or more on the SSC [odds ratio (OR) 1.8, 95% CI 1.1, 3.1], scoring eight or more on the Illness Behaviour subscale of the IAS (OR 3.3, 95% CI 2.3, 4.8), and nine or more on the Sleep Problem Scale (OR 2.7, 95% CI 1.6, 3.2). Subjects exposed to all three factors were at 12 times the odds of new CWP than those with low scores on all scales., Conclusion: Subjects are at substantial increased odds of developing CWP if they display features of somatization, health-seeking behaviour and poor sleep. Psychosocial distress has a strong aetiological influence on CWP.

This article summarizes the work of the Arthritis Research Campaign Epidemiology Unit in the field of pain and soft tissue rheumatism during the 50 years 1954-2004. It reviews the information gathered on the occurrence of symptoms and its causes, which began with Kellgren and Lawrence's pioneering work during the 1950s in the coal fields and general population of Leigh, Greater Manchester. They studied the roles of posture, mechanical load and the physical environment (dampness) on back pain. This was followed by the Calderdale study in the 1980s examining the prevalence of disability and its causes in the population, which demonstrated the important role of regional pain in causing disability. More recent studies in the 1990s and at the beginning of the 21st century have allowed us to define the relative roles of mechanical (load) factors, individual (psychological) factors and the social environment, and the biological mechanisms by which they may result in symptoms. The further challenge over the coming decade is to use our knowledge of the aetiology and influences on outcome to design management strategies which demonstrate improved outcomes for patients.

Objective: To test the hypothesis that the prevalence of specific musculoskeletal pain symptoms has increased over time in the northwest region of England. To meet this objective we have examined the difference in the prevalence of low back, shoulder and widespread pain between the 1950s and today using historical data collected by the Arthritis Research Campaign (arc)., Methods: Two cross-sectional surveys conducted over 40 yr apart in the northwest region of England. The status of two regional pain sites and widespread pain was determined using interview and questionnaire responses, for the earlier and later studies respectively. Subjects were classified positively if they reported low back pain, shoulder pain or widespread pain on the day of the survey. Rates were standardized to the Greater Manchester population., Results: There were large differences in the prevalence of musculoskeletal pain between the two surveys. For all three symptoms examined prevalence increased from 2- to 4-fold between the two surveys. In both surveys low back pain was more common in women. Shoulder and widespread pain was less prevalent in women than in men in the earlier survey but by the time of the later survey women reported more pain at these sites., Conclusions: The prevalence of musculoskeletal pain is much higher than that reported over 40 yr ago. The change in prevalence is unlikely to be entirely due to the study design; other possible explanations such as the increased reporting or awareness of these symptoms is discussed.

Objectives: The relationship between hip pain and radiographic change in the population is unclear due to lack of agreed definition for hip pain and difficulties in obtaining radiographs from asymptomatic random samples. Our objective was to assess the relationship between hip pain and radiographic change in osteoarthritis (OA) in a population sample aged over 45., Methods: One thousand and seventy-one responders to a postal questionnaire using a recently validated approach to defining hip pain were stratified into hip pain-positive and -negative groups and samples of each were X-rayed and scored for OA using both minimum joint space and the Croft score. The association between pain and X-ray score was estimated, weighting back to the age and gender distribution of the original population., Results: Hip pain prevalence was 7% in males and 10% in females. Severe OA was present in 16% of those with and 3% of those without pain. Adjusting for age and gender, there was a very strong association of pain with severe OA [odds ratio (OR) 17.4, 95% confidence interval (CI) 3.0-102], but no association with mild/moderate OA (OR 1.4, 95% CI 0.4-4.7). By contrast, only 22% of men aged 45-54 with severe OA had current pain, though in older age groups the proportions with pain were higher (54-70%)., Conclusions: Hip pain is relatively infrequent in the general population compared with the published reports of other regional pain syndromes. Mild/moderate radiographic change is very frequent and not related to pain, whereas severe change is rare but strongly related. In younger males, severe radiographic change is much less likely to be associated with pain.

Background: We have recently demonstrated that individual psychosocial factors are important predictors of the onset of chronic widespread pain. It has been hypothesized that excessive mechanical exposure may also be associated with symptom onset, although this has not been formally examined. We therefore determined the relative contributions of individual psychosocial and work-related mechanical, posture and environment factors in symptom onset., Methods: We conducted a population-based prospective survey and identified 1658 adults aged 18-65 yr who were symptom-free. At baseline, detailed information was obtained on work-related mechanical and environment factors using validated instruments. Individual psychosocial features were also measured. Subjects free of chronic widespread pain at baseline were followed up at 12 and 36 months to identify those reporting the onset of new symptoms., Results: In all, 1445 (91%) returned the questionnaire at 12 months and 978 (89%) at 36 months. Of these, 81 and 92 respectively reported new chronic widespread pain. Symptom onset was predicted by workplace factors [pushing/pulling heavy weights [relative risk (RR) = 1.8, 95% confidence interval (CI) 1.1, 3.0]; repetitive movements of the wrists (RR = 1.8, 95% CI 1.2, 2.7); kneeling (RR = 2.2, 95% CI 1.2, 4.1)] and individual factors [aspects of illness behaviour (RR = 2.9, 95% CI 1.6, 5.3); somatic symptoms (RR = 1.9 95% CI 1.1, 3.3); fatigue (RR = 1.9, 95% CI 1.2, 3.1); baseline pain symptoms (RR = 2.5, 95% CI 1.6, 3.9)]. In multivariate analysis, pushing/pulling heavy weights, repetitive wrist movements, kneeling and other pain at baseline were associated with new-onset chronic widespread pain. However, the strongest predictor was a high score on the illness behaviour scale., Conclusion: This study provides only limited support for the hypothesis that low-level mechanical injury may be a risk factor for developing chronic widespread pain. The onset of chronic widespread pain appears to be multifactorial and is strongly predicted by individual psychosocial factors.

Objectives: To test the hypothesis that work-related mechanical, psychosocial and physical environment factors would predict new-onset low back pain (LBP) in newly employed workers., Methods: A total of 1186 newly employed workers were recruited from a variety of occupational settings. Those who were free from LBP at baseline were identified. Subjects were followed up at 12 and 24 months. Work-related mechanical, psychosocial and physical environment exposures were measured. Generalized estimating equations were used to assess predictors of new-onset LBP., Results: New-onset LBP was reported by 119 (19%) and 81 (19%) subjects at 12 and 24 months, respectively. Several work-related mechanical exposures predicted new-onset LBP including lifting heavy weights with one or two hands, lifting heavy weights at or above shoulder level, pulling heavy weights, kneeling or squatting for 15 min or longer. Of the psychosocial factors examined, stressful and monotonous work significantly predicted symptom onset. In addition, hot working conditions and pain at other sites also predicted new-onset LBP. On multivariate analysis these risks were only moderately attenuated but the 95% confidence intervals excluded unity only for the latter, non-mechanical, exposures., Conclusion: In this cohort of newly employed workers, from a range of occupations, several aspects of the work-place environment, other than mechanical factors, were important in predicting new-onset LBP. These results emphasize that interventions aimed at reducing the occurrence of LBP are likely to be most successful if they intervene across these domains.

The study objectives were to measure time from birth to first exposure to antibacterials in children and compare the characteristics of children who submit urine samples with the general population. Antibacterials were dispensed to 63% of children within 1 year of birth, increasing to 75% within 2 years after birth. Boys had earlier exposure to antibacterials than girls. Children submitting urine samples were more likely to be socio-economically deprived, have prior exposure to antibacterials and have prior hospital admission. In conclusion, urine samples are unsuitable for a prospective cohort study of the relationship between antibacterial exposure and resistance in children.

Objective: The observation of higher rates of chronic widespread pain, the cardinal feature of fibromyalgia, in women has led to hypotheses about the role of sex hormonal factors in the aetiology of symptoms. There is little available evidence from epidemiological studies on their importance or role., Methods: A population postal survey was carried out involving 1178 female participants living in south-east Cheshire in the north-west of England., Results: Amongst pre- and peri-menopausal women, the risk of chronic widespread pain was unrelated either to the length of the menstrual cycle or the usual length of period reported by participants. Risk was similar in current users and non-users of the oral contraceptive pill, and amongst users there was no relationship with duration of use. However, the reporting of chronic widespread pain showed a relationship with total score on a premenstrual symptom questionnaire. However, this relationship was explained by pain symptoms. Amongst post-menopausal women, reporting chronic widespread pain was not related to age at menopause. An increased (but non-significant) risk of chronic widespread pain was associated with current hormone replacement therapy (HRT), which may be a consequence of HRT being prescribed for menopausal symptoms., Conclusion: This study, conducted on a large unselected population, has not demonstrated an association between sex hormonal factors and chronic widespread pain.

Objectives: The primary objective was to test the hypothesis that new attenders in primary care with hip pain and radiographic osteoarthritis (OA) have a decreased range of movement compared with those without OA. The secondary objective was to define the planes of movement and thresholds that were the most discriminatory for OA., Methods: Men and women aged 40 yr and over presenting with a new episode of hip pain were recruited from 36 general practices across the UK. A standardized radiographic and clinical examination was performed. The discriminating ability of the range of movement for each plane to identify those with radiographic OA was assessed using receiver operating characteristic curves., Results: New hip pain attenders with radiographic OA had restricted movement at the hip compared with those without radiographic change. Restriction in internal rotation was the most predictive and flexion the least predictive of radiographic OA. At this cut-off, restriction in any single plane had a sensitivity of 86% for moderate and 100% for severe OA (specificity was 54 and 42% respectively). Restriction in all three planes had greater discrimination (sensitivity was 33% for mild to moderate OA and 54% for severe OA; specificity was 93 and 88% respectively)., Conclusions: Restriction in range of movement was predictive of the presence of OA in these new presenters to primary care with hip pain, and the results of this examination could be used to inform decisions regarding radiography.

Background: Chronic widespread pain is the cardinal clinical feature of the fibromyalgia syndrome, which, in the majority of clinic patients, is persistent. By contrast, in community-derived patients, pain is persistent in only half of the affected individuals, particularly those with psychological distress. Whether such distress is a consequence of the pain or a manifestation of a wider process of somatization which is associated with the persistence of pain is unclear., Objectives: We tested in a large, prospective, population-based study the hypothesis that features of somatization predict the persistence of chronic widespread pain., Methods: In all, 252 (13%) of 1953 adult subjects selected from a population register were classified as having chronic widespread pain based on a detailed questionnaire which included a pain drawing. The patients also completed a number of psychosocial instruments which measure features known to be associated with somatization. Two hundred and twenty-five (91%) of the patients were successfully followed up after 12 months and provided data on pain status using the same instruments., Results: In all, 126 (56%) patients reported chronic widespread pain at follow-up, 74 (33%) reported other pain and 25 (11%) reported no pain. Persistent chronic widespread pain was strongly associated with baseline test scores for high psychological distress and fatigue. In addition, these subjects were more likely to display a pattern of illness behaviour characterized by frequent visits to medical practitioners for symptoms which disrupt daily activities. The prevalence of persistent pain increased with the number of risk factors the subjects were exposed to., Conclusions: Although almost half of the cases of chronic widespread pain resolved within 1 yr, this study has demonstrated for the first time that those subjects who display features of somatization are more likely to have widespread pain which persists. These findings have implications for the identification and treatment of persons with persistent chronic widespread pain.

Chemostats were used to study the effects of carbon and nitrogen limitation and specific growth rate on 16S rRNA synthesis and cellular fatty acid (CFA) profiles in four human intestinal bacteria (Bacteroides thetaiotaomicron, Bifidobacterium adolescentis, Clostridium bifermentans and Cl. difficile). Cellular fatty acid synthesis varied with dilution rate and nutrient availability in different species, but these cellular constituents were relatively stable phenotypic characteristics in Bact. thetaiotaomicron, where branched chain and hydroxy CFA were good taxonomic markers. Conversely, CFA in the Gram-positive bacteria varied markedly with changes in growth environment. For example, in chemostats, cyclopropane CFA were only synthesized in Cl. bifermentans and Cl. difficile under N-limited conditions. Similarly, Dimethyl acetal (DMA) fatty acids in Bif. adolescentis were primarily produced during N-limited growth, and this was inversely related to dilution rate. At low growth rates, 16S rRNA concentrations (microg rRNA per ml culture) correlated with viable bacterial counts, but were more closely related to specific growth rate when expressed as a function of cell mass (microg rRNA per mg dry weight bacteria). However, this did not reveal differences in bacterial population size and rRNA concentration in C-limited cultures. Thus, at low dilution rates, C limitation strongly reduced rRNA synthesis in Cl. bifermentans, despite viable cell counts being similar to those in N-limited cultures. These results indicate that, while 16S rRNA is a useful indicator of microbial activity, cell growth rate does not necessarily relate to rRNA concentration under all nutritional conditions. Consequently, bowel habit and diet will affect both CFA and rRNA content in bacteria isolated from intestinal samples, and this should be taken into consideration when interpreting such data measurements.

Objective: To determine the prevalence of radiographic osteoarthritis in subjects with hip pain newly presenting to primary care., Methods: The study was cross-sectional in design, set in 35 general practices across the UK. It included 195 men and women aged 40 yr and over (median 63 yr) presenting with a new episode of hip pain. Hip radiographs were scored for minimum joint space (MJS) and overall-Croft's modification of the Kellgren and Lawrence (Croft)-grade of osteoarthritis., Results: In all, definite evidence of radiographic change in the painful joint was common: Croft grade > or =2 in 44%, > or =3 in 34%. MJS of 2.5 mm or less was seen in 30% of whom half were below 1.5 mm. There were no significant gender differences in radiographic severity., Conclusions: Radiographic change is common in patients newly presenting with hip pain and many already have advanced disease.

When repeated measures of an exposure variable are obtained on individuals, it can be of epidemiologic interest to relate the slope of this variable over time to a subsequent response. Subject-specific estimates of this slope are measured with error, as are corresponding estimates of the level of exposure, i.e., the intercept of a linear regression over time. Because the intercept is often correlated with the slope and may also be associated with the outcome, each error-prone covariate (intercept and slope) is a potential confounder, thereby tending to accentuate potential biases due to measurement error. Under a familiar mixed linear model for the exposure measurements, we present closed-form estimators for the true parameters of interest in the case of a continuous outcome with complete and equally timed follow-up for all subjects. Generalizations to handle incomplete follow-up, other types of outcome variables, and additional fixed covariates are illustrated via maximum likelihood. We provide examples using data from the Multicenter AIDS Cohort Study. In these examples, substantial adjustments are made to uncorrected parameter estimates corresponding to the health-related effects of exposure variable slopes over time. We illustrate the potential impact of such adjustments on the interpretation of an epidemiologic analysis.

Background: The analytical validation of multiple lots of the PRO-Trac II ELISA (DiaSorin) for the determination of tacrolimus in whole blood is described., Methods: The analytical parameters assessed included analytical sensitivity, dilution linearity, functional sensitivity, values in samples containing no tacrolimus, intra- and interassay precision, supplementation and recovery, metabolite cross-reactivity, interference studies, and method comparisons HPLC-tandem mass spectrometry (HPLC/MS/MS) and the IMx Tacrolimus II multiparticle enzyme immunoassay. Where appropriate, assessments were performed according to NCCLS guidelines., Results: The mean analytical detection limit was <0.25 microg/L for all lots, whereas the functional sensitivity was 1.0 microg/L. Excellent linear correlation (r = 0.985) was observed for dilution linearity. The intraassay imprecision was <7%, and the total imprecision by ANOVA was <10%. Recovery was 109% +/- 11%. Metabolite cross-reactivity was consistent with previous reports for this antibody. No interference was observed for 35 tested drugs. Method comparison with HPLC/MS/MS showed no statistically significant differences. Samples exhibited stability through four freeze/thaw cycles and for 1 week at room temperature., Conclusion: These data demonstrate that the PRO-Trac II ELISA is a robust, accurate, and precise tool for the assessment and management of tacrolimus blood concentrations in transplant patients.

Objective: We examine the descriptive epidemiology of chronic widespread pain using the 'Manchester' definition [CWP(M)] and assess psychosocial and other features which characterize subjects with such pain according to these more stringent criteria., Methods: A population postal survey of 3004 subjects was conducted in the Greater Manchester area of the UK., Results: The point prevalence of Manchester-defined chronic widespread pain was 4.7%. CWP(M) was associated with psychological disturbance [risk ratio (RR) = 2.2, 95% confidence interval (CI) (1.4-3.5)], fatigue [RR = 3.8, 95% CI (2.3-6.1)], low levels of self-care [RR = 2.2, 95% CI (1.4-3.6)] and with the reporting of other somatic symptoms [RR = 2.0, 95% CI (1.3-3.1)]. Hypochondriacal beliefs and a preoccupation with bodily symptoms were also associated with the presence of CWP(M)., Conclusion: This definition of chronic widespread pain is more precise in identifying subjects with truly widespread pain and its associated adverse psychosocial factors. Clear associations with other 'non-pain' somatic symptoms were identified, which further supports the hypothesis that chronic widespread pain is one feature of somatization.

Ecological and physiological effects of the sulphate-reducing bacterium (SRB) Desulfovibrio desulfuricans on other intestinal organisms were investigated in anaerobic chemostats (dilution rate approximately 0.2 h-1). Reproducible defined bacterial communities were used in these experiments, comprising 14 different saccharolytic and amino acid fermenting species: Bifidobacterium longum, Bif. adolescentis, Bif. pseudolongum, Bif. infantis, Bacteroides thetaiotaomicron, Bact. vulgatus, Lactobacillus acidophilus, Enterococcus faecalis, Ent. faecium, Escherichia coli, Clostridium perfringens, Cl. butyricum, Cl. innocuum, Cl. bifermentans. Lactobacillus and Cl. bifermentans populations never rose above minimum detection limits (log10 2.0 and 4.0, respectively) under the experimental conditions employed in these studies. Inclusion of Des. desulfuricans in bacterial cultures (c. log10 8.4 viable cells ml-1) resulted in marked reductions (i.e. greater than 1 log) in planktonic cell population densities of several species, particularly Bif. longum, Cl. perfringens and Bif. pseudolongum. The two bacteroides species were unaffected by Des. desulfuricans, while numbers of Cl. butyricum increased. Extensive wall growth developed in the SRB culture, consisting mainly of Des. desulfuricans (log10 9.2 viable cells ml-1), Bact. thetaiotaomicron and Bact. vulgatus, with lesser numbers of facultative anaerobes, Cl. perfringens and Bif. longum. Wall growth was associated with a reduction in planktonic cell mass and increased acid production by the cultures. Chemotaxonomic study of chemostat microbiotas, on the basis of cellular fatty acid methyl ester (FAME) analyses, showed the existence of characteristic bacteroides (C15) and bifidobacterial (C18) markers, but desulfovibrio markers (i-C15:0, C16:0, i-C17:1) could be identified. The metabolic activities of saccharolytic organisms were altered in the SRB chemostat, including synthesis of a number of hydrolytic enzymes involved in carbohydrate breakdown, such as alpha-galactosidase, alpha-glucosidase and beta-galactosidase, together with several mucinolytic enzymes. High concentrations of sulphide (8.2 mmol 1-1) were detected in the SRB chemostat, suggesting that this metabolite may have been inhibitory to some species. Saccharolytic organisms growing in the SRB fermenter utilized more starch, but less galactose-containing polymers, which correlated with the observed glycosidase activities. Profound differences were also recorded with respect to fermentation product formation in the chemostats, where a major switch to acetate production occurred in the SRB culture, with concomitant reductions in propionate, butyrate and lactate, which is an important electron donor for desulfovibrios.

Bacteroides ovatus preferentially utilized starch and pectin when grown on a mixture of polysaccharides in batch culture, indicating that these carbohydrates are important substrates for the bacterium in the human large intestine. Further studies on starch breakdown showed that continuous cultures grew on the polysaccharide when it provided the sole carbohydrate source, to yield a single hydrolytic product at low dilution rates (D = 0.04 h-1), with an estimated molecular mass of 13 kDa. In contrast, two major types of oligomeric products were formed at higher dilution rates (D = 0.44 h-1), with approximate molecular weights of 11 and 140 kDa. Analysis of cell-associated starch-degrading enzymes produced by Bact. ovatus using ion exchange chromatography and HPLC gel-filtration showed that amylase and alpha-glucosidase activities eluted in the same fractions. The single peak containing amylase and alpha-glucosidase activities obtained by HPLC gel-filtration chromatography corresponded to a molecular mass of approximately 140 kDa, and activity staining of gels for alpha-glucosidase activity after polyacrylamide gel electrophoresis, in the presence of sodium dodecyl sulphate, gave an estimated molecular mass of 70 kDa, indicating this enzyme to be a dimer. After renaturation, the 70 kDa band was cut from the gels and solubilized. The extract hydrolysed gelatinized starch and p-nitrophenyl-alpha-D-glucopyranoside.

Prevalence studies suggest that shoulder pain is very common (7-20%) in the adult population, though little is known about the severity and impact of such pain. Disability results, in part, from the restriction of movement and we therefore determined the frequency of restricted shoulder movement in individuals in a general population sample reporting shoulder pain and associated disability. In all, 232 individuals were interviewed about shoulder pain and related disability, and their range of shoulder movement in the following planes was measured: elevation, forward flexion, backward flexion, external rotation and internal rotation, together with the minimum difference achieved between the tip of a thumb and the spinous process of C7. In total, 48 (21%) subjects reported current pain and disability in one or both shoulders. Using receiver operating characteristic (ROC) analysis, cut-offs for restricted movements were selected at the point of maximal discrimination between painful and pain-free shoulders. There was considerable overlap in the distribution of range of movement, at all six sites, between these two groups. The highest positive predictive value for pain was observed in restriction of the thumb to cervical spine movement (53%), but this also had the lowest negative predictive value. By contrast, the highest negative predictive value was observed for restriction of external rotation (96%). Restriction in any plane was observed in 77% of those individuals with pain, but was also present in half of those without pain. In summary, most people with self-reported shoulder pain in the community do not have widespread restriction of movement. Reduction in external rotation was the most discriminatory, but it is necessary to examine movement in multiple planes to assess the true burden of shoulder pain in the community.

Eight species of bifidobacteria were tested for their abilities to grow on a range of monosaccharides (glucose, arabinose, xylose, galactose and mannose). In contrast to the other sugars, glucose and galactose were utilized by all species and, in general, specific growth rates were highest on these sugars. Different substrate preferences were observed between species when the bacteria were grown in the presence of all five monosaccharides. For example, glucose and xylose were coutilized by Bifidobacterium longum, whereas glucose repressed uptake of all other sugars in B. bifidum and B. catenulatum. Galactose was the preferred substrate with B. pseudolongum. In B. angulatum, glucose and galactose were utilized simultaneously. B. breve did not grow on arabinose when this sugar provided the sole source of energy. However, glucose and arabinose were preferentially taken up during growth on sugar mixtures.

Bacteroides fragilis NCDO 2217 produced a wide range of cell-associated hydrolytic enzymes (neuraminidase, alpha-fucosidase, alpha-N-acetylgalactosaminidase, beta-galactosidase, beta-N-acetylglucosaminidase) that could potentially degrade the carbohydrate moieties of mucin, a complex glycoprotein. The type of substrate used for growth markedly influenced their formation in batch cultures. Synthesis of neuraminidase, alpha-fucosidase, alpha-N-acetylgalactosaminidase and to a lesser extent, beta-N-acetylglucosaminidase, was inversely related to growth rate in continuous cultures (D = 0.03 h-1-0.23 h-1) in which porcine gastric mucin provided the sole source of carbon and nitrogen.

Chemotactic behavior is a complex cellular response to chemical environmental stimuli. For polymorphonuclear leukocytes (PMNs), such behavior involves net migration as well as changes in cell shape and cell orientation. Accordingly, we have applied computer-interfaced video microscopy to analyze cell shape and orientation in control and patient PMNs migrating under agarose. From a digitized tracing of the PMNs at the leading front of migration, cells were characterized in terms of area, circumference, and longest dimension. A shape factor and angle of orientation were computed. Numerical shape factors discriminated three PMN morphologies: polar, apolar, and hyperpolar. Only polar cells could be oriented. Orientation of polar cells was defined as toward, away, or disoriented with respect to the chemotactic gradient. Apolar cells were considered to be nonoriented. Of PMNs from healthy controls, 30 +/- 5% of the cells were oriented toward and 11 +/- 4% of the cells were oriented away from the gradient. For PMNs from patients with localized juvenile periodontitis, a 40% deficit in net migration was associated with reduced orientation toward (5 +/- 2%) and elevated orientation away from the gradient (33 +/- 9%). PMNs from a panel of patients with thermal injury showed reduced migration and orientation toward the gradient associated with elevated percentages of apolar cells. Such analysis of PMN polarization and orientation of the leading front permitted calculation of a chemotactic behavior index. Application of this multiparameter index to the analysis of the chemotactic response may identify PMNs that are defective, but not by evaluation of any single variable.