Severe mental illness, race/ethnicity, multimorbidity and mortality following COVID-19 infection: nationally representative cohort study.

BACKGROUND: The association of COVID-19 with death in people with severe mental illness (SMI), and associations with multimorbidity and ethnicity, are unclear. AIMS: To determine all-cause mortality in people with SMI following COVID-19 infection, and assess whether excess mortality is affected by multimorbidity or ethnicity. METHOD: This was a retrospective cohort study using primary care data from the Clinical Practice Research Database, from February 2020 to April 2021. Cox proportional hazards regression was used to estimate the effect of SMI on all-cause mortality during the first two waves of the COVID-19 pandemic. RESULTS: Among 7146 people with SMI (56% female), there was a higher prevalence of multimorbidity compared with the non-SMI control group (n = 653 024, 55% female). Following COVID-19 infection, the SMI group experienced a greater risk of death compared with controls (adjusted hazard ratio (aHR) 1.53, 95% CI 1.39-1.68). Black Caribbean/Black African people were more likely to die from COVID-19 compared with White people (aHR = 1.22, 95% CI 1.12-1.34), with similar associations in the SMI group and non-SMI group (P for interaction = 0.73). Following infection with COVID-19, for every additional multimorbidity condition, the aHR for death was 1.06 (95% CI 1.01-1.10) in the SMI stratum and 1.16 (95% CI 1.15-1.17) in the non-SMI stratum (P for interaction = 0.001). CONCLUSIONS: Following COVID-19 infection, patients with SMI were at an elevated risk of death, further magnified by multimorbidity. Black Caribbean/Black African people had a higher risk of death from COVID-19 than White people, and this inequity was similar for the SMI group and the control group.

Ethnic differences in physical and mental multimorbidity in working age adults with a history of depression and/or anxiety.

BACKGROUND: The current study used data from an ethnically diverse population from South London to examine ethnic differences in physical and mental multimorbidity among working age (18-64 years) adults in the context of depression and anxiety. METHOD: The study included 44 506 patients who had previously attended Improving Access to Psychological Therapies services in the London Borough of Lambeth. Multinomial logistic regression examined cross-sectional associations between ethnicity with physical and mental multimorbidity. Patterns of multimorbidity were identified using hierarchical cluster analysis. RESULTS: Within 44 056 working age adults with a history of depression or anxiety from South London there were notable ethnic differences in physical multimorbidity. Adults of Black Caribbean ethnicity were more likely to have physical multimorbidity [adjusted relative risk ratio (aRRR) = 1.25, 95% confidence interval (CI) 1.15-1.36] compared to adults of White ethnicity. Relative to adults of White ethnicity, adults of Asian ethnicity were more likely to have physical multimorbidity at higher thresholds only (e.g. 4 + conditions; aRRR = 1.53, 95% CI 1.17-2.00). Three physical (atopic, cardiometabolic, mixed) and three mental (alcohol/substance use, common/severe mental illnesses, personality disorder) multimorbidity clusters emerged. Ethnic minority groups with multimorbidity had a higher probability of belonging to the cardiometabolic cluster. CONCLUSION: In an ethnically diverse population with a history of common mental health disorders, we found substantial between- and within-ethnicity variation in rates of physical, but not mental, multimorbidity. The findings emphasised the value of more granular definitions of ethnicity when examining the burden of physical and mental multimorbidity.

The relationship between air pollution and multimorbidity: Can two birds be killed with the same stone?

Air pollution and multimorbidity are two of the most important challenges for Public Health worldwide. Although there is a large body of evidence linking air pollution with the development of different single chronic conditions, the evidence about the relationship between air pollution and multimorbidity (the co-occurrence of multiple long-term conditions) is sparse. To obtain evidence about this relationship could be challenging and different aspects should be considered, such as its multifaceted and complex nature, the specific pollutants and their potential influence on health, their levels of exposure over time, or the data that could be used for its study. This evidence could be instrumental to inform the development of new recommendations and measures to reduce harmful levels of air pollutants, as means to prevent the development of multimorbidity and reduce its burden.

Physical multimorbidity, depressive symptoms, and social participation in adults over 50 years of age: findings from the English Longitudinal Study of Ageing.

OBJECTIVES: The aim of the current study was to identify specific patterns of physical multimorbidity and examine how these patterns associated with changes in social participation over time. METHODS: We used latent class analysis to identify clusters of physical multimorbidity in 11,391 older adults. Mixed effects regression models were used to assess associations between physical multimorbidity clusters and changes in social participation over 15 years. RESULTS: Four clusters of physical multimorbidity were identified. All physical multimorbidity clusters were associated with a reduction in cultural engagement (e.g. visits to theatre, cinema, museums) over time, with the strongest association seen in the complex/multisystem cluster (ß = -0.26, 95% CI = -0.38 to -0.15). Similar results emerged for leisure activities. Adjusting for depressive symptoms fully attenuated some associations. All physical multimorbidity clusters were associated with an increase in civic participation over time. CONCLUSIONS: Physical multimorbidity reduced some aspects of social participation over time, with specific combinations of conditions having increased risk of reductions.Supplemental data for this article is available online at http://dx.doi.org/10.1080/13607863.2021.2017847.

Multimorbidity and fit note receipt in working-age adults with long-term health conditions.

BACKGROUND: Research on sickness absence has typically focussed on single diagnoses, despite increasing recognition that long-term health conditions are highly multimorbid and clusters comprising coexisting mental and physical conditions are associated with poorer clinical and functional outcomes. The digitisation of sickness certification in the UK offers an opportunity to address sickness absence in a large primary care population. METHODS: Lambeth Datanet is a primary care database which collects individual-level data on general practitioner consultations, prescriptions, Quality and Outcomes Framework diagnostic data, sickness certification (fit note receipt) and demographic information (including age, gender, self-identified ethnicity, and truncated postcode). We analysed 326 415 people's records covering a 40-month period from January 2014 to April 2017. RESULTS: We found significant variation in multimorbidity by demographic variables, most notably by self-defined ethnicity. Multimorbid health conditions were associated with increased fit note receipt. Comorbid depression had the largest impact on first fit note receipt, more than any other comorbid diagnoses. Highest rates of first fit note receipt after adjustment for demographics were for comorbid epilepsy and rheumatoid arthritis (HR 4.69; 95% CI 1.73-12.68), followed by epilepsy and depression (HR 4.19; 95% CI 3.60-4.87), chronic pain and depression (HR 4.14; 95% CI 3.69-4.65), cardiac condition and depression (HR 4.08; 95% CI 3.36-4.95). CONCLUSIONS: Our results show striking variation in multimorbid conditions by gender, deprivation and ethnicity, and highlight the importance of multimorbidity, in particular comorbid depression, as a leading cause of disability among working-age adults.

How do ethnicity and deprivation impact on life expectancy at birth in people with serious mental illness? Observational study in the UK.

BACKGROUND: Across international contexts, people with serious mental illnesses (SMI) experience marked reductions in life expectancy at birth. The intersection of ethnicity and social deprivation on life expectancy in SMI is unclear. The aim of this study was to assess the impact of ethnicity and area-level deprivation on life expectancy at birth in SMI, defined as schizophrenia-spectrum disorders, bipolar disorders and depression, using data from London, UK. METHODS: Abridged life tables to calculate life expectancy at birth, in a cohort with clinician-ascribed ICD-10 schizophrenia-spectrum disorders, bipolar disorders or depression, managed in secondary mental healthcare. Life expectancy in the study population with SMI was compared with life expectancy in the general population and with those residing in the most deprived areas in England. RESULTS: Irrespective of ethnicity, people with SMI experienced marked reductions in life expectancy at birth compared with the general population; from 14.5 years loss in men with schizophrenia-spectrum and bipolar disorders, to 13.2 years in women. Similar reductions were noted for people with depression. Across all diagnoses, life expectancy at birth in people with SMI was lower than the general population residing in the most deprived areas in England. CONCLUSIONS: Irrespective of ethnicity, reductions in life expectancy at birth among people with SMI are worse than the general population residing in the most deprived areas in England. This trend in people with SMI is similar to groups who experience extreme social exclusion and marginalisation. Evidence-based interventions to tackle this mortality gap need to take this into account.

The association between colorectal cancer and prior antibiotic prescriptions: case control study.

BACKGROUND: Antibiotic use over several decades is believed to be associated with colorectal adenomas. There is little evidence, however, for the effect of more recent antibiotic use on frequency of colorectal cancers. METHODS: A case control study used the RCGP's Research and Surveillance Centre cohort of patients drawn from NHS England. In all, 35,214 patients with a new diagnosis of colorectal cancer between 1 January 2008 and 31 December 2018 were identified in the database and were matched with 60,348 controls. Conditional logistic regression was used to examine the association between antibiotic prescriptions and colorectal cancer. RESULTS: A dose-response association between colorectal cancers and prior antibiotic prescriptions was observed. The risk was related to the number and recency of prescriptions with a high number of antibiotic prescriptions over a long period carrying the highest risk. For example, patients prescribed antibiotics in up to 15 years preceding diagnosis were associated with a higher risk of colorectal cancer (odds ratio (OR) = 1.90, 95% confidence intervals (CI), 1.61-2.19, p < 0.001). CONCLUSIONS: Antibiotic use over previous years is associated with subsequent colorectal cancer. While the study design cannot determine causality, the findings suggest another reason for caution in prescribing antibiotics, especially in high volumes and over many years.

Influence of prior antibiotic use on risk of rheumatoid arthritis: case control study in general practice.

OBJECTIVES: To test the hypothesis that prior antibiotics influences the risk of developing RA. METHODS: A case-control study was conducted over 15 years using the UK's Royal College of General Practitioners Research and Surveillance Centre database. The frequency and type of antibiotic prescription for patients who subsequently developed RA were compared with antibiotic prescriptions in a control group of patients who remained free of RA. Cases, defined as patients with a new diagnosis of RA made between 2006 and 2018, were matched with up to four RA-free controls on practice, age, gender and date of diagnosis. Exposure was measured by the number and type of prescriptions for antibiotics prior to the RA diagnosis or to the index date in controls. RESULTS: A total of 8482 patients with a new diagnosis of RA between 2006 and 2018 were compared with 22 661 controls. There was a higher likelihood of an RA diagnosis after antibiotic prescriptions within 1 year, 5 years and ever with a strong dose-response. Patients receiving >10 antibiotics in a 5 year period were more than twice as likely to receive an RA diagnosis as controls [adjusted odds ratio 2.65 (CI 2.40, 2.93)]. CONCLUSION: Exposure to antibiotics prior to the diagnosis was a significant risk factor for RA. This could reflect an immunological response to a compromised microbiome. Alternatively, patients with pre-symptomatic or early undiagnosed RA may have been more likely to present to their general practitioner with infections due to an unrecognized effect of RA.

Systolic Blood Pressure Trajectory, Frailty, and All-Cause Mortality >80 Years of Age: Cohort Study Using Electronic Health Records.

BACKGROUND: Clinical trials show benefit from lowering systolic blood pressure (SBP) in people ≥80 years of age, but nonrandomized epidemiological studies suggest lower SBP may be associated with higher mortality. This study aimed to evaluate associations of SBP with all-cause mortality by frailty category >80 years of age and to evaluate SBP trajectories before death. METHODS: A population-based cohort study was conducted using electronic health records of 144 403 participants ≥80 years of age registered with family practices in the United Kingdom from 2001 to 2014. Participants were followed for ≤5 years. Clinical records of SBP were analyzed. Frailty status was classified using the e-Frailty Index into the categories of fit, mild, moderate, and severe. All-cause mortality was evaluated by frailty status and mean SBP in Cox proportional-hazards models. SBP trajectories were evaluated using person months as observations, with mean SBP and antihypertensive treatment status estimated for each person month. Fractional polynomial models were used to estimate SBP trajectories over 5 years before death. RESULTS: During follow-up, 51 808 deaths occurred. Mortality rates increased with frailty level and were greatest at SBP <110 mm Hg. In fit women, mortality was 7.7 per 100 person years at SBP 120 to 139 mm Hg, 15.2 at SBP 110 to 119 mm Hg, and 22.7 at SBP <110 mm Hg. For women with severe frailty, rates were 16.8, 25.2, and 39.6, respectively. SBP trajectories showed an accelerated decline in the last 2 years of life. The relative odds of SBP <120 mm Hg were higher in the last 3 months of life than 5 years previously in both treated (odds ratio, 6.06; 95% confidence interval, 5.40-6.81) and untreated (odds ratio, 6.31; 95% confidence interval, 5.30-7.52) patients. There was no evidence of intensification of antihypertensive therapy in the final 2 years of life. CONCLUSIONS: A terminal decline of SBP in the final 2 years of life suggests that nonrandomized epidemiological associations of low SBP with higher mortality may be accounted for by reverse causation if participants with lower blood pressure values are closer, on average, to the end of life.

Association between prior antibiotic therapy and subsequent risk of community-acquired infections: a systematic review.

Background: Antibiotic use can have negative unintended consequences including disruption of the human microbiota, which is thought to protect against pathogen overgrowth. We conducted a systematic review to assess whether there is an association between exposure to antibiotics and subsequent risk of community-acquired infections. Methods: We searched MEDLINE, EMBASE and Web of Science for studies published before 30 June 2017, examining the association between antibiotic use and subsequent community-acquired infection. Infections caused by Clostridium difficile and fungal organisms were excluded. Studies focusing exclusively on resistant organism infections were also excluded. Results: Eighteen of 22588 retrieved studies met the inclusion criteria. From these, 16 studies reported a statistically significant association between antibiotic exposure and subsequent risk of community-acquired infection. Infections associated with prior antibiotic use included Campylobacter jejuni infection (one study), recurrent furunculosis (one study), invasive Haemophilus influenzae type b infection (one study), infectious mastitis (one study), meningitis (one study), invasive pneumococcal disease (one study), Staphylococcus aureus skin infection (one study), typhoid fever (two studies), recurrent boils and abscesses (one study), upper respiratory tract infection and urinary tract infection (one study) and Salmonella infection (five studies), although in three studies on Salmonella infection the effect was of marginal statistical significance. Conclusions: We found an association between prior antibiotic use and subsequent risk of a diverse range of community-acquired infections. Gastrointestinal and skin and soft tissue infections were most frequently found to be associated with prior antibiotic exposure. Our findings support the hypothesis that antibiotic use may predispose to future infection risk, including infections caused by both antibiotic-resistant and non-resistant organisms.

Chronic inflammatory disorders and risk of type 2 diabetes mellitus, coronary heart disease, and stroke: a population-based cohort study.

BACKGROUND: This study sought to evaluate whether risks of diabetes mellitus and cardiovascular disease are elevated across a range of organ-specific and multisystem chronic inflammatory disorders. METHODS AND RESULTS: A matched cohort study was implemented in the UK Clinical Practice Research Datalink including participants with severe psoriasis (5648), mild psoriasis (85 232), bullous skin diseases (4284), ulcerative colitis (12 203), Crohn's disease (7628), inflammatory arthritis (27 358), systemic autoimmune disorders (7472), and systemic vasculitis (6283) and in 373 851 matched controls. The main outcome measures were new diagnoses of type 2 diabetes mellitus, stroke, or coronary heart disease. The outcomes were evaluated for each condition in a multiple outcomes model, with adjustment for conventional cardiovascular risk factors. Estimates for different inflammatory conditions were pooled in a random-effects meta-analysis. There were 4695 new diagnoses of type 2 diabetes mellitus, 3266 of coronary heart disease, and 1715 of stroke. The hazard ratio for pooled multiple failure estimate was 1.20 (95% confidence interval [CI], 1.15-1.26). The highest relative hazards were observed in systemic autoimmune disorders (1.32; 95% CI, 1.16-1.50) and systemic vasculitis (1.29; 95% CI, 1.16-1.44). Hazards were increased in organ-specific disorders, including severe psoriasis (1.29; 95% CI, 1.12-1.47) and ulcerative colitis (1.26; 95% CI, 1.14-1.40). Participants in the highest tertile of C-reactive protein had greater risk of multiple outcomes (1.52; 95% CI, 1.37-1.68). CONCLUSIONS: The risk of cardiovascular diseases and type 2 diabetes mellitus is increased across a range of organ-specific and multisystem chronic inflammatory disorders with evidence that risk is associated with severity of inflammation. Clinical management of patients with chronic inflammatory disorders should seek to reduce cardiovascular risk.

Incidence and mortality of relapsing polychondritis in the UK: a population-based cohort study.

OBJECTIVE: Relapsing polychondritis is a rare disease characterized by cartilage inflammation. Our aim was to estimate the incidence, prevalence and mortality of relapsing polychondritis and describe the clinical features of relapsing polychondritis in a large population. METHODS: All participants diagnosed with relapsing polychondritis were sampled from the Clinical Practice Research Datalink. Prevalence and incidence rates for 1990-2012 were estimated. Relative mortality rates were estimated in a time-to-event framework using reference UK life tables. A questionnaire validation study assessed diagnostic accuracy. RESULTS: There were 117 participants with relapsing polychondritis ever recorded. Fifty (82%) of 61 cases were validated by a physician and unconfirmed cases were excluded. The analysis included 106 participants (42 men, 64 women) diagnosed with relapsing polychondritis. The mean age (range) at diagnosis in men was 55 (range 17-81) years and in women 51 (range 11-79) years. The median interval from first symptom to diagnosis was 1.9 years. The incidence of relapsing polychondritis between 1990 and 2012 was 0.71 (95% CI 0.55, 0.91) per million population per year. There were 19 deaths from any cause. There were 16 observed deaths eligible for survival analysis and 7.4 deaths expected for the UK population of the same age, sex and period. The standardized mortality ratio was 2.16 (95% CI 1.24, 3.51), P < 0.01. Respiratory disease, cardiac conditions and cancer were the most frequent causes of death. CONCLUSION: The incidence of relapsing polychondritis may be lower than previously estimated, and diagnostic misclassification and delay are common. Mortality in relapsing polychondritis is more than twice that of the general population.

Estimating the yield of NHS Health Checks in England: a population-based cohort study.

BACKGROUND: This study aimed to evaluate the yield of the NHS Health Checks programme. METHODS: A cohort study, conducted in the Clinical Practice Research Datalink in England. Electronic health records were analysed for patients aged 40-74 receiving an NHS Health Check between 2010 and 2013. RESULTS: There were 65 324 men and 75 032 women receiving a health check. For every 1000 men assessed, there were 205 smokers (95% confidence interval 195-215), 355 (340-369) with hypertension (≥140/90 mmHg) and 633 (607-658) with elevated cholesterol (≥5 mmol/l). Among 1000 women, there were 161 (151-171) smokers, 247 (238-257) with hypertension and 668 (646-689) with elevated cholesterol. In the 12 months following the check, statins were prescribed to 18% of men and 21% of women with ≥20% cardiovascular risk and antihypertensive drugs to 11% of men and 16% of women with ≥20% cardiovascular risk. Slight reductions in risk factor values were observed in the minority of participants with follow-up values recorded in the 15 months following the check. CONCLUSIONS: A universal primary prevention programme identifies substantial risk factor burden in a population without known cardiovascular disease. Research is needed to monitor interventions, and intermediate- and long-term outcomes, in those identified at high risk.

Point-of-care cluster randomized trial in stroke secondary prevention using electronic health records.

BACKGROUND AND PURPOSE: The aim of this study was to evaluate whether the remote introduction of electronic decision support tools into family practices improves risk factor control after first stroke. This study also aimed to develop methods to implement cluster randomized trials in stroke using electronic health records. METHODS: Family practices were recruited from the UK Clinical Practice Research Datalink and allocated to intervention and control trial arms by minimization. Remotely installed, electronic decision support tools promoted intensified secondary prevention for 12 months with last measure of systolic blood pressure as the primary outcome. Outcome data from electronic health records were analyzed using marginal models. RESULTS: There were 106 Clinical Practice Research Datalink family practices allocated (intervention, 53; control, 53), with 11 391 (control, 5516; intervention, 5875) participants with acute stroke ever diagnosed. Participants at trial practices had similar characteristics as 47,887 patients with stroke at nontrial practices. During the intervention period, blood pressure values were recorded in the electronic health records for 90% and cholesterol values for 84% of participants. After intervention, the latest mean systolic blood pressure was 131.7 (SD, 16.8) mm Hg in the control trial arm and 131.4 (16.7) mm Hg in the intervention trial arm, and adjusted mean difference was -0.56 mm Hg (95% confidence interval, -1.38 to 0.26; P=0.183). The financial cost of the trial was approximately US $22 per participant, or US $2400 per family practice allocated. CONCLUSIONS: Large pragmatic intervention studies may be implemented at low cost by using electronic health records. The intervention used in this trial was not found to be effective, and further research is needed to develop more effective intervention strategies. CLINICAL TRIAL REGISTRATION URL: http://www.controlled-trials.com. Current Controlled Trials identifier: ISRCTN35701810.

Electronic health records for intervention research: a cluster randomized trial to reduce antibiotic prescribing in primary care (eCRT study).

PURPOSE: This study aimed to implement a point-of-care cluster randomized trial using electronic health records. We evaluated the effectiveness of electronically delivered decision support tools at reducing antibiotic prescribing for respiratory tract infections in primary care. METHODS: Family practices from England and Scotland participating in the Clinical Practice Research Datalink (CPRD) were included in the trial; 53 family practices were allocated to intervention and 51 practices were allocated to usual care. Patients aged 18 to 59 years consulting for respiratory tract infections were eligible. The intervention was through remotely installed, computer-delivered decision support tools accessed during the consultations. Control practices provided usual care. The primary outcome was the proportion of consultations for respiratory tract infections with an antibiotic prescribed based on electronic health records. Family practice-specific proportions were included in a cluster-level analysis. RESULTS: Data were analyzed for 603,409 patients: 317,717 at intervention practices and 285,692 at control practices. Use of the intervention was less than anticipated, varying among practices. There was a reduction in proportion of consultations with antibiotics prescribed of 1.85% (95% CI, 0.10%-3.59%, P=.038) and in the rate of antibiotic prescribing for respiratory tract infections (9.69%; 95% CI, 0.75%-18.63%, fewer prescriptions per 1,000 patient-years, P=.034). There were no adverse events. CONCLUSIONS: Cluster randomized trials may be implemented efficiently in large samples from routine care settings by using primary care electronic health records. Future studies should develop and test multicomponent methods for remotely delivered intervention.

Is sodium valproate, an HDAC inhibitor, associated with reduced risk of stroke and myocardial infarction? A nested case-control study.

BACKGROUND: This study aimed to evaluate whether treatment with sodium valproate (SV) was associated with reduced risk of stroke or myocardial infarction (MI). METHODS: Electronic health records data were extracted from Clinical Practice Research Database for participants ever diagnosed with epilepsy and prescribed antiepileptic drugs. A nested case-control study was implemented with cases diagnosed with incident non-haemorrhagic stroke and controls matched for sex, year of birth, and study start date (ratio of 1:6). A second nested study was implemented with MI as outcome. The main exposure variable was SV therapy assessed as: ever prescribed, pre-stroke year treatment, number of SV prescriptions, and cumulative time on SV drug therapy. Odds ratios were estimated using conditional logistic regression. RESULTS: Data were analysed for 2002 stroke cases and 13,098 controls. MI analyses included 1153 cases and 7109 controls. Pre-year stroke SV treatment (28%) was associated with increased stroke risk (odds ratio 1.22, 95% confidence interval (CI): 1.09 to 1.38, p < 0.001). No association was observed between ever being prescribed SV with ischemic stroke (OR = 1.01, 95% CI: 0.91 to 1.12, p = 0.875). A significant association was observed between ever being prescribed SV with MI (OR = 0.78, 95% CI: 0.67 to 0.90, p < 0.001). Patients in the highest quarter of SV treatment duration had lower odds of ischemic stroke (OR = 0.57, 95% CI: 0.44 to 0.72, p < 0.001) and MI (OR = 0.29, 95% CI: 0.20 to 0.44, p < 0.001). CONCLUSION: Sodium valproate exposure was associated with the risk of MI, but not ischemic stroke. However, longer exposure to SV was associated with lower odds of stroke, but this might be explained by survivor bias.

Process evaluation of a point-of-care cluster randomised trial using a computer-delivered intervention to reduce antibiotic prescribing in primary care.

BACKGROUND: The study aimed to conduct a process evaluation for a cluster randomised trial of a computer-delivered, point-of-care intervention to reduce antibiotic prescribing in primary care. The study aimed to evaluate both the intervention and implementation of the trial. METHODS: The intervention comprised a set of electronic educational and decision support tools that were remotely installed and activated during consultations with patients with acute respiratory infections over a 12 month intervention period. A mixed method evaluation was conducted with 103 general practitioners (GPs) who participated in the trial. Semi-structured telephone interviews were conducted with 20 GPs who had been in the intervention group of the trial and 4 members of the implementation staff. Questionnaires, consisting of both intervention evaluation and theory-based measures, were self-administered to 83 GPs (56 control group and 27 intervention group). RESULTS: Interviews suggested that a key factor influencing GPs' use of the intervention appeared to be their awareness of the implementation of the system into their practice. GPs who were aware of the implementation of the intervention reported feeling confident in using it if they chose to and understood the purpose of the intervention screens. However, GPs who were unaware that the intervention would be appearing often reported feeling confused when they saw the messages appear on the screen and not fully understanding what they were for or how they could be used. Intervention evaluation questionnaires indicated that GPs were satisfied with the usability of the prompts, and theory-based measures revealed that intervention group GPs reported higher levels of self-efficacy in managing RTI patients according to recommended guidelines compared to GPs in the control group. CONCLUSIONS: Remote installation of a computer-delivered intervention for use at the point-of-care was feasible and acceptable. Additional measures to promote awareness of the intervention may be required to promote health care professionals' utilisation of the intervention and these might sometimes compromise the pragmatic intention of a trial. TRIAL REGISTRATION: ISRCTN47558792 (registered on 17 March 2010).

Risk of fibromyalgia following antibiotic prescriptions: A population-based case-control study.

BACKGROUND: The health of the gut microbiome is now recognized to be an important component of the gut-brain axis which itself appears to be implicated in pain perception. Antibiotics are known to create dysbiosis in the microbiome, so whether fibromyalgia is more commonly diagnosed after antibiotic prescriptions provides a means of exploring the role of the microbiome in the experience of chronic pain. METHODS: A case-control study was carried out using electronic health records collected in the UK's Clinical Practice Research Datalink (CPRD), a comprehensive database of primary care consultations. For each case of diagnosed fibromyalgia, three controls were identified and matched by age, gender and GP practice. The exposure variable was the number and timing of antibiotic prescriptions over previous years. The analysis involved adjusting for a wide range of co-variates that might be possible confounders. RESULTS: A total of 44,674 cases of fibromyalgia were identified together with 133,513 controls. After adjusting for co-variates, it was found that both the total number of prescriptions and their timing was associated with an FM diagnosis. For example, the quartile with the highest number of prescriptions and that with the longest exposure had a greater than three-fold increase in FM diagnoses (number of prescriptions: odds ratio 3.92; 95% CIs: 3.71-4.13; exposure odds ratio 3.28; CIs: 3.13-3.43). Some antibiotics (such as tetracyclines and metronidazole) seemed to confer greater risk than others. CONCLUSIONS: The results lend support for prior antibiotics being an important risk factor for a diagnosis of FM. SIGNIFICANCE: This study shows an association between the volume as well as timing of prior antibiotic prescriptions and of a subsequent diagnosis of fibromyalgia in primary care.