Discontinuity Factors Research Articles

A new prescribed-time stability theorem for impulsive piecewise-smooth systems and its application to synchronization in networks

In this paper, the prescribed-time synchronization (PTs) issue in networks of nonlinear piecewise-smooth (PWS) systems with impulse effects is discussed. Firstly, a time-varying piecewise function is constructed to develop a novel theorem with respect to the prescribed-time stability for nonlinear impulsive PWS systems, in which the convergence time is pre-set by users. Secondly, under the designed feedback controller with the discontinuous factor, by utilizing generalized Lyapunov functional method, non-smooth analysis theory, and inequality analysis technique, the global prescribed-time stability of synchronization error system is proved analytically. Meanwhile, the PTs conditions are addressed in terms of linear matrix inequalities (LMIs). Finally, an application to Chua’s chaotic circuit system is given to verify the correctness of theoretical results and the feasibility of the designed control strategy.

Evaluation of Pharmacy Inquiries in Physician Order Reviews for Medication Safety: A Cross-Sectional Study.

Background and Objectives: Despite the effort to prevent drug-related problems (DRPs) in healthcare settings, prescribing errors are common in the medication use process. In a Korean teaching hospital, pharmacists verify prescription orders during their routine order review process and document the details in a homegrown health information system (HIS). The objectives of this study were to identify the annual trends in pharmacy inquiries and to evaluate the prevalence of the inquiries by drug ingredients, including a description of the “pharmacy inquiry” screen in the HIS. Materials and Methods: A retrospective cross-sectional study was conducted to describe pharmacy inquiries related to preventing potential DRPs during order reviews and to evaluate the associated factors for discontinuation of prescription orders on medication among inquiries using data from January 2008 to December 2021. A descriptive analysis was performed using 128,188 inquiries, documented by 245 pharmacists for 14 years. Results: The frequency of inquiry steadily increased annually. The most frequent cause was “inappropriate dose or regimen” (49.1%) and “piperacillin and beta-lactamase inhibitor” was the most mentioned drug ingredient in the inquiries (3.4%). The overall acceptance rate of the pharmacists’ recommendation was 82.4%, and the cause of the highest acceptance was “inappropriate mix solution” (96.5%). Hospitalization and certain inquiry topics were significantly associated with discontinuation of prescription orders on inquired medications by clinicians. Conclusions: The findings indicate that pharmacy inquiries with integrated HIS could resolve inaccuracy during physicians’ order reviews and ensure safe patient care. As a tool for preventing prescribing errors, the pharmacy inquiry data can help maximize consistent improvement and optimize the medication use process in healthcare settings.

Association between Adverse Events and Prognosis in Patients with Hepatocellular Carcinoma Treated with Atezolizumab Plus Bevacizumab: A Multicenter Retrospective Study.

Simple SummaryThis study aimed to evaluate the correlation between adverse events (AEs) and overall survival (OS) in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (atezo/beva). Liver injuries were significantly correlated with shorter survival. In a logistic regression analysis, fatigue ≥ grade 2, liver injury ≥ grade 3, and modified albumin–bilirubin grade 2b were identified as independent factors for discontinuation due to AEs. We concluded that the development of liver injury was a negative factor for OS and that we should be vigilant in monitoring AE during atezo/beva treatments.This study aimed to evaluate the correlation between adverse events (AEs) and overall survival (OS) in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab (atezo/beva). This was a multicenter study in which 130 patients were enrolled. Hypertension and skin disorders had a significant correlation with longer survival (median survival time (MST): not reached vs. 14.3 months and not reached vs. 14.8 months, p = 0.001 and p = 0.047, respectively). In contrast, liver injuries were significantly correlated with shorter survival (MST: 14.7 months vs. not reached, p = 0.036), and the median development time was 21 days. In a logistic regression analysis, fatigue ≥ grade 2, liver injury ≥ grade 3, and modified albumin–bilirubin grade 2b were identified as independent factors for discontinuation due to AEs. The OS in the no discontinuation due to AE group was significantly longer than that in the discontinuation due to AEs group (MST not reached vs. 11.2 months, p = 0.001). We concluded that the development of liver injury was a negative factor for OS and that we should be vigilant in monitoring AE during atezo/beva treatments.

Associated factors for discontinuation of statin use one year after discharge in patients with acute coronary syndrome in China

ObjectivesTo determine the associated factors for discontinuation of statin use 1 year after discharge in patients who survived from acute coronary syndrome (ACS) in China.Settings75 hospitals across China.DesignA cohort follow-up...

Commentary on Glanz et al.: Longer buprenorphine treatment duration is associated with lower rates of opioid overdose, but can we address barriers to staying in treatment?

Glanz et al. examine the association between treatment duration and outcomes including all-cause mortality and overdose, demonstrating that treatment of at least 12 months is associated with lower opioid overdose rates. We now need to understand why people leave treatment after shorter periods of time, and what can be done to improve treatment retention. Opioid dependence, and particularly untreated opioid dependence, places an enormous health and economic burden on individuals and society. As opioid-related deaths in North America have continued to increase, and increase more steeply [1], the provision of evidence-based treatments such as buprenorphine has been increasingly critical. The study by Glanz et al. [2] addresses one key aspect of providing buprenorphine treatment for which there is currently limited information—optimal treatment duration. The study examines buprenorphine discontinuation with different treatment durations in relation to the critical outcomes of all-cause mortality and overdose. The study provides evidence that risk of opioid overdose may be greater following discontinuation of treatment episodes of shorter duration relative to treatment of 12 months duration or longer, with the authors concluding that their findings did not support limitations on treatment duration. It is well established that short-term treatments are ineffective for most and that longer-term treatments such as opioid agonist treatment are critical in reducing mortality [3]. This new study represents an addition to the limited evidence on how long opioid agonist treatment should continue. Clinical guidelines vary, but often propose that there should not be a hard limit on how long treatment continues. The World Health Organization guidelines state that opioid agonists treatments can be continued indefinitely, and for some patients this may be optimal [4]. For patients who may seek advice regarding ‘how long is long enough?’, providing a clear answer based on the existing evidence is currently challenging, but the work by Glanz and others helps to address this evidence gap. Questions regarding how long treatment should be continued become particularly important where access to treatment is restricted to arbitrary periods of time due to limitations placed by national or jurisdictional policies, health insurers or treatment providers. Despite the evidence that longer treatment with opioid agonists produces better outcomes, philosophical debates continue to arise regarding whether staying on opioid treatment for extended periods of time represents a poor outcome [5]. There is also a range of critical factors that can influence treatment cessation, which often centre on barriers to remaining in treatment. These include cost, attendance requirements, requirements to disclose treatment to employers and lack of family support. Glanz et al. speculate that treatment contracts and requirements for frequent and expensive urine drug screening, psychotherapy and follow-up visits may influence treatment discontinuation. Other studies examining the perspectives of people who receive treatment have identified cost to patients and the inconvenience of travelling for regular supervised dosing as critical factors in treatment discontinuation [6, 7]. Experiences of stigma and discrimination that are commonplace when receiving opioid agonist treatment can also contribute to decisions to leave treatment or perhaps shift to treatment modalities that are less ‘observable’ [8, 9]. Individually and combined, these factors can often influence treatment duration despite evidence suggesting that treatment cessation will increase overdose and other risk. Importantly, the majority of these factors are not inherent to the treatment itself but pertain to how treatment is delivered, and represent modifiable factors that could be addressed to improve treatment retention. Future research may be able to further unpack these individual circumstances and complexities and determine how we might increase treatment retention. Ultimately, it is critical that our treatment systems are set up so that people are able to remain in treatment for as long as they need, which would be determined by the patient and their treatment provider. These decisions should not be driven by arbitrary policies or due to treatment systems that make remaining in treatment too difficult. Open access publishing facilitated by Monash University, as part of the Wiley - Monash University agreement via the Council of Australian University Librarians. S.N. is a named investigator on an implementation trial of depot buprenorphine funded by Indivior. S.L. has received untied educational grant funding from Indivior. Suzanne Nielsen: Conceptualization. Sarah Larney: Conceptualization.

Factors associated with adjuvant systemic anti-cancer treatment discontinuation for early breast cancer during the COVID-19 pandemic.

ObjectiveThe Covid‐19 pandemic led to challenging discussions between oncology clinicians and patients regarding additional risks posed by SARS‐CoV‐2 infection whilst receiving systemic anti‐cancer therapies (SACT). We assess the potential factors affecting discontinuation of adjuvant early breast cancer treatment during the pandemic.MethodsData were collected on all patients with early breast cancer undergoing adjuvant SACT, between 16 March and 17 April 2020 at a single UK cancer centre. Univariate binary logistic regression analysis was performed on variables including age, recurrence risk, Index of Multiple Deprivation decile, presence of physical comorbidities, modality of treatment (neoadjuvant or adjuvant), type of treatment (cytotoxic chemotherapy or monoclonal antibodies), percentage of cycles completed and availability of alternative treatments, with a binary dependent variable on treatment discontinuation.ResultsSixty‐two patients with early breast cancer were identified: 18 receiving neoadjuvant and 44 adjuvant therapies. Median age was 57.5 years (range 31–75 years). Age (P = 0.02), percentage of treatment cycles completed (P = 0.014) and presence of alternative treatment options (P = 0.019) were significant factors for SACT discontinuation during the height of the Covid‐19 pandemic.ConclusionFactors affecting patients' decisions to discontinue SACT for early breast cancer during the Covid‐19 pandemic were elucidated, which may help identify patients requiring additional support.

The influence of nutrients on the composition and quantity of buried organic carbon in a eutrophic plateau lake, Southwest China.

The regulation of lacustrine organic carbon (OC) burial by nutrient is an outstanding knowledge gap in the current understanding of lake carbon cycles. In this study, we determined how nutrients quantitatively correspond with OC burial using the parallel factor analysis (PARAFAC) method in Dianchi Lake, southwest China. Factors were classified into three types according to their historical sedimentation characteristics: the background factor (BF), response factor (RF), and contingency factor (CF). The BF represented the original OC input combination in the lake and was insensitive to nutrient changes. The RF represented the OC input combination that was induced or promoted by nutrient changes in the lake. The CF represented short-term discontinuous factors in sedimentary history, which may be related to unique historical events. The results indicate that changes in the total nitrogen (TN) to total phosphorus (TP) ratio correlated with changes in the BF contribution; whereas the quantity of OC was mainly correlated with TN. The >90% of OC buried in sediment was quantitatively simulated by BF and RF; the driving effect of RF on OC burial was approximately 13 times higher than that of BF. It was observed that a 1 mg kg-1 increase in TN led to approximately 2.2 units increase in RF contribution in Dianchi Lake, while the BF was insensitive to changes in TN. Thus, changes in lake nutrients may effectively change the composition and quantity of OC buried in lake sediment.

Ocular Surface Immune Cell Profiles in Contact Lens-Induced Discomfort.

PurposeContact lens–induced discomfort (CLD) remains a primary factor in discontinuation or prevention of contact lens wear. Thus, we investigated the role of ocular surface immune cells in subjects with CLD.MethodsHabitual contact lens (CL) wearers with CLD (n = 19; 38 eyes) and without CLD (n = 21; 42 eyes) as determined by the Contact Lens Dry Eye Questionnaire-8 was included in a trial. Enrolled subjects used either of the two types of CL (designated as CL-A or CL-D). Ocular surface cells from the bulbar conjunctiva were obtained by impression cytology. The collected cells were phenotyped using fluorochrome-conjugated antibodies specific for leukocytes (CD45+), neutrophils (CD66b+,High,Low), macrophages (CD163+), T cells (CD3+CD4+, CD3+CD8+), natural killer (NK) cells (CD56+, High, Low), natural killer T (NKT) cells (CD3+CD56+), and gamma delta T (γδT) cells (CD3+γδTCR+) by flow cytometry. Further, corneal dendritic cell density (cDCD) was also determined using in vivo confocal microscopy.ResultsSignificantly higher proportions of CD45+ cells were observed in subjects with CLD compared to those without CLD. The percentages of CD66bTotal,Low, CD163+, pan T cells, CD4+T cells, CD8+T cells, CD56Total,High,Low (NK) cells, and NKT cells, as well as the CD4/CD8 ratio, were significantly higher in CLD subjects. The proportion of T cells (CD4, CD8, CD4/CD8 ratio, NKT cells) and macrophages exhibited a direct association with discomfort score. The percentages of CD45+, CD66bTotal,Low, CD163+, CD3+, CD56Total,High,Low, and NKT cells and cDCD were significantly higher in CLD subjects wearing CL-D. The percentages of CD66bHigh, CD4+T cells, CD8+T cells, NKT cells, and CD4/CD8 ratio were significantly higher in CLD subjects wearing CL-A.ConclusionsIncreased proportions of ocular surface immune cells are observed in CLD, and the lens type could impact the immune cells associated with CLD.Translational RelevanceThe association between the proportion of altered ocular surface immune cell subsets and contact lens–induced discomfort underpins the importance of considering immune-related aspects during contact lens development and in the clinical management of ocular surface pain.

Risk factors for denosumab discontinuation in patients with postmenopausal osteoporosis.

Persistence with treatment is key to achieving successful treatment outcomes in patients with osteoporosis. We investigated risk factors for denosumab discontinuation in patients with postmenopausal osteoporosis (PMO). A total of 333 patients with PMO who had never received osteoporosis treatment were included in this study. Baseline demographics and retention rate of denosumab were evaluated in all patients. Univariate analysis was performed in patients divided into two groups according to whether they had continued or discontinued denosumab. A Cox proportional hazards model was used to determine risk factors for denosumab discontinuation. The mean age was 80.7 years, the body mass index (BMI) was 21.5 kg/m2, and T-scores for the lumbar spine and femoral neck were -2.7 and -2.8, respectively. The retention rate of denosumab at 36 months was 50.3%. Patients who continued denosumab were younger and had higher BMI, serum albumin (Alb) levels, lumbar spine bone mineral density, and fewer vertebral fractures (VFs), compared with those who discontinued denosumab. The Cox proportional hazards model revealed that a low BMI, low serum Alb levels, and a high number of VFs are independent risk factors for denosumab discontinuation. A low BMI, low serum Alb levels, and a high number of VFs were associated with denosumab discontinuation in patients with PMO.

Examination of risk factors for discontinuation of follow-up care in patients with head and neck cancer.

Little research has examined discontinuation of follow-up care in patients with head and neck cancer. This exploratory study sought to examine key demographic, disease, and behavioral factors as possible correlates of discontinuation (N=512). Cross-sectional study examined correlates of discontinuation of follow-up care within 1 year. The primary outcome was defined as a disease-free survivor not returning to cancer clinic for two consecutive follow-up appointments within the first year of care and not reentering oncologic care at any point thereafter. Demographic, disease, and behavioral factors were examined using multivariable logistic regression. One hundred twenty-six (24.6%) patients discontinued by 12-month follow-up. Being unmarried (OR=1.28, 95% CI=1.01-1.63, p=0.041) and having elevated depressive symptomatology (OR=1.04, 95% CI=1.01-1.07, p=0.034) were significantly associated with discontinuation. Receipt of a single (vs. multimodal) treatment approached significance (OR=1.71, 95% CI=0.96-3.07, p=0.071). Approximately one quarter of patients disengaged from important follow-up care within 1 year. Lack of social support, depressive symptomatology, and single treatment modality may be important correlates of discontinuation of care in patients with head and neck cancer. Additional studies of this outcome are needed. Improved understanding of correlates associated with discontinuation could facilitate the identification of at-risk patients and further development of interventions to keep patients engaged at a crucial time in the survivorship care trajectory.

Assessment of risk factors of treatment discontinuation among patients on paliperidone palmitate and risperidone microspheres in France, Germany and Belgium

BackgroundLong-acting antipsychotics (e.g. 1-monthly (PP1M) / 3-monthly (PP3M) injection forms of paliperidone palmitate) have been developed to improve treatment continuation in schizophrenia patients. We aim to assess risk factors of treatment discontinuation of patients on paliperidone palmitate and risperidone microsphere. Additionally, treatment discontinuation between patients with PP1M and PP3M was compared.MethodsThe IQVIA Longitudinal Prescription databases were used. Risk factors of treatment discontinuation were identified by a multilevel survival regression using Cox proportional hazards model. Kaplan Meier analyses were performed by identified significant risk factors.ResultsTwenty-five thousand three hundred sixty-one patients (France: 9,720; Germany: 14,461; Belgium: 1,180) were included. Over a one-year follow-up period, a significant lower treatment discontinuation was observed for patients newly initiated on paliperidone palmitate (53.8%) than those on risperidone microspheres (85.4%). Additionally, a significantly lower treatment discontinuation was found for ‘stable’ PP3M patients (19.2%) than ‘stable’ PP1M patients (37.1%). Patients were more likely to discontinue when drugs were prescribed by GP only (HR = 1.68, p < 0.001 vs. psychiatrist only) or if they were female (HR = 1.07, p < 0.001), whereas discontinuation decreased with age (31–50 years: HR = 0.95, p = 0.006 and > 50 years: HR = 0.91, p < 0.001 vs. 18–30 years).ConclusionsThis study demonstrates that patients stay significantly longer on treatment when initiated on paliperidone palmitate as compared to risperidone microspheres. It also indicated a higher treatment continuation of PP3M over PP1M. Treatment continuation is likely to be improved by empowering GPs with mental health knowledge and managing patients by a collaborative primary care-mental health model. Further research is needed to understand why females and younger patients have more treatment discontinuation.

Effectiveness and safety of sacubitril/valsartan for patients with hypertension and heart failure in the real-world setting: A retrospective study in China.

Hypertension (HP) is associated with heart failure (HF). Sacubitril/valsartan (sac/val) has been approved for primary HP by China Food and Drug Administration (CFDA) in June 2021. The present study aimed to provide evidence on the effectiveness and safety of sac/val in Chinese patients complicated with HP and HF. This retrospective study was conducted on adult patients diagnosed with HP and HF and treated with sac/val between July 2020 and December 2020. The potential risk factors for the discontinuation events caused by sac/val-related adverse events (AEs) were explored. The data, including blood pressure (BP), cardiac indicators, corresponding values on echocardiographic parameters, unplanned visits, and AEs throughout 3-12 months, were collected. A total of 446 eligible patients were included in this study. The discontinuation events of sac/val were mainly attributed to its AEs (hypotension, hyperkalemia, and deterioration in kidney function). Univariate analysis revealed that history of chronic kidney disease, atrial fibrillation, higher values of serum creatinine, serum uric acid, serum N-terminal pro B-type natriuretic peptide, and lower estimated glomerular filtration rate were potential risk factors for discontinuation. Patients who maintained sac/val therapy throughout 3-12 months showed significantly improved values of clinical BP, cardiac indicators, and echocardiographic parameters compared to those at baseline (p < 0.0001). Sac/val was effective on BP and improved cardiac function in patients complicated with HP and HF. The physicians should focus on patients with renal dysfunction to take timely precautions to improve tolerability for sac/val.

Patterns of treatment discontinuation in patients receiving anti-vascular endothelial growth factor for neovascular age-related macular degeneration.

Purpose:To report the reasons for treatment discontinuation within 5 years in patients receiving intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD).Methods:A retrospective case-notes review of patients commenced on anti-VEGF for nAMD who failed to complete 5 years of follow-up was undertaken. The reasons for treatment discontinuation, baseline age, baseline visual acuity (VA) in Early Treatment Diabetic Retinopathy Study (ETDRS) letters, and the VA change at the last follow-up were recorded. Age-specific all-cause mortality was calculated for deceased patients.Results:Of the 1177 patients, 551 patients (46.8%) failed to complete the 5-year follow-up. The reasons for treatment discontinuation were death (251), early discharge due to stable disease (110), further treatment deemed futile (100), failure to attend (15), ill health (14), patient choice (7), and transfer of care (1). In 53 patients, no reason was documented. The mean baseline age of those who completed the 5-year follow-up (77.4 ± 7.8 years, 95% confidence interval (CI): 76.8–77.9) was significantly lower than those who discontinued the treatment for any reason (82 ± 7.7 years, 95% CI: 81.4–82.6) (P < 0.0001). Survival analysis showed that baseline VA was not a factor in treatment discontinuation; however, visual stability (±5 letters from baseline) was associated with treatment continuation. The age-specific all-cause mortality in deceased patients was lower than that in the general population.Conclusion:At 5 years, only 53% of patients remained in active care, and death was the most common reason for treatment discontinuation. Lower baseline age and VA stability during therapy were associated with treatment continuation.

The association of abdominal adiposity with premature discontinuation of postoperative chemotherapy in colon cancer

Patients with colon cancer who prematurely discontinue postoperative chemotherapy may have an increased risk of disease recurrence and death. This study tested the hypothesis that the quantity and distribution of abdominal adipose tissue predict premature chemotherapy discontinuation. This cohort study included 533 patients with stage II-III colon cancer who initiated a planned regimen of 24-weeks of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy. The primary exposures were body mass index (BMI) and computed tomography-derived abdominal adiposity measures (e.g., visceral, subcutaneous, and intramuscular adipose tissue). The primary endpoint was premature chemotherapy discontinuation, defined as receiving <6 cycles of FOLFOX. Generalized linear models quantified the relative risk (RR) of premature chemotherapy discontinuation adjusted for age, sex, cancer stage, height, and muscle area, using two-sided statistical tests. Forty-two patients [7.9% (95% CI: 5.7, 10.5)] prematurely discontinued chemotherapy. Visceral adipose tissue [RR: 3.27 (95% CI: 1.26, 8.49)] and intramuscular adipose tissue [RR: 2.79 (95% CI: 1.09, 7.12)] were statistically significantly associated with an increased risk of premature chemotherapy discontinuation. BMI [RR: 2.07 (95% CI: 0.75, 5.73)] and subcutaneous adipose tissue [RR: 2.32 (95% CI: 0.91, 5.94)] were not statistically significantly associated with premature chemotherapy discontinuation. Among patients with stage II-III colon cancer who initiate postoperative chemotherapy, excess visceral and intramuscular adiposity may be risk factors for the premature discontinuation of chemotherapy.

HIV Care Disengagement and Antiretroviral Treatment Discontinuation in Mexico: A Qualitative Study Based on the Ecological Model Among Men Who Have Sex With Men.

In 2018, 24% of Mexican men living with HIV were disengaged from HIV care, which impedes their use of antiretroviral treatment (ART). To identify HIV care disengagement and/or ART discontinuation factors using an ecological framework, we conducted 22 semi-structured interviews with men who have sex with men from the HIV state clinic of Tabasco, Mexico. HIV care disengagement was attributed to interpersonal, organizational, and community factors, whereas ART discontinuation was attributed to intrapersonal and interpersonal factors. Intrapersonal factors were burden of ART, substance use, mental health problems, and feeling well or ill. Interpersonal factors included family stigma or support, and partner discouragement. Factors at the organizational level were HIV care-related: inconvenient follow-ups, negative provider interactions, and reentry obstacles; and work-related: absences, work stigma, and travel. Community factors were social stigma and economic means. Interventions should target multiple levels of interdependent factors, distinguishing between HIV care disengagement and ART discontinuation factors.

Identifying key risk factors for premature discontinuation of opioid use disorder treatment in the United States: A predictive modeling study

BackgroundTreatment for opioid use disorder (OUD), particularly medication for OUD, is highly effective; however, retention in OUD treatment is a significant challenge. We aimed to identify key risk factors for premature exit from OUD treatment. MethodsWe analyzed 2,381,902 cross-sectional treatment episodes for individuals in the U.S., discharged between Jan/1/2015 and Dec/31/2019. We developed classification models (Random Forest, Classification and Regression Trees (CART), Bagged CART, and Boosted CART), and analyzed 31 potential risk factors for premature treatment exit, including treatment characteristics, substance use history, socioeconomic status, and demographic characteristics. We stratified our analysis based on length of stay in treatment and service setting. Models were compared using cross-validation and the receiver operating characteristic area under the curve (ROC-AUC). ResultsRandom Forest outperformed other methods (ROC-AUC: 74%). The most influential risk factors included characteristics of service setting, geographic region, primary source of payment, and referral source. Race, ethnicity, and sex had far weaker predictive impacts. When stratified by treatment setting and length of stay, employment status and delay (days waited) to enter treatment were among the most influential factors. Their importance increased as treatment duration decreased. Notably, importance of referral source increased as the treatment duration increased. Finally, age and age of first use were important factors for lengths of stay of 2–7 days and in detox treatment settings. ConclusionsThe key factors of OUD treatment attrition identified in this analysis should be more closely explored (e.g., in causal studies) to inform targeted policies and interventions to improve models of care.

Analysis of diffusion coefficient correction methods applied for small-core, high-leakage reactors

Nodal diffusion codes have been successfully used for decades as a primary tool of commercial power reactor design, safety calculations and plant cycle simulations. The large-size, small-leakage property of these reactor cores and the appropriately generated and applied auxiliary parameters (such as albedos, discontinuity factors etc.) provide a calculation environment, where diffusion theory is fairly accurate, giving the industry the ultimate advantage of fast neutronic computation. Recently, several efforts have been made to extend this methodology to small-core, high-leakage research reactors, in which the validity of diffusion theory is not straightforward. In this paper, the appropriate generation of the diffusion coefficients and their effect on the overall performance of the simulations are investigated in light of recent developments. For the numerical analysis, the two-dimensional DIMPLE benchmarks and the BME TR core benchmark problems were chosen. Group constants were generated with the Serpent 2 Monte Carlo code, while nodal diffusion calculations were carried out with the PARCS code. The results were assessed in terms of multiplication factor, assembly level power and two-group flux distributions.

Suboptimal adherence to prescribed daily growth hormone regimen among medicaid beneficiaries in the United States

Objective The objective of this retrospective cohort study was to describe the adherence and discontinuation patterns of somatropin over 3 years among children with pGHD insured by Medicaid across the United States. Methods Eligible children were aged ≥3 and <16 years with Medicaid coverage, diagnosed with pGHD, and had ≥2 new prescriptions for somatropin between 1 July 2014 and 31 December 2018. Four non-exclusive patient cohorts were constructed (≥3, 12, 24, and 36 months of continuous enrollment after initial prescription). Suboptimal adherence was defined as medication possession ratio <0.80, and discontinuation as a gap of >60 days between somatropin fills. Logistic and proportional hazards regression methods were used to estimate odds of suboptimal adherence and time to discontinuation, respectively. Results In the 12-month cohort (n = 3623), mean age was 10.5 ± 3.2 years, 70.8% were male, 44.4% White, 29.1% Hispanic, 7.1% Black, and 1.7% Asian. At months 12, 24, and 36, the proportion with suboptimal adherence was 40.9, 50.4, 54.4%, respectively, and 49.2% of patients with ≥3 months of follow-up discontinued therapy. At 12 months, lower age and race/ethnicity (Black vs. White referent) had greater odds of suboptimal adherence. Discontinuation was associated with Black (vs. White referent) race and geographic region. Conclusions Sociodemographic characteristics may be risk factors for suboptimal adherence and/or discontinuation of prescribed somatropin therapy. Improving GH regimen adherence among this at-risk population, and specifically among subgroups at highest risk, is warranted to improve clinical outcomes.

Persistence, effectiveness, and real-world outcomes in psoriasis patients treated with secukinumab in Portugal.

To characterize moderate to severe psoriasis (PsO) adult patients treated with secukinumab, estimate drug persistence and assess any reasons for treatment discontinuation. Non-interventional, retrospective, longitudinal record-based study including patients diagnosed with PsO who started secukinumab between January 2018 and January 2020. Baseline characteristics were analyzed by descriptive statistics; drug persistence and predictive factors were assessed through Kaplan-Meier curves and univariate and multivariate analysis, respectively. A total of 302 patients were included in the study: mean age was 48.4 years, 41.7% were female, median time since diagnosis was 12.9 years. 51.3% of patients were bio-naïve while 48.7% had previously been treated with biologics. PsO in difficult-to-treat locations (DTL) was present in 82.1% of patients, with scalp PsO in about half of patients. At 5-years follow-up, 84 patients discontinued secukinumab, 45 of which due to loss of efficacy. At week 104, overall treatment persistence was 71.7%. A higher probability of drug persistence was identified among those patients who initiated secukinumab ≥5 years after diagnosis, were bio-naïve or treated with only one previous biologic, had no PsO on DTL, and had diabetes mellitus. The predictive factors for discontinuation identified in our study were the start of secukinumab <5 years after diagnosis (p= 0.001), the bio-experimented status with ≥2 biologics (p= 0.007), and the presence of PsO on DTL (p= 0.014). A time since diagnosis of ≥5 years, naïve status or previous use of only one biologic are predictors for secukinumab persistence, whereas the presence of PsO on DTL predicts drug discontinuation.

Apremilast Survival and Reasons for Discontinuation in Psoriasis: Five-Year Experience From a Greek Tertiary Care Centre.

IntroductionDrug survival is an indirect measure of efficacy and safety and its post-marketing assessment using real-life data is invaluable.ObjectivesTo investigate the survival of apremilast in a cohort of psoriasis patients treated with apremilast in a Greek hospital.MethodsA retrospective cross-sectional study examined adult psoriasis patients receiving apremilast (March 2016 to January 2021). Primary endpoint was the cumulative survival probability at 52 weeks. Kaplan-Meier analysis was used to calculate survival probability. Cox regression analysis was performed to investigate potential risk factors for apremilast discontinuation.ResultsOne hundred and two patients (29.4% females) with a mean age of 55.9 years (standard deviation 15.21) were included. Sixty-five patients (63.7%) had discontinued treatment by lock date: 19 (18.6%) due to lack of efficacy, 24 (23.5%) due to loss of efficacy, 15 (14.7%) due to adverse reactions, and 7 (6.9%) due to other reasons. Cumulative survival probability at 52 weeks was 52.1%. Median survival time for all reasons for discontinuation was 58 weeks (95% Confidence Interval 40.02, 75.98).ConclusionsApproximately half of patients remained on apremilast after 1 year of treatment. Secondary drug failure was the most common reason for discontinuation.