Discontinuity Factors Research Articles

Psoriatic arthritis, biologic therapy experience, body mass index, and onset age of psoriasis were independent factors of secukinumab discontinuation in patients with psoriasis

ABSTRACT Introduction Despite the availability of several treatments for psoriasis (PsO), factors influencing the persistence of secukinumab (SEC) therapy remain inadequately understood. This study aimed to identify predictors of SEC persistence in PsO. Methods A retrospective analysis was conducted on 109 PsO patients who received SEC treatment at least 1 year. Patients were categorized based on continued or discontinued SEC therapy. Results Among the 109 patients, 64 continued SEC treatment while 45 discontinued. Univariate analysis demonstrated that PsA presence and previous biologic therapy use increased the risk of SEC discontinuation 3.56- and 2.33-fold (p = 0.001, %95 CI: 1.66–7.65 and p = 0.032, %95 CI: 1.08–5.04, respectively). Additionally, the risk of SEC discontinuation is 57% higher in patients with a body mass index (BMI) above 26.5 compared to those with a BMI below 26.5 (p = 0.016, %95 CI: 0.22–0.85). Additionally, patients with PsO onset age below 26.5 years were found to have a 2.93-times higher risk of discontinuing SEC compared to those with PsO onset age above 26.5 years (p = 0.004, %95 CI: 1.40–6.13). Conclusion PsA presence, previous biologic therapy experience, BMI, and PsO onset age were identified as independent predictors of SEC discontinuation. These findings underscore the importance of personalized treatment strategies for PsO patients receiving SEC therapy.

Drug survival and risk factors for ADHD medication discontinuation in adults: A Danish Nationwide Registry-based cohort study.

Attention deficit hyperactivity disorder (ADHD) medication has proven effective for treating ADHD in adults, nonetheless previous studies have shown high rates of medication discontinuation. To assess drug survival and identify risk factors associated with discontinuation of ADHD medication. A nationwide registry-based cohort study in Danish adults who redeemed a prescription for ADHD medication for the first time between 2010 and 2015. All patients were followed for 5 years from the first redeemed prescription. Discontinuation was defined as a gap of 12 months between redemptions. Logistic regression analysis with odds ratio (OR) and Kaplan Meier analysis were used to examine risk factors (sex, age, socioeconomic status, substance use disorders, and comorbidities) associated with discontinuation. Twenty three thousand nine-hundred and sixteen patients with ADHD were identified. The 5-year overall drug survival was 29% in women vs. 23.5% in men. The risk of medication discontinuation was significantly higher in men compared to women, OR 1.26 (95% CI 1.19-1.34, p < 0.001). Adults aged 31-50 years had a significantly decreased risk of medication discontinuation compared to adults aged 18-30 years, OR 0.57 (95% CI 0.53-0.61, p < 0.001). Switching ADHD medication two times or three times or more significantly decreased the risk of discontinuation; OR 0.53 (95% CI 0.49-0.56, p < 0.001) and OR 0.26 (95% CI 0.23-0.30, p < 0.001), respectively. Substance use disorders and certain comorbidities were associated with medication discontinuation. Eating disorders, OR 0.71 (95% CI 0.64-0.78, p < 0.001), intellectual disabilities, OR 0.65 (95% CI 0.59-0.73, p < 0.001) and sleep disorders, OR 0.42 (95% CI 0.37-0.49, p < 0.001) were associated with continuation of ADHD medication. The 5-year overall drug survival was longer in women compared to men. Women with ADHD; adults aged 31-50; and patients with comorbid eating disorder; intellectual disability; sleep disorder and medication switching were individually associated with continuation of ADHD medication. Various factors were associated with medication discontinuation. Discontinuation should be acknowledged as a common phenomenon in patients with ADHD and calls for increased attention from the treatment responsible prescriber or team. Moreover, our findings suggest that timely, frequent medication switching, or temporary regimens may indeed represent optimal management strategies for a significant proportion of the ADHD population.

Rock Mass Characterization and Slope Stability Analysis Inlet Portal of Jragung Dam Diversion Tunnel, Indonesia

Abstract Slope stability is a serious problem that academics are still looking into in terms of human safety, equipment, and structures along the slope. Failure on slopes happens for a variety of reasons, including rock physical and mechanical properties, discontinuity factors, slope geometry, and external variables like as rainfall and seismic activity. The research location was conducted on the Jragung dam diversion tunnel, administratively located in Candirejo village, Pringapus sub-district, Semarang, Central Java Province. The purpose of this study was to use an empirical and numerical method to investigate the impact of rock mass categorisation on slope stability. The RMR (Rock mass rating) method is used to characterize rock mass, and the SMR (Slope mass rating) method is used to measure slope stability. The numerical slope stability analyses were carried out with the help of Phase2 (Rocscience, Inc.). The results showed that the slope at the intake portal was class IV (poor), and that it was unstable utilizing the SMR technique. According to numerical research, the basic design cut slopes with a 51° inclination were found to be unstable even after strengthening. It was suggested that the slope geometry and support measures be adjusted even more. Modified cut slopes were found to be stable after the slope inclinations were changed from 51° to 27° and shotcrete and rock bolt reinforcement were added.

Attention-Deficit/Hyperactivity Disorder in Medication Treated Preschool-Age Children Without and With Autism Spectrum Disorder: A Developmental-Behavioral Research Network Study

Abstract: Objectives: The study objective was to compare preschool children with attention-deficit/hyperactivity disorder without autism spectrum disorder (ADHD − ASD) with those with ADHD and ASD (ADHD + ASD), treated with stimulant or alpha-2-agonist (A2A) medications. Methods: Retrospective electronic health record review of 497 children from 7 developmental behavioral pediatrics research network sites. Children were younger than 72 months when treated with medication for ADHD from January 1, 2013, to January 7, 2017. We analyzed differences in children with ADHD − ASD versus ADHD + ASD treated with stimulants or A2As, including demographics, coexisting conditions, medication effectiveness, medication, discontinuation factors, and adverse effects. Results: Of the 497 preschool-age children with ADHD, 389 had ADHD − ASD and 108 had ADHD + ASD. No statistically significant differences were found in demographics between the groups. At baseline, ADHD + ASD group reported more sleep problems. For the ADHD − ASD group, stimulant medication was significantly more effective than A2As; no significant differences were found in medication effectiveness of stimulants versus A2As for the ADHD + ASD group. Children with ADHD − ASD experienced more appetite suppression and stomachaches on stimulants. No associations were found between ASD status and rates of common adverse effects for children initiated on A2As. Conclusion: We found more similarities than differences when comparing ADHD − ASD preschool-age children with those with ADHD + ASD. For children with ADHD − ASD, stimulant medications were significantly more effective than A2As. Overall, there was notable overlap in presentation, response to medication, coexisting conditions, and effectiveness of medication classes.

Age Is a Risk Factor for Olaparib Dose Modification and Discontinuation in Patients With Ovarian Cancer.

Olaparib, a poly (ADP-ribose) polymerase inhibitor, is widely used as maintenance therapy for ovarian cancer. Dose modification, such as dose reduction and treatment interruption, are frequently performed to manage adverse events (AEs) of olaparib. By identifying patients at high risk for dose modification before administration, interventions related to appropriate control of AEs can be implemented. This study aimed to evaluate risk factors of olaparib dose modification and its clinical usefulness. Sixty patients with ovarian cancer who received olaparib were included in this retrospective cohort study. Associations between patients' characteristics and dose modification were evaluated by multivariate logistic regression analysis. We also examined whether risk factors of dose modification were associated with treatment discontinuation due to AEs. Twenty-five (41.7%) patients required dose modification. Patients who required dose modification were significantly older (p=0.018) and tended to be more underweight (p=0.078) than those who did not require dose modification. In multivariate analysis, increasing age was significantly associated with dose modification (odds ratio=1.056; 95% confidence interval=1.002-1.112; p=0.034). The optimal cutoff of age as a risk factor for dose modification, calculated from receiver operating characteristic curves, was 65.0 years. Patients aged 65.0 years and older were significantly more likely to discontinue olaparib owing to AEs (p=0.0437). Age is a risk factor of olaparib dose modification due to AEs. Older patients, who frequently require dose modification, are more likely to discontinue olaparib, suggesting that strict management of AEs is particularly necessary in this patient group.

Long-Acting Injectable Antipsychotics in the Geriatric Population: A longitudinal Study

ObjectiveThis study compares demographic, clinical characteristics, and outcomes in older adults on long-acting injectable antipsychotics (LAI-AP) vs. oral antipsychotics (PO-AP). DesignThis observational study with a retrospective cohort utilized the electronic medical record's search engine to review charts of geriatric patients on LAI-AP for a two-year period. A convenience sample on PO-AP formed the comparison group. LAI-AP patients were subcategorized into discontinuation and continuation groups. SettingConducted at an urban, psychiatric outpatient clinic, using charts from October 2020 to 2022. ParticipantsPatients at least 60 years-old with psychotic or mood disorders on antipsychotics for at least 3-months during the study period. MeasurementsDemographic and clinical variables, including diagnosis, medication type, side effects, medical comorbidities, neurocognitive status, and secondary medications, were collected for both PO-AP and LAI-AP groups. Outcome variables included missed appointments, psychiatric and medical hospitalizations, and emergency room visits. Correlates of discontinuation of LAI-AP were also assessed. ResultsLAI-AP had a higher proportion than PO-AP of primary psychotic disorders (87.8% vs. 64.3%). During the study, PO-AP had higher rates of missed appointments (median 18% vs. 13% for LAI-AP) and psychiatric admissions (mean 0.019/month vs. 0.006/month for LAI-AP;); Female sex was a risk factor for discontinuation of LAI-AP (86.7% of discontinuation group vs. 55.2% of continuation group). ConclusionsThe LAI-AP group showed reduced hospitalizations, better treatment engagement, and comparable tolerability to PO-AP. Preliminary data suggests gender may influence LAI-AP discontinuation rates. This study adds to the sparse literature investigating the efficacy and tolerability of LAI-AP in geriatric patients.

Attention Deficit Hyperactivity Disorder: A Risk Factor for Premature Discontinuation of Inpatient Opioid Withdrawal Treatment.

Background: Substance use disorders present a tremendous challenge within contemporary healthcare systems. Specifically, in the domain of opioid use disorders (OUDs), several foundational elements are crucial for the efficacious management of afflicted individuals. Regrettably, the premature discontinuation of inpatient opioid withdrawal treatment is a prevalent phenomenon. This study aims to elucidate the prevalence of the premature termination of inpatient opioid withdrawal treatment among patients with comorbid ADHD. Methods: We conducted a comprehensive assessment of all participants currently undergoing inpatient opioid withdrawal treatment. Our assessment protocol included the administration of the ADHD Self-Report Scale (ADHD-SR) and the Wender Utah Rating Scale (WURS-k). Additionally, participants who met the thresholds on one or both questionnaires underwent further evaluation using the Diagnostic Interview for ADHD in Adults (DIVA-2.0). Results: The prevalence of individuals diagnosed with ADHD within the studied cohort was determined to be 29.3%. Among the subset of participants identified as ADHD-positive, a notable 54.5% prematurely ceased therapy. In contrast, among those identified as ADHD-negative, the premature discontinuation rate was substantially lower at 28.3%. Conclusions: In summary, the impact of ADHD as a comorbid condition on the efficacy of inpatient opioid withdrawal treatment has been underscored. By identifying comorbid ADHD early in the treatment process, tailored therapeutic approaches may help to maximize the effectiveness of interventions and may improve patient outcomes. This underscores the importance of proactive screening for ADHD as a psychiatric comorbidity in optimizing the management of individuals undergoing inpatient opioid withdrawal treatment.

Factors Associated With the Discontinuation of Two Short-Course Tuberculosis Preventive Therapies in Programmatic Settings in the United States.

The objective of this study was to investigate timing and risk factors for discontinuation of short-course tuberculosis preventive therapy (TPT) comparing directly observed 3-month isoniazid/rifapentine (3HP) vs self-administered 4-month rifampin (4R). This was a subanalysis of a 6-month health department cohort (2016-2017) of 993 latent tuberculosis infection (LTBI) patients initiating 3HP (20%) or 4R (80%). Time at risk of TPT discontinuation was compared across regimens. Risk factors were assessed using mixed-effects Cox models. Short-course TPT discontinuation was higher with 4R (31% vs 14%; P < .0001), though discontinuation timing was similar. Latino ethnicity (hazard ratio [HR], 1.80; 95% CI, 1.20-2.90) and adverse events (HR, 4.30; 95% CI, 2.60-7.30) increased 3HP discontinuation risk. Social-behavioral factors such as substance misuse (HR, 12.00; 95% CI, 2.20-69.00) and congregate living (HR, 21.00; 95% CI, 1.20-360.00) increased 4R discontinuation risk. TPT discontinuation differed by regimen, with distinct risk factors. Addressing social determinants of health within TPT programs is critical to enhance completion rates and reduce TB disease risk in marginalized populations.

521P Risk factors for early discontinuation of anamorelin hydrochloride in patients with cancer cachexia: A multicenter, retrospective cohort study (HGCSG2201)

521P Risk factors for early discontinuation of anamorelin hydrochloride in patients with cancer cachexia: A multicenter, retrospective cohort study (HGCSG2201)

A study on the applicability of simplified few-group GET (Generalized Equivalence Theory) to cylindrical molten salt fast reactor

One of the essential requirements for molten salt reactor (MSR) design is methodology for analyzing multi-physics phenomena, such as the behavior of liquid fuel. In the research of Molten Salt Fast Reactors (MSFRs), the Neutron Diffusion Equation (NDE) is widely employed. This study introduces a method to enhance the accuracy of neutronic analysis of MSFR using the NDE. Using the simple structure of MSFR and the characteristics of liquid nuclear fuel, it is intended to enable the application of the simple equivalence method, which is difficult to perform on the existing fast reactor. A straightforward yet effective approach named the simplified Generalized Equivalence Theory (simplified GET) is proposed for applying flux-volume-weighted homogenized cross-sections and representative Discontinuity Factor (DF) values obtained at material. This approach, while similar to the General Equivalence Theory (GET) method, significantly simplifies the enhancement of accuracy in reactor analysis, minimizing computational efforts. Our investigation spans from the initial core to the burned core, ensuring the applicability of this simple method throughout the reactor's operational life. The proposed method demonstrates promising results, offering a viable solution to improve the accuracy of NDE-based calculations in MSFRs.

Long-Term Compliance of Self-Care Pessary in Symptomatic Pelvic Organ Prolapse.

Continuation of using a pessary for the treatment of pelvic organ prolapse (POP) is important for improving symptoms but the data on long-term compliance is very limited. Therefore, we conducted this study aimed at evaluating the compliance of patients in the long-term use of a pessary. The medical records of women with symptomatic POP were retrospectively reviewed to recruit cases opting for pessary use. The inclusion criteria were women who had a successful pessary fitting and completed at least 5 years of follow-up. Exclusion criteria were pregnancy, death during the follow-up period, and loss to follow-up. Demographic data, pelvic organ prolapse stage, associated symptoms, type and size of pessary, and reason for discontinuation were reviewed. A total of 261 patients opted for pessary use. Of them, 88.9% (231 out of 261) were successful in initial pessary fitting and 54 were excluded for various reasons. The remaining 178 patients were available for analysis. The continuation rate of self-care pessary at the 5-year follow-up was 53.93% (96). The discontinuation rate was 46.07% (82). The main reasons for discontinuation were desire for surgery (39.1%) and discomfort (31.7%). The highest rate of discontinuation (46.63%) was found in the 1st year of follow-up. The significant risk factors of discontinuation included digitation symptoms on univariate analysis and prior hysterectomy on multivariate analysis, with an odds ratio (95% CI) of 5.98 (1.56-22.88). Among Thai women, the adherence to self-care pessary in symptomatic pelvic organ prolapse at the 5-year follow-up was 53.93%. The main reason for discontinuation was a prior hysterectomy.

Abstract PO4-11-04: Early Discontinuation of Adjuvant Chemotherapy in Older Adults with Early Breast Cancer: Results from the Prospective Multicenter HOPE Study

Abstract Background: Older adults with early breast cancer (EBC) treated with adjuvant chemotherapy frequently experience severe toxicities. As a result of such toxicities, many older adults do not complete all planned chemotherapy cycles (i.e., discontinue chemotherapy early). Early discontinuation may increase the risk of recurrence and decrease survival. However, aging is heterogeneous and identifying which older adult is at risk of early discontinuation before starting chemotherapy remains a key knowledge gap. To fill this gap, we examined the incidence, reasons, and risk factors for early discontinuation of adjuvant chemotherapy in older adults with EBC. Methods: This is a post-hoc analysis of 501 older adults (age&amp;gt;65) with EBC enrolled in the Hurria Older PatiEnts (HOPE) with Breast Cancer Study (NCT01472094, R01AG037037), a prospective multicenter study. All participants were treated with neo/adjuvant chemotherapy. Prior to initiating chemotherapy, participants completed survey measures on sociodemographic, clinical, and geriatric assessment characteristics. The primary outcome was early discontinuation (yes/no; yes, defined as failure to complete all planned chemotherapy cycles). Multivariable logistic regression with stepwise selection was used to evaluate the association between baseline variables (demographic, clinical, geriatric assessment) and early discontinuation. Results: A total of 501 participants (median [range] age, 70 [65-86] years and mean [SD] physician-rated KPS 93 [9.3]) were included. One hundred and thirteen (23%) had early discontinuation. Among participants with early discontinuation, 69% discontinued treatment within the last 3 cycles. In bivariate analysis, early discontinuation was associated with older age (continuous), higher stage (II/III), use of non-TC regimens (anthracycline-based or trastuzumab-based), lower albumin level (continuous), a history of diabetes, ≥1 fall in the last 6 months, and lower activities of daily living (ADL) score (&amp;lt; 85). Multivariable stepwise logistic regression analysis identified that ≥1 fall in the last 6 months, ADL score &amp;lt; 85, and regimen were associated with early discontinuation at p &amp;lt; 0.05. In the final model, after accounting for clinically meaningful variables including age, stage, and regimen, the results for falls (odds ratio [OR] = 2.04, 95% CI: 1.10-3.78, p=0.02) and ADL (OR=2.10, 95% CI: 1.32-3.34, p=0.002) remained highly significant. Compared to participants with no falls and ADL scores &amp;gt;85, participants with who reported both falls and an ADL score &amp;lt; 85 prior to initiation of chemotherapy had more than 4-fold increased odds of early discontinuation (Table). Conclusion: In this cohort of older adults with EBC, nearly 1 in 4 older patients initiated neo/adjuvant chemotherapy but did not complete all planned chemotherapy cycles. Older patients at risk for early discontinuation should be identified and targeted upfront before initiating chemotherapy. Table. Multivariable associations between falls, ADL score, and early discontinuation. *Adjusted for age (continuous), stage (I vs. II/III), and regimen (anthracycline based + no trastuzumab vs. non-anthracycline based + no trastuzumab vs. anthracycline based + trastuzumab vs. platinum/CMF + trastuzumab vs. taxol only + trastuzumab vs. other). ** Five patients missing fall information. Two patients missing ADL score. Citation Format: Jingran Ji, Canlan Sun, Rachel Freedman, Harvey Cohen, Heidi Klepin, William Tew, Beverly Moy, Andrew Chapman, Tanya Wildes, Efrat Dotan, Allison Magnuson, Tracey O'Connor, Mary Anne Fenton, Heeyoung Kim, Vani Katheria, Cary Gross, Hyman Muss, Mina Sedrak. Early Discontinuation of Adjuvant Chemotherapy in Older Adults with Early Breast Cancer: Results from the Prospective Multicenter HOPE Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-11-04.

Abstract PO2-17-05: Pharmacy fills but not baseline distress or other clinical factors can identify those at high risk for early adjuvant endocrine therapy discontinuation

Abstract Background Completion of the recommended 5-10 year course of adjuvant endocrine therapy (AET) course is low, and few risk factors for discontinuation have been identified. We examined factors associated with early AET discontinuation in a large cohort with patient-reported outcomes (PROs) and other measures routinely used in clinical care at four sites within an academic health system's multidisciplinary cancer center. Methods We examined postmenopausal women with stage I-III hormone-receptor positive breast cancer identified using the registry at an academic multidisciplinary cancer center 2014-19 who received a prescription for AET, and followed them for up to 5 years. Breast cancer extent of disease and treatments, Elixhauser comorbidity index, medication number and sociodemographic characteristics (age, race/ethnicity, insurance, area deprivation index of zip code of residence) were abstracted from the electronic health record (EHR). PRO measures included the Distress Thermometer (DT, scored 0-10) and its associated problem list (39 yes/no questions), and the Patient Health Questionnaire-9 (depression), all administered routinely as part of clinical care between diagnosis date and start of AET. If &amp;gt;1 PRO performed during that time, the measure closest to AET start was used. DT was dichotomized using the clinically accepted score of 4 as the threshold for severe distress, as was Patient Health Questionnaire-9 (PHQ-9) depression ( &amp;gt;5). AET prescription information included both prescription date from the EHR, and prescription fills assessed using an all-payer pharmacy data source. AET was defined as discontinued (d/c) when no prescription had been filled at any pharmacy for at least 90 days. We used nonparametric hypotheses test for two-samples (d/c vs. no d/c) as well as Kaplan-Meier product-limit time-to-event analyses with censoring for recurrence, death, or change of provider, and advanced machine learning to examine the association of these variables with discontinuation prior to five years. 54 curated covariates were examined in all, corresponding to a Bonferroni statistical significance p-value threshold of 0.001 to control type I error. Sensitivity analyses were performed to 1)use alternative date of DT (closest to diagnosis date) and 2)to examine d/c defined as 180 days. Results Among the cohort of 985 women (74% stage I, 25% Elixhauser comorbidity score &amp;gt;2), 36.9% had a DT &amp;gt;4, and 6.7% a PHQ-9 &amp;gt;5. The cohort had a median followup time of 954 days, and during followup 291 women ( 29.5) % discontinued before completion of the 5-year course or censoring for death, change to a provider outside the system or study end date in 2021. Over 40% of women who stopped filling prescriptions never had their prescriptions discontinued by their physician in the EHR. None of the examined variables including those for Distress and PL, PHQ-9 and measures of extent of disease, cancer treatments, medication number and sociodemographic characteristics were associated with early discontinuation. Results were similar in analyses using the DT date closest to diagnosis or a 180-day prescription fill gap. We also used advanced machine learning with respect to time to event discontinuation had similar results. Conclusions. Clinically available EHR data including two PRO measures were not reliable predictors of early discontinuation. However, many women who had discontinued still had orders for AET in the EHR, suggesting that their physicians were unaware that they had stopped filling prescriptions. Future work should examine whether routine monitoring of prescription fills might be enlisted to identify these women and assist with education, supportive care or other assistance to restart. Citation Format: Joan Neuner, Rodney Sparapani, Jacob Tiegs, Vaia Makris, Melinda Stolley, Sailaja Kamaraju, Bradley Crotty, Kathryn Flynn. Pharmacy fills but not baseline distress or other clinical factors can identify those at high risk for early adjuvant endocrine therapy discontinuation [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-17-05.

Long-Term Effectiveness of Brodalumab for the Treatment of Moderate-To-Severe Psoriasis: A Real-Life Multicenter Study of Up to 3 Years in a Real-Life Italian Cohort.

Data about the long-term effectiveness of brodalumab could be valuable in assessing patient adherence to treatment and improving psoriasis management. The aim of our study was to evaluate the drug survival of brodalumab and identify any predictive factors for discontinuation. A multicenter retrospective study was conducted in patients with moderate-to-severe psoriasis who were treated for up to 3 years. We extracted data from patient files, related to the characteristics of the patients and the disease. Drug survival analysis was descriptively analyzed using Kaplan-Meier survival curves. Univariable and multivariable analyses were performed to assess baseline patient characteristics that predicted clinical response. The study included 90 patients. Among them, 28 (31.1%) suspended brodalumab through the observation period. At weeks 52, 104 and 156 the median PASI score were 0.0 [0.0 - 0.8], 0.0 [0.0 - 1.0] and 0.0 [0.0 - 0.0], respectively. The estimated cumulative survival rates at weeks 52 and 104 were 86.32% and 78.09%, respectively. In the multivariable survival analysis, predictor factors for overall discontinuation included body mass index (BMI) (OR 1.10, 95% CI 1.03 - 1.18), baseline PASI (OR 1.06, 95% CI 1.02 - 1.10), and psoriatic arthritis (OR 5.05, 95% CI 0.89 - 13.50). Brodalumab has shown long-term effectiveness for up to 3 years. Considering baseline disease severity and patient characteristics could aid in optimizing the long-term management of psoriasis.

Real-world adalimumab survival and discontinuation factors in hidradenitis suppurativa.

Survival analyses can provide valuable insights into effectiveness and safety as perceived by prescribers. Here, we aimed to evaluate adalimumab (ADA) survival and the interruption risk factors in a multicentre cohort of patients with hidradenitis suppurativa (HS). Moreover, we performed a subanalysis considering the periods before and after the onset of the COVID-19 pandemic. We conducted a retrospective study including 539 adult patients with HS who received ADA from 1 May 2015 to 31 December 2022. Overall drug survival was analysed using Kaplan-Meier survival curves and compared between the subgroups via stratified log-rank test. Possible predictors for overall drug survival and reasons for discontinuation were assessed using univariate and multivariate Cox regression. Overall, 50.1% were females with a mean age of 43.5 ± 1 years and a mean BMI of 29.5 ± 6.7. At the start of ADA, 95.29% were biologic-naïve and 24.63% had undergone surgical treatment. During follow-up, 9.46% of patients required dose escalation, while 39.92% interrupted ADA. Concomitant therapy was used in 64.89% of cases. A subanalyses comparing pre- and post-pandemic periods revealed a tendency to initiate ADA treatment at a younger age, among patient with higher BMI and at a lower HS stage after COVID-19 pandemic. Interestingly, ADA demonstrated extended survival compared to previous studies, with a median overall drug survival of 56.2 months (95% CI 51.2 to 80.3). The primary causes for discontinuation were inefficacy (51.69%), followed by adverse effects (21.35%). Female sex, longer delay in HS diagnosis, higher baseline IHS4 score and concomitant spondyloarthritis were associated with poorer ADA survival or increased risk of discontinuation. ADA demonstrated prolonged survival (median 56.2 months). While addition of antibiotics did not have a positive effect on survival rate, basal IHS4 proved useful in predicting ADA survival.

Efficacy and safety of flumatinib in the treatment of newly diagnosed chronic myeloid leukemia in the chronic phase: A real-world single-center retrospective study, with a focus on premature drug discontinuation

PurposeTo assess the real-world efficacy and safety of flumatinib as first-line and post-line treatments for chronic myeloid leukemia in the chronic phase (CML-CP). ResultsAmong 141 patients receiving flumatinib as first-line and post-line treatment, the 12-month major molecular response (MMR) rates were 69.4% and 67.6%, respectively. The median time to response was 6 and 10.5 months, respectively. In post-line treatment, the early molecular response (EMR) of flumatinib as second-line is significantly superior to that of third-line treatment (3-month EMR rate: 79.2% vs. 39.3%, P<0.001; 3-month MMR rate: 45.8% vs. 21.4%, P=0.033). Contrastively, patients who switched to flumatinib due to intolerance had significantly higher MMR rates at 3, 6, and 12 months compared to patients who switched due to inadequate response (60.6% vs. 24.2%, P=0.003; 66.7% vs. 36.0%, P=0.027; 84.2% vs. 50.0%, P=0.038). Premature drug discontinuation was observed in 28.4% of the patients. Grades 3–4 hematologic adverse events (AEs) were identified as independent risk factors for premature drug discontinuation. Patients who discontinued treatment and those who previously received only imatinib therapy had a poorer molecular response and failure-free survival. ConclusionsFlumatinib demonstrates favorable efficacy and safety. Treatment discontinuation can result in a poorer molecular response and long-term prognosis.

An explainable machine learning framework for predicting the risk of buprenorphine treatment discontinuation for opioid use disorder among commercially insured individuals

ObjectivesBuprenorphine is an effective evidence-based medication for opioid use disorder (OUD). Yet premature discontinuation undermines treatment effectiveness, increasing the risk of mortality and overdose. We developed and evaluated a machine learning (ML) framework for predicting buprenorphine care discontinuity within 12 months following treatment initiation. MethodsThis retrospective study used United States (US) 2018–2021 MarketScan commercial claims data of insured individuals aged 18–64 who initiated buprenorphine between July 2018 and December 2020 with no buprenorphine prescriptions in the previous six months. We measured buprenorphine prescription discontinuation gaps of ≥30 days within 12 months of initiating treatment. We developed predictive models employing logistic regression, decision tree classifier, random forest, extreme gradient boosting, Adaboost, and random forest-extreme gradient boosting ensemble. We applied recursive feature elimination with cross-validation to reduce dimensionality and identify the most predictive features while maintaining model robustness. For model validation, we used several statistics to evaluate performance, such as C-statistics and precision-recall curves. We focused on two distinct treatment stages: at the time of treatment initiation and one and three months after treatment initiation. We employed SHapley Additive exPlanations (SHAP) analysis that helped us explain the contributions of different features in predicting buprenorphine discontinuation. We stratified patients into risk subgroups based on their predicted likelihood of treatment discontinuation, dividing them into decile subgroups. Additionally, we used a calibration plot to analyze the reliability of the models. ResultsA total of 30,373 patients initiated buprenorphine and 14.98% (4551) discontinued treatment. C-statistic varied between 0.56 and 0.76 for the first-stage models including patient-level demographic and clinical variables. Inclusion of proportion of days covered (PDC) measured after one month and three months following treatment initiation significantly increased the models’ discriminative power (C-statistics: 0.60 to 0.82). Random forest (C-statistics: 0.76, 0.79 and 0.82 with baseline predictors, one-month PDC and three-months PDC, respectively) outperformed other ML models in discriminative performance in all stages (C-statistics: 0.56 to 0.77). Most influential risk factors of discontinuation included early stage medication adherence, age, and initial days of supply. ConclusionML algorithms demonstrated a good discriminative power in identifying patients at higher risk of buprenorphine care discontinuity. The proposed framework may help healthcare providers optimize treatment strategies and deliver targeted interventions to improve buprenorphine care continuity.

Temporal characteristics and associated factors of discontinuation and outcomes after percutaneous coronary intervention.

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.

Retention of triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine compared to combination methotrexate and leflunomide in rheumatoid arthritis

ObjectiveThere are various combination conventional synthetic disease-modifying-antirheumatic drug (csDMARD) treatment strategies used in rheumatoid arthritis (RA). A commonly used csDMARD combination is triple therapy with methotrexate (MTX), sulfasalazine (SSZ) and hydroxychloroquine (HCQ). Another approach is double therapy with MTX and leflunomide (LEF). We compared the real-world retention of these two treatment combinations. MethodsPatients with RA from the Ontario Best Practices Research Initiative (OBRI) who received triple or double therapy on or after OBRI enrolment were included. Retention rates were compared between these two groups. We also analyzed which medication in the combination was discontinued and the reasons for treatment discontinuation. Disease activity was assessed at baseline, 6 and 12 months after treatment initiation as well as at time of discontinuation. Risk factors for treatment discontinuation were also examined. ResultsSix hundred and ninety-two patients were included (258 triple and 434 double therapy). There were 175 (67.8%) discontinuations in the triple therapy group and 287 (66.1%) discontinuations in patients on double therapy. The median survival for triple therapy was longer (15.1 months; 95% CI: 11.2–21.2) compared to double therapy (9.6 months; 95%CI: 7.03–12.2). However, this was not statistically significant. Disease activity at 6 and 12 months, measured by 28-joint count Disease Activity Score based on erythrocyte sedimentation rate (DAS28-ESR) was lower with triple therapy (mean DAS28 at 6 months 3.4 vs. 3.9, P<0.0001 and at 12 months 3.2 vs. 3.5, P=0.0005). ConclusionPatients on triple therapy remained on treatment longer than patients on double therapy. However, this difference was not statistically significant.

Sarcopenia is associated with chemoradiotherapy discontinuation and reduced progression-free survival in glioblastoma patients

PurposeSarcopenia may complicate treatment in cancer patients. Herein, we assessed whether sarcopenia measurements derived from radiation planning computed tomography (CT) were associated with complications and tumor progression during radiochemotherapy for glioblastoma.MethodsConsecutive patients undergoing radiotherapy planning for glioblastoma between 2010 and 2021 were analyzed. Retrocervical muscle cross-sectional area (CSA) was measured via threshold-based semi-automated radiation planning CT analysis. Patients in the lowest sex-specific quartile of muscle measurements were defined as sarcopenic. We abstracted treatment characteristics and tumor progression from the medical records and performed uni- and multivariable time-to-event analyses.ResultsWe included 363 patients in our cohort (41.6% female, median age 63 years, median time to progression 7.7 months). Sarcopenic patients were less likely to receive chemotherapy (p < 0.001) and more likely to be treated with hypofractionated radiotherapy (p = 0.005). Despite abbreviated treatment, they more often discontinued radiotherapy (p = 0.023) and were more frequently prescribed corticosteroids (p = 0.014). After treatment, they were more often transferred to inpatient palliative care treatment (p = 0.035). Finally, progression-free survival was substantially shorter in sarcopenic patients in univariable (median 5.1 vs. 8.4 months, p < 0.001) and multivariable modeling (hazard ratio 0.61 [confidence interval 0.46–0.81], p = 0.001).ConclusionSarcopenia is a strong risk factor for treatment discontinuation and reduced progression-free survival in glioblastoma patients. We propose that sarcopenic patients should receive intensified supportive care during radiotherapy and during follow-up as well as expedited access to palliative care.