A Covid -19 Virtual Ward Model: A Preliminary Retrospective Clinical Evaluation From a UK District General Hospital

Objective: This study aims to evaluate the safety, utilization, ability to reduce length of hospitalization and overall outcomes of a COVID-19 virtual ward providing ongoing treatment at home. Method: A retrospective single-center study of patients discharged to the COVID-19 virtual “step down” ward between January 27th 2021 and March 2nd 2021. The referral process, length of hospitalization, length of stay on the virtual ward, readmissions, and ongoing treatment requirements including supplemental oxygen, antibiotics, and/or steroids were all noted. Results: A total of 50 patients were referred to the virtual ward. 43 referrals were accepted, 39 of which were from the respiratory ward. Four patients were readmitted, all due to hypoxia. All readmissions occurred within 5 days of discharge. 72% (n = 31) were discharged home with an ongoing oxygen requirement. 14.3% of patients were discharged with antibiotics only, 9.5% with steroids only and 23.8% with both antibiotics and steroids. The mean length of hospital stay for patients discharged to the virtual ward was 10.3 ± 9.7 days and 11.9 ± 11.6 days for all covid positive patients during this time. On average, patients spent 13.7 ± 7.3 days on the virtual ward. The average number of days spent on oxygen on the virtual ward was 11.6 ± 6.0 days. Conclusion: The virtual ward model exemplifies the potential benefits of collaborative working between primary and secondary care services, relieving pressure on hospitals whilst providing ongoing treatments at home such as supplemental oxygen. It also facilitates an early supported discharge of clinically stable patients with an improving clinical trajectory by managing them in the community.

Desistance from crime following substance use treatment: the role of treatment retention, social network and self-control

Background Reductions in crime are often reported following substance use treatment. We explore the relationship between desistance from crime, treatment type, treatment retention and positive changes in known risk factors for crime. Methods We used data from the NorComt-study; a longitudinal study of substance users (n = 341) enrolled in comprehensive treatment in Norway (2012–2015). At treatment initiation (T0) and 1 year later (T1), we collected self-reported data on criminal involvement, treatment, substance use, social network and self-control. We calculated adjusted odds ratios (aOR) and 95% confidence intervals (CI) with multinomial logistic regression analysis. Results Overall, 1 year following treatment initiation 69% reported desistance from crime, 18% reported continued crime and 12% reported no crime at all in the study period. Desistance was high for OMT patients in ongoing treatment (79% desisted) and for inpatients regardless of treatment status (79–93% desisted), while not as high among OMT patients with interrupted treatment (47% desisted). For participants that continued crime during follow-up, the average number of criminal acts per month was reduced (p < 0.001). Desistance at follow-up was associated with being older (aOR: 1.05, CI: 1.00–1.10), inpatient treatment (aOR: 3.71, CI: 1.12–12.29), being in ongoing treatment (inpatient or OMT) (aOR: 2.90, CI: 1.01–8.36), having no stimulant use in the study period (aOR: 4.86, CI: 1.72–13.70), leaving a substance using social network (aOR 2.87, CI: 1.15–7.18) and improvement in self-control score (aOR: 1.08, CI: 1.04–1.13). Conclusions Retention in treatment is particularly important for crime outcomes among OMT patients. Positive changes in social network and self-control are potential contributors to desistance from crime. Targeted interventions towards crime reduction are recommended for patients with stimulant use, which appears to be a persistent risk factor for crime over time.

O03 Continuation of golimumab (anti-TNF) in a patient with SpA and low-risk prostate cancer, what is the right decision?

Case report - Introduction Golimumab is an anti-TNF alpha drug used in the treatment of inflammatory arthritis including spondyloarthritis (SpA). The introduction of this drug class has revolutionised the treatment of SpA over the last 20 years with significantly improved patient outcomes. Despite their treatment benefits multiple adverse effects of TNF-alpha inhibition have been reported through clinical trials including a possible increased risk of malignancy. We describe a case of a patient with known ankylosing spondylitis (AS) on golimumab who was diagnosed with low-grade prostate carcinoma and discuss the factors taken into consideration in guiding our decision-making process regarding ongoing treatment. Case report - Case description A 57-year-old gentleman with known AS presented to the rheumatology clinic for routine review. His AS was well controlled, and he had been taking golimumab for the past 3 years. Upon review he was in clinical remission with a CRP &lt;1 and ESR 5. Prior to the initiation of anti-TNF therapy his disease had been poorly controlled. However, following commencement his symptoms had significantly improved and he was able to work as a professional sports coach whilst bringing up a young family. On review he had recently been diagnosed with low-risk cancer of the prostate by his urologist. A prostate biopsy found Gleason 3 + 3 adenocarcinoma involving 2 out of 22 cores on each side, with a prostate specific antigen (PSA) of 3.95ng/ml. An MRI had shown chronic prostatitis. He was in the lowest risk category of grade group 1 prostate cancer and no treatment for his prostate cancer was indicated. The plan from his urology team was active surveillance with PSA monitoring. Whilst being investigated for possible malignancy his golimumab had been held for six months and during this period he had a significant flare in symptoms. He experienced severe back pain that forced him to stop working. Following his prostate cancer diagnosis, golimumab was restarted by his urologist with a subsequent improvement in his AS symptoms. To guide ongoing treatment his case was reviewed in the local biologics multi-disciplinary team meeting, alongside close communication with his urologist. The patient was informed of the risks of continuing golimumab in relation to his malignancy. Despite this he was reluctant to stop anti-TNF therapy or switch to another treatment, citing concerns about the impact it might have on his symptoms and ability to work. Case report - Discussion This case highlights the complexities involved in the management of a patient on anti-TNF therapy, who receives a diagnosis of malignancy, particularly when the diagnosis is classed as low risk. Traditionally anti-TNF therapy was contraindicated for patients with a history of a solid organ tumour within the previous five years. The British Society of Rheumatology (BSR) guidelines recommends that patients should be advised that there is no conclusive evidence for an increased risk of solid organ tumours but that on-going vigilance is required. A holistic patient-centred approach needs to be taken in these contexts, and consideration of cases on an individual basis is needed. Inter-disciplinary and multi-speciality team input, with the effective use of a biologics MDT, is crucial. The patient was understandably reluctant to stop his treatment due to the significant impact this may have on his quality of life. On liaison with his urologist his prostate cancer was in the lowest risk category with 99% 5-year survival rates with low risk of disease progression or spread. Evidence in this field to date has been conflicting and studies have predominantly focused on the safety of anti-TNFs in rheumatoid arthritis patients. Recent large national registry data has been reassuring. Few studies have looked at the AS and psoriatic arthritis anti-TNF treated population; however, a meta-analysis of RCTs found no evidence of increased incidence of malignancy. Taking into account his low-risk cancer, the patient’s wishes and clinical evidence in this field we have made to decision to continue anti-TNF treatment for now but with ongoing surveillance for any tumour progression. The patient will undergo urology follow up alongside regular PSA monitoring, and there will be a low threshold to stop or switch treatment in the future Case report - Key learning points

Lower response to BNT162b2 vaccine in patients with myelofibrosis compared to polycythemia vera and essential thrombocythemia

In a population of 42 Philadelphia negative myeloproliferative neoplasm patients, all on systemic active treatment, the likelihood of responding to anti-SARS-CoV-2 BNT162b2 vaccine at 2 weeks after the second dose was significantly lower in the ten patients with myelofibrosis compared to the 32 with essential thrombocythemia (n = 17) and polycythemia vera (n = 15) grouped together, both in terms of neutralizing anti-SARS-CoV-2 IgG titers and seroprotection rates (32.47 AU/mL vs 217.97 AU/mL, p = 0.003 and 60% vs 93.8%, p = 0.021, respectively). Ruxolitinib, which was the ongoing treatment in five patients with myelofibrosis and three with polycythemia vera, may be implicated in reducing vaccine immunogenicity (p = 0.076), though large prospective study is needed to address this issue.

Audit of ADHD medication prescription and monitoring in intellectual disability services, Greater Glasgow & Clyde

AimsStudies have shown that people with intellectual disability (ID) show a greater severity of attention deficit hyperactivity disorder (ADHD) symptoms and atypical presentation, as well as having a greater risk of developing comorbidities, such as challenging behaviour, anxiety, tic disorders and sleep problems. It is estimated that 1.5% of patients with ID will have a clinical diagnosis of ADHD.The aim of this audit was to find whether individuals with ID and ADHD, who are prescribed medication for ADHD are adequately monitored and reviewed in accordance with the ADHD medication prescription guidance by NICE and the Royal College of Psychiatrists (RCPsych).MethodThis audit looked at ADHD medication prescription for the ID population within Greater Glasgow & Clyde NHS. This is the 6th audit cycle where electronic records (EMIS) were analysed between 28/9/19 to 09/10/20. (The 5th cycle data collection period ended on 28/9/19). We collected data on all patients aged over 18 years.An audit tool was developed to find whether the following were documented; patient demographics, physical health monitoring, symptom severity, medication dosage, side effects, need for ongoing treatment and frequency of review. 100% of patients should have all components on the ADHD audit tool documented, as per NICE/ RCPsych prescription guidance.Result32 patients were identified as being diagnosed with ADHD prescribed medication. One patient was impacted by the COVID-19 pandemic which meant that the required monitoring was not fully carried out. The age ranged from 18 to 56 years. 75% had mild intellectual disability, 19% had moderate and 6% had severe, with no cases of profound intellectual disability. Blood Pressure/pulse was recorded in 84% of patients. Height/weight/ BMI was recorded in 81% of patients. 97% of patients had ADHD symptom severity, medication dosage, side effects, need for ongoing treatment and frequency of review recorded.ConclusionThere is further scope for improvement in the monitoring and documentation of physical health observations, however there was a significant improvement compared to the previous cycle of the audit. Other aspects of monitoring and documentation appear to be recorded in almost 100% of patients. This finding emphasises the challenges of physical health monitoring and compliance in psychiatry as a whole. We need to continue to encourage awareness and education around the physical health risks to our patients, not only due to their comorbidities but also as a result of the psychotropic medications we prescribe them.

An analysis of the reasons and motives of patients seeking telehealth-based second opinion for cancer.

e13621 Background: Incidence of cancer is rising with each passing year in India and a majority number of patients get diagnosed in later stages of disease that leads to poor outcomes. Studies have reported that patients and their caregivers feel the need to get more information about their treatment options making them opt for second opinions due to need for reassurance or inadequate time for communication with their treating oncologists. We sought to analyse the primary concerns and motives of patients seeking second opinion services through onco.com. Methods: A cohort of 918 eligible patients who availed online multidisciplinary tumour board opinion through Onco.com was included in the study. We analysed the primary concerns of 918 eligible patients who availed online second opinion through onco.com between January 2019 & December 2020. We looked at the specific questions they had for the multidisciplinary panel of oncologists. We also correlated the concerns with the stage of disease to understand if there was a variation for different stages of disease. Results: Of the total 918 patients, 864 had solid malignancies, out of which 16% had early (stage 1 & 2) disease, 27% had locally advanced (stage III) disease, 47% had metastatic disease & and 16% had recurrent disease. The most frequent motive for seeking a second opinion was the need for validation of ongoing treatment (72.5%) followed by enquiry for more advanced treatment options (37%), and to know any alternative treatment options (19%). Interestingly, only a minority of all patients were keen to know about clinical trials (3%). Conclusions: Our findings suggest that validation of ongoing treatment is the most frequent motive for patient driven second opinions in oncology. There was minimal interest to seek clinical trial options among patients, which could be due to general lack of awareness about clinical trials and some form of stigma associated with clinical trials due to negative perceptions and fears about adverse events. [Table: see text]

Intra-patient comparison from larotrectinib clinical trials in TRK fusion cancer: An expanded dataset.

3114 Background: Larotrectinib is a highly selective, CNS-active tropomyosin receptor kinase (TRK) inhibitor that demonstrated rapid and durable responses in three phase I/II single-arm studies of patients (pts) with TRK fusion cancer. In single-arm studies the growth modulation index (GMI) can be used to provide a comparative analysis. GMI is an intra-patient comparison that uses pts as their own control by comparing progression-free survival (PFS) on current therapy to time to progression or treatment failure (TTP) on the most recent prior therapy; namely the ratio of PFS/TTP (EMA Guidelines. Guideline on the Evaluation of Anticancer Medicinal Products in Man, EMA/CHMP/205/95 Rev.5). A GMI ratio ≥1.33 has been used as a threshold of meaningful clinical activity. In a previous analysis of 122 pts with TRK fusion cancer treated with larotrectinib, 84 pts (69%) had a GMI ≥1.33. Conversely, 38 pts (31%) had a GMI < 1.33, but of these, 9 pts were ongoing treatment and censored for PFS as of July 2019 (Italiano et al, ESMO 2020). Here, we report the GMI of this initial group with a longer follow-up as well as an expanded dataset to more accurately assess the treatment effect of larotrectinib in pts with TRK fusion cancer previously treated with ≥1 line of therapy. Methods: Pts with TRK fusion cancer from three clinical trials on larotrectinib treatment with ≥1 prior line of systemic therapy were eligible for retrospective GMI analysis. TTP on the prior line of therapy was investigator-assessed. PFS on larotrectinib was determined by independent review committee per RECIST v1.1. Pts who had not progressed were censored as of date of last visit. Kaplan–Meier (KM) analyses were used to estimate median GMI, in addition to median PFS and TTP. The data cut-off was July 2020. Results: With an extended follow up of the original 122 pts, 90 (74%) pts had a GMI ≥1.33, including 6 of the 9 pts who were previously censored with a GMI < 1.33 and ongoing treatment; 6 pts (5%) had a GMI ≥1 to < 1.33 and 26 (21%) had a GMI < 1. The KM estimated median GMI increased from 7.6 (95% CI 5.7–88.0) to 9.5 (95% CI 5.7–17.4). In the expanded dataset of 140 pts, 103 pts (74%) had GMI ≥1.33, 7 (5%) had a GMI ≥1 to < 1.33 and 30 (21%) had a GMI < 1. Six of the 37 pts with a GMI < 1.33 were censored and still ongoing treatment. The KM estimated median GMI was 8.9 (95% CI 6.2–17.4). Among pts who had received 1, 2, or ≥3 prior lines of therapy, 74%, 65%, and 80%, respectively, had GMI of ≥1.33. Median TTP on the prior therapy was 3.0 months (95% CI 2.1–3.5) and median PFS on larotrectinib was 33.0 months (95% CI 16.6–34.9). Conclusions: With a longer follow-up, nearly three-quarters of pts with TRK fusion cancer treated with larotrectinib had a prolonged PFS compared to their most recent prior therapy. These results further validate the use of larotrectinib in treating patients with TRK fusion cancer. Clinical trial information: NCT02576431, NCT02122913, NCT02637687.

POS0105 PREDICTORS OF FLARE IN SLE PATIENTS ATTAINING LUPUS LOW DISEASE ACTIVITY STATE: A REAL-LIFE COHORT STUDY OF 292 PATIENTS WITH 36-MONTH FOLLOW-UP

Background:Lupus Low Disease Activity State (LLDAS) is a target for management of patients with SLE, that should be maintained in the long-term by preventing flares. Stratification of flare risk would be useful to optimize management.Objectives:To identify predictors of flare in SLE patients attaining LLDAS.Methods:Patients with SLE fulfilling classification criteria [ACR (1997) and/or SLICC and/or EULAR/ACR], followed at an academic lupus clinic from January 2017 to March 2020 were eligible. Baseline for each patient was the first visit with LLDAS within the study period. Patients never fulfilling LLDAS were excluded. Flares were identified as change from baseline by 3 instruments: revised SELENA flare index (r-SFI); SLEDAI-2K; Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS). Time to first flare up to 36 months was identified separately for each instrument. Predictors of flare were sought through survival analysis, with distinct models for each of the three definitions of flare. Univariate analysis was performed using Kaplan-Meir curves and Log-Rank tests. Tested variables at baseline were: gender; age at time of SLE diagnosis; disease duration; cumulative SLE organ involvement (arthritis; mucocutaneous; renal; neurologic; haematological; anti-phospholipid syndrome); cumulative immunological features (anti-dsDNA; anti-Sm; anti-RNP, anti-phospholipid antibodies; hypocomplementemia); ongoing treatment (hydroxychloroquine; prednisone; immunosuppressants). Variables with p<0.1 were further tested in multivariate Cox regression models. Hazard ratios (HR) were determined with 95% confidence intervals (95%CI).Results:From 322 patients in this SLE cohort, 292 (90.7%) fulfilled LLDAS and were included in the analyses (female: 87.3%; mean age: 46.2±14.5 years; previous lupus nephritis: 36.0%; receiving ongoing antimalarials, immunosuppressants, glucocorticoids: 92.8%, 34.6% and 29.8%, respectively. Over follow-up, the proportion of patients with flares according to each definition were: 28.4% (r-SFI), 24.7% (SLE-DAS) and 13.4% (SLEDAI-2K). The r-SFI flares were moderate in 28.9% and severe in 9.6% of the cases. From all patients, 54.1% maintained stable glucocorticoid-free control of the disease, without flares during follow-up. In the multivariate models, the following parameters were independent predictors of flare, as defined by any of the definitions (Table 1): anti-RNP+; oral glucocorticoids; immunosuppressants.Conclusion:Patients attaining LLDAS but requiring ongoing treatment with immunosuppressants and/or glucocorticoids present a higher risk of flare and thus might need a tighter clinical monitoring. Anti-RNP+ was newly identified as a potential biomarker for higher risk of flares. Glucocorticoid-free, stable low disease activity is an achievable target.References:[1]Mathian A, Pha M, Haroche J, Cohen-Aubart F, Hié M, Pineton de Chambrun M, et al. Withdrawal of low-dose prednisone in SLE patients with a clinically quiescent disease for more than 1 year: a randomised clinical trial. Ann Rheum Dis. 2020;79(3):339-46.[2]Inês L, Duarte C, Silva RS, Teixeira AS, Fonseca FP, da Silva JA. Identification of clinical predictors of flare in systemic lupus erythematosus patients: a 24-month prospective cohort study. Rheumatology (Oxford). 2014;53(1):85-9.Table 1.Predictors of flare in multivariate Cox regression according to each of the flare definitions (r-SFI; SLE-DAS; SLEDAI-2K)r-SFISLE-DASSLEDAI-2KAnti-RNP+2.11 (1.30-3.42)2.39 (1.44-3.95)2.22 (1.11-4.42)Immunosuppressants1.96 (1.22-3.15)2.32 (1.38-3.88)2.26 (1.12-4.54)Prednisone*1.93 (1.19-3.14)1.99 (1.18-3.35)2.17 (1.07-4.38)Blood cytopenias§2.08 (1.03-4.17)n.s.n.s.Arthritis§n.s.n.s.2.23 (1.12-4.44)* Prednisone ≤7.5 mg/day as required by LLDAS. § Blood cytopenias; arthritis: cumulative SLE features up to baseline. Risk for each predictor reported as Hazard Ratio (95% Confidence Interval); n.s.: non-significantDisclosure of Interests:None declared

Discontinuation of BRAF/MEK-Directed Targeted Therapy after Complete Remission of Metastatic Melanoma—A Retrospective Multicenter ADOReg Study

The advent of BRAF/MEK inhibitors (BRAFi/MEKi) has significantly improved progression-free (PFS) and overall survival (OS) for patients with advanced BRAF-V600-mutant melanoma. Long-term survivors have been identified particularly among patients with a complete response (CR) to BRAF/MEK-directed targeted therapy (TT). However, it remains unclear which patients who achieved a CR maintain a durable response and whether treatment cessation might be a safe option in these patients. Therefore, this study investigated the impact of treatment cessation on the clinical course of patients with a CR upon BRAF/MEK-directed-TT. We retrospectively selected patients with BRAF-V600-mutant advanced non-resectable melanoma who had been treated with BRAFi ± MEKi therapy and achieved a CR upon treatment out of the multicentric skin cancer registry ADOReg. Data on baseline patient characteristics, duration of TT, treatment cessation, tumor progression (TP) and response to second-line treatments were collected and analyzed. Of 461 patients who received BRAF/MEK-directed TT 37 achieved a CR. TP after initial CR was observed in 22 patients (60%) mainly affecting patients who discontinued TT (n = 22/26), whereas all patients with ongoing TT (n = 11) maintained their CR. Accordingly, patients who discontinued TT had a higher risk of TP compared to patients with ongoing treatment (p < 0.001). However, our data also show that patients who received TT for more than 16 months and who discontinued TT for other reasons than TP or toxicity did not have a shorter PFS compared to patients with ongoing treatment. Response rates to second-line treatment being initiated in 21 patients, varied between 27% for immune-checkpoint inhibitors (ICI) and 60% for BRAFi/MEKi rechallenge. In summary, we identified a considerable number of patients who achieved a CR upon BRAF/MEK-directed TT in this contemporary real-world cohort of patients with BRAF-V600-mutant melanoma. Sustained PFS was not restricted to ongoing TT but was also found in patients who discontinued TT.