Abstract Background Behavioral therapies are effective in the management of irritable bowel syndrome (IBS). Mahana™ IBS is a mobile phone application designed to deliver 10 sessions (10-12 weeks) of gut-directed cognitive behavioral therapy (CBT) to adults with IBS. Objectives To evaluate patient compliance with the Mahana™ mobile phone CBT application and the change in gastrointestinal and psychological symptoms in a real-world UK setting. Methods This single-center prospective study recruited adults with Rome IV IBS from a tertiary care outpatient setting. At baseline and 12-week follow-up, patients completed questionnaires assessing gastrointestinal symptoms (IBS symptom severity scale [IBS-SSS]), depression (patient health questionnaire-9 [PHQ-9]), and anxiety (generalized anxiety disorder-7 [GAD-7]). Results Thirty patients (20/30 female, mean [SD] age 44.57 [14.70]) consented to treatment and completed pre-intervention questionnaires, among whom 20 (66.7%) provided follow-up questionnaire data. Among the 20 individuals with two-point data, there was a statistically significant reduction in the IBS-SSS (P<0.001), GAD-7 (P=0.02), and PHQ-9 (P=0.04) scores. Fourteen (70%) patients reported a clinically significant improvement (≥50 point reduction) in the IBS-SSS; these individuals tended to be older (P=0.04) and male (P=0.04). Patients with IBS-diarrhea reported the greatest improvement in the IBS-SSS versus those with IBS-constipation and IBS-mixed subtypes. The baseline IBS-SSS (P=0.35), GAD-7 (P=0.19) and PHQ-9 (P=0.19) scores were not significantly different between persons who completed the entire CBT intervention versus those who did not. Conclusion This study provides preliminary evidence that the Mahana™ IBS CBT application is associated with a statistically significant improvement in gastrointestinal and psychological symptoms in a real-world UK clinical setting. Trial registration This trial was registered on ClinicalTrials.gov (trial registration number: NCT07008404) on 6 June 2025

BACKGROUND:Inflammatory bowel disease (IBD) and colorectal cancer (CRC) share overlapping symptoms. Faecal immunochemical testing (FIT) is mandated in UK primary care to triage symptomatic patients suspected of having CRC, but the extent to which IBD is identified in these patients remains unclear. The aim of this study was to assess the 1-year IBD diagnosis rate in symptomatic patients after FIT for suspected CRC and how this varies with age, FIT level, and faecal calprotectin (FCP) result. METHODS:A population-based cohort study of symptomatic patients who underwent FIT in the UK Clinical Practice Research Datalink (CPRD) (January 2019-June 2023) with 1-year follow-up was conducted. Kaplan-Meier estimates were used to assess cumulative 1-year IBD risk, stratified by age, FIT level, and FCP result. RESULTS:Of 473 402 patients, 2762 patients (0.58%) were diagnosed with IBD within 1 year of FIT. Patients aged <50 years (110 501 patients) accounted for 53.6% of all IBD diagnoses (1481 patients), but only 6.9% of all CRC diagnoses (347 patients). Overall IBD risk was 2.3% with FIT ≥10 µg Hb/g compared with 0.1% with FIT <10 µg Hb/g. Among 63 469 patients with elevated FCP results and FIT levels, IBD risk in those aged <50 years was 21.0% with FIT ≥10 µg Hb/g and FCP >50 µg/g. The combined risk of CRC or IBD in those with FIT ≥10 µg Hb/g was 7.1%. This fell to 3.3% in the subset of patients who also had FCP ≤50 µg/g. CONCLUSION:IBD is more common than CRC in patients aged <50 years referred on symptomatic FIT pathways using FIT ≥10 µg Hb/g. In a selected cohort of dual-tested patients, FCP results provided additional risk stratification. Incorporating routine FCP testing into symptomatic FIT pathways may better target further investigations.

OBJECTIVE:To explore the acceptability of an individualized risk-stratified approach to monitoring for target-organ toxicity in adult patients with immune-mediated inflammatory diseases established on immune-suppressing treatment(s). METHODS:Adults (≥18 years) taking immune-suppressing treatment(s) for at least six months, and healthcare professionals (HCPs) with experience of either prescribing and/or monitoring immune-suppressing drugs were invited to participate in a single, remote, one-to-one, semi-structured interview. Interviews were conducted by a trained qualitative researcher and explored their views and experiences of current monitoring and acceptability of a proposed risk-stratified monitoring plan. Interviews were transcribed verbatim and inductively analysed using thematic analysis in NVivo. RESULTS:Eighteen patients and 13 HCPs were interviewed. While participants found monitoring of immune-suppressing drugs with frequent blood-tests reassuring, the current frequency of these was considered burdensome by patients and HCPs alike, and to be a superfluous use of healthcare resources. Given abnormalities rarely arose during long-term treatment, most felt that monitoring blood-tests were not needed as often. Patients and HCPs found it acceptable to increase the interval between monitoring blood-tests from three-monthly to six-monthly or annually depending on the patients' risk profiles. Conditions of accepting such a change included: allowing for clinician and patient autonomy in determining individuals' frequency of monitoring blood-tests, the flexibility to change monitoring frequency if someone's risk profile changed, and endorsement from specialist societies and healthcare providers such as the National Health Service. CONCLUSION:A risk-stratified approach to monitoring was acceptable to patients and health care professionals. Guideline groups should consider these findings when recommending blood-test monitoring intervals.

Background:Understanding the reasons for delays in leaving hospital once an in-patient is considered ready for discharge is important to inform the development of interventions to improve patient flow through resource-stressed healthcare systems. Aims:To identify risk factors for delayed discharge from hospital during the COVID-19 pandemic. Methods:The study population was all patients admitted with COVID-19 infection from February 2020 to September 2021 to a large UK teaching hospital. Results:Data were available from 7929 admission events with a median delay of 0.20 days from being considered medically safe for discharge and the discharge date. Age older than 60 years (+2.23 days), White ethnicity (+1.58 days compared to SE Asian), living in an area of increased affluence (+0.13 days per decile decrease in deprivation) and having two or more comorbidities (+1.82 days; compared to no comorbidities) were associated with delayed discharge.There was a total potential saving of over 22,000 bed-days if all patients had been discharged when they were considered medically safe. Conclusions:Early identification of patients at an increased risk of a delayed discharge may allow development of appropriate anticipatory interventions, and inform policymakers to help identify and minimise bottlenecks at the institutional level.

OBJECTIVE:The uptake and safety of pneumococcal vaccination in people with immune-mediated inflammatory diseases (IMIDs) is poorly understood. We investigated the UK-wide pneumococcal vaccine uptake in adults with IMIDs and explored the association between vaccination and IMID flare. METHODS:Adults with IMIDs diagnosed on or before 1 September 2018, prescribed steroid-sparing drugs within the last 12 months and contributing data to the Clinical Practice Research Datalink Gold, were included. Vaccine uptake was assessed using a cross-sectional study design. Self-controlled case series analysis investigated the association between pneumococcal vaccination and IMID flare. The self-controlled case series observation period was up to 6 months before and after pneumococcal vaccination. This was partitioned into a 14-day pre-vaccination induction, 90 days post-vaccination exposed and the remaining unexposed periods. RESULTS:We included 32 277 patients, 14 151 with RA, 13 631 with IBD, 3804 with axial SpA and 691 with SLE. Overall, 57% were vaccinated against pneumococcus. Vaccine uptake was lower in those younger than 45 years old (32%), with IBD (42%) and without additional indication(s) for vaccination (46%). In the vaccine safety study, data for 1067, 935 and 451 vaccinated patients with primary-care consultations for joint pain, autoimmune rheumatic disease flare and IBD flare, respectively, were included. Vaccination against pneumococcal pneumonia was not associated with primary-care consultations for joint pain, autoimmune rheumatic disease flare and IBD flare in the exposed period, with incidence rate ratios (95% CI) 0.95 (0.83-1.09), 1.05 (0.92-1.19) and 0.83 (0.65-1.06), respectively. CONCLUSION:Uptake of pneumococcal vaccination in UK patients with IMIDs was suboptimal. Vaccination against pneumococcal disease was not associated with IMID flare.

Few studies have explored the variability of the oxygen-haemoglobin dissociation curve in vivo.96,428 blood gas measurements were obtained (80,376 arterial, 6,959 venous) from a cohort of 7,656 patients who were admitted to a large UK teaching hospital between 1 February 2020 and 31 December 2021 for a Covid-19 related admission with a positive PCR. There was consistent variation of the distribution of the oxygen-haemoglobin curve across most oxygen saturation strata with typical values at 91-92% saturation (mean 8.1kPa, standard deviation sd 0.6 kPa or 60.8mmHg sd 4.5mmHg), with the exception of the highest strata of oxygen saturation of 99-100% (mean 17.7 kPa, sd 8.1kPa or 132mmHg sd 60.8).The higher oxygen partial pressures at higher oxygen saturations are a concern in view of the increased mortality observed in RCTs of higher oxygen saturation targets. However, the observational study design precludes any attribution of causality.

ABSTRACT Background Chest radiographs are generally used for diagnostic purposes. They also have potential to quantify disease severity. This analysis tested the hypothesis that there was an association between chest radiograph opacification and measures of respiratory physiological status and systemic inflammation in patients with Covid‐19 infection. Methods Data on chest radiograph opacification were compared with concurrent measures of oxygen requirements and saturation and serum C‐reactive protein. Results Data were available from 628 individuals. The median opacification on chest radiographs was 20% (interquartile range 5–45). This was associated both SFR (oxygen saturation/supplementary oxygen) with an r value of −0.38 (95% confidence intervals CI: −0.45 to −31, Pearson's correlation coefficient) and CRP (+0.33; 95% CI: +0.24 to +0.41, Pearson's correlation coefficient). Conclusion Chest radiograph opacification scores are associated with both respiratory physiology status and systemic inflammation levels in patients with Covid‐19 infection.

ObjectiveTo develop and validate a prognostic model for risk-stratified monitoring of 5-aminosalicylate nephrotoxicity.MethodsThis UK retrospective cohort study used data from the Clinical Practice Research Datalink Aurum and Gold for model development and validation respectively. It included adults newly diagnosed with inflammatory bowel disease and established on 5-aminosalicylic acid (5-ASA) treatment between 1 January 2007 and 31 December 2019. Drug discontinuation associated with 5-ASA nephrotoxicity defined as a prescription gap of ≥90 days with decline in kidney function was the outcome. Patients prescribed 5-ASAs for ≥6 months were followed-up for up to 5 years. Penalised Cox regression was used to develop the risk equation with bootstrapping for internal validation and optimism adjustment. Model performance was assessed in terms of calibration and discrimination.Results13 728 and 7318 participants who contributed 40 378 and 20 679 person-years follow-up formed the development and validation cohorts with 170 (1.2%) and 98 (1.3%) outcome events respectively. Nine predictors were included in the final model, including chronic kidney disease stage 3 and hazardous alcohol use as strong predictors. Age and Body Mass Index were weak predictors. The optimism-adjusted calibration slope, C and D statistics in the development and validation data were 0.90, 0.64 and 0.98, and 1.01, 0.66 and 0.94 respectively.ConclusionThis prognostic model used information from routine clinical care and performed well in an independent validation cohort. It can be used to risk-stratify blood test monitoring during established 5-ASA treatment. A key limitation is that the decline in kidney function could have been due to factors other than 5-ASA nephrotoxicity.

Background Sulfasalazine-induced cytopenia, nephrotoxicity and hepatotoxicity is uncommon during long-term treatment. Some guidelines recommend 3 monthly monitoring blood tests indefinitely during long-term treatment while others recommend stopping monitoring after 1 year. To rationalise monitoring, we developed and validated a prognostic model for clinically significant blood, liver or kidney toxicity during established sulfasalazine treatment.Design Retrospective cohort study.Setting UK primary care. Data from Clinical Practice Research Datalink Gold and Aurum formed independent development and validation cohorts.Participants Age ≥18 years, new diagnosis of an inflammatory condition and sulfasalazine prescription.Study period 1 January 2007 to 31 December 2019.Outcome Sulfasalazine discontinuation with abnormal monitoring blood-test result.Analysis Patients were followed up from 6 months after first primary care prescription to the earliest of outcome, drug discontinuation, death, 5 years or 31 December 2019. Penalised Cox regression was performed to develop the risk equation. Multiple imputation handled missing predictor data. Model performance was assessed in terms of calibration and discrimination.Results 8936 participants were included in the development cohort (473 events, 23 299 person-years) and 5203 participants were included in the validation cohort (280 events, 12 867 person-years). Nine candidate predictors were included. The optimism adjusted R2D and Royston D statistic in the development data were 0.13 and 0.79, respectively. The calibration slope (95% CI) and Royston D statistic (95% CI) in validation cohort was 1.19 (0.96 to 1.43) and 0.87 (0.67 to 1.07), respectively.Conclusion This prognostic model for sulfasalazine toxicity uses readily available data and should be used to risk-stratify blood-test monitoring during established sulfasalazine treatment.

BACKGROUND:Consultation with primary healthcare professionals may provide an opportunity to identify patients at higher suicide risk. AIM:To explore primary care consultation patterns in the 5 years before suicide to identify suicide high-risk groups and common reasons for consulting. DESIGN AND SETTING:This was a case-control study using electronic health records from England, 2001 to 2019. METHOD:An analysis was undertaken of 14 515 patients aged ≥15 years who died by suicide and up to 40 matched live controls per person who died by suicide (n = 580 159), (N = 594 674). RESULTS:Frequent consultations (>1 per month in the final year) were associated with increased suicide risk (age- and sex -adjusted odds ratio [OR] 5.88, 95% confidence interval [CI] = 5.47 to 6.32). The associated rise in suicide risk was seen across all sociodemographic groups as well as in those with and without psychiatric comorbidities. However, specific groups were more influenced by the effect of high-frequency consultation (>1 per month in the final year) demonstrating higher suicide risk compared with their counterparts who consulted once: females (adjusted OR 9.50, 95% CI = 7.82 to 11.54), patients aged 15-<45 years (adjusted OR 8.08, 95% CI = 7.29 to 8.96), patients experiencing less socioeconomic deprivation (adjusted OR 6.56, 95% CI = 5.77 to 7.46), and those with psychiatric conditions (adjusted OR 4.57, 95% CI = 4.12 to 5.06). Medication review, depression, and pain were the most common reasons for which patients who died by suicide consulted in the year before death. CONCLUSION:Escalating or more than monthly consultations are associated with increased suicide risk regardless of patients' sociodemographic characteristics and regardless of the presence (or absence) of known psychiatric illnesses.

Background There is no evidence base to support the use of 6-monthly monitoring blood tests for the early detection of liver, blood and renal toxicity during established anti-tumour necrosis factor alpha (TNF alpha) treatment. Objectives To evaluate the incidence and risk factors of anti-TNF alpha treatment cessation owing to liver, blood and renal side-effects, and to estimate the cost-effectiveness of alternate intervals between monitoring blood tests. Methods A secondary care-based retrospective cohort study was performed. Data from the British Association of Dermatologists Biologic and Immunomodulators Register (BADBIR) were used. Patients with at least moderate psoriasis prescribed their first anti-TNF alpha treatment were included. Treatment discontinuation due to a monitoring blood test abnormality was the primary outcome. Patients were followed-up from start of treatment to the outcome of interest, drug discontinuation, death, 31 July 2021 or up to 5 years, whichever came first. The incidence rate (IR) and 95% confidence intervals (CIs) of anti-TNF alpha discontinuation with monitoring blood test abnormality was calculated. Multivariate Cox regression was used to examine the association between risk factors and outcome. A mathematical model evaluated costs and quality-adjusted life years (QALYs) associated with increasing the length of time between monitoring blood tests during anti-TNF alpha treatment. Results The cohort included 8819 participants [3710 (42.1%) female, mean (SD) age 44.76 (13.20) years] that contributed 25 058 person-years (PY) of follow-up and experienced 125 treatment discontinuations owing to a monitoring blood test abnormality at an IR of 5.85 (95% CI 4.91-6.97)/1000 PY. Of these, 64 and 61 discontinuations occurred within the first year and after the first year of treatment start, at IRs of 8.62 (95% CI 6.74-11.01) and 3.44 (95% CI 2.67-4.42)/1000 PY, respectively. Increasing age (in years), diabetes and liver disease were associated with anti-TNF alpha discontinuation after a monitoring blood test abnormality [adjusted hazard ratios of 1.02 (95% CI 1.01-1.04), 1.68 (95% CI 1.00-2.81) and 2.27 (95% CI 1.26-4.07), respectively]. Assuming a threshold of 20 pound 000 per QALY gained, no monitoring was most cost-effective, but all extended periods were cost-effective vs. 3- or 6-monthly monitoring. Conclusions Anti-TNF alpha drugs were uncommonly discontinued owing to abnormal monitoring blood tests after the first year of treatment. Extending the duration between monitoring blood tests was cost-effective. Our results produce evidence for specialist society guidance to reduce patient monitoring burden and healthcare costs.

Background Immune-suppressing drugs can cause liver, kidney or blood toxicity. Prognostic factors for these adverse-events are poorly understood.Purpose To ascertain prognostic factors associated with liver, blood or kidney adverse-events in people receiving immune-suppressing drugs.Data sources MEDLINE, Web of Science, EMBASE and the Cochrane library (01 January 1995 to 05 January 2023), and supplementary sources.Data extraction and synthesis Data were extracted by one reviewer using a modified CHARMS-PF checklist and validated by another. Two independent reviewers assessed risk of bias using Quality in Prognostic factor Studies tool and assessed the quality of evidence using a Grading of Recommendations Assessment, Development and Evaluation-informed framework.Results Fifty-six studies from 58 papers were included. High-quality evidence of the following associations was identified: elevated liver enzymes (6 studies) and folate non-supplementation (3 studies) are prognostic factors for hepatotoxicity in those treated with methotrexate; that mercaptopurine (vs azathioprine) (3 studies) was a prognostic factor for hepatotoxicity in those treated with thiopurines; that mercaptopurine (vs azathioprine) (3 studies) and poor-metaboliser status (4 studies) were prognostic factors for cytopenia in those treated with thiopurines; and that baseline elevated liver enzymes (3 studies) are a prognostic factor for hepatotoxicity in those treated with anti-tumour necrosis factors. Moderate and low quality evidence for several other demographic, lifestyle, comorbidities, baseline bloods/serologic or treatment-related prognostic factors were also identified.Limitations Studies published before 1995, those with less than 200 participants and not published in English were excluded. Heterogeneity between studies included different cut-offs for prognostic factors, use of different outcome definitions and different adjustment factors.Conclusions Prognostic factors for target-organ damage were identified which may be further investigated for their potential role in targeted (risk-stratified) monitoring.PROSPERO registration number CRD42020208049.

BACKGROUND:People with immune-mediated inflammatory disease are at increased risk of pneumococcal pneumonia. The effectiveness of pneumococcal vaccination in people with immune-mediated inflammatory diseases has not been evaluated. We investigated the effectiveness of pneumococcal vaccination in preventing morbidity and mortality associated with pneumonia in patients with immune-mediated inflammatory diseases. METHODS:In this matched case-control study, we used primary-care electronic health record data from the Clinical Practice Research Datalink Gold database in the UK, with linked hospitalisation and mortality data. Adults with incident common immune-mediated inflammatory diseases diagnosed between April 1, 1997, and Dec 31, 2019, were followed up from the first diagnosis date to the occurrence of an outcome or date of last follow-up. Cases (ie, those with an outcome of interest) were age-matched and sex-matched to up to ten contemporaneous controls by use of incidence density sampling. Outcomes were hospitalisation due to pneumonia, death due to pneumonia, or primary-care consultation for lower respiratory tract infection requiring antibiotics. We defined hospital admission for pneumonia using hospital discharge diagnoses, death due to pneumonia using death certification data, and lower respiratory tract infection as present when primary-care consultation and antibiotic prescription occurred on the same date. We used multivariable, unconditional, logistical regression and constructed three models to examine the association between pneumococcal vaccination as an exposure and each of the three outcomes. FINDINGS:The first nested case-control analysis included 12 360 patients (7326 [59·3%] women and 5034 [40·7%] men): 1884 (15·2%) who were hospitalised due to pneumonia and 10 476 (84·8%) who were not admitted to hospital due to pneumonia. The second analysis included 5321 patients (3112 [58·5%] women and 2209 [41·5%] men): 781 (14·7%) who died due to pneumonia and 4540 (85·3%) who were alive on the index date. The third analysis included 54 530 patients (33 605 [61·6%] women and 20 925 [38·4%] men): 10 549 (19·3%) with lower respiratory tract infection treated with antibiotics and 43 981 (80·7%) without infection. In the multivariable analysis, pneumococcal vaccination was negatively associated with hospitalisation due to pneumonia (adjusted odds ratio 0·70 [95% CI 0·60-0·81]), death due to pneumonia (0·60 [0·48-0·76]), and lower respiratory tract infection treated with antibiotics (0·76 [0·72-0·80]). INTERPRETATION:Pneumococcal vaccination is associated with protection against hospitalisation and death due to pneumonia in patients with immune-mediated inflammatory diseases, without apparent residual confounding. However, residual unmeasured confounding cannot be fully excluded in observational research, which includes nested case-control studies. These findings should also be corroborated with data from other countries, given that this study used UK-based data. FUNDING:National Institute for Health and Care Research.

INTRODUCTION:Patients with alcohol-related cirrhosis (ALD cirrhosis) have an increased risk of primary liver cancer (hepatocellular carcinoma [HCC] or intrahepatic cholangiocarcinoma [iCCA]). England recommends surveillance for HCC in these patients, while Denmark does not. METHODS:We performed an observational cohort study using the English Clinical Practice Research Datalink and the nationwide Danish healthcare registries to identify 17,110 English (2000-2016) and 22,122 Danish (1994-2022) patients with diagnosis codes of ALD cirrhosis. We computed and compared incidence rates and cumulative incidence of primary liver cancer, annual ultrasound scan rates, and mortality following diagnosis of primary liver cancer. RESULTS:The overall risk of primary liver cancer was similar in England and Denmark: 5-year risk was 2.24% (95% confidence interval 2.00-2.49) in England (iCCA 0.07%, HCC 2.16%) and 2.36% (2.15-2.57) in Denmark (iCCA 0.05%, HCC 2.30%). The annual rate of ultrasound scans per person was 0.65 (0.63-0.67) in England and 0.44 (0.42-0.46) in Denmark. The 1-year mortality after a diagnosis of primary liver cancer was 59.2% (54.4-64.0) in England and 60.9% (57.4-64.4) in Denmark. The 3-year risks of HCC in those on vs off surveillance in England were 2.3% (1.0-4.6) vs 1.5% (1.0-2.2). DISCUSSION:The risk of primary liver cancer was the same in English and Danish patients with ALD cirrhosis, and HCCs constituted 97% of primary liver cancers. Mortality with primary liver cancer was equally high in both countries. Notably, in England, where guidance recommends biannual HCC surveillance with ultrasound, patients with ALD cirrhosis were undergoing fewer than 1 ultrasound scan per year.

Background Pulse oximetry measures oxygen saturation non-invasively by using differential absorption of infrared signals which are dependent on the oxyhaemoglobin:deoxyhaemoglobin ratio. We tested the hypothesis that pulse oximetry error in measurements of blood oxygen saturations may be associated with blood haemoglobin levels.Methods The study design was an observational study of all adult patients admitted to a large teaching hospital with suspected or confirmed COVID-19 infection from February 2020 to December 2021 who had arterial blood gases (ABG) drawn. The pulse oximetry reading was compared with the arterial saturation on the ABG and the measurement error was determined according to the ABG haemoglobin. A secondary analysis was performed among a subset of patients with venous haemoglobins drawn within 24 hours, comparing measurement error between ABG arterial saturation and pulse oximetry readings between those with normal (150 g/L) and low (70 g/L) haemoglobins.Results The analysis used 5922 paired oxygen saturations from 3994 patients with contemporaneous haemoglobin measurements by ABG. A 1 g/L decrease in blood haemoglobin was associated with an 0.021% (95% CI: +0.008% to +0.033%) increase in the measurement error (in the direction of a falsely elevated reading.). In the 1086 patients who had had a venous haemoglobin there was a 0.055% (95% CI: +0.020% to +0.090%) increase in the measurement error of oxygen saturation per 1 g/L decrease in blood haemoglobin. The measurement error was thus greater in those with anaemia than in those with normal haemoglobin.Conclusion As blood haemoglobin decreases, the oxygen saturation measurement derived from a pulse oximeter reads erroneously higher than the true value measured by ABG. While this study was confined to patients with COVID-19, physicians should be aware of this potential discrepancy among all patients with haemorrhage or known anaemia

Background/Aims The safety and effectiveness of pneumococcal vaccine in people with immune mediated inflammatory diseases (IMIDs) is not known, which may contribute to suboptimal uptake. We investigated UK wide pneumococcal vaccine uptake in adults with IMIDs, the association between pneumococcal vaccination and disease flares, and the effectiveness of pneumococcal vaccine in preventing pneumonia in this at-risk population. Methods Adults with incident rheumatoid arthritis (RA), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE) and spondyloarthritis (SpA) prior to 31(st) August 2018 in the Clinical Practice Research Datalink (CPRD) Gold were included. The study was approved by CPRD research data governance (Reference 21_000614). We calculated the proportion of patients vaccinated against pneumococcal pneumonia. To investigate the association between vaccination and IMID flare, we employed a self-controlled case series analysis, adjusted for season. The study period was up-to six-month before and six-month after the date of pneumococcal vaccination. This period was partitioned into induction (14 days pre-vaccination) and exposed periods (up-to 90 days post vaccination) with the remaining time considered unexposed. Incidence rate ratios (IRR) and 95% CI were calculated. We conducted a multivariable nested case-control study to assess vaccine effectiveness. Cases were patients hospitalised with pneumonia and were matched to up to ten controls for age and sex. Multivariable conditional logistic regression was used to calculate odds ratio (OR) and 95% CI. Results We included 32,277 IMID patients: 14,151 with RA, 13,631 with IBD, 3,804 with SpA and 691 with SLE. Overall uptake of pneumococcal vaccination was 50% (95% CI 49.4% -50.5%). Vaccination uptake was significantly lower in the under 45-year-olds, in patients with IBD and in those without additional indication for vaccination at 29.7%, 38.4%, 42.7% respectively. In the safety study, data for 1001, 854, 424 vaccinated patients with primary care consultations for joint pain, AIRD flare, and IBD flare respectively were included. Vaccination against pneumococcal pneumonia was not associated with AIRD flare (IRR (95% CI) 1.07 (0.93-1.22)), primary care consultations for joint pain (IRR (95% CI) 0.95 (0.83-1.10)), and IBD flare (IRR (95% CI) 0.82 (0.64-1.06)) in the 90-days post vaccination. The vaccine effectiveness study included 25,707 patients, either with (n=2,771) or without (n=22,936) a hospitalisation record for pneumonia after IMID diagnosis. Patients hospitalised for pneumonia compared with their matched controls, had higher odds of current smoking, deprivation, corticosteroid prescriptions, additional indication for vaccination, primary care consultations, hospital admissions and prescriptions. In the multivariable adjusted model, pneumococcal vaccination was associated with reduced odds of hospitalisation for pneumonia (OR (95% CI) 0.88 (0.78-0.98). Conclusion The uptake of pneumococcal vaccine is low in IMID patients. Pneumococcal vaccination is not associated with IMID flare and is protective against pneumonia. These findings call for promotion of pneumococcal vaccination in IMID by health professionals. Disclosure G. Nakafero: None. M.J. Grainge: None. C.D. Mallen: Grants/research support; NIHR, MRC, Versus Arthritis and BMS. T. Card: None. J.S. Nguyen Van-Tam: Consultancies; CSL Seqirus and Moderna. Royalties; AstraZeneca and Sanofi Pasteur. A. Abhishek: Consultancies; NGM Bio, Limbic and Inflazome.. Royalties; UpToDate, Springer, Cadilla Pharmaceuticals.. Grants/research support; AstraZeneca and Oxford Immunotech..