Reasons For Discontinuation Research Articles

Completion and reporting of COVID-19 clinical trials registered on ClinicalTrials.gov during the first 6 months of the pandemic: cohort study

BackgroundEarly in the COVID-19 pandemic, numerous clinical trials were initiated. Although concerns were raised regarding the quality of the trials, the eventual research output yielded from the trials remains unknown....

Persistence With Human Immunodeficiency Virus Pre-exposure Prophylaxis in an Active-Duty Military Population.

There is limited data on Human Immunodeficiency Virus Pre-exposure Prophylaxis (PrEP) use and persistence in the military. Despite universal access to care, there is concern that PrEP persistence may be lower in military populations due to logistical challenges and perceived stigma. This study evaluated the persistence rates as well as reasons for PrEP discontinuation in a military cohort. This study evaluated all active-duty service members who received PrEP between 2020 and 2022 at a large military infectious diseases clinic. All charts were examined to determine patient characteristics. Patients who discontinued PrEP were contacted to determine the reason for discontinuation and invited to restart PrEP. In total, 112 service members received PrEP during the study period. The cohort was predominantly male (99%) with a median age 30 [IQR: 26-34] and a median of 2 years [IQR: 0-3] receiving PrEP. The most common indication was multiple sexual partners with less than 100% condom use (88%). At the end of the study, most (79%) patients were still receiving PrEP including 33 (37%) at other facilities. Of the twenty-four service members who were no longer receiving PrEP, 18 (75%), were able to be contacted. No patients contacted were interested in restarting PrEP. In this cohort with universal access to care, PrEP persistence rates were greater than seen in other populations. While the most common reason for discontinuation was changes in sexual behavior, systemic factors still contributed to PrEP discontinuation. Future studies should elucidate the challenges to PrEP care in the military.

Discontinuation of family planning use among women of reproductive age in Rwanda: analysis from three Rwandan Demographic Health Survey (RDHS) 2010-2020.

Family planning (FP) is fundamental in addressing unwanted pregnancies, unplanned pregnancies, unsafe abortions, maternal and child mortalities. It plays a crucial role in achieving the Sustainable Development Goals (SDGs), especial Goal 3. However, despite a high FP discontinuation percentage of 30% in Rwanda, there is limited studies on the contributing factors. Thus, the purpose of this study was to assess the discontinuation of FP use and associated factors among women aged 15-49 years in Rwanda. A pooled data analysis of three consecutive Rwandan Demographic and Health Surveys (RDHS) for the years 2010-11, 2014-15, and 2019-20 was performed using Stata Version 17.0. A multistage stratified sampling method was used to select study participants, and weighted analysis was conducted. Both bivariate and multivariate logistic regression models were used to identify factors associated with FP discontinuation. A statistical significance was determined at p < 0.05. The findings showed that 17%, 28%, and 29% of Rwandan women of reproductive age discontinued using FP in 2010-11, 2014-15, and 2019-20, respectively. Pooled multivariate analysis indicated that FP discontinuation rates was more than double folds higher in 2014-15 (AOR: 2.17; 95% CI: 2.01 to 2.35) and 2019-20 (AOR: 2.71; 95% CI: 2.49 to 2.93) compared to 2010-11. The odds of FP discontinuation were higher among women aged 20-34 years (AOR: 7.71; 95% CI: 5.87 to 10.13) and women aged 35-49 years (AOR: 3.43; 95% CI: 2.59 to 4.55); those with four or more children (AOR: 1.38; 95% CI: 1.28 to 1.49); women from poor households (AOR: 5.19; 95% CI: 1.85 to 14.57); those who attending a health facility in the last year (AOR: 1.56; 95% CI: 1.46 to 1.66); women with a history of pregnancy termination (AOR: 1.17; 95% CI: 1.09 to 1.26); those with no education (AOR: 1.39; 95% CI: 1.28 to 1.51) and currently married women (AOR: 11.57; 95% CI: 10.21 to 13.10). Additionally, the most common reasons for FP discontinuation were fear of side effects (31.2%) and the desire to become pregnant (27.5%). The trend of FP discontinuation among reproductive-age women in Rwanda has significantly increased from 200 - 11 to 2019-20. Key contributing factors include region, older age, higher parity, poor household status, health facility attendance, history of pregnancy termination, lack of education, being married and fear of side effects. Therefore, interventions should focus on addressing these factors to reduce FP discontinuation rates.

SURG-50. CLINICAL EXPERIENCE AND PATHOLOGICAL FEATURES IN AUTOPSY CASES TREATED WITH TUMOR TREATING FIELDS

Abstract BACKGROUND Since 2017 Tumor Treating Fields (TTF) was approved for primary glioblastoma in Japan. In this study, we reviewed clinical experience and the pathological characteristics of autopsy cases treated with TTF. METHODS From March 2018 to April 2022, 67 patients (36 males and 31 females, median age 68 years) with primary glioblastoma, IDH-wild type treated at our institution were included in the analysis. RESULTS Twenty-eight patients (19 males and 9 females, median age 66 years) met the TTF indication criteria for induction, 19 cases (67.9%) were 65 years or older, and 14 cases (50.0%) indicated MGMT promoter methylation. The mean duration of TTF treatment was 7.2 months. The main reasons for discontinuation were tumor recurrence in 11 patients (40.7%), skin symptoms in 8 patients (29.6%), and psychological distress in 6 patients (22.2%). Only 12 patients (42.9%) underwent TTF treatment over 18 hours per day, because of discomfort of wearing pad and concern about srrounding. Median PFS and OS in the used patients were 9.9 and 17.7 months, respectively. Autopsies were performed in 3 of the 16 deaths. Histopathological examination of tumor specimen indicate that the Ki-67 labeling index was higher in brainstem (33.6%) than in the supratentorial primary lesion (23.6%). DISCUSSION Comparing to the previous report (Stupp R et al., JAMA. 2017), our cases contained a large number of patients over 65 years old with shorter mean duration of TTF treatment, and shorter OS. After TTF treatment, the Ki-67 labeling index was higher on infratentorial than on supratentorial in the autopsy specimens, suggesting the anti-tumor effect of TTF for the supratentorial lesion. RESULTS High proliferative activity of infratentrial lesion was suggested as a typical form of progression for TTF treatment.

Oral cyclophosphamide monotherapy in advanced resistant ocular cicatricial pemphigoid

Abstract: PURPOSE: The purpose of the study was to study the efficacy of oral cyclophosphamide monotherapy in advanced resistant ocular cicatricial pemphigoid (OCP). MATERIALS AND METHODS: This retrospective case series examines patients diagnosed with advanced resistant OCP at a uveitis tertiary care center who were treated with oral cyclophosphamide therapy. RESULTS: Seventeen patients were included in this study. The average age of the participants was 74.3 ± 10.3 years, ranging from 60 to 99 years. The gender distribution was 8 females to 9 males. Oral cyclophosphamide-induced remission in 7 patients (41.1%) and was prematurely discontinued in 10 patients (58.9%), with 7 (63.7%) citing ineffectiveness and 3 (36.3%) experiencing side effects as reasons for discontinuation. The average therapy dose of cyclophosphamide administered was 116.1 ± 47.5 mg. The average duration required for the induction of remission was 150 ± 128 days. The overall therapy duration averaged 306 ± 189 days. Conducting univariate logistic regression with generalized estimating equations (GEEs) on variables did not reveal statistically significant differences between the two groups (responsive and nonresponsive to oral cyclophosphamide therapy), except for the maximum dose of oral cyclophosphamide therapy (P = 0.007). CONCLUSION: The prognosis of advanced OCP in patients is unlikely to be altered by the stepladder approach and step-up strategy. While oral cyclophosphamide can be efficacious for remission induction in resistant and aggressive OCP cases, a step-down strategy employing less potent agents with safer side effect profiles should be contemplated for subsequent treatment.

Cancer care treatment attrition in adults: Measurement approaches and inequities in patient dropout rates – a rapid review

BackgroundCancer treatment attrition refers to the discontinuation of prescribed cancer therapies before completion. It can significantly impact patient outcomes and cancer survival rates making it a critical concern. There is growing evidence on inequalities in cancer care, the avoidable systematic differences in the health of different groups of people. Understanding the extent of treatment attrition, why it happens, for whom, and associated inequalities may improve cancer care delivery and patient outcomes.MethodsA rapid review was conducted to identify existing evidence on measures of cancer treatment attrition, definitions, reasons for attrition and potential inequalities. The review followed a systematic approach but with abbreviated processes to facilitate quicker evidence synthesis. Searches were restricted to MEDLINE and Embase databases from their inception dates to May 7, 2024. Additional searches were performed in PubMed, Google Scholar, and key grey literature from relevant organizations. Inclusion criteria were adults with any type of cancer undergoing treatment, with studies reporting quantitative or qualitative data on treatment attrition conducted outside of clinical trials. Exclusion criteria included studies on children or adolescents, clinical trials, non-English publications, and various non-research article types. Data extraction and quality assessment were performed using standardized tools, and studies were synthesized narratively.ResultsThe search retrieved 1,353 references, with 40 studies meeting inclusion criteria. Most studies were retrospective. Studies covered various cancer types and treatments, reporting measures of attrition and reasons for treatment drop-out. Factors influencing attrition included disease progression, death, clinical deterioration, treatment toxicity, and socioeconomic factors such as lower income or socioeconomic disadvantage.ConclusionsThis review highlights significant variability in how treatment attrition is measured and defined, and suggests potential inequalities in who discontinues treatment. Standardized measures of attrition and data collection on reasons for discontinuation are essential to improve cancer care outcomes and equity. Future research should focus on developing these standardized metrics and exploring interventions targeting identified disparities to support cancer patients to complete treatment and improve outcomes.

Investigating Inappropriate Discontinuations of Enteral Nutrition Related to Gastric Residual Volume in Critically Ill Patients: A Retrospective Observational Descriptive Study

Background: Gastric residual volume (GRV) is measured by nurses in clinical practice as a simple method to assess gastrointestinal intolerance. Nutrition therapy guidelines recommend avoiding enteral tube feeding (ETF) discontinuation if GRV is &lt; 500 mL. Aim: This study aimed to clarify the status of inappropriate ETF discontinuation related to GRV in critically ill patients. Methods: Patients who were ventilated for more than 48 hours in the intensive care unit of a university hospital in 2021 were retrospectively surveyed, and data were collected up to 2 weeks after admission. ETF discontinuation data were collected and categorized as planned or unplanned. The reasons for unplanned discontinuation were further categorized into high GRV, symptoms, and conditions. The reasons and the amount of GRV were analyzed descriptively. Inappropriate ETF discontinuation related to GRV was defined as ETF discontinuation for a GRV of &lt; 500 mL. Results: ETF was discontinued in 10% (270 events / 2,600 orders) of critically ill patients. Unplanned discontinuations accounted for 37% (99/270) of discontinuations, with GRV being the most common reason (43%), followed by nausea and vomiting (8%), and hemodynamic instability (8%). Conclusions: Thirty-seven percent of ETF discontinuations in critically ill patients were unplanned, and 42% of these were inappropriate ETF discontinuations related to GRV. Research results and guideline recommendations need to be disseminated clearly to make more healthcare providers aware of the GRV criteria for discontinuing ETFs.

Outcomes, unmet needs, and challenges in the management of patients who withdraw from anti-CGRP monoclonal antibodies: A prospective cohort study.

The anti-calcitonin gene-related peptide (CGRP), or its receptor (CGRP/R) monoclonal antibodies (mAbs), offer targeted, effective, and tolerated drugs for migraine. However, about 25% of patients fail to achieve a clinically meaningful response, usually leading to discontinuation. These patients often have a lengthy migraine history and multiple prior preventive treatment failures, resulting in limited therapeutic options. Herein, we describe the cause for and outcome of withdrawal of anti-CGRP/R mAb and evaluate the treatment course until discontinuation. We conducted a prospective analysis on migraine patients attending the Florence Headache Center in Italy, who discontinued treatment with anti-CGRP/R mAbs. The primary objectives were to describe the reasons for anti-CGRP mAbs discontinuation and the treatment course. Secondary objectives were the evaluation of the absolute change from baseline in monthly headache days, response rates, persistence in medication overuse, absolute change from baseline of the overall number and days of analgesics use per month, change of MIDAS and HIT-6 at three, six, and 12 months, and the last month of treatment. Among 472 patients, 136 (28.8%) discontinued mAb treatment after an average of 9.0 ± 6.1 (mean ± SD) months. The majority (96/136, 70.6%) discontinued due to ineffectiveness, followed by lost to follow-up during treatment (18/136, 13.1%) and adverse events (10/136, 7.3%). In total, 77.9% of the 136 patients ceased treatment within the first year. Following discontinuation, 48.5% initiated new pharmacological treatment, 39.7% were lost to follow-up, and 11.8% opted not to start another treatment. The majority of patients that started a new pharmacology treatment switched to another anti-CGRP/R (46/68, 67.6%). The second most-used treatment was onabotulinumtoxinA (7/68, 10.2%; all patients in this subgroup were naïve to this treatment), followed by an anticonvulsive medication (7/68, 10.2%). The response status (≥50% reduction in monthly headache days) was achieved by 30.5%, 34.6%, and 40.0% of patients at month 3, 6, and 12 of treatment, respectively. Considering only the comprehensive last month of treatment before withdrawn the percentage of responders was 16.9%. Although anti-CGRP/R mAbs have provided a substantial amelioration of migraine management, a relevant proportion of patients remains unresponsive and requires additional therapeutic support. Further research is required to identify non-responder features and address unmet needs in migraine treatment.

Exploring the impact of BRCA1 and BRCA2 mutation type and location on Olaparib maintenance therapy in platinum-sensitive relapsed ovarian Cancer patients: A single center report

ObjectiveIn patients with platinum-sensitive relapsed ovarian cancer (PSROC) harboring pathogenic/likely pathogenic variants (PV) in BRCA1 and BRCA2 genes, olaparib maintenance monotherapy (OMT) is a viable option. Our study aimed to evaluate the impact of different BRCA1/2 PV in survival outcomes and safety of OMT in BRCA1/2-mutated PSROC patients, focusing on the type and location of PV. MethodsWe assessed the outcomes of 100 BRCA1/2-mutated PSROC patients treated at our institute, analyzing progression-free survival (PFS) and overall survival (OS). Germline and tumor BRCA1/2 genotyping was conducted using Illumina's next-generation sequencing (NGS). ResultsPFS and OS were significantly shorter in PSROC patients with PV in BRCA1 compared to those with PV in BRCA2 (PFS:14.0 vs. 38.8 months, p = 0.007, OS: 21.8 vs. 62.0 months, p = 0.011). Notably, there was a significant difference in PFS based on the intragenic location of BRCA1 PV, with shorter PFS in patients with 1st/2nd relapse, harboring PV in BRCA1 RING domain compared to those with PV in the DNA binding domain (DBD) and BRCT domains (12.4 vs. 23.0 months, p = 0.046). No differences in PFS and OS were observed between patients with germline versus somatic BRCA1/2 PV (PFS:14.9 vs.19.3, p = 0.316, OS: not reached vs. 25.8 months; p = 0.224). However, there were significant differences in the reasons for OMT discontinuation between patients with germline and somatic BRCA1/2 PV, primarily due to adverse side effects. ConclusionsIn summary, the type and location of BRCA1 and BRCA2 PV provide additional insight into the expected survival outcomes of olaparib MT in PSROC patients.Trial registration number: ISRCTN42408038, Name of registry: ISRCTN registry, Date of registration: 24/11/2015.

Abatacept and tofacitinib in refractory sarcoidosis: drug survival, safety, and treatment response.

To describe drug survival, safety and treatment response in sarcoidosis patients treated with abatacept or tofacitinib in routine care. We identified 41 sarcoidosis patients treated with abatacept and 12 patients treated with tofacitinib. Of the patients treated with tofacitinib 83% had previously been treated with abatacept. Drug survival and reasons for discontinuation of treatment was investigated. Treatment response was evaluated at least once within the first 6 months of treatment by at least one trained clinician and classified as responder or non-responder. No direct comparison of drugs was made. Median (range) disease duration was 3.5 (1-27) and 3 (1-16) years for abatacept and tofacitinib. The patients had previously received a median of 1 DMARD and 1 biological DMARD in both groups. Nearly all patients had been treated with at least one TNFi (95%/92 %). After 6 months, 90% (95%CI 85-90%) of the 41 patients in the abatacept group and 89% (79-99%) of the 12 patients in the tofacitinib group-maintained treatment. At 12 months, it was 80% (73-87%) and 74% (58-90%). No serious adverse events were recorded. For abatacept and tofacitinib 71% and 67% of patients were characterised as responders. In both treatment groups, there was a significant reduction in prednisolone dosage and levels of soluble IL2-receptor at all time points. Sarcoidosis patients treated with abatacept and tofacitinib had long drug survival, achieved high response rates. Both drugs represent good and safe therapeutic options in sarcoidosis patient's refractory to previous TNFi therapy.

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.

Reasons for contraceptive discontinuation among women of reproductive age in Kano, Nigeria: A qualitative study

Women’s attempts to achieve their desired levels of fertility are hindered when they stop using contraceptives, which could lead to unwanted pregnancies. This study aimed to assess reasons for contraceptive discontinuation among women of reproductive age in urban and rural areas of Kano State, Nigeria. Qualitative data were collected in urban and rural communities of Kano State in February to May, 2022 from women of reproductive age group, their male partners, family planning service providers, and community and religious leaders. Focus group discussions (FGD), and key informant interviews (KII), using multi-stage sampling methods explored previous experience with contraceptive use, fertility consequences and reasons for contraceptive discontinuation. Following data collection, digitally recorded data were transcribed verbatim, translated, and coded using thematic analysis through an inductive approach. Study reported the high discontinuation rates and identified side effects as the primary reason for discontinuation, with injectable contraceptives being the most commonly discontinued method. Other reported reasons for contraceptive discontinuation by respondents in both urban and rural groups were: method failure, intention to get pregnant, health concerns, husband disapproval, methods not available, inconvenience to use and interference with body structure or functions. The high contraceptive discontinuation poses significant risks of unintended pregnancies and unsafe abortions, thereby increasing maternal morbidity and mortality rates in Kano State. These consequences emphasize the need for family planning interventions that incorporate quality of care in service provision to address contraceptive discontinuation. Engaging men and other social influencers in family planning programs and services will help gather support for contraception, rather than focusing exclusively on women.

Persistence and predictors for non-persistence to edoxaban therapy in patients with atrial fibrillation: 4-year follow-up data from the ETNA-AF-Europe study

Abstract Background Non-persistence to non-vitamin K antagonist oral anticoagulants (NOACs) is associated with increased stroke risk in atrial fibrillation (AF) patients. To date, most NOAC persistence studies have been retrospective and often did not include patients receiving edoxaban. Identifying predictors for non-persistence may be useful when considering the design of future studies and help develop strategies to reduce non-persistence in clinical practice. Purpose To define and describe patients who did not reach the end of the study period and were non-persistent to edoxaban during the 4-year follow-up of ETNA-AF-Europe. Methods ETNA-AF-Europe was a prospective, observational study conducted in AF patients receiving edoxaban. In this subanalysis, patients not reaching the end of the study period and patients who were non-persistent (defined as permanent discontinuation of edoxaban) after 4 years of treatment were examined, including patients switching to other NOACs and reasons for discontinuation. Baseline predictors for not reaching the end of the study period and baseline predictors for non-persistence with edoxaban treatment during 4 years of follow-up were also examined. Persistent patients may have missed dose/interruption. Results Overall, 13,164 patients were included in the analysis. During the whole study period, 14.3% died. At the end of the study, 27.3% of patients prematurely terminated the study and 71.5% were classified as completing the study. Of patients who left the study (n=3598), 30.2% were lost-to-follow-up, 6.9% withdrew consent, and 5.9% transferred to another institution. Of patients who completed the study (n=9417), 87.4% were classified as persistent within the 4 years. Only 6.2% permanently discontinued edoxaban without switching to another NOAC (Table). Following backwards elimination, baseline characteristics associated with premature study termination (excluding death) were male sex, low body mass index, low renal function, chronic hepatic disease, long standing persistent/permanent AF, smoking, low compliance as judged by investigator, vitamin K antagonist-naïve, and no rate/rhythm control drug at baseline. Characteristics associated with non-persistence were increasing age, male sex, body weight extremes, low renal function, heart failure, vascular disease, chronic hepatic disease, alcohol use, perceived frailty, chronic obstructive pulmonary disease, smoking, current AF symptoms, and ablation (Figure). The criterion for backward elimination was p=0.05. Conclusions Most patients in ETNA-AF-Europe reached the end of the study. Less than a quarter were classified as non-persistent during the 4-year follow-up. The majority of patients who were non-persistent switched to another NOAC with a small number completely stopping anticoagulant therapy. Male sex, low renal function, chronic hepatic disease, and smoking were associated with both treatment discontinuation and non-persistence.Termination and persistence

Real-World Experience with Diroximel Fumarate in Patients with Multiple Sclerosis: A Prospective Multicenter Study.

Current literature and a real-world study suggest that diroximel fumarate (DRF) is safer than dimethyl fumarate (DMF) in the treatment of multiple sclerosis (MS). However, no real-world study to date has significantly addressed the efficacy of this treatment. This study aims to elucidate the safety, tolerability, and efficacy of DRF in a real-world setting, utilizing data from a Spanish national registry of patients commencing DRF therapy post-market introduction. In this multicenter, prospective observational study, data were collected from MS patients who initiated DRF treatment. The study monitored demographic and clinical characteristics, safety outcomes (including adverse events, reasons for discontinuation, and lymphocyte counts), and efficacy outcomes (radiological and clinical activity). A total of 195 MS patients across 26 neurological departments were included, predominantly female (79.5%), with a mean age of 42.17 years, and a mean duration of treatment with DRF of 6.3 months. Most patients (70.3%) reported no adverse events, while gastrointestinal issues and flushing were the most common adverse events observed. The majority of patients (84.6%) continued with DRF treatment, with tolerability issues being the primary reason for discontinuation. Efficacy analysis showed low relapse rates post-DRF initiation, with most patients exhibiting stable or improved Expanded Disability Status Scale scores and radiological assessments demonstrating minimal activity. This comprehensive analysis provides valuable insights into the real-world application of DRF, confirming its safety and tolerability while offering preliminary evidence of its efficacy in managing MS.

LDL-C target attainment and statin use in patients with ASCVD, familial hypercholesterolaemia, and those otherwise at moderate/high-risk of ASCVD in australian general practice (SCOPE-GP)

Abstract Background The proportion of Australian general practice patients not attaining low-density lipoprotein cholesterol (LDL-C) goals is not well described. The SCOPE-GP study evaluated duration of LDL-C exceeding treatment goals, statin use and discontinuation rates in patients with atherosclerotic cardiovascular disease (ASCVD), without ASCVD events but at moderate/high-risk, and familial hypercholesterolemia (FH). Methods This population-based retrospective cohort study used de-identified medical records of adult patients captured in the IQVIA GP-EMR database. Patients were indexed at the earliest date of ASCVD, FH, or hyperlipidemia diagnosis from January 1, 2010 to June 30, 2022, with a variable follow-up period from index to June 30, 2022. Ascertainment of study cohort was based on the 2021 ESC/EAS guidelines and Framingham Risk Equation. LDL-C test result levels were extracted per patient, summarised and analysed. Patients were stratified based on their test results at latest results/closest to censor date. Average time above target levels is the proportion of number of days above LDL-C target levels over total number of follow-up days for each patient. A Poisson distribution was fitted to estimate 95% confidence interval. Lipid lowering therapies (LLT) were stratified by (ASCVD, FH and moderate/high risk of CVD) at last visit/censor date. Combination of LLT were defined as prescriptions for fixed dose combinations or ≥2 separate scripts of LLT from different classes within 180 days from last visit/censor date (look back period). Discontinuation is defined as no statins were prescribed again after the last script for 270 days or more, limited to the first occurrence. Results The average time with LDL-C levels above target was 1077.5 days in ASCVD patients (n=2,688), 938.6 days in moderate-risk ASCVD (n=37,003), 980.9 days in high-risk ASCVD (n=85,199), and 900.8 days in FH (n=279). The proportion of days above target level for all four cohorts is described in Figure 1. Among 107,552 patients with recorded LDL-C levels ≥1.8mmol/L at their last visit/censor date, 30.9% were on statin monotherapy and 1.0% were on statin+ezetimibe. Statin use was highest in ASCVD patients (65.4%), followed by FH (49.5%), high risk (40.0%) and moderate risk subjects (29.5%) (Table 1). Statin discontinuation rates were 60.3%, 76.3, 66.1%, and 65.8% in these groups, respectively. The predominant reason for statin discontinuation was non-specific adverse drug reactions (12.2% ASCVD, 11.7% moderate-risk, 13.2% high-risk and 17.9% FH). The proportion of subjects contraindicated to statins was highest in moderate risk subjects (0.05%). Conclusions Prolonged periods of elevated LDL-C and high statin discontinuation rates were prevalent among at-risk individuals in Australian primary care. This underscores a significant ASCVD burden that could be prevented with more active lipid management.

Baseline Clinical Factors Associated with Cessation of Growth Hormone Therapy in Patients with Severe Growth Hormone Deficiency - Real World Evidence

Background: Growth hormone replacement is indicated in adults with severe growth hormone (GH) deficiency, adult growth hormone deficiency assessment (AGHDA) score of at least 11 and are receiving treatment for other pituitary hormone deficiencies. There are no data looking at the cessation of GH replacement in adult patients with severe GH deficiency and the factors that predict the likelihood of patients continuing or stopping growth hormone replacement. Methods: We audited patients on the GH register between January 2006 and January 2023 in Hull University Teaching Hospitals NHS foundation Trust, a UK tertiary hospital. Baseline characteristics, the cause of GH deficiency, AGHDA score at diagnosis and the reason for stopping GH were collected. Proportions were compared between patients adhering to GH replacement and those who had ceased it. Logistic regression analysis was used to identify factors independently associated with cessation of GH. Results: The study comprised 141 adult patients with a mean age of 52 years, of which 75 (53%) were female. 54 (38%) individuals had discontinued GH replacement therapy. Predominant reasons for discontinuation were lack of therapeutic benefit (46%) and a change in clinical indication (26%). Among patients who discontinued GH therapy, the most frequent cause of GH deficiency was idiopathic (57%), while for those on GH replacement, pituitary surgery was the leading cause of GH deficiency (53%). Logistic regression analysis showed no baseline factor was statistically significantly associated with GH cessation, except female gender which had a borderline significance (P = 0.05). Conclusions: In this real-world investigation of patients with severe GH deficiency, over two in five individuals who discontinued GH therapy cited the absence of perceived benefits. We show a borderline association of female gender with GH cessation and large population-based studies will be needed to investigate this and other causes of GH cessation.

Virologically suppressed switch to Dolutegravir/Lamivudine 2-Drug regimen versus switch to commonly prescribed 3-Drug regimens in the United States

BackgroundTwo-drug regimens (2DRs) have been introduced in recent years to potentially reduce antiretroviral therapy (ART) toxicities and drug-drug interactions while demonstrating comparable efficacy to three-drug regimens (3DRs) for people with HIV (PWH). The objective of this study was to compare the real-world effectiveness and durability of a single-tablet 2DR of dolutegravir/lamivudine (DTG/3TC) with that of commonly prescribed 3DRs in ART-experienced, virologically suppressed PWH during the first 24 months of DTG/3TC availability in the United States.MethodsVirologically suppressed (viral load [VL] < 200 copies/mL) adult PWH initiating DTG/3TC 2DR, bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), or a DTG-based 3DR between 01MAY2019 and 31OCT2020 were identified in the OPERA® cohort and followed through 30APR2021. Univariate Poisson regression (incidence rates) and marginal structural Cox proportional hazards models with inverse probability of treatment weights (hazard ratios) were used to quantify relationships between regimen type and confirmed virologic failure (2 consecutive VLs ≥ 200 copies/mL) or regimen discontinuation. Reasons for discontinuation were examined.ResultsA total of 8,037 ART-experienced, virologically suppressed PWH met the inclusion criteria and switched to DTG/3TC (n = 1,450), BIC/FTC/TAF (n = 5,691), or a DTG-based 3DR (n = 896). Incidence rates of confirmed virologic failure were low for all groups, at 0.66 (DTG/3TC), 0.84 (BIC/FTC/TAF), and 1.78 (DTG 3DR) per 100 person-years (py). Compared to DTG/3TC, only the DTG 3DRs were associated with a statistically significant increased hazard of confirmed virologic failure (hazard ratio: 5.21, 95% confidence interval: 1.85, 14.67). Discontinuation rates per 100 py were highest in the DTG 3DR group (24.90), followed by the DTG/3TC group (17.69) and the BIC/FTC/TAF group (8.30). Regardless of regimen, discontinuations were infrequently attributed to effectiveness (VL ≥ 200 copies/mL; 4%) or tolerability (adverse diagnoses, side effects, or lab abnormalities; 6%).ConclusionsAmong virologically suppressed PWH initiating a new regimen, few individuals experienced virologic failure in real-world clinical care. While rates of regimen discontinuation were high, most discontinuations could not be attributed to a lack of virologic control or poor tolerability. These findings suggest that DTG/3TC is an effective option for ART-experienced, virologically suppressed PWH.

Long-term safety and efficacy of adjunctive lacosamide in the treatment of generalized onset tonic-clonic seizures: An open-label extension trial.

This study was undertaken to assess long-term safety, tolerability, and efficacy of lacosamide (LCM) as adjunctive therapy for generalized onset tonic-clonic seizures (GTCS) in patients aged ≥4 years with idiopathic generalized epilepsy (IGE). EP0012 (NCT02408549) was a phase 3, multicenter, open-label extension (OLE) trial. Patients were enrolled from SP0982 (NCT02408523). Trial duration was ≥2 years (adults) and ≤5 years (children). The trial consisted of a treatment period, ≤4-week taper period, and 30-day safety follow-up. Safety (primary) variables were incidence of treatment-emergent adverse events (TEAEs), discontinuations due to TEAEs, incidence of onset of absence or myoclonic seizures, and increase in days with absence or myoclonic seizures per 28 days. Efficacy (secondary) variable was percent change in GTCS frequency per 28 days. Kaplan-Meier estimated retention rates and analyses by number of lifetime antiseizure medications (ASMs) were performed post hoc. Overall, 239 patients (mean age = 27.9 years, 56.1% female, 18.4% children) were enrolled and received ≥1 dose of LCM in this OLE (median treatment duration = 3.2 years); 157 (65.7%) completed the trial, and 82 (34.3%) discontinued. The most common reason for discontinuation (≥10%) was withdrawn consent (30 [12.6%]). Kaplan-Meier estimated retention rate was 87%, 72%, and 60% at 1, 3, and 5 years, respectively. Overall, 222 (92.9%) patients reported TEAEs; 19 (7.9%) discontinued due to TEAEs. Few patients had an increase in number of days with absence or myoclonic seizures, or incidence of new absence or myoclonic seizures. Median percent change in GTCS frequency per 28 days from the combined baseline was -88.6% (range = -100.0 to 465.4, n = 238). Post hoc analyses demonstrated small numerical differences between patients with 1, 2, and ≥3 lifetime ASMs. The results support the use of long-term adjunctive LCM for GTCS in patients with IGE. Long-term adjunctive LCM was efficacious and well tolerated independent of the number of ASMs used before LCM initiation. ClinicalTrials.gov: NCT02408549.

IMPACT OF CYP2D6 POLYMORPHISMS IN PREDUCTING OCCURRENCE OF ADVERSE EFFECT TO TAMOXIFEN AND DEVELOPING RECCURENCE IN ER+ BREAST CANCER PATIENETS:

Objectives: Breast cancer is a major public health in Algeria. Tamoxifen has been approved in the treatment of ER+ breast cancer. Some of negative side effects of tamoxifen are frequently a reason for discontinuation of therapy during treatment, which would otherwise be potentially lifesaving. In the current study, we assessed the association between CYP2D6 polymorphisms and tamoxifen efficacy in Algerian population receiving tamoxifen as adjuvant therapy in ER+ breast cancer. Methods: A total of 76 Algerian hormone receptor-positive premenopausal breast cancer patients with adjuvant tamoxifen treatment were investigated (45.36±6.13). DNA genotyping was performed by TaqMan Open Array technology. Tamoxifen and its metabolites levels were measured by ultra-high-performance liquid chromatography (UHPLC) followed by electro spray tandem mass spectrometry (LC-MS/MS). Results: A significant association between the presence of deficit copy of enzyme activity and development of adverse effect after the commencement of tamoxifen therapy. Low plasma endoxifen were observed in patients categorized as (NM/PM), (IM/ IM), (IM/PM) and (PM/PM). Patients with increased plasma endoxifen concentrations were significantly more likely than patients with reduced or null activity to not report recurrences (P&lt;0.05). We realized that the combination genotypes NM/PM, IM/IM, IM/PM, with PM/PM were more strongly associated with disease recurrence and adverse effects than NM carries of CYP2D6*1 allele (P&lt;0.05). Conclusion: Our results affirm that CYP2D6 polymorphism should be considered in predicting the occurrence of adverse effect fatty liver in women treated with tamoxifen. Thus, alternative treatment can be intended and lifestyle modifications can be implemented

Why do older adults stop cancer screening? Findings from the Medicare Current Beneficiary Survey.

Prostate and breast cancer screening are prevalent among older adults, even among those unlikely to benefit. We aimed to evaluate why older adults stop cancer screening, including the role of physician recommendations. We used nationally representative data from the 2019 Medicare Current Beneficiary Survey (MCBS). We included women aged 76 and older without a history of breast cancer and men aged 71 and older without a history of prostate cancer. The primary outcome was reason for discontinuing screening, categorized as follows: (1) physician recommendation against screening; (2) absence of a recommendation to screen; and (3) patient-driven reason, such as patient preferences or beliefs. We evaluated reasons for screening discontinuation by health status and educational attainment using age-stratified multinomial logistic regression. The sample included 7350 participants representing a weighted population of 22,498,715. Overall, 53% of women underwent screening mammography in the past year or intended to continue screening. Among those who stopped screening, 5% reported a recommendation to stop screening from their doctor, 48% reported no recommendation, and 32% reported a patient-driven reason for cessation. Findings did not differ by educational attainment or health status, including among the oldest patients. For men, 61% were screened with PSA in the past year or intended to continue. Among those who stopped, 3% reported a recommendation against screening, 54% reported no recommendation, and 27% reported a patient-driven reason for cessation. Men with higher educational attainment were more likely to report that their physician recommended against screening (4% vs. 1%, p = 0.01) and that their doctor did not recommend screening (58% vs. 47%, p = 0.01). Reasons for screening cessation did not differ by health status, including among the oldest patients. Cancer screening remains common, even among those with limited potential for benefit, but discussions around screening cessation are rare. Improving communication between patients and physicians may improve screening decision quality.