IntroductionNICE recommend an ILD clinical nurse specialist (ILD CNS) for all patients with idiopathic pulmonary fibrosis (IPF). The Respiratory GIRFT report advocates a minimum one Band 6 nurse per 300 ILD patients and that their role should be disease-specific. ILD CNS are a requisite for ILD specialist centres but are lacking in most secondary care respiratory services.A collaborative project between Colchester Hospital (CH), Royal Papworth Hospital (RPH) and Boehringer Ingelheim is evaluating the role and impact of an ILD CNS in secondary care.Methods0.6 FTE Band 6 ILD CNS was recruited and trained for this pilot project. Between October 2023 and April 2024, a retrospective review of ILD patients at CH was conducted and anonymised demographic and clinical data were collected. An ILD telephone helpline was established and a subgroup of patients completed a patient experience questionnaire.Results408 ILD patients were identified (figure 1A). 55 of these patients are prescribed antifibrotic therapy (IPF n=37). 107 patients are under shared care with an ILD Specialist Centre and have access to ILD CNS support. 248 ILD patients did not have access to an ILD CNS (figure 1B).An ILD patient telephone helpline started in October 2023 and the number of calls/month has increased from three to 46 by April 2024. Over 50% of calls were directly related to their ILD (figure 1C). Of the calls in April 2024, three resulted in hospital admission avoidance which was estimated to save up to 26 bed days.Per week, the ILD CNS spends 24 hours conducting clinical activities (clinics, blood monitoring, telephone helpline) and 15 hours of non-clinical tasks, of which 70% could be undertaken by an administrator. Patients highly rated feeling supported (6.8/7; n=16) and informed (6.65/7; n=17) as a direct result of their interactions with the ILD CNS.ConclusionThese results highlight the unmet need for ILD patients in secondary care. The data suggests local ILD CNS expertise may help to address inequities and inequalities of care for ILD patients. This will support the transition of the delivery of specialist ILD care to secondary respiratory services. S59 Figure 1(A) A retrospective review of anonymised clinical data at CH identified 408 ILD patients. 53 of these patients were referrals of suspected ILD and awaiting diagnosis. The remaining 355 were categorised based on their working diagnosis, most common being IPF (n=68), sarcoid (n=64) and connective tissue disease-associated ILD (CTD-ILD; n=46). (B) 107 of the 355 patients are under shared care CH with an ILD specialist centre. The dashed horizontal line denotes the advocation by the Respiratory GIRFT Report for a minimum of one disease-specific Band 6 nurse per 300 ILD patients. (C) Breakdown of calls received to the ILD patient helpline at CH during April 2024.

Abstract Generalized pustular psoriasis (GPP) is a rare, chronic inflammatory skin condition that is potentially life-threatening. Accumulating evidence suggests that GPP is distinct from the more common plaque psoriasis in terms of aetiology and clinical and dermatological features. The aim of this study was to describe the epidemiology, comorbidities, mortality and healthcare resource use (HCRU) in patients with GPP compared with those with plaque psoriasis in England. A retrospective cohort study of the Clinical Practice Research Datalink (CPRD) Aurum database linked with hospital and mortality data, between 2008 and 2019, was conducted, and HCRU between 2015 and 2019 was calculated. Prevalence rates, comorbidities and survival rates were estimated for GPP and plaque psoriasis. Diagnoses were based on CPRD medical codes and International Classification of Diseases 10th Revision codes (L40.1 for GPP, and L40.0 for plaque psoriasis). In total, 373 patients with GPP (62.5% female) and 224 223 patients with plaque psoriasis (49.4% female) were identified. The mean age (SD) was 55.9 years (18.6) for GPP, and 48.5 years (19.1) for patients with plaque psoriasis. A higher proportion of patients with GPP had at least one comorbidity, compared with plaque psoriasis (76.4% vs. 55.9%, respectively). From 2008 to 2019, the prevalence rates per 100 000 persons ranged from 1.61 to 3.0 for GPP, and from 1771 to 1904 for plaque psoriasis. In total, 78 of the 373 (20.9%) patients with GPP died during the study period, compared with 20 771 of 224 223 (9.3%) patients with plaque psoriasis. Compared with plaque psoriasis, survival rates were lower for patients with GPP, particularly those who were over 55 years old and those with a history of at least one comorbidity. Overall, 297 patients with GPP and 181 925 with plaque psoriasis were included in HCRU analysis. Hospitalizations, outpatient visits and accident and emergency visits were more frequent in patients with GPP compared with plaque psoriasis (78% vs. 47%, 92% vs. 75% and 71% vs. 52%, respectively). Our results support previous findings that GPP is a distinct disease from plaque psoriasis with a different epidemiology. Compared with plaque psoriasis, patients with GPP had higher mortality and were found to have higher disease burden, demonstrating a high unmet need in this patient group. The study was supported and funded by Boehringer Ingelheim. Boehringer Ingelheim was given the opportunity to review the manuscript for medical and scientific accuracy, as well as intellectual property considerations.

AimsGlutamatergic signalling deficits contribute to the neuropathology of cognitive symptoms in schizophrenia. Iclepertin (BI 425809), a glycine transporter-1 inhibitor, enhances N-methyl-D-aspartate receptor signalling in the brain by increasing synaptic levels of its co-agonist glycine. The Phase III CONNEX programme aims to assess the efficacy, safety and tolerability of iclepertin in improving cognition and functioning in schizophrenia.MethodsCONNEX includes 3 randomised, double-blind, placebo-controlled parallel group trials in patients with schizophrenia from multiple centres across 41 countries in Asia, North and South America, Europe, and Asia Pacific Region (NCT04846868, NCT04846881, NCT04860830) receiving stable antipsychotic treatment. Each trial aims to recruit ~586 patients, 18–50 years old, treated with 1–2 antipsychotic medications (≥12 weeks on current drug; ≥35 days on current dose before treatment), who have functional impairment in day-to-day activities and interact ≥1 hour/week with a designated study partner. Patients with cognitive impairment due to developmental, neurological or other disorders, or receiving cognitive remediation therapy ≤12 weeks before screening will be excluded. Patients will be randomised 1:1 to once-daily oral iclepertin 10 mg (n = 293) or placebo (n = 293) for 26 weeks. Primary endpoint: change from baseline (CfB) in Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) overall composite T-score. Key secondary endpoints: CfB in Schizophrenia Cognition Rating Scale (SCoRS) total score and adjusted total time T-score in the Virtual Reality Functional Capacity Assessment Tool (VRFCAT).ResultsTrial completion is expected in Q1 2025. By 31/01/2024, there have been 811, 699 and 655 patients screened, 533, 474 and 458 randomised, and 320, 299 and 281 who have completed the trial medication for CONNEX-1, -2 and -3, respectively. Most patients are male (CONNEX-1: 69.3%, CONNEX-2: 69.0%, CONNEX-3: 63.3%) with similar age (mean [standard deviation; SD]) (CONNEX-1: 34.0 [8.9], CONNEX-2: 35.9 [8.4], CONNEX-3: 34.0 [8.8] years). For CONNEX-1, -2 and -3, mean (SD) duration of illness is 10.6 (8.3), 12.2 (7.9) and 9.6 (7.6) years and duration of previous schizophrenia treatment is 3.9 (4.6), 4.5 (4.9) and 3.3 (4.4) years. Baseline mean (SD) MCCB overall composite T-score (1: 28.4 [13.7], 2: 27.3 [13.8], 3: 29.7 [13.7]), SCoRS total score (1: 40.5 [11.1], 2: 39.9 [9.7], 3: 38.0 [10.0]) and VRFCAT adjusted total time T-score (1: 29.6 [22.3], 2: 30.7 [20.8], 3: 33.6 [18.1]) were similar across trials.ConclusionIf successful, CONNEX will provide evidence for iclepertin as the first efficacious medication addressing cognitive impairments in schizophrenia.Studies funded by Boehringer Ingelheim.

Abstract Background and Aims Chronic kidney disease (CKD) is associated with high clinical burden for patients and substantial economic costs for healthcare systems. Detailed estimates of healthcare resource utilization (HCRU) for patients with CKD in the UK are limited, particularly by stage of CKD. This study assessed outpatient and non-elective inpatient HCRU by stage of CKD in England. Method This non-interventional study utilised data from primary care electronic health records from Clinical Practice Research Datalink (CPRD) AURUM and Hospital Episode Statistics (HES) admitted patient care (APC). Patients aged ≥18 years registered in CPRD with eligible linkage to HES between January 1, 2010 and December 31, 2019 with 2+ eGFR measurement during the period were identified. CKD was defined by eGFR <60 ml/min/1.73 m2 and/or presence of a uACR measurement ≥3 mg/mmol, both confirmed by a second measurement 90-365 days later. Start of follow-up (index) was set to the earliest date during the study period that CKD was confirmed. Follow-up for HCRU ended at earliest of death, administrative censoring, or 31st December 2019. Patients with end-stage kidney disease (eGFR <9 ml/min/1.73 m2) at index were excluded. Number of HCRU events for each HCRU category was estimated as rates per 1,000 person years (PY) for each calendar year based on cumulative number of events. Event rates were calculated as number of outcomes/total time at risk. Confidence intervals (95%) were calculated assuming a Poisson distribution. Age- and sex-adjusted rates were calculated to compare rates across CKD stages. Results Of 6.1 million adult patients meeting study inclusion criteria, 743,945 adults (12.2%) with CKD were identified. Mean age (SD) was 76.1 (11.5) years, 55.2% were female, and 89.8% White, contributing a total of 3,055,600 years of follow-up. Most (60.9%) patients had stage 3a CKD (eGFR 45-<59 ml/min/1.73 m2). Among patients with uACR measurements (44.4%), 48.0% were A1 (<3 mg/mmol), 44.4% A2 (3-30 mg/mmol), and 7.6% A3 (>30 mg/mmol). Overall, per 1000 PY, there were 24,763 primary care visits, 475 non-elective all-cause hospitalisations, 4,950 attended (722 unattended) outpatient visits, including 308 (43 unattended) outpatient nephrology visits and 368.1 attended (61.2 unattended) cardiology visits. For all HCRU categories, greater KDIGO risk category at index was associated with higher HCRU. For example, after age and sex adjustment, patients with CKD stage 3b had a mean of 0.53/PY non-elective all-cause hospitalisations compared to 0.77/PY for patients with CKD stage 4. Additionally, a mean of 5.18 outpatient visits per PY was observed for patients with CKD stage 3b, of which 0.91 were nephrology outpatient visits compared to 8.39 outpatient visits per PY for stage 4, of which 2.65 were nephrology outpatient visits. Generally, both lower eGFR and higher uACR were individually associated with higher HCRU. Conclusion This study demonstrates high HCRU for patients with CKD, with increasing rates of HCRU with lower kidney function and greater kidney damage. Patients with more advanced CKD contribute at a disproportionally higher rate of outpatient healthcare encounters and non-elective hospitalisations. Efforts to prevent the development and progression of CKD and improving clinical outcomes will reduce frequency and cost of HCRU.

Abstract Background and Aims Patients with chronic kidney disease (CKD) are at higher risk of non-elective hospitalisation compared to the general population, which is associated with an increased risk of death and accounts for disproportionate resource utilisation. There are limited population-level estimates of the causes of non-elective hospitalisation for patients with CKD in England. Therefore, a population-based study was implemented to start to address this shortfall. Method This non-interventional, observational study utilised data from primary care electronic health records from the Clinical Practice Research Datalink (CPRD) AURUM and Hospital Episode Statistics (HES) admitted patient care (APC). Patients aged ≥18 years registered in CPRD with eligible linkage to HES between January 1, 2010-December 31, 2019 with at least two eGFR measurements during that period were identified. CKD was defined by an eGFR <60 ml/min/1.73 m2 and/or presence of a uACR measurement ≥3 mg/mmol, both confirmed by a second measurement 90-365 days later. Start of follow-up (index) was set to the earliest date during the study period where CKD was confirmed. Non-elective admissions were defined as hospitalisations not planned in advance. Follow-up for hospitalisations ended at the earliest of death, administrative censoring, or December 31, 2019. Patients with end stage kidney disease at index were excluded. Causes of hospitalisation during follow-up were based on three character-level ICD codes in the primary position. Where the same ICD-10 code was coded more than once within a hospitalisation, it was only counted once. Results From a total population of 6.1 million adult patients meeting study inclusion criteria, 743.945 adults with CKD were identified (12.2%) with a median follow-up of 3.62 years. The mean age (SD) was 76.1 (11.5) years, 55.2% were female, and 89.8% were White. The majority (60.9%) of patients had stage 3a CKD (eGFR 45-59 ml/min/1.732 m2) and 34.3% and 17.1% had a history of type 2 diabetes and heart failure at time of CKD confirmation, respectively. There were 1.45 million non-elective hospitalisations observed, with 449.128 (60%) of patients experiencing ≥1 non-elective hospitalisation during follow-up. The most frequent ICD-10 chapter indicated as primary cause of all non-elective hospitalisation was diseases of the circulatory system (19.4%), including heart failure (4.9%), ischaemic heart disease (myocardial infarction and angina) (3.5%), stroke (2.2%) and atrial fibrillation/flutter (1.9%). Infection was also a frequent cause of non-elective hospitalisation, including pneumonia of unspecified organism (7.8%), unspecified acute lower respiratory tract (2.5%), and other sepsis (2.7%). Frequent hospitalisation also occurred in patients with CKD due to fractures (3.5%) and injuries to the head (1.7%). Conclusion Non-elective hospitalisations are frequent among patients with CKD. Diseases of the circulatory and respiratory systems are overall most common causes, with pneumonia, ischaemic heart disease, and heart failure the most frequent modifiable reasons for admission. Ensuring that current shortfalls in primary and secondary prevention for patients with CKD through optimization of strategies such as vaccination and evidence based cardiovascular disease management will reduce rates of non-elective hospitalisation and other clinical outcomes and ensure best use of health care resources for patients with CKD.

Abstract Background and Aims The NICE chronic kidney disease (CKD) treatment guidelines recommend regular laboratory measurements of both kidney function (eGFR) and damage (proteinuria) to appropriately inform efforts to prevent and treat progression of CKD. Recommendations also indicate frequency of such testing should increase with CKD progression. There are few data on rates of testing in patients with confirmed CKD with particularly paucity in patients with various stages of CKD. Method This non-interventional, observational study utilised data from primary care electronic health records from Clinical Practice Research Datalink (CPRD) AURUM. Patients aged ≥18 years with CKD registered in CPRD with at least one year of follow-up (FU) between January 1, 2010 and December 31, 2019 were identified. CKD was defined by an eGFR <60 ml/min/1.73 m2 and/or presence of a uACR measurement ≥3 mg/mmol, both confirmed by a second measurement 90-365 days later (index). Patients with eGFR <9 ml/min/1.73 m2 at index were excluded. Frequency of renal testing (eGFR and UACR) for each complete year of FU was quantified starting the day after index and patients were censored the last day of the final complete calendar year of FU after index. Frequency of renal testing per FU year was calculated overall and by CKD stage and level of albuminuria at index. Results In the 650 565 patients with CKD identified, mean age (SD) was 76.1 (11.3) years, 55.4% were female, and 88.5% White. Most (62.0%) patients had stage 3a CKD (eGFR 45-<59 ml/min/1.73 m2) at index. Among patients with UACR measurements within 1 year prior to index (54.1%), 49.3% were A1 (<3 mg/mmol), 43.4% A2 (3-30 mg/mmol) and 7.3% A3 (>30 mg/mmol) at index. During the first year of FU, 81.45% of patients had 1+ eGFR test whereas 39.2% had 1+ UACR test. Patients more frequently received 1+ eGFR per year over subsequent years of FU but the low proportion with 1+ UACR test per year remained stable for UACR. The mean (SD) number of eGFR and UACR tests performed per patient in the first year of FU was 2.09 (2.39) and 0.49 (0.70), respectively. More frequent eGFR testing was observed with lower eGFR at index and across subsequent years of FU. Frequency of UACR testing was lower at more advanced stages of CKD at index in all FU years, however, no trends in UACR testing frequency were observed by level of albuminuria at index. Conclusion This evidence from a population-based sample of patients with confirmed CKD in England, indicates that eGFR is being monitored in the majority of patients, yet UACR testing is suboptimal according to NICE guidelines regardless of level of kidney function or level of albuminuria. Although eGFR testing is more frequent at more advanced stages of CKD, UACR testing seems to become less frequent with more advanced stages of CKD. With emergence of new therapies to prevent progression of CKD, efforts to increase frequency of UACR testing are needed (particularly in earlier CKD stages) to ensure that patients who are at risk of worsening CKD and albuminuria receive appropriate management.

Generalized pustular psoriasis (GPP) and palmoplantar pustulosis (PPP) are chronic inflammatory skin conditions. Accumulating evidence shows that GPP and PPP have different characteristics to plaque psoriasis and are distinct clinical entities. To assess the epidemiology, comorbidities, mortality and healthcare use for patients in England with GPP and PPP versus those with plaque psoriasis. We carried out a cohort study involving analyses of longitudinal electronic health record data in the Clinical Practice Research Datalink Aurum database and linked hospital and mortality data between 2008 and 2019. The primary study outcome was the incidence and prevalence rates of GPP, PPP and plaque psoriasis in England. Secondary outcomes included survival rates and healthcare resource use (HCRU) by disease type. We identified 373 patients with GPP, 1828 with PPP and 224 223 with plaque psoriasis. Mean (SD) age was 55.9 (18.6) years for patients with GPP, 51.5 (16.4) years for those with PPP and 48.5 (19.1) years for those with plaque psoriasis; 62.5% and 65.9% of patients with GPP and PPP, respectively, were women, vs. 49.4% of those with plaque psoriasis. About half of patients were overweight or obese at baseline (GPP 48.6%, PPP 56.0%, plaque psoriasis 45.9%). The incidence rates for GPP, PPP and plaque psoriasis were 0.25 [95% confidence interval (CI) 0.21-0.28], 2.01 (95% CI 1.92-2.11) and 103.2 (95% CI 102.5-103.9) per 100 000 person-years, respectively. From 2008 to 2019, the prevalence rates per 100 000 persons ranged from 1.61 to 3.0 for GPP, from 1.1 to 18.7 for PPP and from 1771.0 to 1903.8 for plaque psoriasis. Survival rates were lower for patients with GPP, particularly those who were > 55 years of age and those with a history of one or more comorbidities in each cohort. HCRU was lower in the cohort with plaque psoriasis and highest in the cohort with GPP, particularly among those who had more than one GPP flare. Our results provide further evidence that, in England, GPP is a distinct disease with different epidemiology, lower survival and higher HCRU than plaque psoriasis.

Objective The sodium-glucose co-transporter-2 inhibitor empagliflozin was approved for treatment of adults with chronic kidney disease (CKD) on the basis of its demonstrated ability to slow CKD progression and reduce the risk of cardiovascular death. This analysis was performed to assess the cost-effectiveness of empagliflozin plus standard of care (SoC) vs SoC alone in the treatment of CKD in the UK. Methods A comprehensive, patient-level CKD progression model that simulates the evolution of risk factors for disease progression based on CKD-specific equations and clinical data was used to project a broad range of CKD-related complications. Patient baseline characteristics, distribution across Kidney Disease Improving Global Outcomes (KDIGO) health states, and changes in estimated glomerular filtration rate (eGFR), urine albumin-creatinine ratio (uACR), and other parameters while on treatment were derived from the EMPA-KIDNEY trial. UK cost and utilities/disutilities were sourced from the literature. Univariate and probabilistic sensitivity analyses were conducted. Annual discounting of 3.5% was applied on costs and outcomes. Results Over a 50-year horizon, SoC resulted in per-patient costs, life years, and QALYs of £95,930, 8.55, and 6.28, respectively. Empagliflozin plus SoC resulted in an incremental gain in life years (+1.04) and QALYs (+0.84), while decreasing per-patient costs by £6,019. Empagliflozin was more effective and less costly (dominant) with a net monetary benefit of £22,849 at the willingness-to-pay threshold of £20,000. Although treatment cost was higher for empagliflozin, this was more than offset by savings in kidney replacement therapy. Empagliflozin remained highly cost-effective in patients with and without diabetes, and across scenario and sensitivity analyses. Limitations This analysis is limited by reliance on short-term clinical trial data and by uncertainties in modelling CKD progression. Conclusions Empagliflozin as an add-on to SoC for treatment of adults with CKD represents cost-effective use of UK National Health Service (NHS) resources.