Interruption Rate Research Articles

Comorbidities and Their Impact on Treatment Tolerance and Outcome in Elderly NSCLC Patients Treated with Concurrent Chemoradiation Using Proton or Photon Followed by Immunotherapy

To investigate comorbidities and their impact on treatment tolerance and survival for elderly NSCLC patients treated with concurrent chemoradiation using proton beam therapy (PBT) or intensity modulated radiation therapy (IMRT) followed by immunotherapy (IO). This is a retrospective study in senior patients (≥ 65 years) with inoperable locally advanced- NSCLC (LA-NSCLC) who received concurrent chemoradiation (CRT) therapy followed by adjuvant IO. Comorbidities are listed in table 1 and scored according to hazard ratios (HRs) of death. Treatment tolerance and comorbidities were compared between modalities using Fisher's exact test. Association between comorbidities and treatment tolerance was analyzed using logistic regression; association between comorbidities and survival was analyzed by Cox proportional hazards regression. Total 218 patients were included with median age of 72 (range 65-86) years. Fifty-three (24.3%) were PBT and 165 (75.7%) were IMRT. Majority patients were white ethnics, had stage III adenocarcinoma disease and good performance score, and received RT dose 60-66 Gy. The median follow-up time for the whole group was 23 months. A 97% of patients had ≥1, and 62% had ≥4 comorbidities. The combined comorbidity scores ranged from 0 to 25. No significant difference in comorbidities between modalities except IMRT had more patients with COPD (36% vs. 51%, p = 0.047). Rates of hospitalization and ER visit during CRT+IO were 28% and 5%, respectively. Rates of IO discontinuation and interruption were 55% and 8%, respectively. Patients received >6 months IO had significantly lower risk of death (HR: 0.25, p<0.001). No significant difference in treatment tolerance between modalities. In multivariable analysis, atrial fibrillation, pulmonary disease, and depression were the comorbidities associated with hospitalization during CRT+IO (p<0.05); dementia was the comorbidity associated with IO interruption (p = 0.042); heart failure, COPD, asthma, osteoporosis and HIV were the comorbidities associated with poor OS (p<0.05). Combined comorbidity score was associated with OS with HR of 1.13 (p<0.001) with adjustment of race, GTV and induction chemotherapy. Comorbidities were associated with hospitalization and IO interruption during the whole course of CRT and IO therapy, with increased IO discontinuation which negatively impacted survival. Evaluating and scoring comorbidities at diagnosis could be a useful method to predict risk of death before treatment start.

A nomogram based on clinical characteristics and nutritional indicators for relative and absolute weight loss during radiotherapy in initially inoperable patients with locally advanced esophageal squamous cell carcinoma

ObjectiveRadiation for locally advanced esophageal squamous cell carcinoma often is accompanied by radiation esophagitis, which interferes with oral intake. We aimed to develop a nomogram model to identify initially inoperable patients with relative and absolute weight loss who need prophylactic nutritional supplementation. MethodsA total of 365 initially inoperable patients with locally advanced esophageal squamous cell carcinoma receiving radiotherapy between January 2018 and December 2022 were included in the study, which was divided into discovery and validation cohorts. Receiver operating characteristic and Kaplan-Meier curve analyses were performed to compare the areas under the curve and survival benefits. ResultsA total of 42.2% (154 of 365) of the patients had been diagnosed with cancer cachexia. The malnourished group had a higher interruption rate of radiotherapy and number of complication diseases (P < 0.05). Meanwhile, patients with malnutrition had lower lymphocytes and prognostic nutritional index (P < 0.05). The combined index showed a higher area under the curve value (0.67; P < 0.001) than number of complication diseases (area under the curve = 0.52) and prognostic nutritional index (area under the curve = 0.49) for relative weight loss (≥ 5%). Similarly, the combined index had a higher area under the curve value (0.79; P < 0.001) than number of complication diseases (area under the curve = 0.56), treatment regimens (area under the curve = 0.56), subcutaneous fat thickness (area under the curve = 0.60), pretreatment body weight (area under the curve = 0.61), neutrophils (area under the curve = 0.56), and prognostic nutritional index (area under the curve = 0.50) for absolute weight loss (≥ 5 kg). Absolute and relative weight loss remained independent prognostic factors, with short overall survival rates compared with the normal group (P < 0.05). Patients with high nomogram scores supported by nutritional intervention had less weight loss, better nutrition scores, and increased plasma CD8+ T cells, and interferon gamma. ConclusionsWe developed a nomogram model that was intended to estimate relative and absolute weight loss in initially inoperable patients with locally advanced esophageal squamous cell carcinoma during radiotherapy, which might help facilitate an objective decision on prophylactic nutritional supplementation.

Efficacy and safety of patient-controlled thoracic epidural analgesia alone versus patient-controlled intravenous analgesia with acetaminophen after laparoscopic distal gastrectomy for gastric cancer: a propensity score-matched analysis.

Laparoscopic gastrectomy is a common procedure for early gastric cancer treatment. Improving postoperative pain control enhances patient recovery after surgery. The use of multimodal analgesia can potentially enhance the analgesic effect, minimize side effects, and change the postoperative management. The purpose of this study was to evaluate and compare the efficacies of the use of patient-controlled intravenous analgesia with regular acetaminophen (PCIA + Ace) and patient-controlled thoracic epidural analgesia (PCEA) for postoperative pain control. We retrospectively collected the data of 226 patients who underwent laparoscopic distal gastrectomy (LDG) with delta-shaped anastomosis between 2016 and 2019. After 1:1 propensity-score matching, we compared 83 patients who used PCEA alone (PCEA group) with 83 patients who used PCIA + Ace (PCIA + Ace group). Postoperative pain was assessed using a numeric rating scale (NRS) with scores ranging from 0 to 10. An NRS score ≥ 4 was considered the threshold for additional intravenous rescue medication administration. Although NRS scores at rest were comparable between the PCEA and PCIA + Ace groups, NRS scores of patients in the PCIA + Ace group during coughing or movement were significantly better than those of patients in the PCEA group on postoperative days 2 and 3. The frequency of additional rescue analgesic use was significantly lower in the PCIA + Ace group than in the PCEA group (1.1 vs. 2.7, respectively, p < 0.001). The rate of reduction or interruption of the patient-controlled analgesic dose was higher in the PCEA group than in the PCIA + Ace group (74.6% vs. 95.1%, respectively, p = 0.0002), mainly due to hypotension occurrence in the PCEA group. Physical recovery time, postoperative complication occurrence, and liver enzyme elevation incidence were not significantly different between groups. PCIA + Ace can be safely applied without an increase in complications or deterioration in gastrointestinal function; moreover, PCIA + Ace use may provide better pain control than PCEA use in patients following LDG.

Optical Diagnostics of Anode Surface Temperature in Vacuum Interrupters with Different CuCr Compositions

The requirements for contact material in vacuum interrupters are demanding because the arc medium is formed by electrode evaporation during the operation. Copper chromium alloy (CuCr) is widely used as contact material. Different compositions could result in a different rate of successful interruption. This work compares vacuum arc properties for two CuCr compositions - 75/25 and 50/50 weight percent. The contact surface temperature is measured during and after the vacuum arc with an AC current flow at 2kA magnitude. Quantitative characterization of the contact surface temperature was obtained with near-infrared spectroscopy using Planck curve fitting and spectrally filtered high-speed photography. Evaluation of the anode surface temperature has shown a slower surface cooling for CuCr 50/50 compared to 75/25. Despite this, CuCr 75/25 has experienced higher temperature with dispersion in a larger area during the arcing time, in a successful current interruption.

Real life data on nintedanib safety: idiopathic pulmonary fibrosis versus systemic sclerosis-interstitial lung disease and strategies adopted to manage adverse effects

ObjectiveNintedanib (NIN) is an antifibrotic drug approved to slow the progression of idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-related interstitial lung disease (SSc-ILD). NIN can frequently cause gastrointestinal adverse effects. We aimed to investigate the NIN safety profile in a real life setting, comparing IPF and SSc-ILD patients and evaluating the strategies adopted to manage NIN adverse effects.MethodsPatients taking NIN for IPF or SSc-ILD were enrolled. Alongside epidemiological and disease-specific data, the period of NIN use and the need for dosage reduction and/or interruption were investigated. Particular attention was paid to possible adverse effects and strategies adopted to manage them.ResultsTwenty-seven SSc-ILD and 82 IPF patients were enrolled. No significant differences emerged between the two cohorts regarding the frequency of any possible adverse effect. Although the rates of NIN dosage reduction or interruption were similar between the two subgroups, SSc-ILD presented a mean period before NIN dosage reduction and NIN interruption significantly shorter than IPF (3 ± 2.6 vs 10.5 ± 8.9 months—p < 0.001 and 2.3 ± 0.5 vs 10.3 ± 9.9 months—p = 0.008, respectively). Several different strategies were tried to manage NIN adverse effects: especially in SSc-ILD, the variable combination of diet adjustment set by a nutritionist, probiotics and diosmectite was ultimately successful in maintaining patients on an adequate dose of NIN.ConclusionWe presented data on the NIN safety profile in a real life setting, which was similar between SSc-ILD and IPF. A combination of multiple managing strategies and dose adjustment appears essential to cope optimally with NIN adverse effects.

Real-world efficacy and safety of cabozantinib following immune checkpoint inhibitor failure in Japanese patients with advanced renal cell carcinoma.

Real-world data of cabozantinib after failure of immune checkpoint inhibitors for advanced renal cell carcinoma in Japanese population are limited. Additionally, prognostic factors of cabozantinib in this setting are still unknown. We retrospectively evaluated data of 56 patients treated with cabozantinib subsequent to failed immune checkpoint inhibitors at four institutions. Regarding the efficacy profile, progression-free survival, overall survival and objective response rate were assessed. In terms of the safety profile, rate of adverse events, dose reduction and treatment interruption were assessed. Furthermore, risk factors of progression-free survival were analyzed. Twenty-nine patients (52%) were treated with cabozantinib as second-line therapy. Most frequent prior immune checkpoint inhibitor treatment was nivolumab plus ipilimumab combination therapy as first-line therapy (n=30, 54%). Median progression-free survival and overall survival were 9.76 and 25.5months, respectively, and objective response rate was 34%. All patients experienced at least one adverse event, and grade≥3 adverse events were observed in 31 patients (55%). Forty-four (79%) and 31 (55%) patients needed dose reduction and treatment interruption, respectively. Multivariate analysis showed that reduced initial dose (i.e. <60mg) (hazard ratio: 2.50, P=0.0355) and presence of lymph node metastasis (hazard ratio: 2.50, P=0.0172) were independent factors of shorter progression-free survival. Cabozantinib in Japanese patients with advanced renal cell carcinoma who failed immune checkpoint inhibitors was efficacious and had a manageable safety profile. These results appear to be similar to those of previous clinical trials.

EEG-based Objective Quality Assessment of Interrupted Speech.

As an important dimension of speech degradation, interruption destroys the acoustic waveform information of a speech signal and seriously affects the quality rating in speech perception. Existing studies assessing the quality of interrupted speech mainly focus on subjective methods. This work used event-related potentials (ERPs) to objectively investigate the effects of two interruption factors (i.e., interruption duty cycle and interruption rate) on the perceived quality of the periodically interrupted speech. An oddball-paradigm based ERP experiment was designed, and the periodically interrupted stimuli were presented to participants in the ERP experiment. Meanwhile, participants were instructed to provide their subjective quality ratings of interrupted speech under the same interruption conditions. The experimental results showed that the degree of both interruption duty cycle and interruption rate affected the peak latency of mismatch negativity (MMN) of the collected ERP response, with a smaller MMN peak latency under conditions with a smaller interruption duty cycle or a larger interruption rate. These findings are largely consistent with the subjective quality rating results, suggesting that the peak latency of MMN response can be potentially used as an objective quality indicator of the periodically interrupted speech.

Multizonal observational study conducted by clinical practitioners on Repatha® use in patients with hyperlipidemia (ZERBINI): Colombian results

BackgroundCardiovascular disease (CVD) represents the primary cause of death and disability globally, with elevated cholesterol as one of the leading risk factors for CVD. We describe the clinical characteristics, treatment patterns, and effectiveness of evolocumab in treating hyperlipidemia. MethodsObservational study conducted through a chart review of patients with hyperlipidemia receiving evolocumab as part of clinical management in Colombia. ResultsThis study included 115 patients treated with evolocumab. A total of 101 patients (87.8%) had a history of CVD, 13 (11.3%) familial hypercholesterolemia (FH), and 23 (20%) type 2 diabetes. Thirty-nine patients reported intolerance to any statin (33.9%). The median value of LDL-C before initiation of evolocumab was 147mg/dL (IQR: 122.5–183.7mg/dL). Within the first 3 months of treatment, LDL-C value dropped to a median value of 53mg/dL (IQR: 34.0–95.5mg/dL), showing a reduction of 63.9%. The median LDL-C values remained below 45mg/dL until the end of follow-up. Among the patients with available data, up to 61% achieved an LDL-C level below 55mg/dL at the 10–12-month follow-up. A total of 72% of patients were persistent with treatment. Safety results showed a low frequency of hospitalizations (≤2%) and treatment-emergent adverse drug reactions (5.2%). No serious adverse events were reported. ConclusionsEvolocumab was associated with reductions in LDL-C levels, with a relative decrease of 63.9% within the first 3 months of treatment. Low rates of interruptions due to adverse events and adequate medication persistence was reported.

THE EFFECT OF PRINCIPAL SUPERVISION AND BURNOUT ON TEACHER WORK ETHICS AT RITA KAKA PUBLIC ELEMENTARY SCHOOL

This research begins with the author's anxiety about the decline in the teacher's work ethic. Many factors affect the decline in work ethic. One of them is Burnout. Due to poor collaboration between superiors and subordinates, teacher incompetence is increasing, and teacher interruption rates are high. This is reflected in the work ethic of SD Negeri Rita-Kaka teachers. The teacher's work ethic still needs to be revised. The type of quantitative research used is descriptive regression, characterized by analyzing interactions between endogenous variables consisting of central school control, teacher burnout, and work ethic as exogenous variables. Regarding the impact of the principal's leadership and Burnout on the morale of SD Rita-Kaka Elementary teachers, it was found that, first, the contribution of the principal's leadership to teacher morale was less impressive. Second, Burnout's contribution to teacher morale is quite impressive. Third, the principal's supervision and burnout contribution are very influential.

QEHLR: A Q-Learning Empowered Highly Dynamic and Latency-Aware Routing Algorithm for Flying Ad-Hoc Networks

With the growing utilization of intelligent unmanned aerial vehicle (UAV) clusters in both military and civilian domains, the routing protocol of flying ad-hoc networks (FANETs) has promised a crucial role in facilitating cluster communication. However, the highly dynamic nature of the network topology, owing to the rapid movement and changing direction of aircraft nodes, as well as frequent accesses and exits from the network, has resulted in an increased interruption rate of FANETs links. While traditional protocols can satisfy basic network service quality (QoS) requirements in mobile ad-hoc networks (MANETs) with relatively fixed topology changes, they may fail to achieve optimal routes and consequently restrict information dissemination in FANETs with topology changes, which ultimately leads to elevated packet loss and delay. This paper undertakes an in-depth investigation of the challenges faced by current routing protocols in high dynamic topology scenarios, such as delay and packet loss. It proposes a Q-learning empowered highly dynamic, and latency-aware routing algorithm for flying ad-hoc networks (QEHLR). Traditional routing algorithms are unable to effectively route packets in highly dynamic FANETs; hence, this paper employs a Q-learning method to learn the link status in the network and effectively select routes through Q-values to avoid connection loss. Additionally, the remaining time of the link or path lifespan is incorporated into the routing protocol to construct the routing table. QEHLR can delete predicted failed links based on network status, thereby reducing packet loss caused by failed route selection. Simulations show that the enhanced algorithm significantly improves the packet transmission rate, which addresses the challenge of routing protocols’ inability to adapt to various mobility scenarios in FANETs with dynamic topology by introducing a calculation factor based on the QEHLR protocol. The experimental results indicate that the improved routing algorithm achieves superior network performance.

Routine Prophylactic Percutaneous Endoscopic Gastrostomy in Head and Neck Cancers with Bilateral Neck Irradiation: A Regional Cancer Experience in New Zealand.

Patients with head and neck cancer (HNC) are particularly susceptible to dysphagia and malnutrition. Prophylactic percutaneous endoscopic gastrostomy (PEG) placement is a method used to manage these issues, but practices vary among institutions. At Midcentral District Health Board, patients receiving radiotherapy to the primary and bilateral neck regions routinely undergo prophylactic PEG placement. This study aimed to review the nutritional and PEG-related outcomes of these patients. Records of 49 patients were retrospectively reviewed. Their demographics, tumour and treatment characteristics were recorded. We evaluated patient weight loss, non-elective hospitalisation, treatment interruption rates, PEG-related complications, usage, dependency rates and late dysphagia rates. Oropharyngeal cancers were the most common primary site (61.2%), and 83.7% of patients received primary chemoradiotherapy. Mean weight loss at treatment completion was 5.6% ± 4.3 (4.6 kg ± 3.9). The rate of non-elective hospitalisations was 26.5%, and only 2% of patients had treatment interruptions. Peristomal infection was the most frequent PEG complication (20.4%). No PEG-related mortality was reported. Median duration of PEG dependency was 97 days (14-388 days). Two patients remained permanently dependent at 3 years due to grade 3 dysphagia, and six patients experienced grade ≥2 late dysphagia. Our study showed that prophylactic PEG tube placement was relatively safe, with a high utilisation rate and low long-term dependence on PEG tubes after treatment completion. However, complications related to their use should be addressed through a multidisciplinary approach, with careful assessment by clinicians. The weight loss and hospitalisation rates observed were consistent with earlier studies that utilised prophylactic PEG tubes.

Efficacy of a shorter chemotherapy regimen in a patient with drug-resistant tuberculosis with early surgical intervention

Introduction. Treatment for multidrug-resistant tuberculosis lasts 18 to 24 months, so there is a high rate of therapy interruptions, including patient-initiated interruptions. In recent years, the use of shorter regimens for the treatment of multidrug-resistant tuberculosis has been actively discussed around the world. The first use of shorter chemotherapy regimens was conducted in three regions of the Russian Federation in 2019. However, the prevalence of the use of shorter chemotherapy regimens in our country remains low.The purpose of the study was to demonstrate the high efficacy of a shortened chemotherapy regimen with surgical intervention.Materials and methods. In the conditions of the Central Research Institute of Tuberculosis, the patient underwent a comprehensive examination, including mandatory, additional and optional methods of investigation. Based on the findings of the comprehensive examination and established broad drug resistance of Mycobacterium tuberculosis, a shorter course of chemotherapy was prescribed and surgical treatment was performed after 2 months of therapy.Results and Discussion It was decided to carry out anti-tuberculosis therapy according to a shortened scheme in the amounts: Linezolid, Bedaquiline, Cycloserine, Levofloxacin, Pyrazinamide. Taking into account positive radiological dynamics after two months of treatment and absence of contraindications, early surgery intervention was performed. At the end of a nine-month course of chemotherapy the patient had a stable radiological picture, “fresh” focal and infiltrative changes in the lungs were not detected. Early surgical treatment with a shorter chemotherapy regimen may become a highly effective method in the cure of drug-resistant tuberculosis in the Russian Federation.Conclusion. A shorter chemotherapy regimen with optimal timing of surgical intervention is highly effective and safe to use.

A Fondazione Italiana Linfomi cohort study of R-COMP vs R-CHOP in older patients with diffuse large B-cell lymphoma

AbstractRituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the most commonly used regimen for the upfront treatment of diffuse large B-cell lymphoma (DLBCL). However, it is associated with cardiotoxicity, especially in older patients. Substituting doxorubicin with non-PEGylated liposomal doxorubicin (R-COMP) may reduce the risk of cardiac events, but its efficacy has never been demonstrated in prospective trials. We describe the characteristics and outcome of patients with DLBCL aged ≥65 years prospectively enrolled in the Elderly Project by the Fondazione Italiana Linfomi and treated with full doses of R-CHOP or R-COMP per local practice. Starting from 1163 patients, 383 (55%) were treated with R-CHOP and 308 (45%) with R-COMP. Patients treated with R-COMP were older (median age, 76 vs 71 years), less frequently fit at simplified geriatric assessment (61% vs 88%; P < .001), and had a more frequent baseline cardiac disorders (grade >1, 32% vs 8%; P < .001). Three-year progression-free survival (PFS) was similar between R-CHOP and R-COMP (70% and 64%); 3-year overall survival was 77%, and 71% respectively. R-CHOP was associated with better PFS vs R-COMP only in the Elderly Prognostic Index (EPI) low-risk group. The two groups had similar rates of treatment interruptions due to toxicities or of cardiac events (P = 1.00). We suggest R-COMP is a potentially curative treatment for older patients with intermediate- or high-risk EPI, even in the presence of a baseline cardiopathy. R-CHOP is confirmed as the standard therapy for low risk patients.

Clinical outcomes of patients who underwent total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC): A single center experience.

e15630 Background: Total neoadjuvant therapy (TNT) has been mainstay of treatment for locally advanced rectal cancer (LARC), with a primary purpose of eradicating minimal residual disease, preserving the rectum, and achieving pathological complete response (pCR). Currently, there lacks consensus on chemotherapy regimen, sequencing, and modality of radiation therapy. The objective of this real-world retrospective analysis is to describe various TNT strategies employed and report patient centered outcomes. Developing a standard protocol based on available evidence and institutional retrospective data is crucial to reduce care variations. Methods: From January 2019 to January 2023, 61 patients with locally advanced rectal cancer were initiated on TNT. Patients were included regardless of whether they received treatment at our academic center or private practice. Retrospective chart review was performed to collect demographic data, chemotherapy regimens, toxicities, dose interruption, dose reduction, timeline of treatment, response rate as well as surgical intervention. Data cutoff was set to 3 years after TNT completion. Combined MRI and flexible sigmoidoscopy were used to evaluate final response. Results: Average age at diagnosis was 59 years old. Majority of patients were stage IIIB (52%), had low rectal disease (51%), received chemotherapy followed by long-course concurrent chemoradiation (80%) and had chemotherapy in an academic center (65%). Complete clinical response (cCR) rate was 36% in the overall cohort. Four out of 22 patients with cCR underwent surgery and the rest were initiated on watch and wait strategy, among these, only one patient had local recurrence requiring surgery. Among all the patients who had surgery, pCR rate was 15.6%. No difference existed in cCR between CAPOX and FOLFOX groups (34.5% vs 33%), however, grade 3/4 toxicities (27% vs 14%), dose reduction (17% vs 7%), dose interruption (11% vs 6%) and hospitalization (6% vs 0%) rates were higher in patients who received CAPOX. Of note, 7 patients received FOLFIRINOX. In this group, disease stage ranged from 2A to oligometastatic stage IV; however, over 50% obtained a cCR with comparable or better toxicity profile. Conclusions: Despite wide range of variations observed in treatment approaches to TNT across the organization and local institutions, organ preservation and complete clinical response rates were observed at the same rate of 1 out of 3 patients. In those patients who pursued surgical intervention, the pCR was lower than expected from trials. Patients who received FOLFOX tolerated treatment better with the same clinical response rate as CAPOX. Greater numbers will be required to determine response rate and superiority of FOLFIRINOX compared to doublet therapy. Further process standardization would likely improve patient outcomes with LARC receiving TNT.

Comparative arrhythmia patterns among patients on tyrosine kinase inhibitors.

Tyrosine kinase inhibitors (TKIs) are widely used in the treatment of hematologic malignancies. Limited studies have shown an association between treatment-limiting arrhythmias and TKI, particularly ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor. We sought to comprehensively assess the arrhythmia burden in patients receiving ibrutinib vs non-BTK TKI vs non-TKI therapies. We performed a retrospective analysis of consecutive patients who received long-term cardiac event monitors while on ibrutinib, non-BTK TKIs, or non-TKI therapy for a hematologic malignancy between 2014 and 2022. One hundred ninety-three patients with hematologic malignancies were included (ibrutinib = 72, non-BTK TKI = 46, non-TKI therapy = 75). The average duration of TKI therapy was 32months in the ibrutinib group vs 64months in the non-BTK TKI group (p = 0.003). The ibrutinib group had a higher prevalence of atrial fibrillation (n = 32 [44%]) compared to the non-BTK TKI (n = 7 [15%], p = 0.001) and non-TKI (n = 15 [20%], p = 0.002) groups. Similarly, the prevalence of non-sustained ventricular tachycardia was higher in the ibrutinib group (n = 31, 43%) than the non-BTK TKI (n = 8 [17%], p = 0.004) and non-TKI groups (n = 20 [27%], p = 0.04). TKI therapy was held in 25% (n = 18) of patients on ibrutinib vs 4% (n = 2) on non-BTK TKIs (p = 0.005) secondary to arrhythmias. In this large retrospective analysis of patients with hematologic malignancies, patients receiving ibrutinib had a higher prevalence of atrial and ventricular arrhythmias compared to those receiving other TKI, with a higher rate of treatment interruption due to arrhythmias.

Predicting Treatment Interruption Among People Living With HIV in Nigeria: Machine Learning Approach

Background Antiretroviral therapy (ART) has transformed HIV from a fatal illness to a chronic disease. Given the high rate of treatment interruptions, HIV programs use a range of approaches to support individuals in adhering to ART and in re-engaging those who interrupt treatment. These interventions can often be time-consuming and costly, and thus providing for all may not be sustainable. Objective This study aims to describe our experiences developing a machine learning (ML) model to predict interruption in treatment (IIT) at 30 days among people living with HIV newly enrolled on ART in Nigeria and our integration of the model into the routine information system. In addition, we collected health workers’ perceptions and use of the model’s outputs for case management. Methods Routine program data collected from January 2005 through February 2021 was used to train and test an ML model (boosting tree and Extreme Gradient Boosting) to predict future IIT. Data were randomly sampled using an 80/20 split into training and test data sets, respectively. Model performance was estimated using sensitivity, specificity, and positive and negative predictive values. Variables considered to be highly associated with treatment interruption were preselected by a group of HIV prevention researchers, program experts, and biostatisticians for inclusion in the model. Individuals were defined as having IIT if they were provided a 30-day supply of antiretrovirals but did not return for a refill within 28 days of their scheduled follow-up visit date. Outputs from the ML model were shared weekly with health care workers at selected facilities. Results After data cleaning, complete data for 136,747 clients were used for the analysis. The percentage of IIT cases decreased from 58.6% (36,663/61,864) before 2017 to 14.2% (3690/28,046) from October 2019 through February 2021. Overall IIT was higher among clients who were sicker at enrollment. Other factors that were significantly associated with IIT included pregnancy and breastfeeding status and facility characteristics (location, service level, and service type). Several models were initially developed; the selected model had a sensitivity of 81%, specificity of 88%, positive predictive value of 83%, and negative predictive value of 87%, and was successfully integrated into the national electronic medical records database. During field-testing, the majority of users reported that an IIT prediction tool could lead to proactive steps for preventing IIT and improving patient outcomes. Conclusions High-performing ML models to identify patients with HIV at risk of IIT can be developed using routinely collected service delivery data and integrated into routine health management information systems. Machine learning can improve the targeting of interventions through differentiated models of care before patients interrupt treatment, resulting in increased cost-effectiveness and improved patient outcomes.

Antiretroviral treatment interruption and resumption within 16 weeks among HIV-positive adults in Jinan, China: a retrospective cohort study.

Treatment interruption has been found to increase the risk of opportunistic infections and death among HIV-positive adults, posing a challenge to fully realizing antiretroviral therapy (ART). However, it has been observed that short-term interruption (<16 weeks) was not associated with significant increases in adverse clinical events. There remains a dearth of evidence concerning the interruption and resumption of ART after short-term discontinuation in China. HIV-positive adults who initiated ART in Jinan between 2004 and 2020 were included in this study. We defined ART interruption as more than 30 consecutive days off ART and used Cox regression to identify predictors of interruption. ART resumption was defined as a return to ART care within 16 weeks following discontinuation, and logistic regression was used to identify barriers. A total of 2,506 participants were eligible. Most of them were male [2,382 (95%)] and homosexual [2,109 (84%)], with a median age of 31 (IQR: 26-40) years old. Of all participants, 312 (12.5%) experienced a treatment interruption, and the incidence rate of interruption was 3.2 (95% CI: 2.8-3.6) per 100 person-years. A higher risk of discontinuation was observed among unemployed individuals [adjusted hazard ratio (aHR): 1.45, 95% CI: 1.14-1.85], with a lower education level (aHR: 1.39, 95% CI: 1.06-1.82), those with delayed ART initiation (aHR: 1.43, 95% CI: 1.10-1.85), receiving Alafenamide Fumarate Tablets at ART initiation (aHR: 5.19, 95% CI: 3.29-8.21). About half of the interrupters resumed ART within 16 weeks, and participants who delayed ART initiation, missed the last CD4 test before the interruption and received the "LPV/r+NRTIs" regimen before the interruption were more likely to discontinue treatment for the long term. Antiretroviral treatment interruption remains relatively prevalent among HIV-positive adults in Jinan, China, and assessing socioeconomic status at treatment initiation will help address this issue. While almost half of the interrupters returned to care within 16 weeks, further focused measures are necessary to reduce long-term interruptions and maximize the resumption of care as soon as possible to avoid adverse clinical events.

Optimizing (O) rifapentine-based (RI) regimen and shortening (EN) the treatment of drug-susceptible tuberculosis (T) (ORIENT) using an adaptive seamless design: study protocol of a multicenter randomized controlled trial

BackgroundStandard treatment for drug-susceptible tuberculosis (DS-TB) includes a multidrug regimen requiring at least 6 months of treatment, and this lengthy treatment easily leads to poor adherence. There is an urgent need to simplify and shorten treatment regimens to reduce interruption and adverse event rates, improve compliance, and reduce costs.MethodsORIENT is a multicenter, randomized controlled, open-label, phase II/III, non-inferiority trial involving DS-TB patients to evaluate the safety and efficacy of short-term regimens compared with the standardized six-month treatment regimen. In stage 1, corresponding to a phase II trial, a total of 400 patients are randomly divided into four arms, stratified by site and the presence of lung cavitation. Investigational arms include 3 short-term regimens with rifapentine 10 mg/kg, 15 mg/kg, and 20 mg/kg, while the control arm uses the standardized six-month treatment regimen. A combination of rifapentine, isoniazid, pyrazinamide, and moxifloxacin is administered for 17 or 26 weeks in rifapentine arms, while a 26-week regimen containing rifampicin, isoniazid, pyrazinamide, and ethambutol is applied in the control arm. After the safety and preliminary effectiveness analysis of patients in stage 1, the control arm and the investigational arm meeting the conditions will enter into stage 2, which is equivalent to a phase III trial and will be expanded to recruit DS-TB patients. If all investigational arms do not meet the safety conditions, stage 2 will be canceled. In stage 1, the primary safety endpoint is permanent regimen discontinuation at 8 weeks after the first dose. The primary efficacy endpoint is the proportion of favorable outcomes at 78 weeks after the first dose for both two stages.DiscussionThis trial will contribute to the optimal dose of rifapentine in the Chinese population and suggest the feasibility of the short-course treatment regimen containing high-dose rifapentine and moxifloxacin for DS-TB.Trial registrationThe trial has been registered on ClinicalTrials.gov on 28 May 2022 with the identifier NCT05401071.

Efficacy of aluminum chloride in severe regorafenib-associated hand-foot skin reactions: a single-arm trial

BackgroundRegorafenib, a multikinase inhibitor, causes a high frequency of hand-foot skin reactions (HFSRs). The present study evaluated the efficacy of topical aluminum chloride, a perspiration suppressant, in reducing the severity of hand-foot skin reactions (HFSRs) caused by regorafenib.MethodsThe present single-arm study included patients with metastatic colorectal cancer receiving regorafenib. Aluminum chloride ointment was applied topically one week prior to the start of regorafenib treatment, and the observation period was 12 weeks. The primary endpoint was the incidence of regorafenib-related grade 3 HFSR. Secondary endpoints were the incidence of all grades of HFSR, time to any grade of HFSR, time to improvement from grade 2 or higher to grade 1 or lower, treatment discontinuation rate, treatment interruption rate or dosage reduction due to HFSR, and incidence of adverse effects of aluminum chloride.ResultsIn total 28 patients were enrolled, and 27 patients were analyzed. The incidence of grade 3 HFSR was 7.4%, meeting the primary endpoint. The incidence of all grades of HFSR was 66.7%, and the median time to the occurrence of any grade of HFSR was 15 days. No patients discontinued or reduced the regorafenib dosage because of HFSR. The most common reason for the interruption of regorafenib therapy was liver dysfunction in nine patients (33%) and HFSR in three patients (11%). No serious adverse events related to aluminum chloride were observed.ConclusionsAluminum chloride ointment, a drug commonly used in routine practice to treat hyperhidrosis, is safe to use, has no serious side effects, and may be effective in reducing the occurrence of severe, regorafenib-related HFSR.Trail registrationClinicalTrials.gov. identifier: jRCTs031180096, Registered on 25/01/2019.

Rates and Reasons for Clozapine Treatment Interruptions: Impact of the Frequency of Hematologic Monitoring and Cardiac Adverse Events.

Differing rates and reasons for interruptions of clozapine treatment have been reported globally. This article evaluated the rates and reasons for clozapine therapy interruptions in Australia and explored the impact of the frequency of hematological monitoring on these parameters. Data of the patients who were newly commenced on clozapine at three metropolitan public mental health services in Western Australia over 11 years were retrospectively collated. The rate and reasons for clozapine therapy interruptions and their association with the frequency of hematological monitoring, age, sex, and treatment site were analyzed using parametric, nonparametric, and correlational analyses. Of the 457 patients whose data were collected, 69.6% had an interruption of treatment with 41.2% of those occurring during the period of mandatory weekly hematological monitoring in the first 18 weeks. Nonadherence (57.4%) and adverse effects (28.8%) were the 2 main reasons for the treatment interruptions. Cardiac issues accounted for the majority of the interruptions (61.8%) due to specified adverse effects, and these occurred significantly more commonly within the first 18 weeks. Location, age, and sex did not predict the possibility of treatment interruptions. The high rates of clozapine treatment interruption observed during the period of weekly monitoring point toward the need to address the burden of frequent hematological monitoring for patients. Disproportionately higher rates of interruption due to cardiac adverse effects observed in this study compared with research from non-Australian settings raise the possibility of geographical differences in the adverse effects leading to treatment discontinuation.