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Introduction Frailty and multimorbidity are common in type 2 diabetes (T2D), including people Methods Analysis of UK Biobank participants (n = 20,566) with T2D aged 40-72 years comparing two frailty measures (frailty phenotype and frailty index) and two multimorbidity measures (Charlson comorbidity index and a simply count of 40 long-term conditions (LTCs)). Outomes: mortality (all-cause, cardiovascular- and cancer-related mortality), Major Adverse Cardiovascular Event (MACE), hospitalization with hypoglycaemia or fall/fracture. Results Measure choice influenced the population identified: 42% of participants were identified as frail/multimorbid by at least one measure; only 2.2% were identified by all four measures. Both frailty and multimorbidity, by all measures, were prevalent throughout the age range studied. Each measure was associated with mortality, MACE, hypoglycaemia and falls. The absolute 5-year mortality risk was higher in older versus younger participants with a given level of frailty (e.g. 1.9%, and 9.9% in men aged 45 and 65, respectively, using frailty phenotype) or multimorbidity (e.g. 1.3%, and 7.8% in men with 4 LTCs aged 45 and 65, respectively). Using frailty phenotype, the relationship between higher HbA1c and mortality was stronger in frail compared with pre-frail or robust participants. Conclusion Assessment of frailty/multimorbidity should be embedded within routine management of middle-aged and older people with T2D. Method of identification as well as features such as age impact baseline risk and should influence clinical decisions (e.g. glycaemic control). more...

Background There is evidence that type 2 diabetes self-management programmes may have a positive impact on health outcomes of adults living in Gulf countries. However, none of the programmes evaluated were developed using evidence about the specific needs of adults with Type 2 diabetes living in the Gulf countries. This study is part of a wider programme of research, which uses a cultural adaptation framework to generate information on how to tailor type 2 diabetes self-management to the Saudi context. Methods Secondary data analysis of the Saudi Health Interview Survey (SHIS) (N = 10,821) was conducted. Bivariate and multivariate logistic regression modelling assessed factors associated with type 2 diabetes and its control / self-management including sociodemographic factors (e.g. age, gender), lifestyle (e.g. diet, physical activity), and health seeking behaviours (e.g. chronic illnesses, health services). Results 7% (N = 808) of all participants had type 2 diabetes (59% male), however it represents 35% at or above 55 years. In multivariate analysis at older age, being overweight or obese, male, having hypertension, and reporting a reduction in health status in the 12 months prior to questionnaire completion, were significantly associated with having type 2 diabetes. Participants who reported walking for more than 10 min per day were less likely to report type 2 diabetes. Unexpectedly there was a significant association between type 2 diabetes and lower frequency of fast food intake, while increased fruit and vegetable intake was associated with poor glycaemic control. Conclusions Being overweight and/or hypertensive are concomitant with type 2 diabetes in Saudi Arabia. Any self-management programmes for type 2 diabetes patients with either of these conditions should be tailored accordingly. Walking behaviours should be prioritised in Saudi self-management programmes. Prediabetes management programmes may be of special importance to the Saudi community. more...

Background Chronic kidney disease (CKD) typically co-exists with multimorbidity (presence of 2 or more long-term conditions: LTCs). The associations between CKD, multimorbidity and hospitalisation rates are not known. The aim of this study was to examine hospitalisation rates in people with multimorbidity with and without CKD. Amongst people with CKD, the aim was to identify risk factors for hospitalisation. Methods Two cohorts were studied in parallel: UK Biobank (a prospective research study: 2006-2020) and Secure Anonymised Information Linkage Databank (SAIL: a routine care database, Wales, UK: 2011-2018). Adults were included if their kidney function was measured at baseline. Nine categories of participants were used: zero LTCs; one, two, three and four or more LTCs excluding CKD; and one, two, three and four or more LTCs including CKD. Emergency hospitalisation events were obtained from linked hospital records. Results Amongst 469,339 UK Biobank participants, those without CKD had a median of 1 LTC and those with CKD had a median of 3 LTCs. Amongst 1,620,490 SAIL participants, those without CKD had a median of 1 LTC and those with CKD had a median of 5 LTCs. Compared to those with zero LTCs, participants with four or more LTCs (excluding CKD) had high event rates (rate ratios UK Biobank 4.95 (95% confidence interval 4.82–5.08)/SAIL 3.77 (3.71–3.82)) with higher rates if CKD was one of the LTCs (rate ratios UK Biobank 7.83 (7.42–8.25)/SAIL 9.92 (9.75–10.09)). Amongst people with CKD, risk factors for hospitalisation were advanced CKD, age over 60, multiple cardiometabolic LTCs, combined physical and mental LTCs and complex patterns of multimorbidity (LTCs in three or more body systems). Conclusions People with multimorbidity have high rates of hospitalisation. Importantly, the rates are two to three times higher when CKD is one of the multimorbid conditions. Further research is needed into the mechanism underpinning this to inform strategies to prevent hospitalisation in this very high-risk group. more...

Introduction The aim of this study was to determine risk of being SARS‐CoV‐2 positive and severe infection (associated with hospitalization/mortality) in those with family history of diabetes. Methods We used UK Biobank, an observational cohort recruited between 2006 and 2010. We compared the risk of being SARS‐CoV‐2 positive and severe infection for those with family history of diabetes (mother/father/sibling) against those without. Results Of 401,268 participants in total, 13,331 tested positive for SARS‐CoV‐2 and 2282 had severe infection by end of January 2021. In unadjusted models, participants with ≥2 family members with diabetes were more likely to be SARS‐CoV‐2 positive (risk ratio‐RR 1.35; 95% confidence interval‐CI 1.24–1.47) and severe infection (RR 1.30; 95% CI 1.04–1.59), compared to those without. The excess risk of being tested positive for SARS‐CoV‐2 was attenuated but significant after adjusting for demographics, lifestyle factors, multimorbidity and presence of cardiometabolic conditions. The excess risk for severe infection was no longer significant after adjusting for demographics, lifestyle factors, multimorbidity and presence of cardiometabolic conditions, and was absent when excluding incident diabetes. Conclusion The totality of the results suggests that good lifestyle and not developing incident diabetes may lessen risks of severe infections in people with a strong family of diabetes., Our aim was to determine risk of severe SARS‐CoV‐2 (infection associated with hospitalization/mortality) in those with family history of diabetes. Using UK Biobank data, the findings suggest that having ≥2 family members with diabetes is associated with higher risk of SARS‐CoV‐2 infection and severe infection, but that such risk may be attenuated by better lifestyle, and by avoiding development of diabetes. more...

Background/Aims Upper gastrointestinal cancers (oesophageal/stomach) have high mortality rates and are often diagnosed after the disease has progressed, making it important to identify populations at greater risk of upper gastrointestinal (UGI) cancer to promote earlier diagnosis. This study aims to determine if there is an association between a broad range of long-term conditions (LTCs) and incidence of UGI cancers. Method A prospective-based cohort of 487,798 UK Biobank participants (age 37–73 years) after excluding previous UGI cancer. Least Absolute Shrinkage and Selection Operator (LASSO) regression used to identify candidate LTCs as predictors for UGI cancer. Strength of association was studied using Cox’s regression adjusting for demographics and lifestyle factors. Results After median follow-up period of 86 months, 598 participants developed oesophageal cancer; 397 developed stomach cancer. In fully adjusted models, participants with alcohol addiction (Hazard Ratio-HR 4.11, 95% Confidence Interval-CI 2.01–8.43), Barrett’s oesophagus (HR 5.68, 95% CI 3.36–9.58), bronchiectasis (HR 2.72, 95% CI 1.01–7.31), diabetes (HR 1.38, 95% CI 1.06–1.81), hiatus hernia (HR 1.69, 95% CI 1.16–2.45), Parkinson’s disease (HR 3.86, 95% CI 1.60–9.37) and psoriasis/eczema (HR 1.53, 95% 1.08–2.17) were observed to have a higher risk of oesophageal cancer. Stomach cancer incidence was higher among participants with anorexia/bulimia (HR 8.86, 95% CI 1.20–65.14), Barrett’s oesophagus (HR 3.37, 95% 1.39–8.14), chronic fatigue syndrome (HR 3.36, 95% CI 1.25–9.03), glaucoma (HR 2.06, 95% CI 1.16–3.67), multiple sclerosis (HR 4.60, 95% CI 1.71–12.34), oesophageal stricture (HR 1.04, 95% CI 1.46–74.46) and pernicious anaemia (HR 6.93, 95% CI 3.42–14.03). Conclusion Previously unrecognised LTCs may have a role in symptom appraisal and risk assessment of UGI cancer in primary care. Further research should explore mechanisms underpinning these findings and determine whether they are replicable in other populations. more...

[This corrects the article DOI: 10.1371/journal.pone.0238091.].

This randomized clinical trial examines a decision support tool that provides lower back pain information and self-management recommendations that are specific to an individual’s characteristics, symptoms, and symptom progression., Key Points Question Is selfBACK, an evidence-based, individually tailored self-management support system that is delivered through an artificial intelligence–based app and in conjunction with usual care, effective for pain-related disability in adults with lower back pain? Findings In this randomized clinical trial involving 461 participants in Denmark and Norway, those who received the selfBACK intervention had reduced pain-related disability compared with those who received usual care alone. However, the effect may be too small to be clinically meaningful. Meaning The findings of this trial and process evaluation may inform and encourage further development of the selfBACK intervention to increase its effectiveness., Importance Lower back pain (LBP) is a prevalent and challenging condition in primary care. The effectiveness of an individually tailored self-management support tool delivered via a smartphone app has not been rigorously tested. Objective To investigate the effectiveness of selfBACK, an evidence-based, individually tailored self-management support system delivered through an app as an adjunct to usual care for adults with LBP-related disability. Design, Setting, and Participants This randomized clinical trial with an intention-to-treat data analysis enrolled eligible individuals who sought care for LBP in a primary care or an outpatient spine clinic in Denmark and Norway from March 8 to December 14, 2019. Participants were 18 years or older, had nonspecific LBP, scored 6 points or higher on the Roland-Morris Disability Questionnaire (RMDQ), and had a smartphone and access to email. Interventions The selfBACK app provided weekly recommendations for physical activity, strength and flexibility exercises, and daily educational messages. Self-management recommendations were tailored to participant characteristics and symptoms. Usual care included advice or treatment offered to participants by their clinician. Main Outcomes and Measures Primary outcome was the mean difference in RMDQ scores between the intervention group and control group at 3 months. Secondary outcomes included average and worst LBP intensity levels in the preceding week as measured on the numerical rating scale, ability to cope as assessed with the Pain Self-Efficacy Questionnaire, fear-avoidance belief as assessed by the Fear-Avoidance Beliefs Questionnaire, cognitive and emotional representations of illness as assessed by the Brief Illness Perception Questionnaire, health-related quality of life as assessed by the EuroQol-5 Dimension questionnaire, physical activity level as assessed by the Saltin-Grimby Physical Activity Level Scale, and overall improvement as assessed by the Global Perceived Effect scale. Outcomes were measured at baseline, 6 weeks, 3 months, 6 months, and 9 months. Results A total of 461 participants were included in the analysis; the population had a mean [SD] age of 47.5 [14.7] years and included 255 women (55%). Of these participants, 232 were randomized to the intervention group and 229 to the control group. By the 3-month follow-up, 399 participants (87%) had completed the trial. The adjusted mean difference in RMDQ score between the 2 groups at 3 months was 0.79 (95% CI, 0.06-1.51; P = .03), favoring the selfBACK intervention. The percentage of participants who reported a score improvement of at least 4 points on the RMDQ was 52% in the intervention group vs 39% in the control group (adjusted odds ratio, 1.76; 95% CI, 1.15-2.70; P = .01). Conclusions and Relevance Among adults who sought care for LBP in a primary care or an outpatient spine clinic, those who used the selfBACK system as an adjunct to usual care had reduced pain-related disability at 3 months. The improvement in pain-related disability was small and of uncertain clinical significance. Process evaluation may provide insights into refining the selfBACK app to increase its effectiveness. Trial Registration ClinicalTrials.gov Identifier: NCT03798288 more...

ObjectivesTo explore the prevalence of multimorbidity as well as individual and combinations of long-term conditions (LTCs) in people with type 2 diabetes (T2D) attending Australian general practice, using electronic health record (EHR) data. We also examine the association between multimorbidity condition count (total/concordant(T2D related)/discordant(unrelated)) and glycaemia (glycated haemoglobin, HbA1c).DesignCross-sectional study.SettingAustralian general practice.Participants69 718 people with T2D with a general practice encounter between 2013 and 2015 captured in the MedicineInsight database (EHR Data from 557 general practices and >3.8 million Australian patients).Primary and secondary outcome measuresPrevalence of multimorbidity, individual and combinations of LTCs. Multivariable linear regression models used to examine associations between multimorbidity counts and HbA1c (%).ResultsMean (SD) age 66.42 (12.70) years, 46.1% female and mean (SD) HbA1c 7.1 (1.4)%. More than 90% of participants with T2D were living with multimorbidity. Discordant conditions were more prevalent (83.4%) than concordant conditions (69.9 %). The three most prevalent discordant conditions were: painful conditions (55.4%), dyspepsia (31.6%) and depression (22.8%). The three most prevalent concordant conditions were hypertension (61.4%), coronary heart disease (17.1%) and chronic kidney disease (8.5%). The three most common combinations of conditions were: painful conditions and hypertension (38.8%), painful conditions and dyspepsia (23.1%) and hypertension and dyspepsia (22.7%). We found no associations between any multimorbidity counts (total, concordant and discordant) or combinations and HbA1c.ConclusionsMultimorbidity was common in our cohort of people with T2D attending Australian general practice, but was not associated with glycaemia. Although we did not explore mortality in this study, our results suggest that the increased mortality in those with multimorbidity and T2D observed in other studies may not be linked to glycaemia. Interestingly, discordant conditions were more prevalent than concordant conditions with painful conditions being the second most common comorbidity. Better understanding of the implications of different patterns of multimorbidity in people with T2D will allow more effective tailored care. more...

Background Frailty has been associated with worse prognosis following COVID-19 infection. While several studies have reported the association between frailty and COVID-19 mortality or length of hospital stay, there have been no community-based studies on the association between frailty and risk of severe infection. Considering that different definitions have been identified to assess frailty, this study aimed to compare the association between frailty and severe COVID-19 infection in UK Biobank using two frailty classifications: the frailty phenotype and the frailty index. Methods A total of 383,845 UK Biobank participants recruited 2006–2010 in England (211,310 [55.1%] women, baseline age 37–73 years) were included. COVID-19 test data were provided by Public Health England (available up to 28 June 2020). An adapted version of the frailty phenotype derived by Fried et al. was used to define frailty phenotype (robust, pre-frail, or frail). A previously validated frailty index was derived from 49 self-reported questionnaire items related to health, disease and disability, and mental wellbeing (robust, mild frailty, and moderate/severe frailty). Both classifications were derived from baseline data (2006–2010). Poisson regression models with robust standard errors were used to analyse the associations between both frailty classifications and severe COVID-19 infection (resulting in hospital admission or death), adjusted for sociodemographic and lifestyle factors. Results Of UK Biobank participants included, 802 were admitted to hospital with and/or died from COVID19 (323 deaths and 479 hospitalisations). After analyses were adjusted for sociodemographic and lifestyle factors, a higher risk of COVID-19 was observed for pre-frail (risk ratio (RR) 1.47 [95% CI 1.26; 1.71]) and frail (RR 2.66 [95% CI 2.04; 3.47]) individuals compared to those classified as robust using the frailty phenotype. Similar results were observed when the frailty index was used (RR mildly frail 1.46 [95% CI 1.26; 1.71] and RR moderate/severe frailty 2.43 [95% CI 1.91; 3.10]). Conclusions Frailty was associated with a higher risk of severe COVID-19 infection resulting in hospital admission or death, irrespective of how it was measured and independent of sociodemographic and lifestyle factors. Public health strategies need to consider the additional risk that COVID-19 poses in individuals with frailty, including which additional preventive measures might be required. more...

ObjectiveTo investigate how the type and number of long-term conditions (LTCs) impact on all-cause mortality and major adverse cardiovascular events (MACE) in people with rheumatoid arthritis (RA).DesignPopulation-based longitudinal cohort study.SettingUK Biobank.ParticipantsUK Biobank participants (n=502 533) aged between 37 and 73 years old.Primary outcome measuresPrimary outcome measures were risk of all-cause mortality and MACE.MethodsWe examined the relationship between LTC count and individual comorbid LTCs (n=42) on adverse clinical outcomes in participants with self-reported RA (n=5658). Risk of all-cause mortality and MACE were compared using Cox’s proportional hazard models adjusted for lifestyle factors (smoking, alcohol intake, physical activity), demographic factors (sex, age, socioeconomic status) and rheumatoid factor.Results75.7% of participants with RA had multimorbidity and these individuals were at increased risk of all-cause mortality and MACE. RA and >4 LTCs showed a threefold increased risk of all-cause mortality (HR 3.30, 95% CI 2.61 to 4.16), and MACE (HR 3.45, 95% CI 2.66 to 4.49) compared with those without LTCs. Of the comorbid LTCs studied, osteoporosis was most strongly associated with adverse outcomes in participants with RA compared with those without RA or LTCs: twofold increased risk of all-cause mortality (HR 2.20, 95% CI 1.55 to 3.12) and threefold increased risk of MACE (HR 3.17, 95% CI 2.27 to 4.64). These findings remained in a subset (n=3683) with RA diagnosis validated from clinical records or medication reports.ConclusionThose with RA and other LTCs, particularly comorbid osteoporosis, are at increased risk of adverse outcomes, although the role of corticosteroids could not be evaluated in this study. These results are clinically relevant for the monitoring and management of RA across the healthcare system, and future clinical guidelines for RA should acknowledge the importance of multimorbidity. more...

ObjectivesTo investigate severe COVID-19 risk by occupational group.MethodsBaseline UK Biobank data (2006–10) for England were linked to SARS-CoV-2 test results from Public Health England (16 March to 26 July 2020). Included participants were employed or self-employed at baseline, alive and aged ResultsOf 120 075 participants, 271 had severe COVID-19. Relative to non-essential workers, healthcare workers (RR 7.43, 95% CI 5.52 to 10.00), social and education workers (RR 1.84, 95% CI 1.21 to 2.82) and other essential workers (RR 1.60, 95% CI 1.05 to 2.45) had a higher risk of severe COVID-19. Using more detailed groupings, medical support staff (RR 8.70, 95% CI 4.87 to 15.55), social care (RR 2.46, 95% CI 1.47 to 4.14) and transport workers (RR 2.20, 95% CI 1.21 to 4.00) had the highest risk within the broader groups. Compared with white non-essential workers, non-white non-essential workers had a higher risk (RR 3.27, 95% CI 1.90 to 5.62) and non-white essential workers had the highest risk (RR 8.34, 95% CI 5.17 to 13.47). Using SOC 2000 major groups, associate professional and technical occupations, personal service occupations and plant and machine operatives had a higher risk, compared with managers and senior officials.ConclusionsEssential workers have a higher risk of severe COVID-19. These findings underscore the need for national and organisational policies and practices that protect and support workers with an elevated risk of severe COVID-19. more...

ObjectivesTo investigate severe COVID-19 risk by occupational group.MethodsBaseline UK Biobank data (2006-10) for England were linked to SARS-CoV-2 test results from Public Health England (16 March to 26 July 2020). Included participants were employed or self-employed at baseline, alive and aged less than 65 years in 2020. Poisson regression models adjusted sequentially for baseline demographic, socioeconomic, work-related, health, and lifestyle-related risk factors to assess risk ratios (RRs) for testing positive in hospital or death due to COVID-19 by three occupational classification schemes (including Standard Occupation Classification 2000).ResultsOf 120,075 participants, 271 had severe COVID-19. Relative to non-essential workers, healthcare workers (RR 7.43, 95% CI:5.52,10.00), social and education workers (RR 1.84, 95% CI:1.21,2.82) and other essential workers (RR=1.60, 95% CI:1.05,2.45) had higher risk of severe COVID-19. Using more detailed groupings, medical support staff (RR 8.70, 95% CI:4.87,15.55), social care (RR 2.46, 95% CI:1.47,4.14) and transport workers (RR= 2.20, 95% CI:1.21,4.00) had highest risk within the broader groups. Compared to white non-essential workers, non-white non-essential workers had a higher risk (RR 3.27, 95% CI: 1.90,5.62) and non-white essential workers had the highest risk (RR 8.34, 95% CI:5.17,13.47). Using SOC2000 major groups, associate professional and technical occupations, personal service occupations and plant and machine operatives had higher risk, compared to managers and senior officials.ConclusionsEssential workers have higher risk of severe COVID-19. These findings underscore the need for national and organizational policies and practices that protect and support workers with elevated risk of severe COVID-19.Trial registration-N/AWhat is already known on this topicEssential workers have a higher exposure to the SARS-CoV-2 virus due to the nature of their work.In comparison to non-essential workers, healthcare workers appear to have a higher risk of SARS-CoV-2 infection.What this study addsHealthcare workers had a more than seven-fold higher risk of severe COVID-19; those working in social care and transport occupations had a two-fold higher risk.Adjusting for potential confounding and mediating variables did not fully account for the differences in the observed risk amongst most occupational groups.Non-white essential workers had the highest risk of severe COVID-19 infection.How might this impact on policy or clinical practice in the foreseeable future?Our findings reinforce the need for adequate health and safety arrangements and provision of PPE, particularly in the health and social care sectors, and highlight the need for national and organizational policies and practices that protect and support workers with elevated risk of SARS-CoV-2 infection. more...

BackgroundUnderstanding of the role of ethnicity and socioeconomic position in the risk of developing SARS-CoV-2 infection is limited. We investigated this in the UK Biobank study.MethodsThe UK Biobank study recruited 40-70 year olds in 2006-2010 from the general population, collecting information about self-defined ethnicity and socioeconomic variables (including area-level socioeconomic deprivation and educational attainment). SARS-CoV-2 test results from Public Health England were linked to baseline UK Biobank data. Poisson regression with robust standard errors was used to assess risk ratios (RRs) between the exposures and dichotomous variables for: being tested, having a positive test and testing positive in hospital. We also investigated whether ethnicity and socioeconomic position were associated with having a positive test amongst those tested. We adjusted for covariates including age, sex, social variables (including healthcare work and household size), behavioural risk factors and baseline health.ResultsAmong 428,225 participants in England, 1,474 had been tested and 669 tested positive between 16 March and 13 April 2020. Black, south Asian and white Irish people were more likely to have confirmed infection (RR 4.01 (95%CI 2.92-5.12); RR 2.11 (95%CI 1.43-3.10); and RR 1.60 (95% CI 1.08-2.38) respectively) and were more likely to be hospital cases compared to the White British. While they were more likely to be tested, they were also more likely to test positive. Adjustment for baseline health and behavioural risk factors led to little change, with only modest attenuation when accounting for socioeconomic variables. Socioeconomic deprivation and having no qualifications were consistently associated with a higher risk of confirmed infection (RR 2.26 (95%CI 1.76-2.90); and RR 1.91 (95%CI 1.53-2.38) respectively).ConclusionsSome minority ethnic groups have a higher risk of confirmed SARS-CoV-2 infection in the UK Biobank study which was not accounted for by differences in socioeconomic conditions, measured baseline health or behavioural risk factors. An urgent response to addressing these elevated risks is required. more...

Background Multimorbidity, the presence of ≥ 2 long-term conditions (LTCs) is common in people with rheumatoid arthritis (RA). However, most research in RA has focused on cardiovascular disease and depression as co-occurring morbidities, rather than multiple LTCs or a wide range of conditions. This study hypothesised that risk of all-cause mortality and major adverse cardiac events (MACE) would be greater in those with RA and ≥2 LTCs than those with RA only. Further, we explored which individual LTCs were associated with increased risk of mortality and MACE. Methods Data from UK Biobank, a cohort of over 500,000 adults aged 37-73 years across England, Scotland and Wales was analysed. RA and 42 other LTCs of interest were self-reported by participants in a questionnaire and nurse-led interview. Information on sociodemographic (age, gender, socioeconomic status) and lifestyle factors (smoking status, BMI, alcohol frequency, physical activity) were also gathered. Rheumatoid factor levels were also determined. MACE and mortality were classified using linked hospitalisations and mortality register data (median follow up time 9 years). Data were analysed using age-adjusted Cox’s proportional hazard modelling to calculate risk of all-cause mortality or MACE, adjusted for variables listed above. Predictor variable: no RA no LTCs (reference group), only RA, RA + 1-3LTCs, RA + ≥4LTCs. Finally, the relationship between comorbidity with individual LTCs (of the 42 studied) and both health outcomes was considered. Results 5,658 (1.1%) of participants in UK Biobank self-reported RA (69.8% female, mean age 59 years). 74.7% of participants reported at least one LTC in addition to RA (1-3 LTCs 64.3%, ≥4 LTCs 10.4%), compared to 63.8% of participants without RA. 7.7% (N = 437) of participants with RA died and 5.9% (n = 331) had MACE events during the follow-up period. There was a dose response relationship in RA between LTC category and all-cause mortality and MACE risk. Only RA: mortality HR 1.42, 95% CI 1.08, 1.87, MACE HR 1.61 95% CI 1.20, 2.18; RA + 1-3LTCs: mortality HR 1.99 95% CI 1.74, 2.27, MACE HR 1.89, 95% CI 1.61, 2.20; RA + ≥4LTCs: mortality HR 3.34, 95% CI 2.64, 4.22; MACE HR 3.45, 95% CI 2.66, 4.49) compared to those with no RA no LTCs (results presented from fully adjusted models). Of the 42 individual LTCs considered, comorbid osteoporosis was the most concerning; participants with both RA and osteoporosis had a two-fold increased risk of all-cause mortality (HR 2.20, 95% CI 1.55, 3.12) and three-fold increased risk of MACE outcomes (HR 3.17, 95% CI 2.17, 4.64) compared to those with neither condition. Conclusion Participants with RA and multimorbidity or comorbidity, particularly osteoporosis, are at increased risk of adverse health outcomes. These results have important clinical relevance for the monitoring and optimal management of RA across the healthcare system. Disclosures B. Nicholl None. R. McQueenie None. B. Jani None. S. Macdonald None. C. McCowan None. J. Canning None. F. Mair None. S. Siebert None. more...

Background Multimorbidity is common in stroke, but the risk factors and effects on mortality remain poorly understood. Objective To examine multimorbidity and its associations with sociodemographic/lifestyle risk factors and all-cause mortality in UK Biobank participants with stroke or transient ischaemic attack (TIA). Design Data were obtained from an anonymized community cohort aged 40–72 years. Overall, 42 comorbidities were self-reported by those with stroke or TIA. Relative risk ratios demonstrated associations between participant characteristics and number of comorbidities. Hazard ratios demonstrated associations between the number and type of comorbidities and all-cause mortality. Results were adjusted for age, sex, socioeconomic status, smoking, and alcohol intake. Data were linked to national mortality data. Median follow-up was 7 years. Results Of 8,751 participants (mean age 60.9±6.7 years) with stroke or TIA, the all-cause mortality rate over 7 years was 8.4%. Over 85% reported ≥1 comorbidities. Age, socioeconomic deprivation, smoking and less frequent alcohol intake were associated with higher levels of multimorbidity. Increasing multimorbidity was associated with higher all-cause mortality. Mortality risk was double for those with ≥5 comorbidities compared to those with none. Having cancer, coronary heart disease, diabetes, or chronic obstructive pulmonary disease significantly increased mortality risk. Presence of any cardiometabolic comorbidity significantly increased mortality risk, as did any non-cardiometabolic comorbidity. Conclusions In stroke survivors, the number of comorbidities may be a more helpful predictor of mortality than type of condition. Stroke guidelines should take greater account of comorbidities, and interventions are needed that improve outcomes for people with multimorbidity and stroke. more...

PURPOSE Anticholinergic burden (ACB), the cumulative effect of anticholinergic medications, is associated with adverse outcomes in older people but is less studied in middle-aged populations. Numerous scales exist to quantify ACB. The aims of this study were to quantify ACB in a large cohort using the 10 most common anticholinergic scales, to assess the association of each scale with adverse outcomes, and to assess overlap in populations identified by each scale.\ud \ud METHODS We performed a longitudinal analysis of the UK Biobank community cohort (502,538 participants, baseline age: 37-73 years, median years of follow-up: 6.2). The ACB was calculated at baseline using 10 scales. Baseline data were linked to national mortality register records and hospital episode statistics. The primary outcome was a composite of all-cause mortality and major adverse cardiovascular event (MACE). Secondary outcomes were all-cause mortality, MACE, hospital admission for fall/fracture, and hospital admission with dementia/delirium. Cox proportional hazards models (hazard ratio [HR], 95% CI) quantified associations between ACB scales and outcomes adjusted for age, sex, socioeconomic status, body mass index, smoking status, alcohol use, physical activity, and morbidity count.\ud \ud RESULTS Anticholinergic medication use varied from 8% to 17.6% depending on the scale used. For the primary outcome, ACB was significantly associated with all-cause mortality/MACE for each scale. The Anticholinergic Drug Scale was most strongly associated with mortality/MACE (HR = 1.12; 95% CI, 1.11-1.14 per 1-point increase in score). The ACB was significantly associated with all secondary outcomes. The Anticholinergic Effect on Cognition scale was most strongly associated with dementia/delirium (HR = 1.45; 95% CI, 1.3-1.61 per 1-point increase).\ud \ud CONCLUSIONS The ACB was associated with adverse outcomes in a middle- to older-aged population. Populations identified and effect size differed between scales. Scale choice influenced the population identified as potentially requiring reduction in ACB in clinical practice or intervention trials. more...

Background Low back pain (LBP) is prevalent across all social classes, in all age groups, and across industrialized and developing countries. From a global perspective, LBP is considered the leading cause of disability and negatively impacts everyday life and well-being. Self-management is a recommended first-line treatment, and mobile apps are a promising platform to support self-management of conditions like LBP. In the selfBACK project, we have developed a digital decision support system made available for the user via an app intended to support tailored self-management of nonspecific LBP. Objective The trial aims to evaluate the effectiveness of using the selfBACK app to support self-management in addition to usual care (intervention group) versus usual care only (control group) in people with nonspecific LBP. Methods This is a single-blinded, randomized controlled trial (RCT) with two parallel arms. The selfBACK app provides tailored self-management plans consisting of advice on physical activity, physical exercises, and educational content. Tailoring of plans is achieved by using case-based reasoning (CBR) methodology, which is a branch of artificial intelligence. The core of the CBR methodology is to use data about the current case (participant) along with knowledge about previous and similar cases to tailor the self-management plan to the current case. This enables a person-centered intervention based on what has and has not been successful in previous cases. Participants in the RCT are people with LBP who consulted a health care professional in primary care within the preceding 8 weeks. Participants are randomized to using the selfBACK app in addition to usual care versus usual care only. We aim to include a total of 350 participants (175 participants in each arm). Outcomes are collected at baseline, 6 weeks, and 3, 6, and 9 months. The primary end point is difference in pain-related disability between the intervention group and the control group assessed by the Roland-Morris Disability Questionnaire at 3 months. Results The trial opened for recruitment in February 2019. Data collection is expected to be complete by fall 2020, and the results for the primary outcome are expected to be published in fall 2020. Conclusions This RCT will provide insights regarding the benefits of supporting tailored self-management of LBP through an app available at times convenient for the user. If successful, the intervention has the potential to become a model for the provision of tailored self-management support to people with nonspecific LBP and inform future interventions for other painful musculoskeletal conditions. Trial Registration ClinicalTrial.gov NCT03798288; https://clinicaltrials.gov/ct2/show/NCT03798288 International Registered Report Identifier (IRRID) DERR1-10.2196/14720 more...

BackgroundThis study investigated differences in cognitive performance between middle-aged adults with and without a lifetime history of mood disorder features, adjusting for a range of potential confounders.MethodsCross-sectional analysis of baseline data from the UK Biobank cohort. Adults aged 40–69 (n = 143,828) were assessed using measures of reasoning, reaction time and memory. Self-reported data on lifetime features of major depression and bipolar disorder were used to construct groups for comparison against controls. Regression models examined the association between mood disorder classification and cognitive performance, adjusting for sociodemographic, lifestyle and clinical confounders.ResultsInverse associations between lifetime history of bipolar or severe recurrent depression features and cognitive performance were attenuated or reversed after adjusting for confounders, including psychotropic medication use and current depressive symptoms. Participants with a lifetime history of single episode or moderate recurrent depression features outperformed controls to a small (but statistically significant) degree, independent of adjustment for confounders. There was a significant interaction between use of psychotropic medication and lifetime mood disorder features, with reduced cognitive performance observed in participants taking psychotropic medication.ConclusionsIn this general population sample of adults in middle age, lifetime features of recurrent depression or bipolar disorder were only associated with cognitive impairment within unadjusted analyses. These findings underscore the importance of adjusting for potential confounders when investigating mood disorder-related cognitive function. more...

Introduction: The emerging interest in multimorbidity (MM) in people with type 2 diabetes (T2D), which can be concordant (T2D-related) or discordant (unrelated), suggests the need to understand the burden of MM in T2D, and its association with all-cause mortality. We explored associations between MM conditions counts (total, concordant and discordant) and all-cause mortality in people with T2D in the UK Biobank. Methods: We examined data from a longitudinal cohort of 20,569 people with T2D in the UK Biobank recruited between 2006-2010. The number of MM conditions in addition to T2D was the primary independent variable based on self-report and hospital admissions data. All-cause mortality was the primary outcome. Multivariable Cox proportional hazard regression was used to examine associations between each of the MM counts and mortality. Results: A significant association between increasing MM and mortality was found. Compared to those with T2D with no additional chronic conditions, having 1, 2, 3 and 4+ conditions in addition to T2D, the HRs (95% CI) for all-cause mortality were 1.23 (0.90-1.68), 1.84 (1.36-2.49), 1.91 (1.40-2.60), and 3.13 (2.33-4.20), respectively. Both concordant and discordant conditions were significantly associated with mortality. For 1, 2, 3 and 4+ concordant conditions in addition to T2D, the HRs (95% CI) were 1.23 (1.04-1.48), 1.76 (1.46-2.13), 2.78 (2.22-3.48), and 4.25 (3.23-5.59), respectively and for discordant conditions 1.32 (1.13-1.55), 1.46 (1.23-1.74), 1.77 (1.45-2.17), and 2.44 (2.01-2.99), respectively. Conclusions: The association between MM and mortality is significant for total, concordant and discordant condition count, but was strongest for concordant. Our findings emphasize the need for clinical guidelines and future MM measures to consider MM in people with T2D, both concordant and discordant. Disclosure J.I. Chiang: None. P. Hanlon: None. B.D. Jani: None. J.E. Manski-Nankervis: Research Support; Self; Australian National Health and Medical Research Council, Boehringer Ingelheim International GmbH, Diabetes Australia, Eli Lilly and Company. Speaker's Bureau; Self; RACGP. J. Furler: Research Support; Self; Abbott, Sanofi. B.I. Nicholl: None. F.S. Mair: None. more...

Aims: \ud To explore associations between multimorbidity condition counts (total; concordant (diabetes-related); discordant (unrelated to diabetes)) and glycaemia (HbA1c; glycaemic variability (GV); time in range (TIR)) using data from a randomised controlled trial examining effectiveness of continuous glucose monitoring (CGM) in people with type 2 diabetes (T2D).\ud \ud Methods: \ud Cross-sectional study: 279 people with T2D using baseline data from the General Practice Optimising Structured MOnitoring To Improve Clinical outcomes (GP-OSMOTIC) trial from 25 general practices in Australia. Number of long-term conditions (LTCs) in addition to T2D used to quantify total/concordant/discordant multimorbidity counts. GV (measured by coefficient of variation (CV)) and TIR derived from CGM data. Multivariable linear regression models used to examine associations between multimorbidity counts, HbA1c (%), GV and TIR.\ud \ud Results: \ud Mean (SD) age of participants 60.4 (9.9) years; 40.9% female. Multimorbidity was present in 89.2% of participants. Most prevalent comorbid LTCs: hypertension (57.4%), painful conditions (29.8%), coronary heart disease (22.6%) and depression (19.0%). No evidence of associations between multimorbidity counts, HbA1c, GV and TIR.\ud \ud Conclusions: \ud While multimorbidity was common in this T2D cohort, it was not associated with HbA1c, CV or TIR. Future studies should explore factors other than glycaemia that contribute to the increased mortality observed in those with multimorbidity and T2D. more...

Background:\ud \ud Saudi Arabia is continuously working on developing its health care system, however with the high prevalence of type 2 diabetes and comorbidities, such as cardiovascular diseases, self-management education programmes are essential. As part of a planned series of studies to develop a culturally sensitive type 2 diabetes self-management programme, this study explores the need versus barriers and facilitators relevant to implementing a national programme for type 2 diabetes self-management education within the community and health care system in Saudi Arabia.\ud \ud Methods:\ud \ud A qualitative methodology was used to explore the views of a multidisciplinary group of diabetes health professionals and adult patients with type 2 diabetes. The views of nine health professionals working at a specialised diabetes care centre were gathered at two focus groups (four and five) that included doctors, nutritionists, health educators and nurses. Individual interviews with 12 patients with type 2 diabetes (six females and six males) attending the centre were also carried out. Recurring themes through the translated transcripts were studied and treated by the research group under pre-set protocols.\ud \ud Results:\ud \ud Focus groups with health professionals revealed three main themes. 1. Resources: availability of resources and how they impacted on performance and patients’ care; 2.Familiarity with self-management education programmes: educating patients and raising awareness among them; and 3. Lifestyle: patients’ lifestyle and how it could affect their compliance with self-management programmes. Interviews with patients also revealed three main themes. 1. Habits: post diagnosis changes in patients’ attitudes and behaviours towards diet and physical activity; 2. Health education: awareness of managing type 2 diabetes through health centre advice or self-education; and 3. Culture and society: a lack of cultural or social support created by some social practices or conventions.\ud \ud Conclusion:\ud \ud The findings from this study highlight a gap in type 2 diabetes care system that can be breached through the development of a Saudi specific self-management programme for type 2 diabetes. The identified barriers and facilitators can be used for adapting a self-management programme to the Saudi context. However, initial training is needed for local health professionals to understand the mechanisms of self-management programmes. Such programmes will need to infiltrate to the society, and the patients’ families, in particular to tackle the rising prevalence of type 2 diabetes in Saudi Arabia and provide a friendlier, more supportive environment for the current patients to self-manage their diabetes. more...

Background:Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterised by inflammation of the synovial joints causing pain, swelling and stiffness. Multimorbidity (the presence of two or more long-term conditions) affects approximately two thirds of people with RA. However, the relationship between RA and multimorbidity is poorly understand, as is the effect of this relationship on mortality and other health-related outcomes, particularly those relating to physical functioning and well-being.Objectives:To explore existing literature to determine what is known about the effect, if any, of multimorbidity on mortality and other health-related outcomes in people with RA.Methods:A systematic review was conducted following a protocol prepared using PRISMA-P 2015 reporting guidelines, ensuring the quality of the review. Studies were sourced from electronic medical databases, specifically MEDLINE, Embase, CINAHL, PsycINFO, The Cochrane Library and Scopus, using a pre-defined search strategy. Studies were selected based on specified eligibility criteria and quality appraised using the Cochrane Prognosis Methods Group-developed, Quality in Prognostic Studies (QUIPS) tool. A narrative synthesis of findings was conducted.Results:In total, 15 studies fulfilled our criteria for inclusion in our review. Of these, 7 studies had mortality as an outcome, with 6 reporting a significant association between multimorbidity and increased risk of all-cause mortality in people with RA. Nine studies had functional status/disability as an outcome, with 2 of these studies also including quality of life. All 9 studies reported significant associations between multimorbidity and the aforementioned health-related outcomes, demonstrating poorer functional status/increased disability and reduced quality of life in people with RA and multimorbidity.Conclusion:Multimorbidity in people with RA is significantly associated with increased mortality and poor health-related outcomes in current literature. A better understanding of this relationship will provide an important foundation of knowledge to guide future health service design.Acknowledgments:This work was supported by the Medical Research Council (MRC) [Grant Reference: MR/N013166/1].Disclosure of Interests:Jordan Canning: None declared, Stefan Siebert Grant/research support from: BMS, Boehringer Ingelheim, Celgene, GlaxoSmithKline, Janssen, Novartis, Pfizer, UCB, Consultant of: AbbVie, Boehringer Ingelheim, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Celgene, Janssen, Novartis, Bhautesh Jani: None declared, Frances Mair: None declared, Barbara Nicholl: None declared more...

IntroductionType 2 diabetes (T2D) is a major health priority worldwide and the majority of people with diabetes live with multimorbidity (MM) (the co-occurrence of ≥2 chronic conditions). The aim of this systematic review was to explore the association between MM and all-cause mortality and glycaemic outcomes in people with T2D.MethodsThe search strategy centred on: T2D, MM, comorbidity, mortality and glycaemia. Databases searched: MEDLINE, EMBASE, CINAHL Complete, The Cochrane Library, and SCOPUS. Restrictions included: English language, quantitative empirical studies. Two reviewers independently carried out: abstract and full text screening, data extraction, and quality appraisal. Disagreements adjudicated by a third reviewer.ResultsOf the 4882 papers identified; 41 met inclusion criteria. The outcome was all-cause mortality in 16 studies, glycaemia in 24 studies and both outcomes in one study. There were 28 longitudinal cohort studies and 13 cross-sectional studies, with the number of participants ranging from 96-892,223. Included studies were conducted in high or upper-middle-income countries. Fifteen of 17 studies showed a statistically significant association between increasing MM and higher mortality. Ten of 14 studies showed no significant associations between MM and HbA1c. Four of 14 studies found higher levels of MM associated with higher HbA1c. Increasing MM was significantly associated with hypoglycaemia in 9/10 studies. There was no significant association between MM and fasting glucose (one study). No studies explored effects on glycaemic variability.ConclusionsThis review demonstrates that MM in T2D is associated with higher mortality and hypoglycaemia, whilst evidence regarding the association with other measures of glycaemic control is mixed. The current single disease focused approach to management of T2D seems inappropriate. Our findings highlight the need for clinical guidelines to support a holistic approach to the complex care needs of those with T2D and MM, accounting for the various conditions that people with T2D may be living with.Systematic review registrationInternational Prospective Register of Systematic Reviews CRD42017079500. more...

Introduction Type 2 diabetes (T2D) is a leading health priority worldwide. Multimorbidity (MM) is a term describing the co-occurrence of two or more chronic diseases or conditions. The majority of people living with T2D have MM. The relationship between MM and mortality and glycaemia in people with T2D is not clear. Methods and analysis Medline, Embase, Cumulative Index of Nursing and Allied Health Complete, The Cochrane Library, and SCOPUS will be searched with a prespecified search strategy. The searches will be limited to quantitative empirical studies in English with no restriction on publication date. One reviewer will perform title screening and two review authors will independently screen the abstract and full texts using Covidence software, with disagreements adjudicated by a third reviewer. Data will be extracted using a using a Population, Exposure, Comparator and Outcomes framework. Two reviewers will independently extract data and undertake the risk of bias (quality) assessment. Disagreements will be resolved by consensus. A narrative synthesis of the results will be conducted and meta-analysis considered if appropriate. Quality appraisal will be undertaken using the Newcastle-Ottawa quality assessment scale and the quality of the cumulative evidence of the included studies will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. This protocol was prepared in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines to ensure the quality of our review. Ethics and dissemination This review will synthesise the existing evidence about the impact of MM on mortality and glycaemic outcomes in people living with T2D and increase our understanding of this subject and will inform future practice and policy. Findings will be disseminated via conference presentations, social media and peer-reviewed publication. PROSPERO registration number CRD42017079500. more...

ObjectiveThis study aims: (1) to describe the pattern and extent of multimorbidity and polypharmacy in UK Biobank participants with chronic obstructive pulmonary disease (COPD) and (2) to identify which comorbidities are associated with increased risk of adverse drug reactions (ADRs) resulting from polypharmacy.DesignCross-sectional.SettingCommunity cohort.ParticipantsUK Biobank participants comparing self-reported COPD (n=8317) with no COPD (n=494 323).OutcomesMultimorbidity (≥4 conditions) and polypharmacy (≥5 medications) in participants with COPD versus those without. Risk of ADRs (taking ≥3 medications associated with falls, constipation, urinary retention, central nervous system (CNS) depression, bleeding or renal injury) in relation to the presence of COPD and individual comorbidities.ResultsMultimorbidity was more common in participants with COPD than those without (17% vs 4%). Polypharmacy was highly prevalent (52% with COPD taking ≥5 medications vs 18% in those without COPD). Adjusting for age, sex and socioeconomic status, those with COPD were significantly more likely than those without to be prescribed ≥3 medications contributing to falls (OR 2.27, 95% CI 2.13 to 2.42), constipation (OR 3.42, 95% CI 3.10 to 3.77), urinary retention (OR 3.38, 95% CI 2.94 to 3.87), CNS depression (OR 3.75, 95% CI 3.31 to 4.25), bleeding (OR 4.61, 95% CI 3.35 to 6.19) and renal injury (OR 2.22, 95% CI 1.86 to 2.62). Concomitant cardiovascular disease was associated with the greatest risk of taking ≥3 medications associated with falls/renal injury. Concomitant mental health conditions were most strongly associated with medications linked with CNS depression/urinary retention/bleeding.ConclusionsMultimorbidity is common in COPD and associated with high levels of polypharmacy. Co-prescription of drugs with various ADRs is common. Future research should examine the effects on healthcare outcomes of co-prescribing multiple drugs with similar potential ADRs. Clinical guidelines should emphasise assessment of multimorbidity and ADR risk. more...

Background - Combinations of unhealthy lifestyle factors can interact synergistically to increase associated mortality. While combinations of 'traditional' risk factors such as smoking and alcohol consumption are well described, the mortality associated with combinations that incorporate a wider range of 'emerging' lifestyle factors' (e.g. television viewing time) is not. The influence of socioeconomic deprivation on wider lifestyle risks also remains unclear. We aimed to examine whether deprivation modifies the association between an 'extended' lifestyle score and adverse health outcomes. Methods - Analyses performed using 328,594 adult participants' data from UK Biobank. Cox-proportional hazard models were used to examine how the association between an extended lifestyle score (incorporating sleep, TV viewing, smoking, alcohol, diet and physical activity) and health outcomes (all-cause mortality and cardiovascular disease (CVD) mortality and incidence) is modified by deprivation. Findings - There was a significant interaction (p more...

Aims:\ud \ud This study aimed to systematically review intervention studies on self-management of type 2 diabetes in Gulf Cooperation Council (GCC) countries to determine the most effective self-management strategies for individuals with type 2 diabetes in this region.\ud Methods:\ud \ud A search strategy was developed using multiple databases: Medline and Embase (via Ovid), CINAHL (via EBSCO), and PubMed. Study and intervention characteristics, intervention structure, content, cultural adaptation, and outcomes were extracted from the included studies. To be included in the review the studies should have met the following criteria: have examined the effectiveness of at least one intervention involving a type 2 DSME programme, have involved participants over 18 years old diagnosed with type 2 diabetes, have taken place to in a GCC country, have a study design that was observational, quasi-experimental or controlled, have reported at least one individual and have a quantitative outcome. A narrative data synthesis was used to describe the studies and comment on their methodological quality.\ud Results:\ud \ud Of the 737 retrieved papers, only eight met the inclusion criteria. Only one study was a randomised controlled trial. A statistically significant improvement in HbA1c was reported in five of the eight studies. There was a significant improvement in physical activity levels as reported in four of the eight studies. Only three studies referred to aspects of cultural design or adaptation of the intervention implemented.\ud Conclusions:\ud \ud Self-management interventions may have a positive impact on HbA1 levels in patients with type 2 diabetes in the GCC area. A greater emphasis placed on culturally appropriate self-management programmes may improve the effectiveness of self-management interventions for adults with type 2 diabetes in the GCC. more...

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterised by articular inflammation and systemic complications. Multimorbidity (the presence of two or more long-term health conditions) is highly prevalent in people with RA but the effect of multimorbidity on mortality and other health-related outcomes is poorly understood. Objective: To determine what is known about the effect, if any, of multimorbidity on mortality and health-related outcomes in individuals with RA. Design: Systematic review of the literature. The following electronic medical databases will be searched: MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, The Cochrane Library and Scopus. Included studies will be quality appraised using the Quality in Prognostic Studies tool developed by the Cochrane Prognosis Methods Group. A narrative synthesis of findings will be undertaken and meta-analyses considered, if appropriate. This protocol adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols 2015 guidelines, ensuring the quality of the review. Conclusions: Understanding the influence of multimorbidity on mortality and other health-related outcomes in RA will provide an important basis of knowledge with the potential to improve future clinical management of RA. PROSPERO registration number: CRD42019137756. more...

Background Symptomatic osteoarthritis poses a major challenge to primary health care but no studies have related accessing primary care ("detection"), receiving recommended treatments ("treatment"), and achieving adequate control ("control").\ud \ud Objective To provide estimates of detection, treatment, and control within a single population adapting the approach used to determine a Rule of Halves for other long-term conditions.\ud \ud Setting General population.\ud \ud Participants 400 adults aged 50+ years with prevalent symptomatic knee osteoarthritis.\ud \ud Design Prospective cohort with baseline questionnaire, clinical assessment, and plain radiographs, and questionnaire follow-up at 18 and 36 months and linkage to primary care medical records.\ud \ud Outcome measures "Detection" was defined as at least one musculoskeletal knee-related GP consultation between baseline and 36 months. "Treatment" was self-reported use of at least one recommended treatment or physiotherapy/hospital specialist referral for their knee problem at all three measurement points. Pain was "controlled" if characteristic pain intensity \ud \ud Results In 221 cases (55.3%; 95%CI: 50.4, 60.1) there was evidence that the current problem had been detected in general practice. Of those detected, 164 (74.2% (68.4, 80.0)) were receiving one or more of the recommended treatments at all three measurement points. Of those detected and treated, 45 (27.4% (20.5, 34.3)) had symptoms under control on at least two occasions. Using narrower definitions resulted in substantially lower estimates.\ud \ud Conclusion Osteoarthritis care does not conform to a Rule of Halves. Symptom control is low among those accessing health care and receiving treatment. more...

Background Despite being a highly prevalent chronic condition managed predominantly in primary care and unlike other chronic conditions, osteoarthritis (OA) care is delivered on an ad hoc basis rather than through routine structured review. Evidence suggests current levels of OA care are suboptimal, but little is known about what general practitioners’ (GPs) consider important in OA care, and, thus, the scope to improve inconsistency or poor practice is, at present, limited. Objectives We investigated GPs’ views on and practice of monitoring OA. Methods This was a cross-sectional postal survey of 2500 practicing UK GPs randomly selected from the Binley's database. Respondents were asked if monitoring OA patients was important and how monitoring should be undertaken. Results Responses were received from 768 GPs of whom 70.8% were male and 89.5% were principals within their practices. Despite 55.4% (n = 405) indicating monitoring patients with OA was important and 78.3% (n = 596) considering GPs the appropriate professionals to monitor OA, only 15.2% (n = 114) did so routinely, and 45% (n= 337) did not monitor any OA patients at all. In total, 61.4% (n = 463) reported that patients should self-monitor. Respondents favored monitoring physical function, pain, and analgesia use over monitoring measures of BMI, self management plans, and exercise advice. Conclusions The majority of respondents felt that monitoring OA was important, but this was not reflected in their reported current practice. Much of what they favored for monitoring was in line with published guidance, suggesting provision of suboptimal care does not result from lack of knowledge and interventions to improve OA care must address barriers to GPs engaging in optimal care provision. more...

Background: Low back pain (LBP) is a common cause of disability and is ranked as the most burdensome health condition globally. Self-management, including components on increased knowledge, monitoring of symptoms, and physical activity, are consistently recommended in clinical guidelines as cost-effective strategies for LBP management and there is increasing interest in the potential role of digital health. Objective: The study aimed to synthesize and critically appraise published evidence concerning the use of interactive digital interventions to support self-management of LBP. The following specific questions were examined: (1) What are the key components of digital self-management interventions for LBP, including theoretical underpinnings? (2) What outcome measures have been used in randomized trials of digital self-management interventions in LBP and what effect, if any, did the intervention have on these? and (3) What specific characteristics or components, if any, of interventions appear to be associated with beneficial outcomes? Methods: Bibliographic databases searched from 2000 to March 2016 included Medline, Embase, CINAHL, PsycINFO, Cochrane Library, DoPHER and TRoPHI, Social Science Citation Index, and Science Citation Index. Reference and citation searching was also undertaken. Search strategy combined the following concepts: (1) back pain, (2) digital intervention, and (3) self-management. Only randomized controlled trial (RCT) protocols or completed RCTs involving adults with LBP published in peer-reviewed journals were included. Two reviewers independently screened titles and abstracts, full-text articles, extracted data, and assessed risk of bias using Cochrane risk of bias tool. An independent third reviewer adjudicated on disagreements. Data were synthesized narratively. Results: Of the total 7014 references identified, 11 were included, describing 9 studies: 6 completed RCTs and 3 protocols for future RCTs. The completed RCTs included a total of 2706 participants (range of 114-1343 participants per study) and varied considerably in the nature and delivery of the interventions, the duration/definition of LBP, the outcomes measured, and the effectiveness of the interventions. Participants were generally white, middle aged, and in 5 of 6 RCT reports, the majority were female and most reported educational level as time at college or higher. Only one study reported between-group differences in favor of the digital intervention. There was considerable variation in the extent of reporting the characteristics, components, and theories underpinning each intervention. None of the studies showed evidence of harm. Conclusions: The literature is extremely heterogeneous, making it difficult to understand what might work best, for whom, and in what circumstances. Participants were predominantly female, white, well educated, and middle aged, and thus the wider applicability of digital self-management interventions remains uncertain. No information on cost-effectiveness was reported. The evidence base for interactive digital interventions to support patient self-management of LBP remains weak. [J Med Internet Res 2017;19(5):e179] more...

In a Norwegian prospective population-based cohort study, we examined whether the number of chronic musculoskeletal pain sites changed over an 11-year period, and if the number of pain sites at follow-up was associated with health-related and lifestyle factors at baseline. The study included data on 78,973 adults participating in the Nord-Trondelag Health Study (HUNT) in 1995 to 1997 (HUNT2) and 2006 to 2008 (HUNT3). On the basis of 3 categories of baseline pain sites, associations between baseline health-related, lifestyle, and demographic factors and number of pain sites at follow-up were analyzed with linear regression models adjusted for age, sex, marital status, physical activity, education, and other chronic diseases. We also estimated within-subject associations. Regardless of pain extent at baseline, anxiety and/or depression, sleeping problems, smoking, and obesity were positively associated with number of pain sites at follow-up, whereas education and physical activity were inversely associated with number of pain sites. The within-subject analyses showed largely similar associations for the health-related factors, whereas associations of lifestyle factors were attenuated. The mean number of pain sites remained unchanged between the 2 surveys. Overall, our study revealed prospective associations between several factors and pain sites 11 years later, regardless of the number of pain sites at baseline. Perspective This prospective study examined the association between development of pain and risk factors in the general population, on the basis of 3 categories of baseline pain sites. It also examined how these factors influence possible long-term changes in pain within individuals. We showed that having no or few baseline pain sites may not differ in its risk factors compared with having multiple pain sites. This article provides an important contribution to the ongoing debate regarding the association between lifestyle, demographic, and psychosocial risk factors, versus the course of multisite chronic pain. Additionally, we provide discussion on potential directions for clinical relevance and further research. more...

To determine the relationship between physically traumatic events and the onset of chronic widespread pain (CWP).This was a case-control study nested within a large prospective cohort. CWP was determined, by questionnaire, as per the American College of Rheumatology fibromyalgia classification criteria. Data were also collected on psychological health, health behavior, and sleep problems. Participants without CWP were then followed up at 4 years, and (new-onset) CWP was determined in the same manner. At followup, participants were also asked to report whether they had experienced any of a series of physically traumatic events between baseline and followup.A total of 2,069 individuals (46.6%) participated at followup, and 241 of these individuals (11.6%) reported CWP. More than one-third of the study population reported at least 1 physically traumatic event; although these individuals were more likely to develop CWP, this relationship was completely attenuated after adjustment for confounding (odds ratio 1.01, 95% confidence interval 0.73-1.40). However, there was some evidence to suggest that involvement in a road traffic accident, specifically, may confer an increase in the risk of CWP onset.This study provides support for the "at risk" phenotype hypothesis, where individuals characterized by poorer health and psychological variables may be predisposed to develop CWP following a traumatic trigger. However, although this has been seen with road traffic accidents, it is not the case with other events. Future research should examine what is peculiar about an accident, or about one's reaction to it, that confers this increase in the risk of CWP onset. more...

This study tested the hypothesis that chronic widespread pain (CWP) would predict low levels of physical activity (PA). Pain status and PA levels were ascertained at baseline and 32 months in community subjects. Three PA questions were used: “in comparison with others your own age, is your PA “the same” (referent), “more-much more” or “less-much less””, and “during the past month on average how many days/week have you taken exercise that has (i) lasted at least 20 min? and (ii) made you sweat?: “4–7” (referent), “1–3” or “none””. Multinomial logistic regression models quantified the relationship between baseline CWP and PA at follow-up (relative risk ratios (RRR) (95% confidence intervals)). Two thousands one hundred and eighty-two subjects participated and provided complete pain and PA information at both timepoints. CWP was reported by 18% (n = 429) of participants at baseline. Compared to subjects who were free of CWP at baseline, those with CWP had an increased odds of reporting “less-much less” PA at follow-up (RRR = 4.5 (3.2–6.2)). This relationship remained after adjustment for confounders (RRR = 1.9 (1.3–2.9)). A similar association was observed with exercise that lasted at least 20 min (RRR = 1.9 (1.3–2.8)). The current study suggests that low self-reported levels of physical activity are a consequence of having CWP. more...

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. more...

ObjectivesTo determine if genetic variation in genes in the hypothalamic–pituitary–adrenal (HPA) axis, the primary stress response system, influences susceptibility to developing musculoskeletal pain.MethodsPain and comorbidity data was collected at three time points in a prospective population-based cohort study. Pairwise tagging single nucleotide polymorphisms (SNPs) were selected and genotyped for seven genes. Genetic association analysis was carried out using zero-inflated negative binomial regression to test for association between SNPs and the maximum number of pain sites across the three time points in participants reporting pain, reported as proportional changes with 95% CIs. SNPs were also tested for association with chronic widespread pain (CWP) using logistic regression reporting odds ratios and 95% CI.ResultsA total of 75 SNPs were successfully genotyped in 994 participants including 164 cases with persistent CWP and 172 pain-free controls. Multiple SNPs in SERPINA6 were associated with the maximum number of pain sites; for example, each copy of the T allele of rs941601 was associated with having 16% (proportional change=1.16, 95% CI 1.04 to 1.28, p=0.006) more pain sites compared to participants with the CC genotype. SERPINA6 gene SNPs were also associated with CWP. Significant associations between the maximum number of pain sites and SNPs in the CRHBP and POMC genes were also observed and a SNP in MC2R was also associated with CWP. Associations between SNPs and comorbidity of poor sleep quality and depression explained some of the associations observed.ConclusionsGenetic variation in HPA axis genes was associated with musculoskeletal pain; however, some of the associations were explained by comorbidities. Replication of these findings is required in independent cohorts. more...

Chronic widespread pain (CWP) is associated with poor health-related quality of life (HRQoL). It is unclear whether pain itself is the cause of poor HRQoL or other factors play a role. We hypothesised that new onset of CWP was associated with poor physical and mental HRQoL but that psychosocial risk markers for CWP onset would explain this relationship. A prospective population-based survey measured pain and psychosocial status at baseline. Subjects free of CWP at baseline were followed up 15 months later, when pain status, threatening life events and HRQoL (SF-12) were assessed. The risk associated with the new onset of CWP and reporting poor SF12-MCS and SF12-PCS was quantified using multinomial logistic regression (relative risk ratios (RRRs) with 95% confidence intervals (95% CI)), adjusted for age and gender. 3000 subjects (77%) free of CWP at baseline participated at follow-up. 2650 subjects (88%) provided full SF-12 and pain data and formed the cohort for this analysis. 9.4% of subjects (n = 248) reported new CWP. New CWP was associated with an increased risk of having the poorest SF12-MCS (RRR = 2.3; 95% CI 1.6–3.2) and SF12-PCS (RRR = 8.0; 95% CI 5.4–11.8) scores. After adjusting for baseline psychosocial status, the relationship between CWP onset and SF12-MCS was attenuated (RRR = 1.2; 95% CI 0.8–1.8), although the association with SF12-PCS remained (RRR = 4.8% CI 3.1–7.47). New onset of CWP is associated with poor mental and physical HRQoL. However, the relationship with mental HRQoL is explained by psychosocial risk markers. more...

Genetic risk factors for pain sensitivity may also play a role in susceptibility to chronic pain disorders, in which subjects have low pain thresholds. The aim of this study was to determine if proposed functional single nucleotide polymorphisms (SNPs) in the GTP cyclohydrolase (GCH1) and μ opioid receptor (OPRM1) genes previously associated with pain sensitivity affect susceptibility to chronic widespread pain (CWP). Pain data was collected using body manikins via questionnaire at three time-points over a four year period from subjects aged 25-65 in the North-West of England as part of a population based cohort study, EPIFUND. CWP was defined at each time point using standard criteria. Three SNPs forming a proposed "pain-protective" haplotype in GCH1 (rs10483639, rs3783641 and rs8007267) and two SNPs in OPRM1 (rs1777971 (A118G) and rs563649) were genotyped in cases with persistent CWP (CWP present at ≥2 time-points) and controls who were pain-free at all time-points. The expectation-maximisation algorithm was used to estimate haplotype frequencies. The frequency of the "pain-protective" (CAT - C allele of rs10483639, A allele of rs3783641 and T allele of rs8007267) haplotype was compared to the frequency of the other haplotypes between cases and controls using the χ2 test. Allele frequencies and carriage of the minor allele was compared between cases and controls using χ2 tests for the OPRM1 SNPs. The frequency of the proposed GCH1 "pain-protective" haplotype (CAT) did not significantly differ between cases and controls and no significant associations were observed between the OPRM1 SNPs and CWP. In conclusion, there was no evidence of association between proposed functional SNPs, previously reported to influence pain sensitivity, in GCH1 and OPRM1 with CWP. Further evidence of null association in large independent cohorts is required to truly exclude these SNPs as genetic risk factors for CWP. more...

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) ¼ 1.7, 95% CI 1.2, 2.5; absence of early wakening, OR ¼ 1.6, 95% CI 1.1, 2.4; and restorative sleep, OR ¼ 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 ¼ 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. more...

Depression is one of the major global health challenges and a leading contributor of health related disability and costs. Depression is a heterogeneous disorder and current methods for assessing its severity in clinical practice rely on symptom count, however this approach is unreliable and inconsistent. The clinical evaluation of depressive symptoms is particularly challenging in primary care, where the majority of patients with depression are managed, due to the presence of co-morbidities. Current methods for risk assessment of depression do not accurately predict treatment response or clinical outcomes. Several biological pathways have been implicated in the pathophysiology of depression; however, accurate and predictive biomarkers remain elusive. We conducted a systematic review of the published evidence supporting the use of peripheral biomarkers to predict outcomes in depression, using Medline and Embase. Peripheral biomarkers in depression were found to be statistically significant predictors of mental health outcomes such as treatment response, poor outcome and symptom remission; and physical health outcomes such as increased incidence of cardiovascular events and deaths, and all-cause mortality. However, the available evidence has multiple methodological limitations which must be overcome to make any real clinical progress. Despite extensive research on the relationship of depression with peripheral biomarkers, its translational application in practice remains uncertain. In future, peripheral biomarkers identified with novel techniques and combining multiple biomarkers may have a potential role in depression risk assessment but further research is needed in this area. more...

Background Chronic pain has a strong association with major depressive disorder (MDD), but there is a relative paucity of studies on the association between chronic multisite pain and bipolar disorder (BD). Such studies are required to help elucidate the complex biological and psychological overlap between pain and mood disorders. The aim of this study is to investigate the relationship between chronic multisite pain and mood disorder across the unipolar-bipolar spectrum. Methods We conducted a cross-sectional study of 149,611 UK Biobank participants. Self-reported depressive and bipolar features were used to categorise participants into MDD and BD groups and a non-mood disordered comparison group. Multinomial logistic regression was used to establish whether there was an association between extent of chronic pain (independent variable) and mood disorder category (dependent variable), using no pain as the referent category, and adjusting for a wide range of potential sociodemographic, lifestyle and comorbidity confounders. Results Multisite pain was significantly more prevalent in participants with BD and MDD, for example, 4–7 pain sites: BD 5.8%, MDD 4.5%, and comparison group 1.8% (p more...

BackgroundThe relative contribution of demographic, lifestyle and medication factors to the association between affective disorders and cardiometabolic diseases is poorly understood.AimsTo assess the relationship between cardiometabolic disease and features of depresion and bipolar disorder within a large population sample.MethodCross-sectional study of 145 991 UK Biobank participants: multivariate analyses of associations between features of depression or bipolar disorder and five cardiometabolic outcomes, adjusting for confounding factors.ResultsThere were significant associations between mood disorder features and ‘any cardiovascular disease’ (depression odds ratio (OR) = 1.15, 95% CI 1.12–1.19; bipolar OR = 1.28, 95% CI 1.14–1.43) and with hypertension (depression OR = 1.15, 95% CI 1.13–1.18; bipolar OR = 1.26, 95% CI 1.12–1.42). Individuals with features of mood disorder taking psychotropic medication were significantly more likely than controls not on psychotropics to report myocardial infarction (depression OR = 1.47, 95% CI 1.24–1.73; bipolar OR = 2.23, 95% CI 1.53–3.57) and stroke (depression OR = 2.46, 95% CI 2.10–2.80; bipolar OR = 2.31, 95% CI 1.39–3.85).ConclusionsAssociations between features of depression or bipolar disorder and cardiovascular disease outcomes were statistically independent of demographic, lifestyle and medication confounders. Psychotropic medication may also be a risk factor for cardiometabolic disease in individuals without a clear history of mood disorder. more...

Objectives UK Biobank is a landmark cohort of over 500,000 participants which will be used to investigate genetic and non-genetic risk factors for a wide range of adverse health outcomes. This is the first study to systematically assess the prevalence and validity of proposed criteria for probable mood disorders within the cohort (major depression and bipolar disorder).\ud \ud Methods This was a descriptive epidemiological study of 172,751 individuals assessed for a lifetime history of mood disorder in relation to a range of demographic, social, lifestyle, personality and health-related factors. The main outcomes were prevalence of a probable lifetime (single) episode of major depression, probable recurrent major depressive disorder (moderate), probable recurrent major depressive disorder (severe), probable bipolar disorder and no history of mood disorder (comparison group). Outcomes were compared on age, gender, ethnicity, socioeconomic status, educational attainment, functioning, self-reported health status, current depressive symptoms, neuroticism score, smoking status and alcohol use.\ud \ud Results Prevalence rates for probable single lifetime episode of major depression (6.4%), probable recurrent major depression (moderate) (12.2%), probable recurrent major depression (severe) (7.2%) and probable bipolar disorder (1.3%) were comparable to those found in other population studies. The proposed diagnostic criteria have promising validity, with a gradient in evidence from no mood disorder through major depression and probable bipolar disorder in terms of gender distribution, socioeconomic status, self-reported health rating, current depressive symptoms and smoking.\ud \ud Significance The validity of our proposed criteria for probable major depression and probable bipolar disorder within this cohort are supported by these cross-sectional analyses. Our findings are likely to prove useful as a framework for a wide range of future genetic and non-genetic studies. more...

Objective. The aim of the current study was to investigate whether genetic variation in genes across the serotoninergic system is associated with chronic widespread pain (CWP) and the number of pain sites reported. Methods. A discovery cohort, with pain data at 3 time points, was used to investigate genetic associations with 2 phenotypes: 1) CWP (at >= 2 time points; n = 164) compared with pain-free controls (at 3 time points; n = 172), and 2) the maximum number of pain sites reported at any 1 of the 3 time points (range of sites 0-29; n = 989). A cohort of 2,285 men for whom a DNA sample and pain data were available (including 203 CWP cases and 929 controls) was used for validation. Pairwise tagging (r(2) > 0.8) single-nucleotide polymorphisms (SNPs) were genotyped. Logistic and zero-inflated negative binomial regression analyses were used to test for SNP associations with CWP and the number of pain sites, respectively. Results. SNPs in HTR2A were associated with both pain phenotypes in the discovery cohort, and a number of these SNP associations were replicated in the validation cohort, some of which were attenuated after adjustment for depression. There was an increased likelihood of having CWP in subjects with 1 or 2 copies of the T allele of rs12584920 (odds ratio [OR] 1.64, 95% confidence interval [95% CI] 1.01-2.60 [P = 0.03] in the discovery cohort, and OR 1.46, 95% CI 1.07-2.00 [P = 0.018] in the validation cohort). A similar association was observed between rs17289394 and the maximum number of pain sites reported in both cohorts. Results from a meta-analysis of the data from the 2 cohorts further strengthened these findings. Conclusion. The findings of this study support the role of HTR2A in the genetic predisposition to musculoskeletal pain. (Less) more...

ObjectivesThe aim of this study was to investigate the association between the catechol-O-methyltransferase (COMT) ‘pain sensitivity’ haplotypes and chronic widespread pain (CWP) in two distinct cohorts.MethodsCases of CWP and controls free of pain were selected from two population-based studies: the Epidemiology of Functional Disorders study (EPIFUND) (UK) and the European Male Ageing Study (European). The number of cases and controls were 164 and 172, and 204 and 935, respectively. Identical American College of Rheumatology criteria were used in both studies to ascertain CWP status. The EPIFUND study had three time points and cases were classified as subjects with CWP at two or three time points and controls as those free of pain at all three time points. Four single nucleotide polymorphisms (SNP): rs6269, rs4633, rs4818 and rs4680 (V158M) were genotyped using Sequenom technology. Allele and genotype frequencies were compared and haplotype analysis was conducted using PLINK software.ResultsNo differences in allele or genotype frequencies for any of the four SNP were observed between cases and controls for either cohort. Haplotype analysis also showed no difference in the frequency of haplotypes between cases and controls.ConclusionsThere was no evidence of association between the COMT ‘pain sensitivity’ haplotypes and CWP in two population-based cohorts. more...

Objective. To determine whether the report of pain is influenced by meteorological conditions. Methods. A population-based study (Epidemiology of Functional Disorders) was conducted in North West England. Subjects were mailed a questionnaire that enquired about pain on the day of completion ('any pain') and chronic widespread pain (CWP) as defined by the ACR, as well as about the potential mediating factors, sleep quality, exercise and mood, between the weather and pain. Hourly information on sunshine, precipitation, air temperature and pressure was available from a local weather station. Analysis of relationships was done by Cox regression and described as prevalence ratios (PRs) with 95% CIs. Results. Between January 2005 and December 2006, questionnaires from 2491 subjects were returned: 42% of the subjects reported 'any pain' on the day of completion, whereas 15% of the subjects had CWP. For both 'any pain' and CWP, the PR was the highest in winter (46.1 and 22.2%, respectively) followed by autumn (45.4 and 17.9%, respectively) and spring (41.9 and 14.7%, respectively) and lowest in summer (35.6 and 9.5%, respectively). Persons were less likely to report pain on days with >5.8 h of sunshine (any pain: PR = 0.87, 95% CI 0.82, 0.93; CWP: PR = 0.56; 95% CI 0.38, 0.84) and with average temperature of >17.5 degrees C (any pain: PR = 0.74, 95% CI 0.66, 0.83; CWP: PR = 0.40; 95% CI 0.34, 0.48). These relationships were partly explained by persons reporting taking more exercise and having better sleep quality and a more positive mood on days with sunshine and higher temperatures. Conclusions. Although a strong relationship between lack of sunshine, lower temperatures and pain reporting has been demonstrated, pain is not an inevitable consequence of such climatic conditions. more...