Reason For Withdrawal Research Articles

Strategies and Management for Psychiatric Drug Withdrawal: A Systematic Review of Case Reports and Series.

In recent years, an increasing number of case reports on psychiatric drug withdrawal have emerged, offering detailed clinical insights and valuable real-world evidence on the withdrawal process. The objective of this review was to evaluate the strategies and management for withdrawing psychiatric drugs, as detailed in case reports and series. A systematic review of case reports and series published between 2013 and 2023 was conducted to capture the latest trends in psychiatric drug withdrawal. Cases were identified following the PRISMA guidelines by searching electronic databases Medline and Scopus. Finally, 47 case reports and series were included. The primary reason for drug withdrawal was attributed to the emergence of adverse events, followed by medication dependence or abuse, and clinical decision-making or symptom resolution. Gradual reduction of doses was implemented through various management approaches as the primary strategy for drug withdrawal, and drug substitution emerged as the second most employed strategy. Also, patients were mostly undergoing polypharmacy. Favorable treatment outcomes were reported in the majority of cases, suggesting that psychiatric drug withdrawal is feasible - though quite challenging in some situations. However, the remarkably low number of unsuccessful cases may create a misleading impression of the significant difficulty associated with withdrawing psychiatric drugs.

QOL-18. MANAGING CANCER AND LIVING MEANINGFULLY (CALM) IN PRIMARY AND SECONDARY MALIGNANT BRAIN TUMOR PATIENTS: INTERIM ANALYSIS OF A PHASE IIC RANDOMIZED CONTROL PILOT TRIAL

Abstract BACKGROUND Patients with both primary and secondary brain tumors demonstrate substantial psychological distress but have been historically excluded from psychological research. Managing Cancer and Living Meaningfully (CALM), a supportive- expressive- psychotherapy, has proven to reduce depression and death-anxiety in advanced cancer patients but trials in neuro-oncology have been limited. Interim analyses (50% accrual) of the first randomized control pilot trial (RCT) of CALM in neuro-oncology are presented here. METHODS In this ongoing NIH ORBIT model Phase IIc pilot RCT, 60 adults with primary or secondary malignant brain tumors and heightened distress (PHQ/DADDS) are randomized (2:1) to a six-session CALM intervention or usual care. Data collection includes established feasibility and acceptability metrics, intervention satisfaction surveys and interviews, and clinically meaningful changes in distress severity scores across three timepoints (pre-, post-CALM, follow-up). RESULTS Of 64 patients screened, 36 were eligible and 32 enrolled (n=20 CALM, n=12 Control; 65% female; 90% White; Mage=46yrs). A multimodal recruitment model was used. Currently, assessment completion rates are: post-CALM (80%) and follow-up (67%). Reasons for withdrawal include disinterest in intervention topics (n=1) and lost to follow-up (n=1). Intervention retention is currently at 90%, with 8 participants still in active treatment. No adverse events have been documented. Perceived benefit appears high (4.1/5) and all participants report they would recommend CALM to others. Pre- to post-CALM, depression severity reductions appear equal across arms (CALM PHQ-9=30%; Control=33%) but death anxiety severity reductions appear more prevalent in the treatment group (CALM DADDS=70%; Control=50%). CONCLUSIONS Interim data suggests promising feasibility and acceptability results in this pilot RCT. Enrollment, retention, and assessment completion rates appear adequate. Participants are reporting high benefit and recommendation of CALM. Improvement in death anxiety appears greater in those treated with CALM compared to controls. These interim RCT findings are promising and suggest completion of the current phase.

Effectiveness and safety analysis of ketogenic diet therapy for drug-resistant epilepsy caused by structural pathology.

To explore the effectiveness and safety of the ketogenic diet (KD) in children with drug resistant epilepsy (DRE) caused by structural etiology. The children were categorized into acquired brain injury group and malformations of cortical development (MCD) group based on the etiology. Follow-up assessments were performed at 1, 3, and 6 months after KD treatment to observe seizure reduction, behavioral and cognitive improvements, adverse reactions events, and reasons for discontinuation withdrawal. Statistical analysis was conducted on the results. We found the seizure-free rates at 1, 3, and 6 months were 4.8% (2/42), 19% (8/42), and 21.4% (9/42), respectively. The seizure control effective rates were 42.9% (18/42), 52.4% (22/42), and 54.8% (23/42) at the corresponding time points. Compared to the acquired brain injury group, the MCD group showed a higher seizure control effective rate. Further analysis within the MCD group revealed the highest efficacy in focal cortical dysplasia (FCD). At the 3-month follow-up, cognitive and behavioral improvements were observed in 69% (29/42) of children. The main reasons for discontinuation were lack of efficacy and poor compliance. Finally, we get that KD is a safe and effective treatment for drug resistant epilepsy caused by structural etiology, with the added benefit of improving behavioral and cognitive abilities in children. The efficacy is higher in children with MCD, particularly in cases of FCD. Early intervention with KD is recommended for this population.

Cohort retention in a pandemic response study: Lessons from the SIREN study

Abstract Background Cohort studies represent an important research-tool, yet participant retention is difficult. SIREN followed a cohort of healthcare workers across 135 NHS sites in the UK during a pandemic. We designed an evolving retention programme, underpinned by our Participant Involvement Panel (PIP). We aimed to evaluate cohort retention over time and identify learnings. Methods Mixed method evaluation of our evolving retention programme in the 12 and 24-month cohort. We described cohort retention by demographics and site, using odds ratios from logistic regression. Withdrawal reasons were collected by survey. We collected participant feedback via cross-sectional survey using a behavioural science approach. We conducted focus groups with research teams and conducted thematic analysis. Results 37,275 (84.7%) participants at 135 sites completed 12-months of follow-up. 12,635 (85.5%) participants at 87 sites completed 24-months. Retention increased with age (24-months: >65 vs < 25 years OR = 2.92; 95%CI: 1.78-4.88; p < 0.001) and was highest in the Asian and Black ethnic groups (24-months OR = 1.78; 95%CI: 1.42-2.25; p < 0.001, and OR = 2.12; 95%CI: 1.41-3.35; p < 0.001, respectively, Ref=white). SIREN scored highly in participant feedback. Lessons for future studies include the need to monitor changing participant motivation; using inclusive and comprehensive communication; acknowledging the contributions of participants and investing in the skillset of research teams. Conclusions Despite challenges to running a large multicentre cohort study in an evolving pandemic, retention in SIREN has remained very high. Some factors impacting retention were outside of study control, including the altruistic motivation of participants. Participant feedback was positive, suggesting SIREN methodology will provide useful learning for future retention programmes. Site feedback provided learning for future multicentre research studies, offering insights into key facilitators and common challenges. Key messages • Cohort retention is difficult. Mixed methods evaluation shows SIREN achieved high retention while following a cohort of healthcare workers across 135 NHS sites in four UK nations during a pandemic. • Lessons learned include the need to monitor changing participant motivation; using inclusive communication; acknowledging participants contributions and investing in the research team skillset.

Management of Glucocorticoid-Induced Hyperglycemia in Cancer Patients: A Feasibility Study.

Glucocorticoids are commonly used in the management of patients with hematological and solid malignancies. However, their use may be associated with impaired glycemic metabolism and increased treatment-related morbidity and mortality. This study aimed to examine the feasibility and acceptability of a nurse-led model of care (MOC) for screening and managing glucocorticoid-induced hyperglycemia (GIH) in non-diabetic patients requiring high-dose glucocorticoid (HDG) therapies, as well as patients' and health professionals' experiences with the MOC. This study was a single-site feasibility study. Patients with hematological or oncological malignancies who were >18 years of age, receiving a chemotherapy regimen including HDGs, had no prior diagnosis of diabetes or prediabetes, and were not at the end of life were considered eligible for this study. Participants were recruited from a district hospital's Cancer Centre in Australia. All consenting participants were screened for diabetes and were provided with a blood glucose meter to monitor their blood glucose levels (BGLs) four times a day on the days of glucocorticoid therapy (GT) plus one extra day following GT, for the first four cycles of their treatment, to screen for the presence of GIH. Feasibility and acceptability were assessed using rates of consent, study completion, and staff and patient surveys. Forty-eight percent (35/74) of patients approached consented to participate in the study and had screening tests for preexisting diabetes. None were diagnosed with diabetes. Six out of 35 patients withdrew, and 10/29 patients did not complete the recommended BGL monitoring. Thirteen percent (4/29) of patients developed GIH. The most common reasons for non-participation and study withdrawal were related to the self-monitoring of BGLs. While clinical stakeholders found the MOC feasible and acceptable, the results of this study suggest that alternative methods for encouraging self-monitoring of BGL and monitoring the presence of GIH during high-dose chemotherapy need to be explored to address issues associated with adherence and sustainability.

Nocturnal continuous subcutaneous infusion of apomorphine in advanced Parkinson's disease: a series of 37 cases

Multiple factors can cause sleep disturbances in Parkinson's disease. The quality of sleep and therefore of life is usually improved with continuous dopaminergic stimulation therapies, such as continuous subcutaneous infusion of apomorphine. We present an observational retrospective study of patients at our centre with advanced Parkinson's disease, treated with continuous infusion of apomorphine, with treatment extended to nights, between 2011 and 2022. We collected data from 37 patients, and evaluated the indication for nocturnal treatment, efficacy, safety and reasons for withdrawal. Fifty percent of patients began nocturnal treatment for motor complications, 19% for non-motor complications and 31% for both. The most common non-motor symptoms were sleep fragmentation and disturbances, neuropathic pain, psychiatric symptoms and intense nocturia. Twenty of the 37 patients (54%) were continuing treatment at the end of the study follow-up, 16 (43%) discontinued the infusion, and one (3%) was lost to follow-up. The adverse reactions that led to termination of the infusion were severe nodules (two), dopaminergic psychosis (one) and a positive Coombs test with/without anaemia (one). Four patients terminated the nocturnal infusions while continuing the daytime infusions due to suboptimal adaptation to the device. Patients whose symptoms improved without any significant adverse effects continued the treatment. Continuous infusion of apomorphine during the night was an effective and safe treatment in our series.

Applicability of a digital health application for cancer patients: a qualitative non-participation analysis

BackgroundThe use of digital health applications (German acronym DiGA) for comprehensive patient care is increasing rapidly. Patients with non-organic insomnia can be prescribed an application to manage insomnia. Due to the high prevalence of insomnia in patients with cancer, we were interested in the effect of it and what barriers need to be overcome for its use. The focus of existing studies on acceptance and benefits prompted us to emphasise the analysis of barriers and thus to formulate possible solutions.MethodsTo analyse the barriers of use, the study population (patients with self-reported tiredness or sleep disturbance via validated instruments and cancer disease) was divided into 3 groups. In groups 1 (patients who refused to participate in advance) and 2 (patients who refused a prescription), short close-ended questionnaires were used for non-response assessment by treating oncologists. Problem-centred guidelines were used for the telephone interviews with group 3 (patients who did not provide information on DiGA use). Alternatively, group 3 was invited to complete and return the close-ended questionnaire. A quantitative analysis of the non-response reasons was conducted using SPSS in groups 1 and 2, while MAXQDA was used for the qualitative data in group 3.ResultsPatients refused to participate at several stages of our study. Quantitative data are available for groups 1 and 2. In the largest group 1, 62% of patients refused to participate due to non-subjective sleep disturbance (177 out of 189 patients) during recruitment by treating oncologists, despite high scores on the screening tool. In the small group 2 (11 out of 15), the most common reasons for withdrawal documented by the oncologists were loss of interest and deteriorating health. The problem-centred qualitative interviews with group 3 (17 patients) revealed that some of them used the prescribed DiGA, despite not being included in the main study and being categorized as lost to follow-up.ConclusionAnalysis of barriers to DiGA use showed that reducing administrative barriers and providing digital and personal support can increase acceptance of the use of DiGAs among cancer patients. Additionally, screening tools can act as a door opener to further communication regarding DiGAs.Trial registrationGerman Register of Clinical Trials DRKS00034198, registration date: 7/05/24 (retrospectively registered).

A Self-led Self-management Intervention Supporting Teens with IBD (ASSIST-IBD): protocol for a feasibility study of a novel digital treatment adherence intervention

IntroductionTreatment non-adherence is common in young people with inflammatory bowel disease (IBD), yet support is lacking. A self-led self-management intervention supporting teens with IBD (ASSIST-IBD) is a new theory-based digital...

Reasons for Early Withdrawal of Etonogestrel Subdermal Implant

Reasons for Early Withdrawal of Etonogestrel Subdermal Implant

Influence of rheumatoid factor levels and TNF inhibitor structure on secondary nonresponse in rheumatoid arthritis patients.

The EXXELERATE study revealed poorer clinical outcomes in patients treated with adalimumab (ADL) and baseline rheumatoid factor (RF) above 203 IU/mL. However, responses were similar in patients treated with certolizumab pegol (CZP) regardless of RF levels. This study investigated the impact of RF levels >203 IU/mL on TNF inhibitors (TNFi) serum levels and the association with secondary nonresponse in RA patients treated with TNFi. We performed an observational ambispective study with RA patients treated with infliximab (IFX), ADL, or CZP. Patients were stratified according to baseline RF levels: ≤ or >203 IU/mL. After 6 months, serum drug levels and antidrug antibodies were measured, and reasons for discontinuation were collected. We included 170 RA patients: 90 (53%) received IFX, 48 (28%) ADL, and 32 (19%) CZP. While CZP serum levels did not differ between RF groups at 6 months (p = 0.6), RF levels >203 IU/mL were linked to lower serum drug levels in patients treated with IFX (p = 0.09) or ADL (p = 0.02). Secondary nonresponse was 3.6 times higher in patients with high versus low RF levels in patients under IFX or ADL. However, the reasons for withdrawal were not affected by RF levels in patients treated with CZP. Baseline RF above 203 IU/mL is associated with lower serum drug levels and an increased risk of discontinuation due to secondary nonresponse in patients treated with IFX or ADL. In contrast, drug levels and clinical outcomes are not significantly impacted by baseline RF levels in patients under CZP.

Resiliency among older adults receiving lung cancer treatment (ROAR-LCT): A novel supportive care intervention for older adults with advanced lung cancer

IntroductionNovel supportive care interventions designed for an aging population with lung cancer are urgently needed. We aimed to determine the feasibility of a novel supportive care physical therapy (PT) plus progressive muscle relaxation (PMR) intervention delivered to older adults with advanced lung cancer in the United States (US). Materials and MethodsThis clinical trial, Resiliency Among Older Adults Receiving Lung Cancer Treatment (ROAR-LCT: NCT04229381), recruited adults aged ≥60 years with unresectable stage III/IV non-small cell (NSCLC) or small cell lung cancer (SCLC) receiving cancer treatment at The James Thoracic Oncology Center (planned enrollment, N = 20). There were no exclusion criteria pertaining to performance status, laboratory values, prior cancer diagnoses, comorbidities, or brain metastases. Participants were evaluated by PT and psychology and given an exercise pedaler, resistance bands, a relaxation voice recording, and instructions at study initiation. Participants were evaluated in-person by PTs and psychologists at the start and end of the 12-session intervention, with the intervening sessions conducted via virtual health. Participants completed self-reported measures of functional status, symptoms, and mood longitudinally with the following instruments: EQ-5D-5L, Patient Health Questionnaire-9, and General Anxiety Disorder-7. PT assessments included the Short Physical Performance Battery (SPPB) and the two-minute walk test. Feasibility was defined as at least 60% of participants completing at least 70% of all intervention sessions. Optional gut microbiome samples and activity monitoring data (ActiGraph®) were also collected. ResultsThe ROAR-LCT study concluded after consenting 22 patients. Among the 22 consented, 18 (81.8%) started the intervention; 11 participants (61.1%) completed at least 70% of all study sessions. All participants with SCLC completed the intervention. Reasons for withdrawal included progression of disease or hospitalization. The majority (88.9%) of patients who started were able to complete at least one virtual health session. Participants' functional status, SPPB, depression, and anxiety scores were stable from pre- to post-intervention. Participants who withdrew had worse baseline scores across domains. Seven microbiome and six ActiGraph® samples were collected. Discussion: This is one of the first PT + PMR supportive care interventions using virtual health among older adults with advanced lung cancer to achieve feasibility in the US.

Quantitative Analysis of Factors of Attrition in a Double-blind rTMS Study for Alzheimer Treatment.

Attrition is a particular concern in studies examining the efficacy of a treatment for Alzheimer disease. Analyzing reasons for withdrawal in Alzheimer studies is crucial to ruling out attrition bias, which can undermine a study's validity. In contrast, attrition in studies using repetitive transcranial magnetic stimulation (rTMS) has received much less attention. Our goal was to identify any commonalities between participants who withdrew for the same reasons. Three independent coders rated each response concerning the reasons for withdrawal, and frequency tables were generated to characterize the participants within each category. This study was conducted on the 28 withdrawn cases from a 7-month study investigating the short-term and long-term therapeutic effects of rTMS for Alzheimer disease among 156 participants across 3 sites of the study. Seven reasons for withdrawal were identified, with health and medical changes being the most commonly reported reason (7 participants). Personal issues involving family or caregivers were the next most common (5 participants), and the remaining 5 categories consisted of 3 participants each. Although the limited sample size prevented the use of inferential statistics, our findings highlight the need for more transparent reporting of attrition rates and withdrawal reasons by rTMS researchers.

Retention rate of a novel autoinjector e-Device introduced to patients with chronic arthritis treated with certolizumab pegol in clinical practice: an observational implementation study

Objectives The objectives were to explore the clinical retention rate of an e-Device aimed at empowering chronic arthritis patients using certolizumab pegol (CZP) and to analyse beliefs about medication in the Danish population. Method Patients treated with CZP were recruited from the Netherlands, Denmark, and Sweden through rheumatology clinics at initiation of, or switching to, the e-Device. Patients were adults (aged 18–85 years) diagnosed with rheumatoid arthritis, axial spondyloarthritis, or psoriatic arthritis. Patients administered three consecutive self-injections at home. Descriptive statistics regarding baseline characteristics, retention rates, and reasons for withdrawal were assessed, along with the Beliefs about Medicines Questionnaire. Results In total, 59 patients participated (Netherlands 25, Denmark 15, Sweden 19). Most subjects (71%) were women, with a mean ± sd age of 55 ± 16.2 years and mean disease duration 12 ± 8.8 years. Six patients (10%) started CZP de novo and the remaining patients switched device. The overall retention rate was 42% after 52 weeks, declining to 38% after 104 weeks. A sharp decline, 34%, was seen at week 8. Between weeks 32 and 112, only four patients (6.8%) withdrew from the study. The primary reason for withdrawal was the patient’s request. Stratification by country showed significant differences for some outcomes. Conclusion An initial large dropout was evident within the first 8 weeks, with almost no dropouts thereafter. The reasons for withdrawal were primarily patient requests. Thus, the injection experience must be tailored carefully when selecting patients for new autoinjector e-Devices to enhance retention rates and patient satisfaction.

Dupilumab in Adults With Moderate to Severe Atopic Dermatitis

Moderate to severe atopic dermatitis (AD) is a chronic inflammatory skin disease that often requires continuous long-term systemic management. Long-term safety and efficacy data for treatment options are critically important. To assess the safety and efficacy of dupilumab treatment for up to 5 years in adults with moderate to severe AD. The 5-year LIBERTY AD open-label extension study was conducted from September 2013 to June 2022 at 550 sites in 28 countries. The study enrolled adult patients with moderate to severe AD who had participated in previous dupilumab clinical trials. Data were analyzed from August 2022 to February 2023. At enrollment, patients initiated a regimen of subcutaneous dupilumab, 200 mg, weekly (400-mg loading dose). The regimen was amended in June 2014 to dupilumab, 300 mg, weekly (600-mg loading dose) based on a dose-ranging study and again in November 2019 to dupilumab, 300 mg, every 2 weeks to align with the regulatory regimen approvals. The primary end points were the incidence and rate of treatment-emergent adverse events (TEAEs). Key secondary end points included incidence and rate of serious TEAEs and adverse events of special interest, proportion of patients achieving an Investigator's Global Assessment (IGA) score of 0 or 1 (clear or almost clear), and proportion of patients with 75% or more improvement in the Eczema Area and Severity Index (EASI) from the parent study baseline. A total of 2677 patients were enrolled and treated in the open-label extension study; 1611 (60.2%) were male, and the mean (SD) age was 39.2 (13.4) years. A total of 334 patients (12.5%) completed treatment up to week 260. The most common reasons for withdrawal were due to regulatory approval of dupilumab in compliance with the study protocol (810 of 1380 [58.7%]), patient withdrawal (248 of 1380 [18.0%]), and adverse events (116 of 1380 [8.4%]). Exposure-adjusted rates of TEAEs were generally stable or declined throughout the study. Common TEAEs (incidence of 5% or greater) included nasopharyngitis, worsening AD, upper respiratory tract infection, conjunctivitis, conjunctivitis allergic, headache, oral herpes, and injection-site reaction. At week 260, 220 of 326 patients (67.5%) achieved an IGA score of 0 or 1 and 288 of 324 (88.9%) achieved 75% or greater improvement in the EASI. The mean (SD) EASI score was 16.39 (14.60) at baseline and 2.75 (5.62) at end of study. In this study, there was sustained safety and efficacy of continuous long-term dupilumab treatment for adults with moderate to severe AD.

Liraglutide in the management of obesity: real world data (Portugal).

Overweight and obesity are major public health issues with increasing incidence and prevalence, affecting more than 50% of the population in developed countries. Due to its complex pathophysiology and multifactorial etiology, disease understanding, diagnostic approach and management remain suboptimal. Together with a structured nutritional intervention and physical activity plan, pharmacological treatment has the potential to magnify weight loss and health related benefits. Liraglutide is one of the most effective and frequently prescribed weight loss medication. Its efficacy and safety have been demonstrated in randomized clinical trials, however, real world data in Portugal is scarce. The authors report on the experience of a University Hospital Endocrine Clinic in the management of patients with overweight and obesity with liraglutide on top of lifestyle intervention. The aim of the study was to evaluate the effectiveness of liraglutide in the management of overweight and obesity. Retrospective, longitudinal observational study. Inclusion criteria were adult patients (>18 years old) with obesity (BMI>30 kg/m2) or overweight (≥27 kg/m2) with at least one obesity related co-morbidity (hypertension, dyslipidemia, obstructive sleep apnea, non-alcoholic fatty liver disease) with at least three months of liraglutide treatment. Diabetes diagnosis and prior bariatric surgery were exclusion criteria. Demographic and clinical variables were included and weight was recorded before and after at least 3 months of liraglutide treatment. One hundred forty-eight patients (85.8% females) with a mean age of 48.7±11.9 years were treated with liraglutide. Mean baseline BMI was 33.8±5.2 kg/m2 and median follow-up was 13 months. At the last appointment, 85.8% were still taking liraglutide. Among patients still taking liraglutide, mean weight loss was 7.6 kg (7.9%), with significantly greater losses in patients treated for more than 6 months (8.6kg vs. 6.2 kg, P=0.016). Patients with obesity lost significantly more weight than overweight patients (8.3 kg vs. 4.5 kg, P=0.028), despite similar treatment duration. The reasons for liraglutide withdrawal were gastrointestinal intolerance (7), medication cost (2), inefficacy (10) and physician instructions (1). The present study documents the long-term efficacy of liraglutide in the treatment of patients with overweight and obesity, with a low rate of drug withdrawal. Mean weight loss was significant and more evident from the 6th month of treatment on. Liraglutide, along with lifestyle intervention, is a good option for weight management in the majority of patients with obesity.

Real-World Experience with Isavuconazole in Allogeneic Stem Cell Transplantation in Spain

Invasive fungal infections (IFI) pose a significant complication after hematopoietic stem cell transplantation (HSCT). Isavuconazole (ISV) is a new generation azole with a favourable adverse effect and interaction profile approved for the treatment of invasive aspergillosis and mucormycosis. We analyzed the indications, effectiveness, adverse event profile and drug interaction management of ISV in the real-world setting in adults who received allogeneic-HSCT (allo-HSCT) within the Spanish Group of HSCT and Cell Therapy (GETH-TC). We conducted a multicenter retrospective study of all consecutive adult allo-HSCT recipients (≥18 years) who received ISV either for IFI treatment or prophylaxis, from December 2017 to August 2021, in 20 centers within the Spanish Group of Hematopoietic Stem Cell Transplantation and Cell Therapy (GETH-TC). A total of 166 adult allografted patients who received ISV from 2017 to 2021 were included. Median age was 48 years with 43% females. In 81 (49%) patients, ISV was used for treatment of IFI, and in 85 (51%) for prophylaxis. Median duration of ISV administration for IFI treatment was 57 days (range 31-126) and 86 days (range 33-196) for prophylaxis. Most frequent indication for treatment was invasive aspergillosis (78%), followed by mucormycosis (6%). Therapeutic success (45%) was the most frequent reason for ISV withdrawal. In the prophylaxis group, the resolution of IFI risk factors was the most frequent reason for withdrawal (62%). Six (7%) breakthrough IFI were reported. The majority of patients (80%) presented pharmacologic interactions. Twenty-one patients (13%) reported adverse events related to ISV, mainly liver biochemistry abnormalities, which led to ISV withdrawal in 7 patients (4%). ISV was effective and well tolerated for IFI treatment and prophylaxis, with a manageable interaction profile.

#1563 Family feedback survey on quality of dialysis withdrawal and end-of-life care on hemodialysis patients in an ICU – a single-center study from India

Abstract Background and Aims End-of-life care in hemodialysis is emerging, with limited implementation in developing countries. There is a sparsity of data on dialysis withdrawal and the quality of end-of-life care in these regions. Developing countries differ in their cultural, social, and spiritual practice compared to the Western world and family plays a major role in decision-making. No survey has been done on family's perception of dialysis withdrawal and end-of-life care in our settings. So, we studied feedback from families regarding the quality of dialysis withdrawal and end-of-life care provided to maintenance hemodialysis (MHD) patients admitted to our intensive care unit (ICU). Method This study was conducted at Kasturba Medical College, Manipal, MAHE, Manipal, India between January 2020 to October 2022 involving the data from end-stage kidney disease (ESKD) patients on MHD admitted in the ICU, who had withdrawn from dialysis before death and received end-of-life care as per the hospital policy (Blue Maple) from Renal supportive and Palliative care team. The baseline data was collected for all patients and indications for withdrawal of dialysis and ICU treatment and end-of-life care provided were collected. The next of kin were interviewed by telephone by a single interviewer using a modified Quality of Death and Dying questionnaire. The data was analyzed using SPSS 20 Results Among 98 ESKD patients on maintenance hemodialysis who died in our ICU, 23 were referred to Palliative care, counselled, had withdrawal of dialysis at least 48 hours before death and received end-of-life care. Table 1 outlines baseline characteristics. The mean age was 57 ± 12.09 years, with a male predominance (82.6%). Common comorbidities included hypertension (100%), type 2 diabetes (69.5%), and ischemic heart disease (65.2%). The primary cause for ICU admission was infectious disease (47.8%). The majority of reasons for dialysis withdrawal and end-of-life care were worsening hemodynamic status (82.6%) and illness deterioration (69.5%). After consent and establishment of futility, dialysis withdrawal was done for all patients (100%), No CPR for 100%, withdrawal of inotropes in 50%, and withdrawal of ventilator was done in 80% of the patients. A successful telephonic interview/survey was conducted with 21 out of the 23 subjects, with the majority of next of kin being the spouse (47.6%) followed by children (33.3%) and siblings (14.3%). The questionnaire and response are given in Table 2. All expressed a need for palliative care involvement. 82% accepted the decision of dialysis withdrawal and end-of-life care put forth by the doctor's team without difficulty;74% of families were present with the patient in their final hours and were grateful for the same 20% had their spiritual leader to visit during the end-of-life event. None of the family members (100%) interviewed had a guilty feeling and all had a positive rating on the involvement of the palliative care team and the need to ease patients' distress and suffering during their final hours (100%). Unfortunately, none of the patients had prior discussions of advance care planning (ACP) with their doctors regarding end-of-life care before the specific event Conclusion Our study highlights that families agree with the withdrawal of artificial life support measures, such as MHD, CPR, withdrawal of inotropes, and/withdrawal of ventilator in ICU settings when these interventions are considered futile for end-of-life care in ESKD patients. It also emphasizes the need for ACP, and early integration of palliative care for discussions about dialysis withdrawal, and withholding futile interventions at end-of-life care in ESKD patients, especially in resource-constrained settings like ours, for high-quality end-of-life care. This will also lead to better end-of-life care outcomes and improved patient and family satisfaction with care.

A scoping review to investigate recruitment and retention of people with dementia in clinical trials

Abstract Introduction The literature acknowledges difficulties in recruiting people with dementia (PwD) to research studies. Despite efforts of researchers and policymakers to improve participant recruitment and retention in clinical studies,[1] challenges remain.[2] Further work is needed to describe recruitment and retention of PwD in clinical studies and strategies used to promote these activities. Aim This scoping review aimed to investigate recruitment and retention of PwD in clinical trials focused on evaluating the pharmacological management of cognitive symptoms of dementia. Methods Five electronic databases (Medline, Embase, PsychINFO, Scopus, Web of Science) and the International Clinical Trials Registry Platform were searched using a variety of search terms to identify articles published in English from date of inception until July 2023. All registered, unregistered, published, and unpublished randomised controlled trials that evaluated pharmacological treatments for cognitive symptom management among PwD, with a mean age ≥65 years and dementia of any sub-type or stage were included; studies were not excluded based on setting. Two reviewers independently reviewed full texts of potentially eligible records. Data were extracted by one reviewer using a table constructed in Microsoft Excel; a 10% subset was checked by a second reviewer. Findings were summarised using frequencies and percentages and/or narratively presented in tables. Results In total, 3,253 records were found, with 2,953 records remaining after removal of duplicates. Following title/abstract screening, 229 full-text articles were assessed for eligibility. A total of 129 records met the inclusion criteria for this review. Fifty-eight studies (45.0%) recruited community dwelling PwD. Common reasons for participants to be excluded from trials were having no carer present (n=128 studies, 99.2%), using specific medications such as anticholinergic medications (n=28 studies, 21.7%), and being unable to swallow tablets without crushing (n=10 studies, 7.7%). A limited number of studies (n=45, 34.9%) provided details about how they recruited participants. A variety of different recruitment sites were used including clinical research facilities (n=16, 12.4%), memory clinics (n=17, 13.2%), general practices (n=2, 1.6%), nursing homes (n=2, 1.6%), hospitals (n=2, 1.6%). Few studies recruited through advertisements in local newspapers/radio stations (n=2, 1.6%). Only one study reported that PwD and their carers were supported by research/clinical staff throughout the trial to improve participant retention. The mean sample size was 439 participants, and the mean retention rate was 73.5%. On average, 99 participants per study withdrew from the clinical trials, with common reasons for withdrawal being adverse events (n=45 participants per study), carer no longer available (n=37 participants per study), and death (n=12 participants per study). Conclusion This study has provided important evidence on recruitment and retention of PwD in clinical studies. The findings highlight how poorly recruitment is described in the literature and it is unclear what strategies were used to promote recruitment and retention. Researchers working in this field should consider this when disseminating their work. Whilst a quality assessment of included studies was not undertaken, this is acceptable in scoping reviews. Future research should focus on enhancing transparency of reporting recruitment and retention of PwD in clinical research.

Mechanisms Involved in the Link between Depression, Antidepressant Treatment, and Associated Weight Change.

Major depressive disorder is a severe mood disorder associated with a marked decrease in quality of life and social functioning, accompanied by a risk of suicidal behavior. Therefore, seeking out and adhering to effective treatment is of great personal and society-wide importance. Weight changes associated with antidepressant therapy are often cited as the reason for treatment withdrawal and thus are an important topic of interest. There indeed exists a significant mechanistic overlap between depression, antidepressant treatment, and the regulation of appetite and body weight. The suggested pathomechanisms include the abnormal functioning of the homeostatic (mostly humoral) and hedonic (mostly dopaminergic) circuits of appetite regulation, as well as causing neuromorphological and neurophysiological changes underlying the development of depressive disorder. However, this issue is still extensively discussed. This review aims to summarize mechanisms linked to depression and antidepressant therapy in the context of weight change.

Drug effectiveness of 2nd and 3rd TNF inhibitors in psoriatic arthritis – relationship with the reason for withdrawal from the previous treatment

ObjectiveTo investigate real-world retention and remission rates in PsA patients initiating a 2nd or 3rd TNFi and the association with reason for discontinuation from the previous TNFi-treatment. MethodsProspectively collected routine care data from 12 European registries were pooled. Retention rates (Kaplan-Meier estimation) and crude/LUNDEX-adjusted rates of Disease Activity Score 28 and Disease Activity index for PSoriatic Arthritis (DAS28 and DAPSA28) remission were calculated and compared with adjusted Cox regression analyses and Chi-squared test, respectively). ResultsWe included 5233 (2nd TNFi) and 1906 (3rd TNFi) patients. Twelve-month retention rates for the 2nd and 3rd TNFi were 68% (95%CI: 67–70%) and 66% (64–68%), respectively. Patients who stopped the previous TNFi due to AE/LOE had 12-month retention rates of 66%/65% (2nd TNFi), and 65%/63% (3rd TNFi), respectively. Patients who stopped the previous TNFi due to LOE after less vs more than 24 weeks had 12-month retention rates of 54%/69% (2nd TNFi), and 58%/65% (3rd TNFi). Six-month crude/LUNDEX-adjusted DAS28 remission rates were 48%/35% and 38%/27%, and DAPSA28 remission rates were 19%/14% and 14%/10%, for the 2nd and 3rd TNFi. ConclusionTwo-thirds of patients remained on TNFi at 12months for both the 2nd and 3rd TNFi, while one-third and one-quarter of patients were in DAS28 remission after 6months on the 2nd and 3rd TNFi. While drug effectiveness was similar in patients who stopped the previous TNFi due to AE compared to overall LOE, drug effectiveness was better in patients who had stopped the previous TNF due to secondary LOE compared to primary LOE.