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BACKGROUND: Despite the pivotal role of clinical trials in advancing orthopaedic oncology knowledge and treatment strategies, the persistent issues of trial discontinuation and nonpublication are significant problems. This study conducted an analysis examining clinical trial discontinuation rates, associations between intervention types and discontinuation/nonpublication, and the role of funding, enrollment size, and their implications for trial success and completion. METHODS: This study, conducted on May 1, 2023, utilized a cross-sectional design to comprehensively analyze phase 3 and 4 randomized controlled trials within the realm of orthopaedic oncology. We specifically incorporated Phase 3 and 4 trials as they are designed to evaluate prolonged outcomes in human subjects and are more likely to reach publication. Study characteristics of interest included the intervention utilized in the clinical trial, presence of funding, whether the trial was published, completed, and trial enrollment size. The investigation involved an examination of ClinicalTrials.gov, a prominent online repository of clinical trial data managed by the National Library of Medicine of the USA. Descriptive statistics and multivariate logistic regressions were used to determine statistical significance. RESULTS: Among the cohort of 130 trials, 19.2% were prematurely discontinued. Completion rates varied based on intervention type; 111 pharmaceutical trials demonstrated a completion rate of 83.8%, whereas 19 non-pharmaceutical trials exhibited a completion rate of 8.0% (P

To date, the effectiveness of direct‐acting antivirals (DAAs) discontinued before 4 weeks has not been analysed in routine clinical practice. The study aimed to determine whether such a short therapy will enable achieving a sustained virological response under real‐world experience. The study population of 97 patients who discontinued DAA therapy and had data enabling analysis of patient and disease characteristics, and assessment of treatment effectiveness was selected from 16,815 patients registered in the EpiTer‐2 database. The most common reason for discontinuation was hepatic decompensation (20.6%) or the patient's personal decision (18.6%). Patients who discontinued treatment were significantly older, more frequently therapy‐experienced, more likely to have cirrhosis, a history of decompensation and a Child–Pugh B or C classification than those who completed treatment. SVR was achieved by 93.5% of patients who discontinued treatment after 4 weeks, 60.9% if discontinued at 3 or 4 week and 33.3% at Week 1 or 2. Patients receiving pangenotypic but not genotype‐specific treatment who discontinued after 4 weeks were as likely to achieve SVR as those who completed therapy. Patients who responded to treatment that lasted no longer than 2 weeks had a low baseline viral load (<400,000 IU/mL). Despite discontinuation of therapy after Week 4, the chances of SVR are high. Very early discontinuation does not preclude therapeutic success, especially in patients with low baseline viral load. [ABSTRACT FROM AUTHOR]

Aims: To assess the level of adherence to glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) treatment using real‐world data and to investigate the sociodemographic and clinical factors associated with discontinuation of GLP‐1RAs. Methods: First‐time users of GLP‐1RAs with type 2 diabetes mellitus (T2DM), aged ≥18 years, in the period 2007 to 2020, were identified using Danish registries, allowing all participants a minimum of 18 months' follow‐up. Adherence to GLP‐1RA therapy (medication possession ratio >0.80) and discontinuation of GLP‐1RA therapy was estimated at 6‐ and 12‐month follow‐ups. Multivariable cause‐specific Cox regression was used to identify sociodemographic and clinical factors associated with risk of discontinuation. Results: In total, 44 343 first‐time users of GLP‐1RAs with T2DM were identified (mean age 58.6 years, 42.7% female, median duration of T2DM 6.8 years, median glycated haemoglobin level 65 mmol/mol). The absolute risk of discontinuing GLP‐1RA treatment within 6 months was 14.2% (95% confidence interval [CI] 13.9–14.6) and 21.2% (95% CI 20.8–21.5) within 12 months. At 6 months, 50.4% were adherent to GLP‐1RA therapy and at 12 months, 48.6% remained adherent. In the multivariable model, younger (<40 years) and older age (>75 years), higher Charlson Comorbidity Index score, lower household income, high school and longer university degree as educational attainment level, and longer diabetes duration were associated with a higher risk of discontinuing GLP‐1RA treatment. Conclusion: Approximately one in five patients discontinued GLP‐1RA therapy within the first 12 months and only half were adherent. Overall, lower socioeconomic status and higher comorbidity burden were associated with higher risk of discontinuing GLP‐1RA treatment. [ABSTRACT FROM AUTHOR]

Objective Design Methods Results Conclusions Antipsychotics remain the first‐line treatment for people diagnosed with psychotic disorders despite adverse effects which lead many people to stop their medication. Many stop without the support of the prescriber, who may fear relapse. The objective of this study is to better understand the process of withdrawal from antipsychotics, from the perspective of people taking antipsychotics.Online survey.An international online survey elicited quantitative responses about pre‐withdrawal planning (560) and qualitative responses about what was helpful and unhelpful when withdrawing from antipsychotics (443). Responses came from users of antipsychotics in 29 countries.Forty‐seven per cent did not consult their psychiatrist before discontinuing. Only 40% made preparations, most commonly making a plan, gathering information and informing family. The most frequently reported helpful factors were focussing on the benefits of getting off the drugs (including ending adverse effects and feeling more alive), information about withdrawal symptoms and how to withdraw safely, withdrawing slowly, and support from psychologists, counsellors and psychotherapists. The most common unhelpful factor was the psychiatrist/doctor, largely because of their lack of knowledge, refusal to support the patient's wishes and the threat or use of coercion.Evidence‐based, respectful, collaborative responses to patients' concerns about adverse effects and desires to withdraw would probably reduce relapse rates and improve long‐term outcomes. It would definitely help end pervasive breaching of the principle of informed consent and human rights legislation. [ABSTRACT FROM AUTHOR]

AbstractBackgroundAimDesign and settingMethodsResultsConclusion\nSHORT CONDENSATIONIn the Netherlands, the use of long-acting reversible contraception (LARC) methods increases. Studies show high premature discontinuation rates of LARCs, but comprehensive insights into the Dutch situation remain limited.The aim of this study is to determine (1) the rate and reasons of discontinuation of different types of LARC in the first 2.5 years of use and (2) what patient characteristics are associated with premature discontinuation.Retrospective cohort study utilising data from a Dutch primary care research network.We included all women who received a LARC between 2017 and 2019 with a 2.5-year follow-up period. We performed a descriptive analysis, Kaplan Meier and logistic regression analysis to answer the research questions.We included 642 women. In total, 166 women (25.9%) discontinued their LARC within 2.5 years. Discontinuation rates were 22% for levonorgestrel intra-uterine systems (LNG-IUS) 52 mg, 25% for LNG-IUS 19.5 mg, 39% for copper IUDs and 47% for subdermal implants. Common reasons for discontinuation were: alterations in bleeding pattern (68%), abdominal pain (32%), headache or mood fluctuation (24%) and a preference for natural contraceptive methods (23%). Factors associated with discontinuation for reasons other than pregnancy wish were: age between 30 and 34 years old (OR 5.1, 95% CI [1.26–20.48]) and a history of sexual, physical and/or psychological abuse (OR 3.16, 95% CI [1.60–6.23]). A high educational level (OR 0.33, 95% CI [0.12–0.89]) was associated with a lower risk of discontinuation.The discontinuation rates of LARCs are high. Better counselling might prevent premature discontinuation.Despite their effectiveness premature discontiunuation rates of LARC are high, especially for subdermal implants. The most mentioned reason for discontinuation is alternation in bleeding partern. Better couneling by general practitioners and research into the underlying disturbed endometrial mechanism have to be done. [ABSTRACT FROM AUTHOR]

Background: The therapeutic landscape for ulcerative colitis (UC) has recently broadened to include anti-TNFα, anti-integrin, and anti-IL-12/23p40 antibody agents. These biological agents are tailored to individual patient profiles. However, some patients cease biological treatment. This study investigates factors influencing the discontinuation of biological treatment in UC patients. Methods: This retrospective single-cohort study encompasses UC patients who commenced treatment with biological agents like infliximab, adalimumab, golimumab, vedolizumab, and ustekinumab from April 2019 to March 2022. Patients were categorized into continuation and discontinuation groups based on their one-year treatment status. Baseline characteristics were compared between the groups. Results: Of the 116 UC patients, 102 were included in the study. Among these, 74 (72.5%) continued and 28 (27.5%) discontinued biological therapy. Discontinuation rates for infliximab, adalimumab, golimumab, vedolizumab, and ustekinumab were 33.3%, 25.0%, 50.0%, 30.2%, and 15.6%, respectively. The primary discontinuation reason was lack of efficacy (85.7%), followed by adverse events (7.1%), pregnancy (3.6%), and death (3.6%). The discontinuation group had a significantly lower rate of concomitant thiopurine compared to the continuation group (28.6% vs. 56.8%, p = 0.0132). Multivariable analysis revealed that concomitant thiopurine was independently associated with therapy continuation (p = 0.0075). Conclusion: The study indicates that concomitant thiopurine significantly correlates with the continuation of biological therapies in UC patients, underscoring the importance of concomitant thiopurine in sustaining biological therapy. Further studies are warranted to assess the efficacy of combination therapy. [ABSTRACT FROM AUTHOR]

Background: Oral immunotherapy (OIT) is an increasingly utilized management strategy for IgE-mediated food allergy. Despite promising efficacy and effectiveness, there is still a lack of data surrounding the reasons for discontinuation of OIT. The primary reason stated in the literature for discontinuation is adverse gastrointestinal effects. Social factors contributing to OIT discontinuation have not been well reported. We hypothesize that social considerations are significant contributors to treatment discontinuation. Methods: We completed a retrospective chart review of 50 patients treated in community pediatric allergy practices who discontinued OIT out of 507 patients who were started on OIT between October 1, 2017-October 27, 2022. Reasons for discontinuation were identified and classified into five main categories: unsafe care decisions, anxiety, adverse effects of OIT, uncontrolled comorbidity and social factors. Categories were not exclusive. Results: 507 patients were started on OIT, with data available for 50 patients who discontinued OIT, aged 10 months to 18 years and 2 months. The overall discontinuation rate was 9.8%, of which 40 patients (80%) discontinued during buildup, 9 patients (18%) discontinued during maintenance and one patient on two food OIT discontinued one food during buildup and one during maintenance (2%). Thirty-four patients (68%) had multiple reasons for discontinuing OIT. Social factors were the most common reason for discontinuation and were identified in 32 patients (64%). Twenty-four patients (48%) discontinued OIT due to adverse effects. Gastrointestinal symptoms were the most prevalent, while anaphylaxis contributed to discontinuation in 15 patients (30%). Anxiety led to discontinuation in 17 patients (34%). Conclusions: Our data highlights the importance of social factors and anxiety in the success of OIT completion. Our results support the need to consider not only the patient's medical history, but also their social history and support networks when selecting patients who are good candidates for OIT to optimize the successful completion of OIT. [ABSTRACT FROM AUTHOR]

Introduction: Long‐acting injectable cabotegravir + rilpivirine (CAB + RPV LAI) was approved for use in virally suppressed adults in the England and Wales national health service in November 2021. We describe a service evaluation of delivery processes and outcomes in 12 clinics. Methods: Centres populated a database using information from local policies and clinical records. Services were asked to describe approval processes, clinic pathways, and adherence to national guidelines. Additional data were collected on reasons for regimen choice, treatment discontinuations, and management of viraemia. Results: In total, 518 adults from 12 clinics were approved for CAB + RPV LAI between February 2022 and December 2023. Of the 518 people approved for CAB + RPV LAI, 423 received at least one injection. Median duration on CAB + RPV was 7.5 months (interquartile range 3.7–11.3). In total, 97% of injections were administered within the ±7‐day window. Virological failure occurred in 0.7%, and 6% discontinued CAB + RPV. Conclusion: In this large UK‐based cohort, robust approval processes and clinic protocols facilitated on‐time injections and low rates of both discontinuation and virological failure. [ABSTRACT FROM AUTHOR]

Purpose: The impact of cancer-related diarrhea (CRD) on changes in cancer therapy remains poorly characterized despite its prevalence. Methods: We performed a longitudinal observational study using IQVIA PharMetrics Plus claims data. Patients included adults with CRD identified by diagnosis codes or pharmacy claims and compared their outcomes to matched (1:1) patients without CRD. Treatment parameters (discontinuation, persistence, augmentation, dose titration, adherence) were evaluated and stratified for the first cancer therapy (chemotherapy vs. targeted therapy vs. both). A multivariate Cox proportional hazards model was used to estimate the difference in risk of each treatment parameter between cohorts, adjusting for cancer type, therapy, and comorbidities. Results: We identified 104,135 matched pairs of patients with solid (n = 94,411) or hematologic cancers (n = 9,724) receiving chemotherapy (n = 47,220), targeted therapy (n = 2,427), or both (n = 5,313). Patients with CRD discontinued therapy more frequently than those without CRD (chemotherapy [81.5% vs. 62.3%], targeted therapy [69.2% vs. 64.3%], both [96.0% vs. 85.5%], p < 0.0001). The overall proportion of discontinuation was higher (82.4% vs. 64.6%, p < 0.0001), including a higher risk of discontinuation (HR = 1.40, p < 0.001) for patients with CRD. The mean time to discontinuation (59.6 ± 54.1 vs. 68.3 ± 76.6 days), switch (72.0 ± 48.6 vs. 96.9 ± 84.0 days), persistence (95.1 ± 98.1 vs. 154.3 ± 142.7 days), and adherence (25.5% ± 37.2 vs. 47.9 ± 41%) were all lower (p < 0.0001) among patients with CRD. Conclusion: Patients who develop CRD undergo significant and clinically impactful index treatment discontinuation, treatment switching, and have lower adherence and persistence of anticancer therapy compared to patients without CRD. Strategies to control CRD to optimize cancer therapy are urgently needed. [ABSTRACT FROM AUTHOR]

Thrombopoietin receptor agonists (TPO-Ras; romiplostim/eltrombopag/avatrombopag) have demonstrated high efficacy rates (59–88%) and a good safety profile in clinical trials with adult patients with immune thrombocytopenia (ITP). Similar efficacy and safety results have been observed with romiplostim and eltrombopag in paediatric cohorts. Continuous treatment with TPO-RAs has shown durable responses with long-term use, up to 3 years. The effect of TPO-RAs was generally considered transient, as platelet counts tended to drop to baseline values after a short period of time (about 2 weeks), unless treatment was maintained. Several groups have reported successful discontinuation of TPO-RAs without the need for concomitant treatments. This is referred to as sustained remission off treatment (SROT). Both short- and medium-term treatment with TPO-RAs may reduce costs to our healthcare systems and, more importantly, may reduce the potential side effects that may be associated with continuous TPO-RA treatment. The issue of tapering and discontinuation of TPO-RAs in paediatric patients with ITP has received little attention to date. Given that paediatric ITP has much higher rates of spontaneous remission than ITP in adults, we consider that the possibility of SROT of TPO-RAs in paediatric patients with ITP is a neglected but very relevant issue in this subtype of the disease. [ABSTRACT FROM AUTHOR]

Objectives: The current study uses longitudinal data from the National Alzheimer's Coordinating Center (NACC) to assess the effects of antipsychotic medication use on changes in cognitive functioning among adults in the United States. Methods: Linear mixed models were conducted that included study visits, days between visits, sex, age, education, and medical history (i.e. diabetes, seizures, traumatic brain injury, stroke, and Parkinson's disease). The Neuropsychiatric Inventory Questionnaire (NPI-Q) was used to create variables assessing changes in psychotic symptoms, manic symptoms, and agitation/disinhibition. Results: The results indicated that starting an antipsychotic medication was associated with a greater decline in semantic fluency (Fruit and Vegetable Naming), processing speed (Digit Symbol and Trail Making Test, Part A), and cognitive flexibility (Trail Making Test, Part B). Conversely, stopping an antipsychotic medication was protective against declines in the same cognitive skills. The effect of antipsychotic medications on cognitive functioning did not appear to differ by reported changes in psychiatric symptoms after adjusting for false discovery. Conclusion: The results suggest that prescribers should consider discontinuance of an antipsychotic if the patient is reporting cognitive problems and their symptoms are manageable off the medications. The findings hope to spark future research into the effects of antipsychotic use on biomarkers of progressive dementias (e.g. Alzheimer's disease). [ABSTRACT FROM AUTHOR]

Background Method Results Conclusion Nonadherence/discontinuation of antipsychotic (AP) medications represents an important clinical issue in patients across psychiatric disorders, including schizophrenia spectrum disorders (SSDs). While antipsychotic‐induced weight gain (AIWG) is a reported contributor to nonadherence, a systematic review of the association between AIWG and medication nonadherence/discontinuation has not been explored previously.A systematic search was conducted in MEDLINE, EMBASE, PsychINFO, CINAHL, and CENTRAL databases, among others, to help identify all studies which explored adherence, study dropouts, AP switching and/or discontinuations attributable to AIWG among individuals with severe mental illness. A meta‐analysis was also completed where applicable.We identified two categories of studies for the meta‐analysis. Category 1 included three studies, which compared measures of AP adherence or discontinuation across BMI classes/degrees of self‐reported weight gain. When compared to normal weight individuals receiving APs or those who did not report AIWG, individuals who were either overweight or obese or reported weight gain in relation to AP use had an increased odds of AP nonadherence (OR 2.37; 95% CI 1.51–3.73; p = 0.0002). Category 2 had 14 studies which compared measures of discontinuation related to weight gain reported as an adverse effect across different APs. Olanzapine was associated with a 3.32 times (95% CI 2.32–4.74; p < 0.00001) increased likelihood of nonadherence or discontinuation when compared to other APs with lower weight gain liabilities. Similarly, APs with moderate weight gain liability (paliperidone, risperidone, and quetiapine) increased the odds of nonadherence or discontinuation by 2.25 (95% CI 1.31–3.87; p = 0.003) when compared to APs considered to have lower weight gain liability (i.e. haloperidol and aripiprazole). The qualitative summary also confirmed these findings.This review and meta‐analysis suggests that AIWG influences medication nonadherence/discontinuation, whereby APs with higher weight gain liability are associated with nonadherence/discontinuation. Additional studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Introduction: Continuous renal replacement therapy (CRRT) is a primary form of renal support for patients with acute kidney injury in an intensive care unit. Making an accurate decision of discontinuation is crucial for the prognosis of patients. Previous research has mostly focused on the univariate and multivariate analysis of factors in CRRT, without the capacity to capture the complexity of the decision-making process. The present study thus developed a dynamic, interpretable decision model for CRRT discontinuation. Method: The study adopted a cohort of 1,234 adult patients admitted to an intensive care unit in the MIMIC-IV database. We used the eXtreme Gradient Boosting (XGBoost) machine learning algorithm to construct dynamic discontinuation decision models across 4 time points. SHapley Additive exPlanation (SHAP) analysis was conducted to exhibit the contributions of individual features to the model output. Result: Of the 1,234 included patients with CRRT, 596 (48.3%) successfully discontinued CRRT. The dynamic prediction by the XGBoost model produced an area under the curve of 0.848, with accuracy, sensitivity, and specificity of 0.782, 0.786, and 0.776, respectively. The performance of the XGBoost model was far superior to other test models. SHAP demonstrated that the features that contributed most to the model results were the Sequential Organ Failure Assessment score, serum lactate level, and 24-h urine output. Conclusion: Dynamic decision models supported by machine learning are capable of dealing with complex factors in CRRT and effectively predicting the outcome of discontinuation. [ABSTRACT FROM AUTHOR]

Research indicates that racially and ethnically minoritized populations are more likely to receive low‐value services in comparison to White populations. It is crucial to de‐implement (i.e., replace or discontinue use of) these practices to make room for more effective alternatives and reduce disparities in outcomes. However, there is limited understanding of how, when, and why practices are de‐implemented. De‐implementation has been shown to improve client outcomes through a variety of mechanisms, such as improved service quality. This scoping review had two aims. First, we examined empirical articles related to de‐implementation to determine whether culture (the practitioner's or client's values and beliefs) and race/ethnicity were assessed or reported. Second, we examined how these factors were considered throughout the de‐implementation process. A total of 20 empirical studies were identified. Results suggested there is a gap in the literature regarding how culture and race/ethnicity may impact de‐implementation and ensuing outcomes. We translated research across settings to highlight the importance of considering culture and race/ethnicity when engaging in de‐implementation. Lastly, we provide suggestions for future research and discuss implications for practitioners. Practitioner Points: This article reviews the literature on the de‐implementation of low‐value, ineffective, or harmful practices in schools and other contexts that serve children and adolescents.Results indicated that the de‐implementation literature has thus far failed to fully include culture, race, or ethnicity into the process.Incorporating culture, race, and ethnicity, into the de‐implementation process, might promote positive and equitable outcomes for populations of color. [ABSTRACT FROM AUTHOR]

Purpose of Review: Long-term use of multiple sclerosis (MS) disease-modifying therapies (DMTs) is standard practice to prevent accumulation of disability. Immunosenescence and other age-related changes lead to an altered risk–benefit ratio for older patients on DMTs. This article reviews recent research on the topic of de-escalation and discontinuation of MS DMTs. Recent Findings: Observational and interventional studies have shed light on what happens to patients who de-escalate or discontinue DMTs and the factors, such as age, treatment type, and presence of recent disease activity, that influence outcomes. Summary: Though many questions remain, recent findings have been valuable for the development of an evidence-based approach to making de-escalation and discontinuation decisions in MS. [ABSTRACT FROM AUTHOR]

This study assessed direct-acting oral anticoagulant (DOAC) switching/discontinuation patterns in patients with non-valvular atrial fibrillation (NVAF) in 2019, by quarter (Q1–Q4), and associated socioeconomic risk factors. Adults with NVAF initiating stable DOAC treatment (July 2018–December 2018) were selected from Symphony Health Solutions' Patient Transactional Datasets (April 2017–January 2021). Switching/discontinuation rates were reported in 2019 Q1–Q4, separately. Non-medical switching/discontinuation (NMSD) was defined as the difference between switching/discontinuation rates in Q1 and mean rates across Q2–Q4. The associations of socioeconomic factors with switching/discontinuation were assessed. Of 46,793 patients (78.7% ≥ 65 years; 52.6% male; 7.7% Black), 18.0% switched/discontinued their initial DOAC in Q1 vs. 8.8% on average in Q2–Q4, corresponding to an NMSD of 9.2%. During the quarter following the switch/discontinuation, more patients who switched/discontinued in Q1 remained untreated (Q1: 77.0%; Q2: 74.3%; Q3: 71.2%) and fewer reinitiated initial DOAC (Q1: 17.6%; Q2: 20.8%; Q3: 24.0%). Factors associated with the risk of switching/discontinuation in Q1 were race, age, gender, insurance type, and household income (all p < 0.05). More patients with NVAF switched/discontinued DOACs in Q1 vs. Q2–Q4, and more of them tended to remain untreated relative to those who switched/discontinued later in the year, suggesting a potential long-term impact of NMSD. Findings on factors associated with switching/discontinuation highlight potential socioeconomic discrepancies in treatment continuity. [ABSTRACT FROM AUTHOR]

Abstract Background Oral immunotherapy (OIT) is an increasingly utilized management strategy for IgE-mediated food allergy. Despite promising efficacy and effectiveness, there is still a lack of data surrounding the reasons for discontinuation of OIT. The primary reason stated in the literature for discontinuation is adverse gastrointestinal effects. Social factors contributing to OIT discontinuation have not been well reported. We hypothesize that social considerations are significant contributors to treatment discontinuation. Methods We completed a retrospective chart review of 50 patients treated in community pediatric allergy practices who discontinued OIT out of 507 patients who were started on OIT between October 1, 2017-October 27, 2022. Reasons for discontinuation were identified and classified into five main categories: unsafe care decisions, anxiety, adverse effects of OIT, uncontrolled comorbidity and social factors. Categories were not exclusive. Results 507 patients were started on OIT, with data available for 50 patients who discontinued OIT, aged 10 months to 18 years and 2 months. The overall discontinuation rate was 9.8%, of which 40 patients (80%) discontinued during buildup, 9 patients (18%) discontinued during maintenance and one patient on two food OIT discontinued one food during buildup and one during maintenance (2%). Thirty-four patients (68%) had multiple reasons for discontinuing OIT. Social factors were the most common reason for discontinuation and were identified in 32 patients (64%). Twenty-four patients (48%) discontinued OIT due to adverse effects. Gastrointestinal symptoms were the most prevalent, while anaphylaxis contributed to discontinuation in 15 patients (30%). Anxiety led to discontinuation in 17 patients (34%). Conclusions Our data highlights the importance of social factors and anxiety in the success of OIT completion. Our results support the need to consider not only the patient’s medical history, but also their social history and support networks when selecting patients who are good candidates for OIT to optimize the successful completion of OIT.

Abstract Background The therapeutic landscape for ulcerative colitis (UC) has recently broadened to include anti-TNFα, anti-integrin, and anti-IL-12/23p40 antibody agents. These biological agents are tailored to individual patient profiles. However, some patients cease biological treatment. This study investigates factors influencing the discontinuation of biological treatment in UC patients. Methods This retrospective single-cohort study encompasses UC patients who commenced treatment with biological agents like infliximab, adalimumab, golimumab, vedolizumab, and ustekinumab from April 2019 to March 2022. Patients were categorized into continuation and discontinuation groups based on their one-year treatment status. Baseline characteristics were compared between the groups. Results Of the 116 UC patients, 102 were included in the study. Among these, 74 (72.5%) continued and 28 (27.5%) discontinued biological therapy. Discontinuation rates for infliximab, adalimumab, golimumab, vedolizumab, and ustekinumab were 33.3%, 25.0%, 50.0%, 30.2%, and 15.6%, respectively. The primary discontinuation reason was lack of efficacy (85.7%), followed by adverse events (7.1%), pregnancy (3.6%), and death (3.6%). The discontinuation group had a significantly lower rate of concomitant thiopurine compared to the continuation group (28.6% vs. 56.8%, p = 0.0132). Multivariable analysis revealed that concomitant thiopurine was independently associated with therapy continuation (p = 0.0075). Conclusion The study indicates that concomitant thiopurine significantly correlates with the continuation of biological therapies in UC patients, underscoring the importance of concomitant thiopurine in sustaining biological therapy. Further studies are warranted to assess the efficacy of combination therapy.

This study assessed direct-acting oral anticoagulant (DOAC) switching/discontinuation patterns in patients with non-valvular atrial fibrillation (NVAF) in 2019, by quarter (Q1–Q4), and associated socioeconomic risk factors. Adults with NVAF initiating stable DOAC treatment (July 2018–December 2018) were selected from Symphony Health Solutions’ Patient Transactional Datasets (April 2017–January 2021). Switching/discontinuation rates were reported in 2019 Q1–Q4, separately. Non-medical switching/discontinuation (NMSD) was defined as the difference between switching/discontinuation rates in Q1 and mean rates across Q2–Q4. The associations of socioeconomic factors with switching/discontinuation were assessed. Of 46,793 patients (78.7% ≥ 65 years; 52.6% male; 7.7% Black), 18.0% switched/discontinued their initial DOAC in Q1 vs. 8.8% on average in Q2–Q4, corresponding to an NMSD of 9.2%. During the quarter following the switch/discontinuation, more patients who switched/discontinued in Q1 remained untreated (Q1: 77.0%; Q2: 74.3%; Q3: 71.2%) and fewer reinitiated initial DOAC (Q1: 17.6%; Q2: 20.8%; Q3: 24.0%). Factors associated with the risk of switching/discontinuation in Q1 were race, age, gender, insurance type, and household income (all p < 0.05). More patients with NVAF switched/discontinued DOACs in Q1 vs. Q2–Q4, and more of them tended to remain untreated relative to those who switched/discontinued later in the year, suggesting a potential long-term impact of NMSD. Findings on factors associated with switching/discontinuation highlight potential socioeconomic discrepancies in treatment continuity.

Objectives: To examine how change in benzodiazepine (BZD) use is linked to changes in depressive symptoms intensity, worry intensity, and sleep quality over 16 months. Method: Data come from a larger randomised controlled trial (RCT) named the 'Programme d'Aide du Succès au SEvrage (PASSE-60+)' study (NCT02281175). Seventy-three participants age 60 years and older took part in a 4-month discontinuation programme and were assessed four times over 16 months. Change in BZD use was defined as the difference in reported mg/day between two assessments. Control variables were RCT discontinuation group; BZD use at T1; and either depressive symptoms, worry intensity, or sleep quality at T1. Hierarchical multiple regressions were used to analyse data. Results: In the short term, right after the discontinuation programme, sleep quality worsened with lower BZD use. This link was no longer significant at the 3- and 12-month follow-up. In the long term, depressive symptoms lowered with lower BZD use. No change was found in worry intensity in relation to BZD use at all measurement times. Conclusion: Discontinuation may improve depressive symptoms. Our study also questions the long-term effectiveness of BZD use, since long-term discontinuation was not linked with change in worry intensity and sleep quality. [ABSTRACT FROM AUTHOR]

Christopher Zacker,1 Justin T Puckett,2 Sachin Kamal-Bahl2 1Cerevel Therapeutics, LLC, Cambridge, MA, USA; 2COVIA Health Solutions, Ambler, PA, USACorrespondence: Sachin Kamal-Bahl, COVIA Health Solutions, 915 Brewster Lane Ambler, PA 19002, Tel +1 267-337-4250, Email sachin@coviahealthsolutions.comPurpose: Little is known about adherence to and discontinuation of newly initiated oral antipsychotics (OAPs) as well as associated factors among Medicare beneficiaries with schizophrenia. This study aimed to examine rates of OAP adherence and discontinuation and associated factors in a national sample of fee-for-service Medicare beneficiaries with schizophrenia.Patients and Methods: This retrospective study used 100% fee-for-service Medicare claims data to identify adult beneficiaries with schizophrenia, initiating a new OAP between 01/01/2017 and 12/31/2019 (index date = date of new OAP prescription). Outcomes included adherence and discontinuation. Factors associated with adherence were assessed using logistic and linear regressions; Cox regressions were used to assess factors associated with discontinuation.Results: In our final sample of 46,452 Medicare beneficiaries with schizophrenia, 35.4% were adherent to their newly initiated OAP (mean [SD] PDC: 0.52 [0.37]) over 12 months after initiation. Most patients (79.4%) discontinued their new OAP (median [IQR] time to discontinuation: 3.6 (1.0, 9.9) months). Factors associated with lower odds of adherence included younger age (OR: 0.43; 95% CI: 0.40– 0.47, p < 0.001 for patients aged 18– 35 relative to patients aged ≥ 65 years); non-White race (OR: 0.72; 95% CI: 0.69– 0.75, p < 0.001 relative to White patients); and evidence of prior schizophrenia-related hospitalization (OR: 0.80; 95% CI: 0.77– 0.83, p < 0.001 relative to patients without evidence of prior schizophrenia-related hospitalization). Similar associations were observed for discontinuation outcomes. Twice-daily dosing frequency was also associated with lower odds of adherence (odds ratio [OR]: 0.93; 95% CI: 0.89– 0.97, p = 0.0014) and higher hazard of discontinuation (hazard ratio [HR]: 1.03; 95% CI: 1.00– 1.05, p = 0.0244) relative to once-daily dosing frequency.Conclusion: We found high rates of non-adherence and discontinuation among Medicare beneficiaries initiated on currently available OAPs. We also identified risk factors that contribute to increased odds of medication non-adherence. By identifying at-risk patient populations, targeted interventions can be initiated to facilitate treatment continuity.Plain Language Summary: Although half of patients with schizophrenia are covered by Medicare, little is known about how consistently they take their antipsychotic medications, which is a crucial part of successful treatment. We found that only 1/3 of Medicare beneficiaries consistently took their medications and nearly 80% discontinued treatment, often shortly after starting it. Younger patients, non-White patients, and patients who had to take pills multiple times per day were less likely to consistently take their medications.Keywords: adherence, antipsychotic, Medicare, discontinuation

Hong Lu,&ast; Yanmei Mao,&ast; Ying Zeng, Pengyu Li, Pan Yan, Qunzhi Shi, Lin Liu Department of Pharmacy, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, People’s Republic of China&ast;These authors have contributed equally to this workCorrespondence: Hong Lu, Department of Pharmacy, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, People’s Republic of China, Email 1430368@qq.comPurpose: Voriconazole, a first-line therapeutic agent for chronic pulmonary aspergillosis, is metabolized by the cytochrome 450 enzymes, specifically CYP2C19 and CYP3A4. Rifampicin and rifapentine act as inducers of the cytochrome P450 enzyme. The current study explored the potential drug interactions arising from the co-administration of voriconazole with either rifampicin or rifapentine, as well as the duration of this effect on serum voriconazole levels after discontinuation of rifampicin or rifapentine.Patients and Methods: A retrospective study was conducted in tuberculosis patients with chronic pulmonary aspergillosis. These patients underwent a combination therapy involving voriconazole and rifampicin or rifapentine, or they were treated with voriconazole after discontinuation of rifampicin or rifapentine. The serum concentrations of voriconazole at steady-state were monitored. Data on demographic characteristics and the serum voriconazole levels were used for statistical analyses.Results: A total of 124 serum voriconazole concentrations from 109 patients were included in the study. The average serum concentration of voriconazole fell below the effective therapeutic range in patients treated with both voriconazole and rifampicin or rifapentine. Notably the co-administration of rifapentine led to a substantial (> 70%) decrease in serum voriconazole levels in two patients. Moreover, this interfering effect persisted for at least 7 days following rifampicin discontinuation, while it endured for 5 days or more after discontinuation of rifapentine.Conclusion: Concomitant use of voriconazole and rifampicin or rifapentine should be avoided, and it is not recommended to initiate voriconazole therapy within 5 or 7 days after discontinuation of rifapentine or rifampicin. Therapeutic drug monitoring not only provides a basis for the adjustment of clinical dose, but also serves as a valuable tool for identifying drug interactions.Keywords: voriconazole, rifampicin, rifapentine, serum concentration, discontinuation

Background: Although nucleos(t)ide analogues (NAs) are thought to reduce the risk of hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC), the effect of NA discontinuation on the prognosis of HBV‐related HCC after hepatectomy is rarely reported. We aimed to investigate the potential for hepatitis B virus e antigen (HBeAg)‐negative HBV‐related HCC patients to discontinue NAs based on preoperative hepatitis B virus surface antigen (HBsAg) status. Methods: This historical cohort study involved 1232 NA‐treated HBeAg‐negative patients who underwent curative hepatectomy for HBV‐related HCC from 2014 to 2019. The recurrence‐free survival (RFS) and overall survival (OS) of patients discontinuing NAs before surgery were compared with those continuing NAs. Propensity score matching (PSM) was used to balance baseline characteristics. Results: Of all enrolled patients, 839 (68.1%) patients continued NAs, and 393 (31.9%) patients discontinued NAs. Continuation of NAs was identified as an independent risk factor for RFS (HR 2.047, 95% CI 1.348–3.109, p < 0.001 before PSM and HR 2.756, 95% CI 1.537–4.942, p < 0.001 after PSM) in HBsAg‐negative patients. Similarly, subgroup survival analyses showed that NA discontinuation was associated with better RFS (p = 0.029 before PSM and p < 0.001 after PSM) and comparable OS (p = 0.935 before PSM and p = 0.115 after PSM) than NA continuation in HBsAg‐negative patients. The interaction between HBsAg status and continuation or discontinuation of NAs was significant (p for interaction <0.001). Conclusions: These findings demonstrate the potential for HBeAg‐negative HBV‐related HCC patients who have achieved HBsAg seroclearance to discontinue NAs under strict monitoring. [ABSTRACT FROM AUTHOR]

Objectives: Risperidone is commonly prescribed off-label in children and adolescents to manage disruptive behavior. This study aimed to investigate continued benefits of risperidone after at least 1 year of treatment and effects of discontinuation on physical health. Methods: Thirty-five youths (aged 6–18 years, intelligence quotient [IQ] >70) who were treated with risperidone for at least 1 year in regular clinical practice receiving outpatient care were randomly assigned to double-blind continuation of risperidone during 16 weeks or continuation for 2 weeks, gradual dose lowering over 6 weeks, and placebo for 8 weeks. Primary outcome was the total Disruptive Behavior (D-total) score of the parent-reported Nisonger Child Behavior Rating Form—Typical IQ (NCBRF-TIQ). Secondary outcome measures were the clinician-rated Clinical Global Impressions—Improvement scale (CGI-I), the parent, child, and teacher-rated Strengths and Difficulties Questionnaire (SDQ), the parent-rated Retrospective Modified Overt Aggression Scale (R-MOAS), and several health parameters (Udvalg for Kliniske Undersøgelser Side Effect Rating Scale [UKU-SERS], dyskinesia, akathisia, parkinsonism, body mass index (BMI), waist circumference, and laboratory outcomes). Mixed models for repeated measures were conducted for continuous outcomes and a chi-square test for the CGI-I. Results: Discontinuation of risperidone, as compared with continuation, was not associated with significant changes in parent-reported disruptive behaviors. However, discontinuation was related to significant deterioration in parent-rated verbal aggression, teacher-rated behavioral functioning, clinician-rated general functioning, and significant improvements in weight, BMI, waist circumference, and glucose, insulin, and prolactin levels. Although 56% of participants in the discontinuation group experienced relapse, causing premature withdrawal from the study, 44% was able to successfully discontinue risperidone. Conclusion: Discontinuation of risperidone was associated with deterioration on some, but not all behavioral measures according to this explorative study. Discontinuation was associated with important health gains. Despite long-term benefits of risperidone, attempts to withdraw risperidone should be undertaken in individual children. This is a crucial step in preventing harm and fostering health. [ABSTRACT FROM AUTHOR]

Purpose of review: Calcitonin gene-related peptide (CGRP)-targeting agents are potential candidates for disease-modifying migraine drugs. However, most studies on CGRP-targeting agents have assessed efficacy outcomes rather than long-term effects after discontinuation. This review aimed to synthesize and scrutinize the latest clinical data on the outcomes after the discontinuation of CGRP-targeting therapy in patients with episodic and chronic migraine, with a particular focus on chronic migraine. Recent findings: Real-world studies involving patients with migraine have reported consistent findings of worsened headache frequency and quality of life after the discontinuation of CGRP monoclonal antibodies (CGRP mAbs). Although many patients maintain improvements for up to 4 months after discontinuation compared to baseline (before starting CGRP mAbs), no studies have evaluated the effects of stopping treatment for > 5 months, which is the five-half-life of CGRP mAbs. Several studies have suggested that patients treated with CGRP receptor mAbs experience more rapid deterioration than those treated with CGRP ligand mAbs after discontinuing CGRP mAbs. Summary: The results of real-world studies suggest that for many patients with migraine, the benefits of CGRP mAbs diminish months after discontinuation. Therefore, anti-CGRP therapies may not be considered disease-modifying. However, the comprehensive assessment of the disease-modifying potential of these drugs requires studies with extended treatment and cessation durations. [ABSTRACT FROM AUTHOR]

Long-term antidepressant (AD) use, much longer than recommended, is very common and can lead to potential harms. To investigate the existing literature on perspectives of health professionals (HPs) regarding long-term AD treatment, focusing on barriers and facilitators to discontinuation. A systematic review with thematic synthesis. Eight electronic databases were searched until August 2023 including MEDLINE, PubMed, Embase, PsycINFO, CINAHL, AMED, Health Management Information Consortium, and the Networked Digital Library of Theses and Dissertation. Thirteen studies were included in the review. Of these, nine focused on general practitioner perspectives, one on psychiatrist perspectives, and three on a mix of HPs perspectives. Barriers and facilitators to discontinuing long-term ADs emerged within eight themes, ordered chronologically based on HP considerations during an AD review: perception of AD use, fears, HP role and responsibility, HPs' perception of AD discontinuation, HPs' confidence regarding their ability to manage discontinuation, perceived patient readiness to stop, support from patient's trusted people, and support from other HPs. Coding and development of subthemes and themes was performed by one researcher and further developed through discussion within the research team. Deprescribing long-term ADs is a challenging concept for HPs. The review found evidence that the barriers far outweigh the facilitators with fear of relapse as a main barrier. HP education, reassurance and confidence-building is essential to increase the initiation of the discontinuation process. Further research into the perspectives of pharmacists and mental health workers is needed as well as exploring the role of trusted people. • Long-term antidepressant use is common and can lead to potential harms. • The discontinuation of antidepressants is a challenging concept for health care professionals. • Confidence-building is essential to increase the initiation of the discontinuation process. • Further research into pharmacist's and mental health workers' perspective is needed. [ABSTRACT FROM AUTHOR]

Psychopharmacological treatment may be an independent risk factor for increased length of stay and readmission after hip and knee replacement. Thus, temporary perioperative discontinuation may be beneficial. However, little is known regarding the treatments, and not all are feasible to discontinue. Therefore, the aim of this study was to describe the treatments in terms of type, dose, duration, indication and initiating physician to assess the feasibility of temporary perioperative discontinuation. We included 482 patients planned for hip or knee replacement in psychopharmacological treatment for psychiatric disorders from 2021 to 2023 at five orthopaedic departments in Denmark. Most patients were treated with antidepressants (89%); most frequently, either selective serotonin reuptake inhibitors (SSRIs; 48%) or serotonin‐norepinephrine reuptake inhibitors (SNRIs; 21%). The majority received monotherapy (70%); most frequently, an SSRI (36%) or an SNRI (12%). Most antidepressants were initiated by general practitioners (71%), and the treatments had lasted for more than a year (87%). The doses of SSRIs/SNRIs were moderate, and the most frequent indication for antidepressants was depression (77%). These results imply that temporary perioperative SSRI/SNRI discontinuation may be feasible in hip and knee replacement patients and support a future randomized controlled trial investigating the potential benefits of temporary discontinuation. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitor (ICI)-related type 1 diabetes is an immune-related adverse event (irAE), occurring in slightly less than 1% of patients undergoing ICI therapy. Most cases develop during ICI treatment, with occurrences long after discontinuation being extremely rare. A 76-year-old woman, with no history of glucose tolerance issues, was diagnosed with lung adenocarcinoma with pleural invasion and underwent chemotherapy, including atezolizumab, an anti-programmed death-ligand 1 antibody. This treatment was discontinued due to disease progression, although she continued with other chemotherapy regimens. Approximately 5.5 months (166 days) after her last atezolizumab dose, she developed diabetic ketoacidosis, fulfilling the diagnostic criteria for fulminant type 1 diabetes. Anti-glutamic acid decarboxylase antibodies were positive. The patient carried susceptibility human leukocyte antigen (HLA) haplotypes, which are associated with type 1 diabetes. To date, including our patient, only nine cases of ICI-related type 1 diabetes developed after ICI discontinuation have been precisely reported. Eight cases originated from East Asia, with six exhibiting fulminant type 1 diabetes, and seven tested negative for islet-related autoantibodies. The reported cases were independent of ICI types, cycle number, or HLA haplotypes. Median time from the last ICI administration to diabetes onset was 4 months (range: 2–7 months). Although reports of cases occurring after ICI discontinuation are currently limited, their frequency may increase with the wider use of ICIs and improved survival rates of patients post-treatment. Therefore, it is crucial to remain vigilant for the development of ICI-related type 1 diabetes, not only during ICI administration, but also long after discontinuation. [ABSTRACT FROM AUTHOR]

Simple Summary: This study analyzed patients with metastatic bladder cancer. A total of 108 patients received immunotherapy, but 11 had to stop their immunotherapy because of adverse events to the therapy. Despite stopping the therapy, the treatment effect could be seen for a longer time, and many patients did not have to start therapy again. This study helps us to understand what happens when patients have to stop immunotherapy due to adverse events and what to do next regarding cancer therapy for those patients. Immune checkpoint inhibitor (ICI) therapies have been established as the standard-of-care in various uro-oncological cancers. Immune-related adverse events (irAEs) are frequent, but their degree rarely leads to the discontinuation of immunotherapies. Unplanned permanent treatment discontinuation may negatively impact the outcomes of patients, but there are emerging data about a positive correlation between emergence of severe irAEs and therapeutic cancer responses. In this study, a retrospective analysis of patients treated for urothelial carcinoma (UC) with ICI-based immunotherapy was conducted. irAEs were classified according to the Common Terminology Criteria for Adverse Events (CTCAEs) and radiological responses according to the Response Evaluation Criteria In Solid Tumors (RECISTs). Out of 108 patients with metastatic urothelial cancer that underwent immunotherapy, 11 experienced a severe irAE that required permanent discontinuation of ICI therapy. The most frequent irAEs leading to discontinuation were hepatitis (n = 4), pneumonitis (n = 2), and gastritis or colitis (n = 2). Prior to discontinuation (R1), the radiological best response was complete remission (CR) in three patients, partial response (PR) in six, and stable disease (SD) in wo patients. After the discontinuation of ICI therapy (R2), the best responses were CR in six, PR in three, and SD in two patients. Following discontinuation, the majority of these patients showed a sustained treatment response, despite not receiving any cancer-specific treatment. The median time of response after discontinuation of ICI therapy was 26.0 (5.2–55.8) months. We propose accurate counseling and close follow-ups of patients following their discontinuation of ICI therapy due to irAEs, as responses can be durable and deep, and many patients do not require immediate subsequent therapies, even in urothelial cancer. More data are required to find predictors of the length of response to appropriately counsel patients. [ABSTRACT FROM AUTHOR]

While antidepressants are frequently used, less is known about contemporary discontinuation patterns, especially across different sociodemographic populations. Patients 16–84 years initiating antidepressants between 2016 and 2019 within a large US health insurer were identified. The association between patient characteristics and time until antidepressant discontinuation was evaluated using adjusted Cox proportional hazard regression. Across 1,365,576 patients, mean time to discontinuation was 168.1 days (SD: 223.6). Men were more likely to discontinue than women (HR: 0.94, 95%CI: 0.94–0.94). Younger patients (16–24 years) were more likely to discontinue than older patients. Patients who were non-White (Asian HR: 1.33, 95%CI: 1.31–1.34; Black HR: 1.27, 95%CI: 1.27–1.28; Hispanic HR: 1.34, 95%:CI 1.34–1.35), with evidence of a substance use disorder (HR: 1.31, 95%CI: 1.27–1.35), or taking tricyclic antidepressants (HR:1.26, 95%CI: 1.25–1.27) were more likely to discontinue. Information on reasons for discontinuation was not available, and wide standard deviations for the primary outcome were reported. The results may not be generalized to non-commercially insured beneficiaries. Discontinuation is common within the first 6 months of treatment but varies across populations, highlighting patients who may benefit from potential intervention. • Most patients discontinued their antidepressants around 6 months post-initiation. • Discontinuation patterns varied across different patient characteristics. • Younger, male, non-White race patients were more likely to discontinue. • Patients with certain diagnoses and drugs were more likely to discontinue. [ABSTRACT FROM AUTHOR]

Antipsychotics are routinely prescribed to people diagnosed with schizophrenia or psychosis on a long-term basis. Considerable literature explores service users' opinions and experiences of antipsychotics, but studies investigating family members' views are lacking. To explore family members' perspectives on antipsychotics, particularly their views on long-term use, reduction and discontinuation of antipsychotics. Semi-structured interviews were conducted with 11 family members of people experiencing psychosis. Participants were recruited through community support groups and mental health teams. Interviews were analysed thematically. The majority of family members valued antipsychotic medication primarily in supporting what they saw as a fragile stability in the person they cared for. Their views of medication were ambivalent, combining concerns about adverse effects with a belief in the importance of medication due to fears of relapse. They described a need for constant vigilance in relation to medication to ensure it was taken consistently, and often found changes, particularly reduction in medication difficult to contemplate. Findings highlight that family members' attitudes to medication sometimes conflict with those of the people they care for, impacting on their health and the caring relationship. Family members may need more support and could be usefully involved in medication decision-making. [ABSTRACT FROM AUTHOR]

Current recommendations for RA treatment determine the need to reduce the dose and duration of glucocorticoid(GC) use. This is due to the wide spectrum and high frequency (up to 100%) of serious adverse events (AE) during GC treatment. However, in real practice GCs in RA are used very often (in Russia, Western Europe and the USA they are used in about 50% of patients), and often in long-term courses. This is explained by the fact that the combination of disease-modifying antirheumatic drugs (DMARDs), including biologics (bDMARDs) and Janus kinase inhibitors (JAK), with GCs allows to achieve faster improvement of patients’ condition and therefore is very “convenient” for many patients and physicians.However, it is very difficult to ensure dose reduction and (especially!) complete discontinuation of GC administration afterwards. Clinical and observational studies show that 30–40% of patients manage to discontinue the use of GCs during treatment with bDMARDs and JAK. In addition, discontinuation of GCs may significantly increase the risk of RA flare, even with complex pathogenetic therapy.Nevertheless, prolonged use of GCs, including low doses (less than 7.5 mg/day of prednisolone) should be considered as an indicator of the severity of the disease course and inadequacy of the current therapy. Therefore, we should strive for personalization of RA therapy, selection of DMARDs based on the assessment of the disease phenotype and predictors of response to treatment with different drugs, achieving the main goal of therapy – remission/low disease activity and achievement of acceptable quality of life, without the use of GCs.

Abstract Background Lithium is effective in the long-term treatment of bipolar disorder. Concerns have been raised about non-responsiveness after discontinuation and resuming previously effective lithium prophylaxis. We reviewed the available literature on this so-called lithium-discontinuation-induced treatment refractoriness (LDITR). Results We found 11 case reports and six cohort studies including 403 patients addressing LDITR, and one nation-wide register study providing some additional data on LDITR. Pooling all cohort studies, the percentages of non-responders during re-treatment with lithium ranged from 3.6 to 27.7%, with an average of 17.3%. Non-responsiveness was associated with longer duration of lithium treatment before discontinuation, longer duration of bipolar disorder before start of lithium, faster tapering off lithium, and longer duration of discontinuation. Conclusions There may be a subgroup in whom lithium discontinuation-induced treatment refractoriness exists. However, the vast majority of people respond when lithium is restarted. Moreover, it may be necessary to continue lithium beyond the first relapses to restore long-term prophylactic efficacy.

Abstract Background The main public health problem that has a significant impact on the high fertility rate, unintended pregnancies, and induced abortion is Implanon cessation. In addition to Implanon being underutilized in Ethiopia, the rate of cessation is higher among women who started using it. Nevertheless, little is known about the factors that lead to Implanon cessation. Objectives The study was aimed to determine the factors that led women to discontinue Implanon in Gedeo Zone, Southern Nation Nationalities and Peoples Region, southern Ethiopia, 2019. Method A community-based unmatched case–control study design was carried out. Cases and controls were selected by a multi-stage sampling with a 1:2 case-to-control ratio. Data was entered into EPi-data version 3.1 and exported to Statistical Package for Social Sciences (SPSS) version 20 for analysis. A bivariate and multivariable logistic regression was used to identify the factors affecting Implanon discontinuation. The adjusted odd ratio (AOR) with 95% Confidence Interval (CI) was used to determine the precision of estimates, and statistical significance was declared at a p-value of 0.05. Result From 516 women included in to the study, 495 (cases = 166 and controls = 329) women have responded to the questionnaires making a response rate of 96%. Monthly income 500—1000 birr [AOR: 0.3; 95% CI (0.2–0.5)], above 1000 birr [AOR: 0.2; 95% CI (0.1–0.4)], history of abortion [AOR: 2.0; 95% CI (1.0–4.1)], birth spacing [AOR: 0.6; 95% CI (0.3–0.9)], partner objection [AOR: 2.4; 95% CI (1.4–4.2)] were significantly associated factors. Conclusion This study identified that monthly income, having abortion history, birth spacing, partner objection were the factors that affect Implanon discontinuation. To reduce implanon discontinuation, reducing abortion, involving partner and increasing the birth spacing, appropriate counseling before the insertion and appropriate follow-up by a health care practitioner are highly recommended.

Objective: We conducted a survey of UK endocrine clinicians between June 2022 and August 2022 to understand current practices regarding GH treatment discontinuation in adults with growth hormone deficiency. Design and methods: Using Survey Monkey®, a web-based multiple-choice questionnaire was disseminated to the UK Society for Endocrinology membership. It consisted of 15 questions on demographics, number of patients receiving GH and current practice on GH treatment discontinuation. Results: In total, 102 endocrine clinicians completed the survey. Of these, 65 respondents (33 endocrinologists and 32 specialist nurses) indicated active involvement in managing patients with growth hormone deficiency. In total, 27.7% of clinicians were routinely offering a trial of GH discontinuation to adults receiving long-term GH therapy. Only 6% had a clinical guideline to direct such practice. In total, 29.2% stated that GH discontinuation should be routinely offered as an option to patients on long-term treatment, whilst 60% were not clearly in favour or against this approach but stated that it should probably be considered, and 9.2% were against. During the GH withdrawal period, most clinicians monitor signs and symptoms (75.4%), measure IGF-1 (84.6%), and complete a quality-of-life assessment (89.2%). Conclusion: The practice of offering a trial of GH discontinuation in growth hormone deficiency adults on long-term GH therapy is highly variable, reflecting the lack of high-quality evidence. Around a quarter of clinicians offer GH withdrawal for a number of reasons, but only a few have a local clinical guidance. A further 60% of clinicians stated they would probably consider such an approach. Methodologically sound studies underpinning the development of safe and cost-effective guidance are needed. Significance statement In this UK survey of endocrine clinicians managing adults with growth hormone deficiency on long-term GH therapy, we explored for the first-time current practice and views on offering GH treatment discontinuation. In total, 27.7% of clinicians were routinely offering this option for a variety of reasons. Only 6% have local clinical guideline available to direct their practice on this. The majority of clinicians (60%), were not clearly in favour or against this approach but indicated it should probably be considered. In the absence of robust evidence on consequences of GH withdrawal, clinicians proposed monitoring of various clinical, biochemical and quality-of-life parameters during the period of discontinuation. Methodologically sound studies that will underpin the development of a safe, cost-effective guidance are needed.

Abstract Background/Purpose Little is known about long-term clinical outcomes or urate-lowering (ULT) therapy use following pegloticase discontinuation. We examined ULT use, serum urate (SU), inflammatory biomarkers, and renal function following pegloticase discontinuation. Methods We conducted a retrospective analysis of gout patients who discontinued pegloticase using the Rheumatology Informatics System for Effectiveness (RISE) registry from 1/2016 to 6/2022. We defined discontinuation as a gap ≥ 12 weeks after last infusion. We examined outcomes beginning two weeks after last dose and identified ULT therapy following pegloticase discontinuation. We evaluated changes in lab values (SU, eGFR, CRP and ESR), comparing on- treatment (≤ 15 days of the second pegloticase dose) to post-treatment. Results Of the 375 gout patients discontinuing pegloticase, median (IQR) laboratory changes following discontinuation were: SU: +2.4 mg/dL (0.0,6.3); eGFR: -1.9 mL/min (− 8.7,3.7); CRP: -0.8 mg/L (-12.8,0.0); and ESR: -4.0 mm/hr (-13.0,0.0). Therapy post-discontinuation included oral ULTs (86.0%), restarting pegloticase (4.5%), and no documentation of ULT (9.5%), excluding patients with multiple same-day prescriptions (n = 17). Oral ULTs following pegloticase were: 62.7% allopurinol, 34.1% febuxostat. The median (IQR) time to starting/restarting ULT was 92.0 days (55.0,173.0). Following ULT prescribing (≥ 30 days), only 51.0% of patients had SU

Abstract Indigo naturalis is an effective treatment for ulcerative colitis. However, long-term use of indigo naturalis causes adverse events, such as pulmonary hypertension. The natural history of patients with ulcerative colitis who discontinued indigo naturalis after induction therapy is unknown. Moreover, the clinical features of patients who relapsed within 52 weeks after the discontinuation of indigo naturalis are unclear. This study aimed to assess the clinical outcomes of patients with ulcerative colitis after discontinuation of indigo naturalis and to identify potential markers responsible for relapse. This single-center retrospective study investigated the follow-up of 72 patients who achieved a clinical response 8 weeks after indigo naturalis treatment. We observed relapse in patients with ulcerative colitis after the discontinuation of indigo naturalis. We analyzed the factors predicting long-term outcomes after discontinuation of indigo naturalis. Relapse was observed in 24%, 57%, and 71% of patients at 8, 26, and 52 weeks, respectively. There were no predictive markers in patients who relapsed within 52 weeks after the discontinuation of indigo naturalis. The ulcerative colitis relapse rate after indigo naturalis discontinuation was high. Follow-up treatment is required after the discontinuation of indigo naturalis in patients with ulcerative colitis.

Tyrosine kinase inhibitors (TKI) have revolutionized the treatment of patients with chronic myeloid leukemia. Patients who achieve sustained deep molecular response are eligible for treatment discontinuation. DES-CML is an ongoing, phase 2 multicentric discontinuation trial. Adult patients with CML in chronic phase with typical BCR::ABL1 transcripts, stable deep molecular response (MR4.5 IS) for two years, and no previous resistance were eligible. Patients underwent a phase of TKI dose de-escalation for six months before discontinuation. TKI was reintroduced at the previous dose if the patient lost major molecular response (MMR) at any time. This study aimed to assess the impact of BCR-ABL transcript kinetics during TKI de-escalation and discontinuation phases on treatment-free survival. So far, the study recruited 41 patients, and 38 patients discontinued therapy (4 were in the second discontinuation attempt). Eleven patients lost MMR, one during the de-escalation phase and ten after discontinuation. 24-month treatment-free survival was 66% (95% CI: 48-84%) in a median follow-up of 7 (1-30) months. No patient lost hematological response or had disease progression. A higher rate of molecular relapses occurred in patients with fluctuating BCR::ABL1 levels after the discontinuation phase (with loss of MR4.5, but no loss of MMR) (P=0.04, HR-4.86 (1.03-22.9) but not confirmed in the multivariate analysis. The longer duration of TKI treatment (P=0.03, HR-1.02, 95%CI - 1.00-1.04) and MMR (P=0.004, HR-0.95, 95%CI - 0.92-098) were independent factors of a lower relapse rate. [ABSTRACT FROM AUTHOR]

Background: Lithium is effective in the long-term treatment of bipolar disorder. Concerns have been raised about non-responsiveness after discontinuation and resuming previously effective lithium prophylaxis. We reviewed the available literature on this so-called lithium-discontinuation-induced treatment refractoriness (LDITR). Results: We found 11 case reports and six cohort studies including 403 patients addressing LDITR, and one nation-wide register study providing some additional data on LDITR. Pooling all cohort studies, the percentages of non-responders during re-treatment with lithium ranged from 3.6 to 27.7%, with an average of 17.3%. Non-responsiveness was associated with longer duration of lithium treatment before discontinuation, longer duration of bipolar disorder before start of lithium, faster tapering off lithium, and longer duration of discontinuation. Conclusions: There may be a subgroup in whom lithium discontinuation-induced treatment refractoriness exists. However, the vast majority of people respond when lithium is restarted. Moreover, it may be necessary to continue lithium beyond the first relapses to restore long-term prophylactic efficacy. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs) are widely used in the long-term treatment of gastroesophageal reflux disease (GERD) and other upper gastrointestinal disorders, such as the healing of peptic ulcers and/or prophylactic treatment of peptic ulcers. PPIs are also widely used as symptomatic treatment in patients with functional dyspepsia. One of the adverse effects of the long-term use of PPI is rebound acid hypersecretion (RAHS), which can occur after the withdrawal of PPI therapy due to a compensatory increase in gastric acid production. Mechanisms of the RAHS have been well established. Studies have shown that pentagastrin-stimulated acid secretion after the discontinuation of PPIs increased significantly compared to that before treatment. In healthy volunteers treated with PPIs, the latter induced gastrointestinal symptoms in 40–50% of subjects after the discontinuation of PPI therapy but after stopping the placebo. It is important for practicing physicians to be aware and understand the underlying mechanisms and inform patients about potential RAHS before discontinuing PPIs in order to avoid continuing unnecessary PPI therapy. This is important because RAHS may lead patients to reuptake PPIs as symptoms are incorrectly thought to originate from the recurrence of underlying conditions, such as GERD. Mechanisms of RAHS have been well established; however, clinical implications and the risk factors for RAHS are not fully understood. Further research is needed to facilitate appropriate management of RAHS in the future. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate long-term continuation rates, adverse events of ring pessary use at a minimum of 5 years follow-up, and factors associated with discontinuation in symptomatic pelvic organ prolapse (POP). Methods: Women with symptomatic POP who were treated with vaginal ring pessary and had successful fittings were included. Adverse events and reasons for discontinuation of pessary use were recorded. Patients who were lost to follow-up were defined as discontinuation. Results: During 12 year-period, 239 of 329 POP patients (72.6%) had successful fittings with ring pessary. The mean age was 67.8 ± 8.9 years (range 27–86) and 70% of patients had advanced stage. The cumulative probability of continued ring pessary use was 84.1%, 64.4%, 49.3%, and 33.5%, at 1, 3, 5, and 10 years, respectively. Most common reason for discontinuation was frequent expulsion (21.6%), followed by vaginal erosion (16.5%), no prolapse improvement (12.4%), and inability or inconvenience to do self-care (9.3%). However, 9 patients (9.3%) had improvement of prolapse and were able to discontinue pessary insertion. Age above 70 years, wide introitus, and incapability of self-care are independent factors associated with long-term discontinuation. Adverse events occurred in 23.4% of patients, 18.8% of them had vaginal erosion, 11.7% vaginal discharge/infection, and 18.4% de novo SUI. However, no statistical significance existed between those who continued and discontinued pessary use due to these adverse events. Conclusion: Ring pessary is an effective treatment in symptomatic POP, with acceptable long-term continuation rates and minor adverse events. Self-care of pessary is very important aiming to minimize adverse events. Advanced age, wide introitus and incapability of self-care were associated factors for long-term discontinuation. [ABSTRACT FROM AUTHOR]

Gambling disorder affects 0.5–2% of the population, and of those who receive treatment, dropout tends to be relatively high. Very little is known about participant-specific variables linked to treatment discontinuation/dropout in gambling disorder, especially in pharmacological clinical trial settings. Data were pooled from eight previous randomized, controlled pharmacological clinical trials conducted in people with gambling disorder. Demographic and clinical variables were compared between those who did versus did not subsequently dropout from those treatment trials. The sample comprised data from 635 individuals, and the overall rate of treatment dropout was 40%. Subsequent treatment dropout was significantly associated with the following: positive family history of gambling disorder in one or more first degree relatives (relative risk [RR] of dropout in those with positive history vs not = 1.30), preference for mainly strategic vs non-strategic gambling activities (RR = 1.43), lower levels of education (Cohen's D = 0.22), and higher levels of functional disability (Cohen's D = 0.18). These variables did not differ significantly as a function of treatment condition (medication versus placebo). Dropouts and completers did not differ significantly in terms of the other demographic or clinical variables that were considered. This study identified several candidate participant-specific predictors of pharmacological treatment dropout in gambling disorder. The findings highlight the need for future studies to address a wider range of contextual variables at large scale (including also study-specific variables e.g. trial/intervention duration), including in naturalistic treatment and clinical trial settings, with a view to developing algorithms that might usefully predict dropout risk. [ABSTRACT FROM AUTHOR]

Objectives: While a single 12-month treatment cycle (TrC) with anti-CGRP mAbs is not disease-modifying for most patients, there is limited understanding of the effects of multiple TrCs on migraine course. We evaluated whether a second TrC might modify the migraine course by comparing the occurrence of migraine relapse after discontinuation of the second TrC to that following the cessation of the first TrC. Methods: In a real-life, multicenter, prospective study we considered all consecutive patients diagnosed with high-frequency episodic migraine (HFEM) or chronic migraine (CM) with > 3 treatment failures and treated with any anti-CGRP mAbs for ≥ 2 consecutive 12-month TrCs who were responders at week 12. The primary endpoint was the change in monthly migraine days (MMD) for HFEM or monthly headache days (MHD) for CM at the first month of treatment discontinuation after the second TrC (D2) compared to the first TrC (D1). Secondary endpoints included variations in monthly analgesic medications (MAM), Numeric Rating Scale (NRS), and Headache Impact Test (HIT-6) scores, ≥ 50%, ≥ 75%, and 100% response rates, and relapse from episodic migraine to CM and from no-medication overuse (MO) to MO at D2 vs. D1. Results: One-hundred-seventy-eight patients completed two 12-month TrCs with anti-CGRP mAbs. At D2, patients experienced a significant reduction in MMD (– 0.6, p = 0.028), MHD (– 2.6, p < 0.001), monthly analgesic medications (– 2.0, p < 0.001), and HIT-6 score (– 2.2, p < 0.001) compared to D1, indicating improved effectiveness. The ≥ 50% response rate at weeks 45–48 during the first TrC was 95.5%, while at weeks 45–48 of the second TrC was 99.4%. Corresponding rates at D1 was 20.2% whereas at D2 was 51.6% (p < 0.0001). No statistical difference emerged in ≥ 75% and 100% responders. The relapse rate from episodic migraine to CM at D2 was lower than at D1 (12.3% vs 30.4%; p = 0.0002) Fewer patients experienced relapse from no-MO to MO at D2 compared to D1 (29.5% vs 68.7%; p = 0.00001). Discussion: A second TrC with anti-CGRP mAbs demonstrated clinical improvements compared to the first one, as indicated by a milder migraine relapse at D2 compared to D1. Multiple TrCs with anti-CGRP mAbs could progressively modify migraine evolution by reducing CGRP-dependent neuroinflammatory nociceptive inputs to the brain. [ABSTRACT FROM AUTHOR]

Early initiation of intensive insulin therapy has been demonstrated to be effective in controlling glycemia and possibly preserving beta-cell function. Innovations in insulin formulations and delivery systems continue. However, we have seen an acceleration in the development of new classes of diabetes medications for individuals with type 2 diabetes and obesity, such as, for example, glucagon-like peptide-1 receptor agonists (GLP-1 RAs). These formulations have been shown to confer significant benefits in achieving good glycemic control with reduced hypoglycemia risk, weight loss, and cardiorenal protection. Therefore, it is reasonable to question whether there is still a role for insulin therapy in the management of type 2 diabetes. However, there are clear limitations inherent to GLP-1 RA therapy, including high rates of suboptimal adherence and treatment discontinuation due to high cost and side effects, which diminish long-term efficacy, and supply issues. In addition, newer formulations have shown improvements in convenience and tolerability, and have been shown to be even more effective when used in conjunction with basal insulin. In this narrative review, we discuss current evidence that supports GLP-1 RA use in combination with insulin therapy and the potential pitfalls of reliance on GLP-1 RAs as a substitute for insulin therapy. [ABSTRACT FROM AUTHOR]

Background: Medication adherence in patients after percutaneous coronary intervention (PCI) is suboptimal, and discontinuation is common. Information on the temporal characteristics and associated factors of discontinuation and outcomes after PCI is insufficient to improve medication adherence interventions. Methods: We conducted a single-center retrospective study of post-PCI patients by telephone survey and medical record extraction. Temporal characteristics and associated factors of discontinuation and outcomes were examined by survival curve analysis, Cox regression, or time-dependent Cox regression. Results: Discontinuation and major adverse cardiovascular events (MACE) after PCI had similar temporal characteristics, with the highest incidence in the first year, followed by a decline. Temporary discontinuation was associated with pre-PCI medication nonadherence (HR 1.63; 95% CI: 1.09-2.43), lack of medication necessity (HR 2.33; 95% CI: 1.44-3.78), economic difficulties (HR 2.09; 95% CI: 1.26-3.47), routine disruption (HR 2.09; 95% CI: 1.10-3.99), and emotional distress (HR 2.76; 95% CI: 1.50-5.09). Permanent discontinuation was associated with residence in rural areas (HR 4.18; 95% CI: 1.84-9.46) or small to medium-sized cities (HR 4.21; 95% CI: 1.82-9.73), lack of medication necessity (HR 10.60; 95% CI: 6.45-17.41), and side effects (HR 3.30; 95% CI: 1.94-5.62). The MACE after PCI was associated with pre-PCI hypertension (HR 1.42; 95% CI: 1.04-1.96), two coronary stents (HR 1.42; 95% CI: 1.01-1.99) or three coronary stents (HR 1.66; 95% CI: 1.11-2.49) compared to one coronary stent up to this PCI, and temporary discontinuation (=60 months HR 2.18; 95% CI: 1.47-3.25; >60 months HR 8.82; 95% CI: 3.65-21.28). Conclusion: Discontinuation and MACE after PCI have similar temporal characteristics, temporary discontinuation and permanent discontinuation have different associated factors, and the former is associated with MACE. These findings may provide guidance for medication adherence interventions. [ABSTRACT FROM AUTHOR]

• About 38 % of women continued antidepressant treatment in the perinatal period. • Treatment trajectories are not affected by genetic liability or demographics. • Continued antidepressant use is influenced by the severity of the disease. Pregnant women on antidepressants must balance potential fetal harm with the relapse risk. While various clinical and sociodemographic factors are known to influence treatment decisions, the impact of genetic factors remains unexplored. We conducted a cohort study among 2,316 women with diagnosed affective disorders who had redeemed antidepressant prescriptions six months before pregnancy, identified from the Danish Integrated Psychiatric Research study. We calculated polygenic risk scores (PGSs) for major depression (MDD), bipolar disorder (BD), and schizophrenia (SCZ) using individual-level genetic data and summary statistics from genome-wide association studies. We retrieved data on sociodemographic and clinical features from national registers. Applying group-based trajectory modeling, we identified four treatment trajectories across pregnancy and postpartum: Continuers (38.2 %), early discontinuers (22.7 %), late discontinuers (23.8 %), and interrupters (15.3 %). All three PGSs were not associated with treatment trajectories; for instance, the relative risk ratio for continuers versus early discontinuers was 0.93 (95 % CI: 0.81–1.06), 0.98 (0.84–1.13), 1.09 (0.95–1.27) for per 1-SD increase in PGS for MDD, BD, and SCZ, respectively. Sociodemographic factors were generally not associated with treatment trajectories, except for the association between primiparity and continuing antidepressant use. Women who received ≥2 classes or a higher dose of antidepressants had a higher probability of being late discontinuers, interrupters, and continuers. The likelihood of continuing antidepressants or restarting antidepressants postpartum increased with the previous antidepressant treatment duration. Our findings indicate that continued antidepressant use during pregnancy is influenced by the severity of the disease rather than genetic predisposition as measured by PGSs. [ABSTRACT FROM AUTHOR]