Reason For Withdrawal Research Articles

Second and third TNF inhibitors in European patients with axial spondyloarthritis: effectiveness and impact of the reason for switching.

To investigate real-world effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA) and the association with (i) treatment line (second and third TNFi-series) and (ii) reason for withdrawal from the preceding TNFi [lack of efficacy (LOE) vs adverse events (AE)]. Prospectively collected routine care data from 12 European registries were pooled. Rates for 12-month drug retention and 6-month remission [Ankylosing Spondylitis Disease Activity Score C-reactive protein inactive disease (ASDAS-ID)] were assessed in second and third TNFi-series and stratified by withdrawal reason. We included 8254 s and 2939 third TNFi-series; 12-month drug retention rates were similar (71%). Six-month ASDAS-ID rates were higher for the second (23%) than third TNFi (16%). Twelve-month drug retention rates for patients withdrawing from the preceding TNFi due to AE vs LOE were similar for the second (68% and 67%) and third TNFi (both 68%), while for the second TNFi, rates were lower in primary than secondary non-responders (LOE <26 vs ≥26 weeks) (58% vs 71%, P < 0.001). Six-month ASDAS-ID rates for the second TNFi were higher if the withdrawal reason was AE (27%) vs LOE (17%), P < 0.001, while similar for the third TNFi (19% vs 13%, P = 0.20). A similar proportion of axSpA patients remained on a second and third TNFi after one year, but with low remission rates for the third TNFi. Remission rates on the second TNFi (but not the third) were higher if the withdrawal reason from the preceding TNFi was AE vs LOE.

Pre-participation Withdrawal and Noncompletion of Cardiac Rehabilitation in Peripheral Artery Disease: MATCHED COMPARISONS TO CORONARY ARTERY DISEASE.

Despite the mortality benefit of cardiac rehabilitation (CR) participation, as well as its cost-effectiveness for people with peripheral artery disease (PAD), there are limited data on adherence and completion of CR in those with and without concomitant coronary artery disease (CAD). The objective of this study was to compare CR pre-participation withdrawal and noncompletion between patients with PAD and concomitant PAD and CAD (PAD/CAD) versus matched and unmatched patients with CAD (uCAD). Consecutively referred patients between 2006-2017 with PAD (n = 271) and PAD/CAD (n = 610) were matched to CAD by age, sex, diabetes, smoking status, and referral year. The uCAD (n = 14 487) group was included for comparison. Reasons for withdrawal were ascertained by interview. There were no significant differences in pre-participation withdrawal between PAD and matched CAD (46 vs 43%, P = .49), nor in noncompletion (22 vs 18%, P = .28). Results were similar for PAD/CAD and matched CAD (withdrawal: 36 vs 34%, P = .37) and (noncompletion: 25 vs 23%, P = .46). A smaller proportion of patients with uCAD withdrew (28%) than patients with PAD ( P < .001) and PAD/CAD ( P < .001), with no difference in noncompletion ( P > .40, both). There were no differences between PAD and PAD/CAD and their matched counterparts for medical and nonmedical reasons for withdrawal and noncompletion ( P ≥ .25, all). Pre-participation withdrawal rates were similar between patients with PAD, PAD/CAD, and their matched cohorts but greater than patients with uCAD. Once patients started CR, there were similar completion rates among all groups. Reports that patients with PAD are less likely to start CR may be related to their complex medical profile rather than PAD alone. Strategies to improve participation among patients with PAD should focus on the immediate post-referral period.

Results of a Phase Ib Study Investigating Durvalumab in Combination with Eribulin in Patients with HER2-Negative Metastatic Breast Cancer and Recurrent Ovarian Cancer

Introduction: The release of tumor-associated antigens with cytotoxic chemotherapy treatment may enhance the response to immune checkpoint blockade. Eribulin is a microtubule inhibitor with proven overall survival (OS) benefit in metastatic breast cancer (MBC), which may also enhance intratumoral vascular remodeling. Durvalumab, a humanized monoclonal antibody, targets the programmed cell death ligand-1 (PD-L1) receptor. This study sought to determine the maximum tolerated dose and recommended phase II dose (RP2D) of eribulin in combination with durvalumab, as well as the safety and preliminary antitumor activity of the combination in patients with previously treated HER2-negative (HER2−) MBC and recurrent ovarian cancer (ROC). Methods: Cohorts of 3–6 patients with HER2− MBC and ROC were treated in a modified 3+3 design. Eligible patients received escalating doses of eribulin (1.1 mg/m2 or 1.4 mg/m2 IV on day 1 and day 8) with durvalumab (1.12 g IV on day 1) in 21-day cycles until dose-limiting toxicity (DLT), intolerable adverse events (AEs), disease progression, or other reasons for withdrawal. Primary endpoint: the rate of DLTs during cycles 1 and 2 of therapy. Secondary endpoints: AE rate, objective response rate (ORR), progression-free survival (PFS), and OS. Results: Nine patients with a median of 4 prior therapies for advanced disease were treated: 5 patients with HER2− MBC (1 with triple-negative disease and 4 with hormone-positive disease) and 4 patients with ROC. The RP2D of eribulin was 1.4 mg/m2 in combination with durvalumab. There were no DLTs experienced during the first two cycles of therapy. The most common treatment-related AEs (>50%) were fatigue, neutropenia, decreased white blood cell count, anemia, AST and alkaline phosphatase elevation, hyperglycemia, and nausea; most were grade 1 or 2. There was one immune-related AE of grade 3 (hepatitis) after 5 cycles of treatment, for which patient came off study. Two other patients discontinued study drug related to toxicity (neutropenia [n = 1], hepatic toxicity [n = 1]). ORR was 55%, and 4 additional patients experienced stable disease. All MBC patients exhibited a response to therapy. Median PFS was 6.2 months. Median OS was 15.0 months. Conclusion: The combination of eribulin at a dose of 1.4 mg/m2 with standard dose durvalumab had a favorable AE profile in patients with previously treated HER2− MBC and ROC. The early antitumor activity observed in all MBC patients enrolled in the study suggests that further investigation of this combination is warranted.

Acceptability of a Personal Contact Intervention among People Living with Dementia: Might Baseline Contact Matter?

Our study aimed to explore how perceived baseline contact may influence acceptability of Connecting Today, a personal contact intervention, among people living with dementia. We aimed to generate hypotheses for testing in future studies. This was a sub-group analysis of pilot study data. Fifteen people living with mild to moderate dementia participated in Connecting Today. We explored how perceptions of intervention acceptability may differ in groups reporting weekly contact (n = 8) compared with groups reporting monthly/unknown (n = 7) contact at baseline. Measures of acceptability included a treatment perceptions and preferences questionnaire, and the number of and reasons for non-consent, missing data, and study withdrawal. We used descriptive statistics and content analysis. In visits one and two, a larger proportion (85.7-100%) of low baseline contact participants reported feeling better, and indicated that the visits helped them and were easy "mostly" or "a lot", compared with the high baseline contact group (37.5-62.5%). Most missing data (71%) and all study withdrawals occurred in the high baseline contact group. Scheduled in-person visits with family, friends, or a volunteer may appeal to residents in care homes who have few existing opportunities for routine, one-on-one visits with others. Hypotheses generated should be tested in future studies.

Incidence of cardiovascular and bleeding events and reasons for discontinuation in patients with chronic lymphocytic leukemia treated with ibrutinib-A retrospective analysis on consecutive patients from a well-defined region.

Ibrutinib treatment is associated with cardiovascular side effects, in particular atrial fibrillation (AF) and hypertension, as well as increased risk of bleeding. Here, we aimed at describing the incidence of these events during long-term follow-up in patients with chronic lymphocytic leukemia treated outside clinical trials as well as identifying clinical factors predictive of developing AF. Additionally, other reasons for treatment withdrawal were analyzed. The study was retrospective, data were collected from medical records. A total of 134 patients were identified. Median follow-up was 32 months (range 3-103) and median duration of ibrutinib treatment was 26 months (range 1-103). Of 110 patients with no prior history of AF, 24.5% were diagnosed during treatment. Newly diagnosed or worsening of pre-existing hypertension occurred in 15.7%. Sixty-six % of the patients experienced bleeding events, of which 7.5% grade 3-4. Treatment discontinuation and dose reduction occurred in 68% and 47% of the patients, respectively, mostly due to toxicity. The incidence of AF was high and at a median follow-up of 2.5 years, two-thirds of the patients discontinued treatment mostly due to bleeding and infections. Treatment-related toxicity of any grade should be regarded as a concern of prolonged ibrutinib therapy.

Prehabilitation for frail patients undergoing total hip or knee replacement: protocol for the Joint PREP feasibility randomised controlled trial

BackgroundApproximately, 8% of community-based adults aged ≥ 50 years in England are frail. Frailty has been found to be associated with poorer outcomes after joint replacement. Targeting frailty preoperatively via exercise and protein supplementation has the potential to improve outcomes for people undergoing joint replacement. Prior to proceeding with a randomised controlled trial (RCT), a feasibility study is necessary to address key uncertainties and explore how to optimise trial design and delivery.MethodsThe Joint PRehabilitation with Exercise and Protein (Joint PREP) study is a feasibility study for a multicentre, two-arm, parallel group, pragmatic, RCT to evaluate the clinical and cost-effectiveness of prehabilitation for frail patients undergoing total hip or knee replacement. Sixty people who are ≥ 65 years of age, frail according to the self-reported Groningen Frailty Indicator, and scheduled to undergo total hip or knee replacement at 2–3 hospitals in England and Wales will be recruited and randomly allocated on a 1:1 ratio to the intervention or usual care group. The usual care group will receive the standard care at their hospital. The intervention group will be given a daily protein supplement and will be asked to follow a home-based, tailored daily exercise programme for 12 weeks before their operation, in addition to usual care. Participants will be supported through six follow-up calls from a physiotherapist during the 12-week intervention period. Study questionnaires will be administered at baseline and 12 weeks after randomisation. Embedded qualitative research with patients will explore their experiences of participating, reasons for nonparticipation, and/or reasons for withdrawal or treatment discontinuation. Primary feasibility outcomes will be eligibility and recruitment rates, adherence to the intervention, and acceptability of the trial and the intervention.DiscussionThis study will generate important data regarding the feasibility of a RCT to evaluate a prehabilitation intervention for frail patients undergoing total hip and knee replacement. A future phase-3 RCT will determine if preoperative exercise and protein supplementation improve the recovery of frail patients after primary joint replacement.Trial registrationISRCTN11121506, registered 29 September 2022.

PREHABILITATION FOR FRAIL PATIENTS UNDERGOING TOTAL HIP OR KNEE ARTHROPLASTY: PROTOCOL FOR THE JOINT PREP FEASIBILITY RANDOMIZED CONTROLLED TRIAL

AbstractIntroductionFrailty is associated with poorer outcomes after joint replacement. Targeting frailty pre-operatively via protein supplementation and exercise has the potential to improve outcomes after joint replacement. Before conducting a randomised controlled trial (RCT), a feasibility study is necessary to address key uncertainties and explore how to optimise trial design.MethodologyJoint PREP is a feasibility study for a multicentre, two-arm, parallel group, pragmatic, RCT to evaluate the clinical and cost-effectiveness of prehabilitation for frail patients undergoing total hip or knee replacement. Sixty people who are ≥65 years of age, frail and scheduled to undergo total hip or knee replacement at 2–3 NHS hospitals will be recruited and randomly allocated on a 1:1 ratio to the intervention or usual care group. The intervention group will be given a daily protein supplement and will be asked to follow a home-based, tailored daily exercise programme for 12 weeks before their operation, supported by fortnightly telephone calls from a physiotherapist. Embedded qualitative research with patients will explore their experiences of participating, reasons for non-participation and/or reasons for withdrawal or treatment discontinuation.ResultsOutcomes to be assessed include eligibility, recruitment and retention rates; intervention adherence; acceptability of the trial and intervention; and data completion. Data collection is ongoing.DiscussionThis study will generate important data regarding the feasibility of a RCT to evaluate a prehabilitation intervention for frail patients undergoing joint replacement. A future RCT will contribute to the evidence on interventions to optimise the benefit that frail patients gain from joint replacement.

Human iPSC-Derived 3D Hepatic Organoids in a Miniaturized Dynamic Culture System.

The process of identifying and approving a new drug is a time-consuming and expensive procedure. One of the biggest issues to overcome is the risk of hepatotoxicity, which is one of the main reasons for drug withdrawal from the market. While animal models are the gold standard in preclinical drug testing, the translation of results into therapeutic intervention is often ambiguous due to interspecies differences in hepatic metabolism. The discovery of human induced pluripotent stem cells (hiPSCs) and their derivatives has opened new possibilities for drug testing. We used mesenchymal stem cells and hepatocytes both derived from hiPSCs, together with endothelial cells, to miniaturize the process of generating hepatic organoids. These organoids were then cultivated in vitro using both static and dynamic cultures. Additionally, we tested spheroids solely composed by induced hepatocytes. By miniaturizing the system, we demonstrated the possibility of maintaining the organoids, but not the spheroids, in culture for up to 1 week. This timeframe may be sufficient to carry out a hypothetical pharmacological test or screening. In conclusion, we propose that the hiPSC-derived liver organoid model could complement or, in the near future, replace the pharmacological and toxicological tests conducted on animals.

Connecting Today: Feasibility and acceptability of a remote visiting program for people living with dementia in long-term care homes.

Social isolation and loneliness affect the quality of life of people living with dementia, yet few interventions have been developed for this population. The purpose of this study was to assess the feasibility and acceptability of 'Connecting Today', a remote visiting program designed for use with care home residents living with dementia. This was a feasibility study to assess whether Connecting Today can be delivered in care homes, and was acceptable to family and friends and people living with dementia. We used a single-group before/after design and included residents ≥ 65 years old with a dementia diagnosis from two care homes in Alberta, Canada. Connecting Today involved up to 60min per week of facilitated remote visits for 6weeks. To understand feasibility, we assessed rates and reasons for non-enrollment, withdrawal and missing data. We assessed acceptability with the Observed Emotion Rating Scale (residents) and a Treatment Perception and Preferences Questionnaire (family and friends). Data were analyzed with descriptive statistics. Of 122 eligible residents, 19.7% (n = 24) enrolled (mean age = 87.9 years, 70.8% females). Three residents withdrew from the study before the first week of calls. Among 21 remaining residents, 62%-90% completed at least 1 call each week. All the calls were completed by videoconference, rather than by phone. Alertness and pleasure were observed for ≥92% of residents during calls. The 24 contacts rated Connecting Today as logical, effective and low risk. Facilitated, remote visits are feasible and highly acceptable to residents and their family and friend contacts. Connecting Today shows promise to address social isolation and loneliness for people living with moderate to severe dementia because it can promote positive engagement in meaningful interactions with their family and friends while they are living in a care home. Future studies will test effectiveness of Connecting Today in a large sample.

417 Safety of long-term dupilumab treatment in adults with moderate-to-severe atopic dermatitis: results from an open-label extension trial up to 5 years

Abstract Atopic dermatitis (AD) is a chronic inflammatory skin disease requiring long-term management; however, sustained AD treatment with systemic immunosuppressants is not recommended due to safety concerns. Dupilumab is a fully human monoclonal antibody that blocks the shared receptor component for interleukin (IL)-4 and IL-13, inhibiting the signaling of these key and central drivers of type 2 inflammation in multiple diseases. Data from the open-label extension (OLE) study, LIBERTY AD OLE (NCT01949311), previously demonstrated acceptable dupilumab safety in adult patients up to 204 weeks (approximately 4 years), consistent with the known safety profile in parent studies. This study aims to assess the long-term safety of dupilumab administered in adult patients with AD up to 5 years (the end of this OLE study). Adults with moderate-to-severe AD who had participated in any dupilumab parent study (phase 1 through phase 3) were enrolled into the long-term, multicenter OLE trial with a duration of up to 5 years. During the OLE, patients were treated with 300-mg dupilumab weekly (qw). In 2019, patients transitioned to 300 mg every 2 weeks to align with approved dosage. Concomitant treatments for AD were permitted, including topical corticosteroids (TCS) and topical calcineurin inhibitors. Because the OLE trial lacked a control arm, LIBERTY AD CHRONOS (NCT02260986) 52-week safety results for adults with moderate-to-severe AD receiving dupilumab 300 mg qw plus TCS were provided as a comparison. Data shown are for the overall study population (n = 2677). Of the 2677 patients who enrolled, 2207 completed treatment up to Week 52, 362 up to Week 172 and 334 up to Week 260. The most common reason for study withdrawals during the OLE study period was dupilumab approval and commercialization in the patient’s country of enrollment [708 (51.3%)]. The exposure-adjusted incidence rate (EAIR) of patients with ≥1 treatment-emergent adverse event (TEAE) was lower in this OLE vs. the 300 mg qw + TCS arm of the 52-week CHRONOS trial (166.0 vs. 322.4 number of patients/100 patient-years). Over this 5-year OLE, 10.6% of patients had ≥1 serious TEAE, 10.0% had ≥1 severe TEAE, 1.2% had ≥1 serious TEAE related to the study drug and 3.8% of patients experienced a TEAE resulting in permanent drug discontinuation. The most common TEAEs observed were nasopharyngitis (28.9%) and conjunctivitis [20.0%, using a narrow customized MedDRA query (CMQ) containing conjunctivitis and related terms conjunctivitis allergic/bacterial/viral, and atopic keratoconjunctivitis]. Of the patients under narrow CMQ, 95.0% reported mild/moderate conjunctivitis TEAEs and 87.7% of conjunctivitis events were recovered/resolved. The safety profile observed in this OLE trial up to 5 years is acceptable and consistent with the known safety profile of dupilumab observed in controlled studies. The EAIRs of TEAEs overall did not increase over time and were lower than previously reported in the 3- and 4-year analyses of this OLE trial and an earlier 52-week placebo-controlled trial.

416 Long-term efficacy of dupilumab in adults with moderate-to-severe atopic dermatitis: results from an open-label extension trial up to 5 years

Abstract Topical therapies often cannot sufficiently control moderate-to-severe atopic dermatitis (AD), a chronic inflammatory skin disease. Systemic immunosuppressants are not recommended for the long-term treatment of moderate-to-severe AD due to safety concerns. Dupilumab is a fully human monoclonal antibody that blocks the shared receptor component for interleukin (IL)-4 and IL-13, inhibiting the key drivers of type 2 inflammation. Data from the open-label extension (OLE) study, LIBERTY AD OLE, (NCT01949311) previously demonstrated acceptable safety and sustained efficacy of dupilumab in adult patients for up to 204 weeks (approximately 4 years). This study aims to assess the long-term efficacy and safety of dupilumab in adult patients with moderate-to-severe AD up to 5 years (the end of this OLE study). Adults (≥18 years) with moderate-to-severe AD who had participated in any dupilumab parent study (phase 1 through phase 3) were enrolled into the long-term, multicenter OLE with a duration of up to 5 years. Initially, patients enrolled in the OLE were treated with 300-mg dupilumab weekly. In 2019, patients remaining in the study transitioned to dupilumab 300 mg every 2 weeks in alignment with the approved dupilumab dose regimen. Concomitant treatments for AD were permitted, including topical corticosteroids and topical calcineurin inhibitors. Data are presented as observed for the overall study population (n = 2677). Of the 2677 patients who enrolled, 2207 completed treatment up to Week 52, 362 up to Week 172 and 334 up to Week 260. The most common reason for study withdrawals during the OLE study period was dupilumab approval and commercialization in the patient’s country of enrollment [708 (51.3%)]. Fifty (1.9%) patients withdrew due to lack of efficacy. At the end of the study period, 88.9% of patients achieved a 75% reduction in Eczema Area and Severity Index (EASI) score from parent study baseline (PSBL) and 76.2% of patients achieved a 90% reduction in EASI score from PSBL. At Week 260, 66.5% of patients achieved a ≥4-point reduction in the Peak Pruritus Numerical Rating Scale score from PSBL. A total of 2276 (85.0%) patients reported treatment-emergent adverse events, and 101 (3.8%) patients discontinued treatment permanently due to reported adverse events. Dupilumab had an acceptable safety profile over 5 years of treatment. In this long-term (5 year/260 weeks) open-label study, dupilumab demonstrated robust efficacy substantiated by sustained improvement of AD signs and symptoms (including skin lesions and pruritus) in adult patients with moderate-to-severe AD. The safety profile was acceptable and consistent with the known safety profile observed in previous dupilumab placebo-controlled studies.

Understanding work inclusion: Analysis of the perspectives of people with intellectual disabilities on employment in the Icelandic labor market.

People with intellectual disabilities experience persistent marginalization in relation to work and employment. The concept of work inclusion provides a way of generating a more specific understanding of the meaning of employment participation. Work inclusion of people with intellectual disabilities focuses not on mere presence, but instead emphasizes relational aspects and potential for meaningful participation. In this paper we report on an empirical study into the experiences of people with intellectual disabilities of employment participation in the Icelandic labor market. We considered their experiences in relation to four key components of work inclusion, placing emphasis on how they perceived opportunities for inclusion related to social relations, belonging, valued contributions and trust. This study used a qualitative research design. Data was collected with semi-structured interviews with 9 participants with intellectual disabilities who all had experience of being employed in the Icelandic labor market. Our findings show the role of the work environment in participants' experiences of opportunities for having good relations at work, having a sense of belonging to the organization, being able to make a contribution to the goals of the organization, and receiving trust in one's professional role and responsibility. When participants experienced opportunities in relation to these basic components of work inclusion, they felt more positively about their employment participation. Lack of opportunities was reported as a reason for segregation and withdrawal. This study shows the importance for work organizations and other actors in the labor market of paying attention to components of work inclusion and their relation with corporate culture.

Peripherally inserted central venous catheter in Autologous Hematopoietic Stem Cell Transplantation: Feasibility and Outcome

Objectives: This study describes our experience using PICC in patients submitted to autologous stem cell transplant (ASCT) regarding the time of use, withdrawal reasons, and complications.&#x0D; Methods: A retrospective cohort of 143 patients from 2017 and 2019, with a PICC inserted before the ASCT. &#x0D; Results: Regarding baseline disease, 104 (73%) of patients had multiple myeloma. The median days of use was 15 (1 – 37) per catheter. More than 80% of PICC remained in place after D+15, and 112 (78%) patients had the PICC removed at discharge. Only 13 (9%) patients had replacement of the PICC. The rates of central line associate bloodstream infection and thrombosis were 1.36 and 1.36 events per 1,000 PICC days, respectively.&#x0D; Conclusions: PICCs were successfully remained until discharge, with manageable rates of complications. All procedures were executed by nurses at the bedside. We concluded that PICC is a safe and feasible alternative to CVC for ASCT.

Remote delivery of a mindfulness-based intervention to decrease stress levels and promote coping among health-care workers during the COVID-19 pandemic.

11007 Background: The COVID-19 pandemic has caused significant stress amongst everyone around the world. Healthcare workers (HCW) in particular, experience substantial stress in these challenging environments. In an effort to find supportive interventions for radiation oncology providers, while respecting the requirements of physical distancing, we proposed the remote delivery of a mindfulness-based intervention (MBI). The primary aim of this study is to determine the association of this intervention with a reduction of perceived stress. Secondary aims are to evaluate the impact on coping and burnout amongst HCW in the Radiation Program (RP). Methods: This is a single-centre, single-arm, pilot study. All HCW associated with the RP were eligible. This was a voluntary effort. The intervention - manualized, mindfulness-based group for HCW, entitled Mindfulness-Based Resilience and Well-Being Training, consisted of four 1-hour sessions per week for 4 weeks. From Nov 2020 to Dec 2021, 6 consecutive closed groups MBI were delivered remotely using Zoom. Each group consisted of 5-12 participants and one professional with a background in mindfulness facilitation. The Perceived Stress Scale (PSS), The Maslach Burnout Inventory and the BriefCOPE questionnaire were collected pre-intervention, and at 1, 4 and 12 weeks post-intervention. Linear mixed effect models with a random intercept to account for the repeated measures were used to assess the change of outcomes over time. Results: Amongst 43 HCWs who expressed initial interest, 33 completed the study. At 1-, 4- and 12-weeks post-intervention 25, 24 and 21 participants provided completed questionnaires respectively. Time constraint was the main reason for withdrawal and missing data. There was a significant decrease in perceived stress at week 1, 4 and 12 when compared to baseline [mean baseline PSS score: 22.5 (SD = 4.6), week 1: 18.4 (4.9), p= 0.002, week 4: 16.8 (6.5), p&lt; 0.001, week 12: 16.3 (6.8), p&lt; 0.001]. Overall, 7 (21%) participants reported high PSS (27-40) at baseline while none reported high levels at 1 and 12 weeks. Problem focused coping( p= 0.02), and active coping ( p= 0.009) were significantly higher at 1 week but not at 4 and 12 weeks. Conclusions: The remote delivery of a MBI is feasible and effective to reduce perceived stress levels and to promote coping across HCWs. These findings need to be validated in a larger cohort. Time was a major constraint preventing the participation of interested HCWs. It would be extremely valuable for departments to support such interventions and programs to help HCWs cultivate skills to meet the demands related to working in healthcare environments throughout and beyond this crisis.

EVALUATION OF THE FEEDBACK ON PHARMACOVIGILANCE BASIC AWARENESS PROGRAM AMONGST THE MEDICAL POST GRADUATE RESIDENTS OF A RURAL TEACHING HOSPITAL

Introduction:The World Health Organization (WHO) defines an Adverse drug reaction (ADR) as a response to a drug which is noxious, unintended, and which occurs at doses normally used in man for the prophylaxis, diagnosis, or therapy of disease, or for the modification of physiological function. Adverse drug reactions (ADRs) are a major clinical problem and are main cause of death and serious disease in patients and a key cause of drug attrition in the pharmaceutical industry, as nearly more than 90% of drug molecules do not succeed in preclinical/clinical studies due to a deficiency of safety and efficacy. The chief reasons for withdrawal of already approved drugs are cardiovascular and hepatic adverse effects. The main goal was, our future healthcare providers should have basic pharmacovigilance knowledge, how to detect and prevent ADRs in order to rationally reporting ADRs and preventing serious health problems. The main aim was to sensitize all the health care providers regarding Pharmacovigilance activities. Materials &amp; Method:The present retrospective and observational study was initiated by collecting necessary information about the Pharmacovigilance awareness program conducted during July 2017. The participants (n=47) were second year MD/MS/Diploma post graduate students (Medical), residents of Dhiraj Hospital attached to Smt. B. K. Shah Medical Institute &amp; Research Centre, Sumandeep Vidyapeeth an Institution deemed to be University, Piparia. Results &amp; Discussion:The participants (n=47) rated the quality of presentations and content from excellent to good for both the sessions. With regard to the usefulness of the sessions, it was also rated from excellent to very good. They felt both the sessions were interactive, interesting &amp; useful in all aspects. The quality of presentation was rated as good to excellent. All 47 (100 %) participants reported that it was an excellent workshop with good interactive session and interesting group activity. Majority of participants, 23 (48.93%) found that the workshop would help them to value add in their patient care in future, which implied that workshop was beneficial to convey the importance of national programme to the participants. Forty six (97.87%) participants said that they will like to attend this type of workshop in future also. The resource persons through interactive sessions, had given an overview on Pharmacovigilance, which was followed by hands on technique, how to fill ADR forms and group discussions, at the end of each workshop feedback forms were distributed to all participants. Pharmacovigilance workshops were conducted to generate awareness regarding ADR reporting amongst doctors is essential to promote the rational and safe use of medicines. Conclusion:Feedback from the post graduate healthcare professionals plays a key role in the reassurance and augmentation of the quality and their understanding on their role in pharmacovigilance and hands on training in ADR form filling group activity. Further, the study implies that workshop was beneficial to convey the importance of national programme to the participants.

Evaluation of Various Support Intensities of Digital Mental Health Treatment for Reducing Anxiety and Depression in Adults: Protocol for a Mixed Methods, Adaptive, Randomized Clinical Trial.

Anxiety and depression are leading causes of disease worldwide, requiring timely access to evidence-based treatment. Digital mental health (dMH) interventions increase accessibility to evidence-based psychological services delivered in a variety of web-based formats (eg, self-help and therapist-assisted interventions). Robust and rigorous studies of adaptive web-based intervention designs are scarce. No identified randomized clinical trial has investigated the efficacy of a 2-stage adaptive design, whereby the program-only condition or no support dMH treatment program is augmented by either low or high therapist assistance, if a participant does not improve or engage in the program-only condition. The primary objective is to assess whether low or high therapist-assisted support delivered via video chat is more effective in reducing anxiety and depressive symptoms compared with a dMH program-only condition. The secondary objective is to evaluate the role of motivation; self-efficacy; and preferences in participant engagement, adherence, and clinical outcomes (anxiety and depression symptoms) among the 3 treatment conditions (program only, low-intensity therapist assistance, and high-intensity therapist assistance). A mixed methods analysis of factors affecting participant attrition, participant reasons for nonengagement and withdrawal, and therapist training and implementation of dMH interventions will be completed. Qualitative data regarding participant and therapist experiences and satisfaction with video chat assessment and treatment will also be analyzed. Australian adults (N=137) with symptoms or a diagnosis of anxiety or depression will be screened for eligibility and given access to the 8-module Life Flex dMH treatment program. On day 15, participants who meet the augmentation criteria will be stepped up via block randomization to receive therapist assistance delivered via video chat for either 10 minutes (low intensity) or 50 minutes (high intensity) per week. This adaptive trial will implement a mixed methods design, with outcomes assessed before the intervention (week 0), during the intervention (weeks 3 and 6), after the intervention (week 9), and at the 3-month follow-up (week 21). The primary outcome measures are for anxiety (Generalized Anxiety Disorder-7) and depression severity (Patient Health Questionnaire-9). Measures of working alliance, health status, health resources, preferences, self-efficacy, and motivation will be used for secondary outcomes. Qualitative methods will be used to explore participant and therapist experiences of video chat assessment and treatment, participant reasons for withdrawal and nonengagement, and therapist training and implementation experiences. Data collection commenced in November 2020 and was completed at the end of March 2022. This is the first mixed methods adaptive trial to explore the comparative efficacy of different intensity levels of self-help and a therapist-assisted dMH intervention program delivered via video chat for adults with anxiety or depression. Anticipated results may have implications for the implementation of dMH interventions. Australian and New Zealand Clinical Trials Registry 12620000422921; https://tinyurl.com/t9cyu372. RR1-10.2196/45040.

Long-term Safety and Efficacy of Add-on Cannabidiol (CBD) for Seizures Associated With Tuberous Sclerosis Complex (TSC): 3-Year Results From GWPCARE6 Open-Label Extension (OLE) (P14-1.004)

Long-term Safety and Efficacy of Add-on Cannabidiol (CBD) for Seizures Associated With Tuberous Sclerosis Complex (TSC): 3-Year Results From GWPCARE6 Open-Label Extension (OLE) (P14-1.004)

Etanercept originator versus etanercept biosimilar for the treatment of rheumatoid arthritis as a first biologic: results from the BSRBR-RA.

Etanercept biosimilars show comparable efficacy to their originators among biologic-naïve patients with RA in randomized controlled trials. Nationwide guidelines have obligated prescribing of etanercept biosimilars from 2016, resulting in significant cost savings. This analysis aimed to compare the effectiveness of etanercept originator vs etanercept biosimilar amongst biologic-naïve RA patients treated in routine clinical practice in the UK. Biologic-naïve RA patients starting etanercept in the British Society for Rheumatology Biologics Register in Rhematoid Arthritis (BSRBR-RA) cohort study from 2010 were included. Data collected at start of therapy includes patient demographics and disease activity. Follow-up data includes changes in disease activity and anti-rheumatic therapy. Six- and 12-month primary outcomes include DAS for 28-joints (DAS28) remission, EULAR response and minimal clinically important difference in function. Etanercept drug survival was assessed using Kaplan-Meier and Cox regression, including reasons for treatment withdrawal. Multiple imputation accounted for missing data. Propensity-decile adjustment was used to account for confounding by indication. A total of 1806 biologic-naïve RA patients started etanercept: 1009 originator, 797 biosimilar. At 6 and 12 months, the proportion of patients achieving DAS28 remission and EULAR response were similar between treatments. During follow-up, 19% of originator patients switched onto etanercept biosimilar. Patients were censored at time of switch. Patients on originator were no more likely to stop therapy vs biosimilar; 71% of originator and 76% of biosimilar patients remained on therapy at 1 year. In one of the largest analyses of patients with RA, biologic-naïve RA patients treated with etanercept originator showed similar outcomes vs biosimilar using real-world data. Drug survival, and disease activity after 6 and 12 months of therapy, was similar between cohorts.

Clinician’s attitude towards clozapine prescription

IntroductionCurrent clinical guidelines recommend the use of clozapine for the treatment of refractory schizophrenia, present in up to a third of patients with this disease. Despite the evidence, the data point to low prescription, underdosing, and delayed initiation.ObjectivesThe objective of the study is to elucidate which factors may interfere in clozpine prescription.MethodsThis is a cross-sectional observational study, carried out using a survey designed specifically for it.It was answered online by seventy psychiatrists affiliated with the Catalan Society of Psychiatry.ResultsMore than half admitted having prescribed two or more antipsychotics without having previously ruled out pseudorefractoriness through depot treatment. 70% recognized the need for monitoring as the main prescription barrier, while the main reason for withdrawal was its adverse effects. The most alarming was considered agranulocytosis, with drooling, drowsiness and weight gain being the most reported.Statistically significant differences (p=0.031) were found in relation to the years of experience and the device where clozapine was preferred to be started: &lt;10 years in hospital, 10-20 years in partial hospitalization and &gt;20 years outpatient office.Statistically significant differences were observed in the preference of the device for its initiation depending on the usual work device: hospitalization (p&lt;0.000) and partial hospitalization (p=0.046) preferred to schedule it from their respective devices, without any preference in consultations.The level of experience and the most reported side effect were statistically significant: for the newest psychiatrists it was weight gain (p=0.031), without presenting differences in the rest of the groups.ConclusionsClozapine is the psychoactive drug of choice in refractory schizophrenia, so efforts should be devoted to reducing prescription barriers, offering training on its management and innovating forms of monitoring to promote its use.Disclosure of InterestNone Declared

Clinical study of complications of a peripherally inserted central catheter in cancer patients.

To evaluate complications after PICC use in cancer patients. This was a clinical and retrospective study in which the risk factors and complications of PICC use were evaluated. This study was carried out in the patient, emergency room, and intensive care units through the evaluation of electronic medical records. To assess the association between qualitative variables, the chi-squared test or Fisher's exact test was used, and to compare the reason for withdrawal, the Kruskal-Wallis test was applied. A total of 359 patients (53.5% men) with 43.1± 14 years who had a PICC (88% with solid tumours) were evaluated. The most common complications were mechanical complications (61.2%), infection (38%), and thrombosis (57.1%). Patients with double-lumen catheters experienced thrombosis (85.7%). This study demonstrated the effectiveness of PICC and that patients with haematological cancer are more prone to multiple PICC passages and more mechanical complications and infections.