Real-world Observational Study Research Articles

A UK real-world observational study of avelumab + axitinib (A + Ax) in advanced renal cell carcinoma (aRCC): Outcomes at 36 months post treatment initiation.

A UK real-world observational study of avelumab + axitinib (A + Ax) in advanced renal cell carcinoma (aRCC): Outcomes at 36 months post treatment initiation.

P936 Ultrasound Transmural Remission in Crohn's disease: Different Rate between First and Second Line of Biological Therapy

Abstract Background Ultrasound transmural remission in Crohn’s disease (CD) has been associated with improved long-term clinical outcomes including reduced hospitalization, surgery, escalation of treatment, and a decrease in clinical relapse over endoscopic remission alone. Albeit transmural remission rate (TRR) in CD patients treated with anti-TNF drugs in first line has been well explored, data on TRR using vedolizumab (VDZ) or ustekinumab (UST) as second-line therapy for CD are still limited. The aim of this study was to evaluate the TRR in CD patients in maintenance treatment, comparing adalimumab (ADA) in first line with VDZ/UST in second line. Methods From 2018 to 2022 we performed a real world observational longitudinal study evaluating the TRR in all consecutive CD patients in a 2-years maintenance treatment with ADA in first line compared with those treated by VDZ or UST in second line. HBI, fecal calprotectin (FC), SES-CD, and bowel wall thickness (BWT) at ultrasound were analyzed in all patients at the baseline (T0) and after 2 years of maintenance treatment (T1). Clinical remission was defined when HBI was <4. Endoscopic remission was defined when SES-CD was <2. Transmural remission was defined when BWT was <3 mm at a "per-patient" analysis. In accordance with recent literature, laboratory remission was defined when FC was <94 ug/gr. Results One hundred and sixty-one CD patients (78 ADA, 41 VDZ, 42 UST) were included in the study. At T1, TRR was recorded in 39.7% of CD patients treated in first line with ADA, and in 17.1% and 21.4% for VDZ and UST, respectively, in second line (ADA vs VDZ/UST: p<0.05; VDZ vs UST: p 0.6). Endoscopic remission rate was 50% for patients treated in first line with ADA, and 31.7% and 35.7% for second line VDZ and UST, respectively (ADA vs VDZ/UST: p<0.05; VDZ vs UST: p 0.7). Laboratory remission rate was 53.8% for patients treated in first line with ADA, and 29.3% and 35.7% for VDZ and UST in second line, respectively (ADA vs VDZ/UST: p<0.05; VDZ vs UST: p=0.5). Clinical remission rate was 58.9% for patients treated in first line with ADA, and 43.9% and 47.6% for second line VDZ and UST, respectively (ADA vs VDZ/UST: p=0.09; VDZ vs UST: p=0.2). Conclusion Our findings showed that in CD patients in maintenance treatment with biologics, ADA in first line showed a higher TRR compared with VDZ/UST in second line. Moreover, VDZ and UST showed similar TRR and other outcomes when used in second line.

P558 Clinical Effectiveness and Safety of Vedolizumab vs. Infliximab in Biologic-Naïve Ulcerative Colitis Patients: A Brazilian Real-World Multicentric Observational Study

Abstract Background Vedolizumab (VDZ) and infliximab (IFX), are considered first-line agents in the treatment of moderate to severe Ulcerative Colitis (UC). However, there are no head-to-head studies comparing the relative effectiveness of the two agents, and Real-world data on the effectiveness and safety of VDZ and IFX in UC are lacking in the Brazilian population. We aimed to compare effectiveness and safety of VDZ to IFX in Biologic-naïve UC patients. Methods We conducted a multicenter retrospective cohort study, including patients with moderate to severe UC (Total Mayo score 6-12, with an endoscopic subscore of 2 or 3) who treated with VDZ or IFX. The primary endpoints were: clinical remission, defined as a partial Mayo score (PMS) ≤2, endoscopic remission (endoscopic Mayo subscore of 1 or 0) and steroid-free clinical remission at week 52. Secondary endpoints included; clinical response at weeks 12 and 26, need for drug optimization, adverse events (AEs), need for hospitalization and colectomy, loss of response and biochemical remission (C-reactive protein [CRP] ≤ 0.5 mg/dl and/or fecal calprotectin [FC] ≤ 150 mcg/g) at week 52. Results A total of 174 UC (79 VDZ and 95 IFX) patients were included. Clinical remission and endoscopic remission at week 52 were achieved by 56 (70.8% vs 68.4%, p= 0.44) and 46 (58.2% vs 55.7%, p=0.18) of VDZ and IFX patients, respectively. Steroid-free clinical remission at week 52 was 84.2% and 54.1% in the VDZ and IFX group, respectively (p = 0.03). Clinical response at weeks 12 and 26 was reached in 80.0% vs 76.2%, p = 0.74 and in 71.4% vs 77.3%, p = 0.71 in the VDZ and IFX group, respectively. The need for drug optimization was higher for IFX than for VDZ (36.8% vs. 21.5%, p = 0.03). The incidence of AEs (26.3% vs 12.6%, p=0.03) and need for hospitalization (26.3% vs 11.4%, p=0.02) were higher for IFX than to VDZ patients. Secondary loss of response was similar in the two groups (16.4 % for VDZ and 16.8% for IFX, p = 1.00). Biochemical remission at week 52 was 75.0% for VDZ, and 63.9% for IFX, respectively (p=0,42). Conclusion In this real-world study VDZ and IFX had similar efficacy in inducing clinical remission, endoscopic remission, clinical response and biochemical remission at week 52. Compared to IFX, VDZ was superior in inducing steroid-free remission, in addition to having a better safety profile and less need for dose escalation. Both VDZ and IFX were effective treatment options in bio-naïve UC patients.

P547 Improved clinical and radiologic healing of Crohn’s perianal fistulas using a novel coordinated care model optimising medical and surgical treatments: A prospective real-world observational study

Abstract Background Despite best standard care, sustained healing rates of Crohn’s perianal fistulas remain low. A novel coordinated multi-disciplinary care model optimising medical and surgical treatment was established with the aim to improve fistula healing rates. Methods A prospective real-world observational study evaluated the efficacy of this new care model in adults with Crohn’s perianal fistulas. Patients seen through the new care model were sequentially invited to participate, between March 2021 to April 2022, and included irrespective of disease activity, duration, or prior treatments. Three dynamic stages of care were directed towards patients’ clinical disease activity: stage A, active disease, focused on medical and surgical treatment optimisation; stage B, optimised treatments with a seton in situ, focused on definitive surgical management; and stage C, healed disease, focused on treatment maintenance. Endpoints included: [1] clinical fistula healing after a minimum of 12 months follow-up; [2] changes in radiologic disease activity and fibrosis on serial magnetic resonance imaging; and [3] proportion of patients requiring treatment optimisation. Results Sixty patients were included. At baseline, 47% were in stage A, 5% stage B, and 48% stage C. Median age was 40 years (IQR: 32-49), 52% were male, median perianal disease duration was 9 years (IQR: 2-16), and median attendance through the preexisting service was 6 years (IQR: 3-9). After a median of 22 months follow-up (IQR: 16-25), 83% had clinical healing which was significantly higher than baseline rates at study inclusion (83 vs 48%, p<0.001). For patients in stage A at baseline, 68% achieved clinical healing with estimated clinical healing rates of 39% (95%CI: 24-60) and 85% (95%CI: 64-97) at 1 and 2 years, respectively. This paralleled a significant reduction in radiologic disease activity and increase in radiologic fibrosis, with radiologic remission observed in 51% and radiologic response in 47% overall (Table 1). Patients who achieved clinical healing had significantly less radiologic disease activity and greater fibrosis compared to patients with non-healing fistulas. Overall, 53% had biologic dose escalation and 10% switched to an alternative biologic agent with the new care model. Thirty-seven percent underwent a median of two perianal surgical interventions (IQR: 1-3), 15% had closure or ablative techniques performed, and 15% had seton removal only. Conclusion A novel coordinated multi-disciplinary care model optimising medical and surgical treatments resulted in high rates of clinical healing and improved radiologic disease activity and fibrosis of Crohn’s perianal fistulas. Controlled-matched studies evaluating treatment optimisation are needed.

P698 Effectiveness and Safety of Ustekinumab for Ulcerative Colitis: A Brazilian Multicentre Real-World Observational Study

Abstract Background Real-world data on the effectiveness and safety of ustekinumab (UST) in ulcerative colitis (UC) are lacking in Latin America. In this study, we aimed to describe the effectiveness and safety of UST in a real-world multicentre cohort of Brazilian patients with UC. Methods We conducted a multicentre retrospective observational cohort study, including patients with moderate to severe UC (Total Mayo score 6-12, with an endoscopic subscore of 2 or 3) who received UST. The co-primary endpoints were clinical remission, defined as a total Mayo score ≤2 at 1 year, with a combined rectal bleeding and stool frequency subscore of ≤1, and endoscopic remission (endoscopic Mayo subscore of zero) within one year from baseline. Secondary endpoints included clinical response between weeks 12-16, endoscopic response within one year of starting UST, steroid-free clinical remission at week 52, and biochemical remission at week 52. We also evaluated UST treatment persistence and safety. Results A total of 50 patients were included (female, n=36, 72.0%), with a median disease duration of 9.2 years (1-27). Most patients had extensive colitis (n=38, 76.0%), and 43 (86.0%) were steroid-dependent at baseline. Forty patients (80.0%) were previously exposed to biologics (anti-TNF drugs, n=31; vedolizumab [VDZ], n=27). The co-primary endpoints of clinical remission and endoscopic remission at 1 year were achieved by 50.0% and 36.0% of patients, respectively. Clinical response at weeks 12-16 was 56.0%, endoscopic response, steroid-free clinical remission, and biochemical remission at week 52 were 68.0%, 67.4%, and 50.0%, respectively. The UST treatment persistence rates at 24 months was 73.7%. During the follow-up, 10 patients (20.0%) were hospitalized, mostly due to disease progression, and three patients required colectomy. Nine patients (18.0%) discontinued the drug mainly due to a lack of effectiveness. Twenty-six adverse events (AEs) were reported, 15 of which were considered as serious AEs. Conclusion This is the first real-world experience study to report the effectiveness and safety of UST specifically in a Latin American population. In this real-world cohort of difficult-to-treat UC patients, UST was associated with improvements in clinical, biochemical, and endoscopic outcomes. The safety profile was favorable, consistent with the known profile of UST.

Efficacy and safety of perampanel as the first add-on therapy for children with epilepsy: A real-world multicenter prospective observational study

ObjectivePerampanel (PER) is a new anti-seizure medication (ASM) with a novel mechanism of action. This study aimed to determine the efficacy and safety of PER when added to monotherapy in children and adolescents (age, 4–18 years) with epilepsy. MethodA multicenter prospective observational study was performed on children and adolescents (age, 4–18 years) with epilepsy who did not respond to ASM monotherapy between July 2021 and October 2022. PER was used as the first add-on therapy for the enrolled patients. Seizure-free rate, response rate, inefficacy rate, and drug retention rate were the main observation indicators during the 6 months of treatment. The patients were grouped based on treatment efficacy, and factors affecting efficacy were statistically analyzed. Adverse reactions were also recorded. ResultsIn this study, 93 patients with epilepsy were enrolled; among them, 9 patients were lost to follow-up (attrition rate, 9.7 %), and 84 were included in the analysis. Five patients with unknown efficacy discontinued taking PER early due to intolerable adverse reactions, and 79 patients (48 males, 31 females; mean age, 11.0 ± 3.9 years) finally remained. Genetic epilepsy and structural epilepsy were found in 22 patients and 36 patients, respectively. The mean duration of epilepsy history at the time of PER initiation was 4.0 ± 3.8 years, and the mean maintenance dosage of add-on PER was 4.5 ± 1.8 mg/day (equivalent to 0.14 ± 0.07 mg/kg/day). Among the 79 patients, 28 patients were diagnosed with epilepsy syndrome, including 13 patients having self-limited epilepsy with centrotemporal spikes, among whom 9 patients were seizure-free after adding PER during the 6-month follow-up (seizure-free rate, 69.2 %). For these 79 patients, the seizure-free, response, and retention rates at the end of follow-up were 45.6 %, 74.7 %, and 82.1 %, respectively. Among the 84 patients included in the analyses, adverse reactions occurred in 20 patients, mainly dizziness (8 patients), somnolence (6 patients), and irritability (4 patients), and 4 patients developed two adverse reactions simultaneously. Univariate analyses revealed statistically significant differences in efficacy between groups with structural and non-structural epilepsy and between groups with different baseline concomitant ASMs, suggesting that these factors affected the efficacy of PER as the first add-on therapy. ConclusionThe overall response rate of PER as the first add-on therapy for children and adolescents with epilepsy who were followed up for 6 months was 74.7 %, indicating a relatively favorable safety and tolerability profile. The group of the baseline concomitant ASM administered and the etiological classification of epilepsy as either structural or non-structural were the factors influencing the efficacy of PER as the first add-on therapy.

A Real-World Observational Study to Evaluate the Safety and Effectiveness of Fluticasone Furoate-Oxymetazoline Fixed Dose Combination Nasal Spray in Patients with Allergic Rhinitis.

Allergic rhinitis (AR) has shown an increasing prevalence leading to a considerable medical and social burden. Nasal congestion is the cardinal symptom of AR, and the upper respiratory tract is most affected by this long-lasting ailment. Intranasal corticosteroids alleviate nasal congestion, along with other symptoms of AR, but their effect is not evident immediately. Oxymetazoline has a rapid onset of action, but its use should be limited to 3-5days. The study aimed to evaluate the safety and effectiveness of the fixed-dose combination nasal spray containing fluticasone furoate and oxymetazoline hydrochloride (FF+OXY) 27.5/50mcg once daily in patients with AR in a real-world clinical setting. The study was a prospective, open-label, single-arm, multicenter, real-world observational study conducted in patients with AR for a period of 28days. Patients (n=388) with a diagnosis of AR were treated with a combination of FF+OXY nasal spray. Total nasal symptom score (TNSS), total ocular symptom score (TOSS) and total symptom score (TSS) were documented at baseline and at the end of study period. The overall effectiveness of treatment with FF + OXY was rated by the investigators as very good/good/satisfactory/poor (4-point Likert scale) for each patient. Treatment with FF+OXY resulted in significant reduction in the TNSS, TOSS and TSS, from 7.18±3.38 at baseline to 0.20±0.84 (p<0.001), from 2.34±2.29 at baseline to 0.09±0.53 (p<0.001), from 9.51±4.94 at baseline to0.29±1.32 (p<0.001) at 28days respectively. With respect to effectiveness, the investigators reported very good effectiveness in 52.12% of patients. No serious adverse events were reported. The fixed-dose combination of once-daily fluticasone furoate and oxymetazoline hydrochloride nasal spray 27.5/50mcg was effective in relieving the nasal congestion and reduction of TNSS, TOSS and TSS in patients suffering from AR. The combination was safe and well tolerated with no rebound congestion throughout the treatment period.

Factors associated with sex differences in viral non-suppression in the Swedish InfCareHIV cohort: An observational real-world study.

Women living with HIV are underrepresented in clinical trials assessing outcomes of antiretroviral treatment (ART), justifying the need for observational studies. We investigated differences in viral non-suppression between women and men in the Swedish InfCareHIV cohort and analysed results in relation to biological and socio-demographic variables and patient-reported outcome measures (PROMs). The study included people living with HIV (PLWH) aged ≥18 years, who initiated ART at least 6 months prior to inclusion. Data from the InfCareHIV registry 2011-2018 were collected. Associations between variables and HIV RNA ≥50 copies/mL were investigated in uni- and multivariable analyses using generalized estimating equations, providing relative risks (RRs) as effect size. The study included 38% (n = 2981) women. Women were more likely to have HIV RNA ≥50 copies/mL than were men [RR = 1.20, 95% confidence interval (CI): 1.10-1.31]. After adjusting for origin and route of transmission, sex at birth was no longer associated with viral non-suppression. PROMs were available in 52.4% of PLWH, and items associated with viral non-suppression were impaired adherence in women (RR = 2.38, 95% CI: 1.79-3.17) and men (RR 1.84, 95% CI: 1.40-2.42), and experience of side effects in women (RR = 1.49, 95% CI: 1.10-2.02). This observational study found a 20% higher relative risk of viral non-suppression in women than in men and the difference was associated with socio-demographic factors. The associations between PROMs and viral non-suppression varied between women and men. PROMs are important health outcomes that may identify PLWH in need of support to achieve viral non-suppression.

Impact of lipodystrophy on health-related quality of life: the QuaLip study

BackgroundLipodystrophy is a rare disease characterized by loss of adipose tissue. Natural history studies have demonstrated significant burden of disease; however, there is limited data on the impact of lipodystrophy on quality of life (QoL) and psychoemotional well-being. The QuaLip study is a prospective observational real-world study that aims to determine the impact of lipodystrophy on QoL and psychoemotional well-being and explore subjective burden of the disease. Sixty-seven adult patients and eight pediatric patients with lipodystrophy were included. Patients were followed up for 24 months and assessments were repeated every three months. Patients were examined by licensed psychiatrists at baseline, and at year 1 and year 2 visits.ResultsEighteen (27.69%) of 65 adult patients (two subjects refused psychiatric assessment) were diagnosed with a psychiatric disorder (e.g., depressive episodes, mixed anxiety and depressive disorder, anxiety disorder, adjustment disorder, recurrent depression, panic disorder, generalized anxiety disorder, unspecified mood disorder, nonorganic sleep disorder, post-traumatic stress disorder, depressive episode comorbidity, social phobia and obsessive–compulsive disorder comorbidity). Lipodystrophy disease and QoL questionnaires revealed a significant disease burden over the study period. More than one-third of patients reported depression symptoms on the Beck Depression Inventory and more than one-fourth of the patients reported significant hunger throughout the study period. Physical appearance, fatigue, and pain contributed to the disease burden. QoL scores were lower in patients with psychiatric disease and in those with poor metabolic control. Attention deficit hyperactivity disorder, depressive disorder, sub-threshold depressive symptoms, obsessive–compulsive disorder, appetite problems, and issues with physical appearance were identified in selected pediatric subjects.ConclusionsLipodystrophy has a significant impact on QoL and psychoemotional well-being. Psychiatric disorders seem to be underdiagnosed among patients with lipodystrophy.

Efficacy and safety of belimumab in patients with lupus nephritis: a real-world retrospective observational study.

To evaluate the differences in efficacy and safety between Lupus Nephritis (LN) patients who received belimumab plus standard therapy and those who received only standard therapy in real world practice. Patients diagnosed with LN at the First Affiliated Hospital of Wenzhou Medical University from November 2012 to July 2023 were identified, and eligible cases were divided into two groups according to whether they received additional treatment with belimumab during the course of the disease. A total of 1,169 LN patients were identified from our follow-up database. 112 patients receiving add-on treatment with belimumab (BLM group) and 112 control patients matched for relevant baseline characteristics were enrolled in this study. The median duration of treatment with belimumab was 13.82 [7.24, 20.29] months. Compared with the control group, the BLM group had more significant improvement in disease activity indicators such as serum albumin and complement levels, significantly lower B cell count, immunoglobulin, and earlier first attainment of renal remission, but there was no significant improvement in renal function and kidney-related events or death during the 2-year follow-up period. In the BLM group, the treatment effect of belimumab was more prominent in patients with lower levels of proteinuria. The safety profile of belimumab treatment was favorable, with a lower incidence of respiratory tract infection in the BLM group than in the control group during the follow-up period (p= 0.015). This real-world study revealed that add-on treatment with belimumab provided better disease remission, and the therapeutic effect was more significant in patients with lower proteinuria levels. In addition, it had a favorable safety profile and reduced the risk of respiratory tract infection.

A real-world observational study assessing relationships between excessive daytime sleepiness and patient satisfaction in obstructive sleep apnea

Objectives/BackgroundTo estimate prevalence and severity of excessive daytime sleepiness among patients with obstructive sleep apnea (OSA) who were prescribed treatment; assess perception and satisfaction of OSA-related care; describe relationships between excessive daytime sleepiness, treatment adherence, and patient satisfaction. Patients/methodsA national population-based cross-sectional sample of US adults with clinician-diagnosed OSA was surveyed in January 2021 via Evidation Health's Achievement App. Patients completed the Epworth Sleepiness Scale, rated satisfaction with healthcare provider and overall OSA care, and reported treatment adherence. Covariates affecting excessive daytime sleepiness (average weekly sleep duration, treatment adherence, sleepiness-inducing medications, age, sex, body mass index, nasal congestion, smoking status, and comorbidities) were adjusted in multivariate regression models. ResultsIn 2289 participants (50.3 % women; 44.8 ± 11.1 years), EDS was highly prevalent (42 %), and was experienced by 36 % of patients with high positive airway pressure (PAP) therapy adherence. Each additional hour of nightly PAP use was associated with improved sleepiness (a 0.28-point lower Epworth score; p < 0.001). Excessive daytime sleepiness was associated with lower patient satisfaction with healthcare providers and overall care (OR [95 % CI] 0.62 [0.48–0.80] and 0.50 [0.39–0.64], respectively; p < 0.0001), whereas PAP adherence was associated with higher patient satisfaction (OR [95 % CI] 2.37 [1.64–3.43] and 2.91 [2.03–4.17]; p < 0.0001), after adjusting for confounders. ConclusionsIn a real-world population-based study of patients with OSA, excessive daytime sleepiness was highly prevalent and associated with poor patient satisfaction ratings. Better patient-centered care among patients with OSA may require interventions aimed at addressing excessive daytime sleepiness and treatment adherence.

Effectiveness and safety of adalimumab in patients with intestinal Behçet’s disease: a real-world prospective observational study in South Korea

BackgroundIntestinal Behçet’s disease (BD) is characterized by typical gastrointestinal ulcers in patients with BD followed by complications such as bleeding, perforation and fistula. Biologic agents are currently under active investigation to delay the disease course. Various data regarding infliximab are available, but there is relatively lack of data regarding adalimumab.MethodsThis was a multicenter, real-world prospective observational study to evaluate the effectiveness and safety of adalimumab in intestinal BD. The primary endpoint was disease activity at each follow up, including disease activity index for intestinal Behçet’s disease (DAIBD), serum C-reactive protein (CRP) level, and endoscopic findings. The secondary endpoint was the incidence of adverse drug reactions (ADRs).ResultsA total of 58 patients were enrolled and 8 of them were excluded. Adverse events were reported in 72.0% of patients with 122 events. ADRs were reported in 24.0% with 28 events. For adverse events, arthralgia was most commonly reported (13.1%: 16/122) and only one experienced critical adverse event (0.82%, 1/122: death due to stroke). On multivariable regression analysis, a longer disease duration was significantly associated with decreased ADRs [Odds ratio 0.976 (0.953–0.999, 95% CI); p = 0.042]. Clinical response rates as assessed by DAIBD were 90.9% at Week 12 and 89.7% at Week 56, respectively. The mean serum CRP level at baseline was significantly decreased after 12 weeks (3.91 ± 4.93 to 1.26 ± 2.03 mg/dL; p = 0.0002).ConclusionAdalimumab was found to be safe and effective in Korean patients with intestinal BD. A longer disease duration was significantly associated with decreased ADRs.

Conversion surgery for initially unresectable hepatocellular carcinoma using lenvatinib combined with TACE plus PD-1 inhibitor: A real-world observational study

BackgroundConversion therapy for initially unresectable hepatocellular carcinoma (iuHCC) using lenvatinib combined with transcatheter arterial chemoembolization (TACE) plus a PD-1 inhibitor (LTP) has achieved promising results. However, further comparative research is necessary to evaluate the effectiveness and safety of conversion surgery (CS) for iuHCC. MethodsData for 32 consecutive patients with iuHCC receiving CS and 419 consecutive patients with resectable HCC receiving initial surgery (IS) between November 2019 and September 2022 were collected retrospectively. After propensity score matching (PSM), 65 patients were selected. ResultsBefore matching, the CS group had longer EFS (not reached vs. 12.9 months, P < 0.001) and similar OS (not reached vs. not reached, P = 0.510) compared with the IS group. Similar results for EFS (P = 0.001) and OS (P = 0.190) were obtained after matching. The multivariable Cox model (HR = 0.231, 95% CI: 0.105–0.504; P < 0.001) and subgroup analyses confirmed that CS could improve EFS. The CS group had significantly lower incidence of microvascular invasion (MVI) than the IS group (3.1% vs. 50.4%, P < 0.001). Moreover, the two groups had similar safety profiles. ConclusionsCS is effective and safe for patients with iuHCC receiving LTP. LTP has the potential to reduce risk factors for postoperative recurrence, especially MVI, which may influence surgical decision-making.

Using Conversational AI to Facilitate Mental Health Assessments and Improve Clinical Efficiency Within Psychotherapy Services: Real-World Observational Study.

Most mental health care providers face the challenge of increased demand for psychotherapy in the absence of increased funding or staffing. To overcome this supply-demand imbalance, care providers must increase the efficiency of service delivery. In this study, we examined whether artificial intelligence (AI)-enabled digital solutions can help mental health care practitioners to use their time more efficiently, and thus reduce strain on services and improve patient outcomes. In this study, we focused on the use of an AI solution (Limbic Access) to support initial patient referral and clinical assessment within the UK's National Health Service. Data were collected from 9 Talking Therapies services across England, comprising 64,862 patients. We showed that the use of this AI solution improves clinical efficiency by reducing the time clinicians spend on mental health assessments. Furthermore, we found improved outcomes for patients using the AI solution in several key metrics, such as reduced wait times, reduced dropout rates, improved allocation to appropriate treatment pathways, and, most importantly, improved recovery rates. When investigating the mechanism by which the AI solution achieved these improvements, we found that the provision of clinically relevant information ahead of clinical assessment was critical for these observed effects. Our results emphasize the utility of using AI solutions to support the mental health workforce, further highlighting the potential of AI solutions to increase the efficiency of care delivery and improve clinical outcomes for patients.

Real-world observational study on the long-term effect of L-glutamine treatment on renal parameters of adult and pediatric patients with sickle cell disease.

Sickle cell disease (SCD) is a rare genetic blood condition affecting millions worldwide. Oxidative stress is a key player in the pathogenesis of SCD and its comorbid consequences. Renal function impairment is a common complication of SCD in both pediatric and adult patients with serious consequences leading to increased risk of mortality. In this observational real-world study, we are reporting the long-term (120 weeks) renal function in 10 patients treated with L-glutamine. Ten patients (4 pediatric and 6 adults), with confirmed diagnoses of SCD (HbSS genotype), were enrolled, these included four patients from Qatar with Arab Indian haplotype and six patients from French Guiana with African haplotype. All patients were treated with L-glutamine oral powder (~0.3 g/kg body weight, Endari®) twice daily for 120 weeks. Clinical events and laboratory parameters (renal function, hemoglobin, reticulocytes, and lactate dehydrogenase [LDH]) were measured at baseline, 48, and 120 weeks. The study showed that with L-glutamine treatment there were improvements in renal and hematological parameters with no vaso-occlusive crisis at both 48-and 120-week follow-up time points in all 10 patients. Improvements were seen in the albumin creatinine ratio (ACR) from baseline to 48 weeks (mean [Standard deviation SD] ACR: -4.19 [9.81] mg/g) and 120 weeks (mean [SD] ACR: -12.31 [21.09] mg/g). Mean (SD) increase in hemoglobin concentrations from baseline to 48 weeks and 120 weeks was 0.72 (1) g/dL and 1.41 (0.79) g/dL, respectively. Mean (SD) reticulocyte counts and LDH levels decreased from baseline to 48 weeks (mean [SD] change from baseline to 48 weeks, reticulocyte counts: -40.30 [101.58] × 109 cells/L; LDH levels: -259 [154.93] U/L) and 120 weeks (mean [SD] change from baseline to 120 weeks, reticulocyte counts: -58.30 [128.38] × 109 cells/L; LDH levels: -344.80 [274.63] U/L). This is one of the first studies that assessed the long-term renal outcomes in SCD using L-glutamine. L-glutamine improved the renal function in patients with SCD along with improvements in clinical outcomes and hemolysis, from 48 weeks and sustained through 120 weeks of treatment.

Coagulation Function and Type 2 Diabetic Kidney Disease: A Real-World Observational Study

Objectives. Type 2 diabetic kidney disease (DKD), a chronic microvascular complication of diabetes, may exhibit a complex interrelation with coagulation function. This study is aimed at elucidating the association between coagulation function and DKD. Methods. This was a real-world observational study conducted in Beijing, involving 2,703 participants. All patients with diabetes were classified into two groups, viz., DKD and non-DKD groups. Effect magnitudes are denoted as odds ratios (OR) with a 95% confidence interval (CI). To mitigate potential bias in group comparisons, we employed propensity score matching (PSM). Results. After adjusting for variables such as age, gender, systolic blood pressure (SBP), hemoglobin A1c (HbA1c), triglyceride (TG), c-reactive protein (CRP), platelet (PLT), and serum albumin (sALB), it was discerned that fibrinogen (FIB) (OR, 95% CI, P : 1.565, 1.289-1.901, &lt;0.001) and fibrinogen degradation products (FDP) (1.203, 1.077-1.344, 0.001) were significantly correlated with an increased risk of DKD. To facilitate clinical applications, a nomogram prediction model was established, demonstrating commendable accuracy for DKD prediction. Conclusions. Our findings suggest that elevated levels of FIB and FDP serve as potential risk indicators for DKD, and coagulation function may play an important role in the occurrence and development of DKD.

Association of autoimmune diseases with the occurrence and 28-day mortality of sepsis: an observational and Mendelian randomization study

BackgroundObservational studies have indicated a potential association between autoimmune diseases and the occurrence of sepsis, with an increased risk of mortality among affected patients. However, whether a causal relationship exists between the two remains unknown.MethodsIn the Mendelian randomization (MR) study, we accessed exposure Genome-wide association study (GWAS) data from both the MRC Integrative Epidemiology Unit (MRC-IEU) and the FinnGen consortium. GWAS data for sepsis and its 28-day mortality were obtained from MRC-IEU. We employed univariable, multivariable, and reverse MR analyses to explore potential associations between autoimmune disorders and sepsis and its 28-day mortality. Additionally, a two-step mediation MR analysis was performed to investigate indirect factors possibly influencing the relationship between autoimmune disorders and sepsis. Afterward, we conducted an observational analysis to further explore the relationship between autoimmune disease and occurrence as well as 28-day mortality of sepsis using a real-world database (the MIMIC-IV database). A cohort of 2537 patients diagnosed with autoimmune disease were extracted from the database for analysis. Multivariable logistic regression models were used to confirm the association between autoimmune diseases and the occurrence of sepsis, as well as the 28-day mortality associated with sepsis.ResultsIn univariable MR analysis, there appeared to be causal relationships between genetically predicted type 1 diabetes (OR = 1.036, 95% CI = 1.023–1.048, p = 9.130E-09), rheumatoid arthritis (OR = 1.077, 95% CI = 1.058–1.097, p = 1.00E-15) and sepsis, while a potential causal link was observed between celiac disease and sepsis (OR = 1.013, 95% CI = 1.002–1.024, p = 0.026). In a subsequent multivariable MR analysis, only rheumatoid arthritis was found to be independently associated with the risk of sepsis (OR = 1.138, 95% CI = 1.044–1.240, p = 3.36E-03). Furthermore, there was no causal link between autoimmune disorders and 28-day mortality from sepsis. In reverse MR analysis, sepsis was suggested to potentially trigger the onset of psoriasis (OR = 1.084, 95% CI = 1.040–1.131, p = 1.488E-04). In the real-world observational study, adjusting for multiple confounders, rheumatoid arthritis (OR = 1.34, 95% CI = 1.11–1.64, p = 0.003) and multiple sclerosis (OR = 1.31, 95% CI = 1.03–1.68, p = 0.02) were associated with a higher risk of sepsis. In addition, we did not find that autoimmune diseases were associated with 28-day mortality from sepsis.ConclusionBoth in observational and MR analysis, only rheumatoid arthritis is highly correlated with occurrence of sepsis. However, autoimmune disease was not associated with an increased 28-day mortality in patient with sepsis. Sepsis may increase the risk of developing psoriasis.

Antiresorptive injections reduce refracture incidence in elderly spinal or hip fractures: A real-world observational study

Antiresorptive injections reduce refracture incidence in elderly spinal or hip fractures: A real-world observational study

S151 Biologic Therapy Sequencing in Ulcerative Colitis: A Real-World Observational Study of Second-Line Therapy After Vedolizumab

S151 Biologic Therapy Sequencing in Ulcerative Colitis: A Real-World Observational Study of Second-Line Therapy After Vedolizumab

Effect of Ursodeoxycholic Acid for Sars-Cov-2 Prevention in Hematological Malignancies: An Observational Real-World Study

Introduction: Disease-2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).After the adjustments and optimizations of Chinese control strategies and policies for COVID-19 on December of 2022, clinical exposure increased rapidly.There are greater concerns for patients with hematological malignancies, particularly those who have undergone hematopoietic stem cell transplantation (HSCT). One promising preventive measure that has recently gained attention is ursodeoxycholic acid (UDCA). This drug is mainly used to treat biliary tract disease and other hepatobiliary disorders, particularly primary biliary cholangitis (Hirschfield GM, et al. Gut 2018); and also has been widely used at a higher dosage to prevent sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) after HSCT in the clinical setting. Recently, Brevini et al. demonstrated that UDCA downregulated ACE2 expression by reducing farnesoid X receptor signaling, resulting in reduced SARS-Cov-2 infection (Brevini T, et al. Nature 2022), indicating that pharmacological prophylaxis using UDCA against COVID-19 in vulnerable groups was feasible, but the clinical data to support this practice is limited. Therefore, we aim to present epidemiological data for Chinese patients with hematological malignancies during this epidemic wave, and investigate the protection effects offered by UDCA against COVID-19 in these patients. Methods: This investigation was a single-center, observational real-world study, and was granted by the ethics committee of the Institute of Hematology &amp; Blood Diseases [No. QTJ2023012-EC-1]. The transplant patients were included in the “NICHE-SKIRT” project (Cao Y, et al. Am J Hematol 2023). Informed consent for the acquisition and the use of patient samples was obtained. Data for hospitalized patients at the Institute of Hematology &amp; Blood Diseases Hospital (Tianjin, China) was reviewed between December 2022 and January 2023. COVID 19 status was assessed using hospital-reported PCR and/or antigen tests for twice a week. We analyzed follow-up records up to 14th February 2023. The primary end-point was the rate of COVID -19 infection. Results: We enrolled 393 patients with a median age of 38 years old. At the cutoff date, 297 patients (75.6%) had confirmed COVID-19 infection (72.5% in the allo-HSCT cohort). Among the 273 evaluable patients, the majority (64.8%) had asymptomatic/mild disease. The severe/critical patients accounted for only 15.8%. Seven hospitalized patients had died from COVID-19 by the last follow-up date. The median period between COVID-19 diagnosis and death was 15 days (range: 2-32 days). Lower proportion of CD3+CD4+T cells associated with more severe COVID-19 clinical spectrum (Asymptomatic/mild [n = 97] moderate [n = 46], adjusted P = 0.001; Asymptomatic/mild vs. severe/critical [n = 25], adjusted P = 0.036). Among these patients, 163 received UDCA (UDCA group) while 230 did not (non-UDCA group). The COVID-19 infection rate was lower in the UDCA group (69.9% vs. 79.6%; P= 0.039). However, patients in the UDCA group had a higher ECOG score and Charlson Comorbidity Index (Table 1), suggesting that they were more likely to have underlying health conditions. To account for this potential bias, we performed PSM, which confirmed that the UDCA group had a significantly lower rate of COVID-19 infection compared to the non-UDCA group (69.0% vs. 81.0%; P = 0.049) in the validated cohort. Univariate logistic regression analysis showed that only UDCA administration was associated with COVID-19 infection (OR: 0.598; P = 0.029). To further investigate the effect of UDCA in specific populations, we carried out an exploratory analysis. Our results suggest that males, patients with a CCI ≥ 2, a history of smoking, and those with acute lymphoblastic leukemia (ALL) may benefit the most from the protective effect of UDCA against COVID-19. Conclusion: This study aimed to investigate the prevalence and clinical outcomes of SARS-CoV-2 infections in Chinese patients with hematologic disorders during the COVID-19 epidemic that began at the end of 2022. Our findings provide support for preclinical studies suggesting that UDCA may have marginal benefit in protecting against COVID-19. However, prospective studies with a higher dose of UDCA need to be performed.