Duration Of Treatment In Patients Research Articles

Real-word experience of pazopanib and sorafenib in patients with desmoid tumors: A CanSaRCC multi-center study

BackgroundSorafenib and pazopanib, two tyrosine kinase inhibitors (TKI), are widely used in patients with progressive symptomatic desmoid tumors (DT). Limited real-word data is available on long-term outcomes of patients who progressed on, stopped, or continued TKIs. MethodsPatients diagnosed with DTs and treated with sorafenib or pazopanib between 2011 and 2022 at 11 institutions were reviewed. Patient history, response to therapy and toxicity were recorded. Statistical analyses utilized Kaplan-Meier and log-rank tests. Results142 patients with DT treated with sorafenib (n = 126, 88.7 %) or pazopanib (n = 16, 11.3 %) were analyzed. The median treatment duration was 10.8 months (range: 0.07- 73.9). The overall response rate and the disease control rate were 26.0 % and 95.1 %, respectively. The median tumor shrinkage was − 8.5 % (range −100.0 %- +72.5 %). Among responders, the median time to an objective response was 15.2 months (range: 1.1 to 33.1). The 1-year and 2-year progression-free survival rates were 82 % and 80 %. Dose reductions were necessary in 34 (23.9 %) patients. Grade 3 or higher adverse events were reported in 36 (25.4 %) patients. On the last follow-up, 55 (38.7 %) patients continued treatment. Treatment discontinuation (n = 85, 59.9 %) was mainly for toxicity (n = 35, 45.9 %) or radiological or clinical progression (n = 30, 35.3 %). For the entire cohort, 36 (25.4 %) patients required subsequent treatment. In the 32 responders, only 1 (3.1 %) patient required a subsequent treatment. In patients who discontinued TKI, 25 (44.6 %) with stable disease received subsequent treatment compared to 0 (0.0 %) of responders. ConclusionThis retrospective study represents the largest cohort of DT patients treated with sorafenib or pazopanib to date. Discontinuation of treatment in responders is safe. The optimal treatment duration in patients with stable disease remains to be defined.

Abstract PO2-17-01: Impact of the introduction of CDK4/6 inhibitors on treatment duration in patients with HR+, HER2– advanced breast cancer: Final analysis of TreatER+ight, a Canadian prospective, real-world, observational study

Abstract Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) are the established first-line targeted therapy (TT) for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2–) advanced breast cancer (ABC). TreatER+ight, the first prospective, real-world study evaluating the treatment patterns, safety and effectiveness of ET alone or ET + TT in Canadian patients with HR+, HER2– ABC (2016 to 2020) recorded ET as the standard of care (SOC) in the first interim analysis report. However, treatment with CDK4/6i combined with ET have rapidly evolved as the SOC in the metastatic setting. Methods: This prospective, multicenter, observational study (NCT02753686) enrolled patients with HR+, HER2‒ ABC with or without prior exposure to ET and up to one line of prior CT in the advanced setting. The patients were enrolled by the line of their therapy (first-line, second-line or third-line) and grouped into 2 cohorts (ET and ET + TT). Duration of therapy, and overall survival (OS) are estimated using Kaplan–Meier method. Here, we report the final outcome with CDK4/6i treatment evolution with sequencing strategy and duration in routine clinical practice. Results: At data cutoff (December 1, 2022), a total of 439 enrolled patients (ET, n=104; ET + TT, n=335) from 25 centers in Canada, constituted the full analysis set. The median age (range) was 71.5 (37.0–96.0) years in ET cohort and 65.0 (23.0-87.0) years in ET + TT cohort. About 84.6% and 66.4% were postmenopausal patients in the ET and ET + TT cohorts, respectively. Patients with ECOG PS scores 0 to 1 composed of 82.0% and 93.5% in the ET and ET + TT cohorts, respectively. In the overall population, ET alone and ET + CDK4/6i were the most common treatment received by patients in first-line (43.5% and 43.3%) and second-line (36.3% and 24.6%) treatment settings. In third-line treatment setting, CT was the most common treatment received by patients (38.4%). Conclusions: Data from final analysis of TreatER+ight have further confirmed the evolution to primary use of CDK4/6i-based combination therapy in the first-line setting for Canadian patients with HR+, HER2– ABC. Additional details on duration of therapy by CDK4/6i agents, overall survival data and age subgroup analysis will be presented at SABCS 2023 Table 1_Baseline characteristics, treatment patterns, and duration of treatment Citation Format: Catherine Doyle, Ana Elisa Lohmann, Nayyer Iqbal, Jan-Willem Henning, Swati Kulkarni, Nadia Califaretti, John Hilton, Cristiano Ferrario, Nathaniel Bouganim, Mihaela Mates, Stephanie Guillemette, Ricardo Leite, Stephen Chia. Impact of the introduction of CDK4/6 inhibitors on treatment duration in patients with HR+, HER2– advanced breast cancer: Final analysis of TreatER+ight, a Canadian prospective, real-world, observational 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 PO2-17-01.

Comparison of the efficacy of first‑/second‑generation EGFR‑tyrosine kinase inhibitors and osimertinib for EGFR‑mutant lung cancer with negative or low PD‑L1 expression.

In epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) with negative or low programmed death ligand-1 (PD-L1) expression, the acquisition rate of the T790M mutation is higher after treatment with first-/second-generation EGFR-tyrosine kinase inhibitors (TKIs) and the progression-free survival (PFS) is longer in patients treated with osimertinib. The present study compared the clinical course after the initiation of each EGFR-TKI monotherapy in patients with EGFR-mutant NSCLC with negative or low PD-L1 expression. Data of patients with EGFR-mutant NSCLC with negative or low PD-L1 expression who were treated with EGFR-TKI monotherapy were retrieved and retrospectively analyzed. Between June 2013 and November 2023, 26 and 29 patients were treated with first-/second-generation EGFR-TKIs and osimertinib, respectively. The PFS time was longer in patients treated with osimertinib (median, 22.5 months) than in those treated with first-/second-generation EGFR-TKIs (median, 12.9 months). However, the EGFR-TKI treatment duration, defined as the PFS for osimertinib, or the sum of the PFS for first-/second-generation EGFR-TKIs and sequential osimertinib therapy after the acquisition of the T790M mutation, was similar between patients treated with first-/second-generation EGFR-TKIs (median, 23.0 months) and osimertinib (median, 22.5 months). The Cox proportional hazard model suggested that there was no significant difference in the EGFR-TKI treatment duration between patients treated with first-/second-generation EGFR-TKIs and patients treated with osimertinib (hazard ratio, 1.31, 95% CI, 0.55-3.13). In conclusion, first-/second-generation EGFR-TKIs and osimertinib were associated with a similar EGFR-TKI treatment duration in patients with EGFR-mutant NSCLC with negative or low PD-L1 expression. The findings suggested that both treatments are promising for this population.

Treatment duration by morphology and location of impacted maxillary canines: A cone-beam computed tomography investigation

This study aimed to identify whether patients with impacted maxillary canines take longer to treat than orthodontic patients without an impacted canine. We also sought to identify factors that are predictive of increased treatment duration in patients with impacted maxillary canines and treated by surgical exposure. A retrospective investigation of 37 patients with an impacted maxillary canine, treated by surgical exposure and fixed appliance therapy, was undertaken. In addition, an age- and sex-matched control group of 39 patients (without impacted canines) was also collected. Patient age, sex, and total treatment duration were recorded. For patients with an impacted canine, patient records and pretreatment cone-beam computed tomography datasets were assessed. Point coordinates identifying relevant landmarks were recorded, and a geometric method was used to calculate variables describing canine location, orientation, and apical morphology. Controlling for age and sex, linear regression identified a statistically significant increase in treatment duration of 46.7 and 41.5 weeks for palatal and labial/midalveolar impacted canines, respectively, vs controls (P<0.002). Age and sex of patients with impacted canines collectively affected treatment duration (P= 0.04), with females of increased age being treated faster than younger males. Rotation of the impacted canine crown had a highly significant effect on treatment duration, with every degree of rotation increasing treatment duration by 0.32 weeks (P<0.001). There was a significant degree of multicollinearity between the other radiographic variables. Collectively, radiographic variables describing canine displacement significantly prolonged treatment duration (P<0.001) and explained 29.8% of the variability in total treatment time. The apical morphology of impacted maxillary canines was significantly associated with increased treatment duration (P= 0.01) and explained 11.3% of the overall treatment variability (P= 0.01). Increased total treatment duration of surgically exposed impacted maxillary canines is associated with increasing mesiopalatal canine crown rotation, worsening displacement, and hooked apical morphology.

Association analyses between the variants of SNAP25, SV2C and ST3GAL2 and the efficacy of botulinum toxin A in the treatment of the primary Meige syndrome

ObjectiveIndividual differences were observed in the clinical efficacy of Botulinum toxin A (BoNT-A) in the treatment of the primary Meige syndrome. Our study aimed to explore the potential associations between the clinical efficacy of BoNT-A in the treatment of the primary Meige syndrome and variants of SNAP25, SV2C and ST3GAL2, which are involving in the translocation of the BoNT-A in vivo. MethodsPatients with the primary Meige syndrome treated with BoNT-A were enrolled. Clinical efficacy was evaluated by the maximum improvement rate of motor symptoms and the duration of efficacy. Variants of SNAP25, SV2C and ST3GAL2 were obtained by Sanger sequencing. Another cohort diagnosed with primary cervical dystonia was also enrolled in the replication stage. ResultsAmong the 104 primary Meige syndrome patients, 80 patients (76.9%) had a good efficacy (the maximum improvement rate of motor symptoms ≥30%) and 24 (23. 1%) had a poor (the maximum improvement rate of motor symptoms <30%). As to the duration of efficacy, 52 patients (50.0%) had a long duration of efficacy (≥4 months), and 52 (50.0%) had a short (<4 months). In terms of primary Meige syndrome, SNAP25 rs6104571 was found associating with the maximum improvement rate of motor symptoms (Genotype: P = 0.02, OR = 0.26; Allele: P = 0.013, OR = 0.29), and SV2C rs31244 was found associating with the duration of efficacy (Genotype: P = 0.024, OR = 0.13; Allele: P = 0.012, OR = 0.13). Besides, we also conducted the association analyses between the variants and BoNT-A-related adverse reactions. Although, there was no statistical difference between the allele of SV2C rs31244 and BoNT-A-related adverse reactions, there was a trend (P = 0.077, OR = 2.56). In the replication stage, we included 39 patients with primary cervical dystonia to further expanding the samples' size. Among the 39 primary cervical dystonia patients, 25 patients (64.1%) had a good efficacy (the maximum improvement rate of motor symptoms ≥50%) and 14 (35.9%) had a poor (the maximum improvement rate of motor symptoms <50%). As to the duration of efficacy, 32 patients (82.1%) had a long duration of efficacy (≥6 months), and 7 (17.9%) had a short (<6 months). Integrating primary Meige syndrome and primary cervical dystonia, SV2C rs31244 was still found associating with the duration of efficacy (Genotype: P = 0.002, OR = 0. 23; Allele: P = 0.001, OR = 0. 25). ConclusionIn our study, SNAP25 rs6104571 was associated with the maximum improvement rate of motor symptoms in patients with primary Meige syndrome treated with BoNT-A, and patients carrying this variant had a lower improvement rate of motor symptoms. SV2C rs31244 was associated with duration of treatment in patients with primary Meige syndrome treated with BoNT-A and patients carrying this variant had a shorter duration of treatment. Patients with primary Meige syndrome carrying SV2C rs31244 G allele have an increase likelihood of BoNT-A-related adverse reactions. Involving 39 patients with primary cervical dystonia, the results further verify that SV2C rs31244 was associated with duration of treatment and patients carrying this variant had a shorter duration of treatment.

Evaluation of Osteoporosis Among Epileptic Patients on Monotherapy

Epilepsy is a common chronic neurological disorder that affects almost 50 million people worldwide. Most patients require long-term, and sometimes lifelong therapy with antiseizure medications (ASMs), our case control study evaluates the long-term effect of carbamazepine (CBZ) and valproate (VPA) on bone mineral density and bone health biochemical markers. 50 patients with newly diagnosed epilepsy who had no history of antiseizure medications (ASMs) intake prior were divided into 2 groups. In the first group, 25 patients started carbamazepine (CBZ) monotherapy, while the second group included 25 patients who started receiving valproate (VPA) monotherapy. Another 25 healthy individuals were considered as a control group. The primary outcome of our study is to evaluate the percentage of osteoporosis compared to the duration of ASM therapy measured by the T score at two different sites in the body at baseline, after 3 and 6 months of therapy, while measurements of bone biomarker variables are considered secondary outcomes. We found that CBZ and VPA significantly decreased the level of vitamin D3, Ca, P, the L3-L5, and right femoral neck T score with prolonged treatment duration, while the level of ALP increased with increasing duration of treatment in patients treated with CBZ but not in the VPA group. Furthermore, CBZ significantly decreased bone health biomarkers and T score before VPA and the control group, as well as there were no significant differences between the two sexes who received CBZ or VPA therapy on bone biomarkers. In conclusion, valproate will not affect bone biomarkers earlier, but with a longer duration of therapy, they may have the same effect as carbamazepine which requires the prescription of supportive vitamin D and Ca along with ASMs.

91P Observational retro-prospective study on immune checkpoint inhibitors (ICIs) treatment duration in patients with advanced non-small cell lung cancer (aNSCLC) (I-STOP study)

91P Observational retro-prospective study on immune checkpoint inhibitors (ICIs) treatment duration in patients with advanced non-small cell lung cancer (aNSCLC) (I-STOP study)

Effect of Lithium on Orthodontic Tooth Movement: a Systematic Review of Animal Studies.

This study aimed to systematically review the effect of lithium on orthodontic tooth movement (OTM). The focus question was "does lithium have an effect on OTM?" A systematic search was conducted using indexed databases and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. The quality assessment of the selected studies was performed according to the systematic review center for laboratory animal experimentation. Five of the initially identified 656 articles fulfilled the eligibility criteria and were selected for this review. The studies reported that lithium administration lowered the rate of OTM by inducing a reduction in the number of osteoclasts and possibly inhibiting osteoclastogenesis. These studies further showed an increase in bone density and bone volume by promoting the Wnt/ß-catenin signaling pathway and osteoblastogenesis. It was also noted that lithium reduced orthodontically induced root resorption during experimental OTM. Further, standardized studies are warranted to understand the impact of lithium in OTM. Overall, the risk of bias for 3 studies was very high, high in 1 study, and moderate in 1 study. On an experimental level in animals, lithium decreased the rate of OTM during the active treatment phase by increasing bone density and bone volume and reducing root resorption. In addition, lithium may enhance alveolar bone formation during orthodontic retention. Clinically, this may impact the orthodontic treatment duration in patients receiving lithium, and further studies are needed to understand the true impact of lithium on OTM.

Whole-genome shotgun sequencing unravels the influence of environmental microbial co-infections on the treatment efficacy for severe pediatric infectious diseases.

The microbiome plays a pivotal role in mediating immune deviation during the development of early-life viral infections. Recurrent infections in children are considered a risk factor for disease development. This study delves into the metagenomics of the microbiome in children suffering from severe infections, seeking to identify potential sources of these infections. The aim of this study was to identify the specific microorganisms and factors that significantly influence the treatment duration in patients suffering from severe infections. We sought to understand how these microbial communities and other variables may affect the treatment duration and the use of antibiotics of these patients with severe infections. Whole-genome shotgun sequencing was conducted on samples collected from children aged 0-14 years with severe infections, admitted to the Pediatrics Department of Xiamen First Hospital. The Kraken2 algorithm was used for taxonomic identification from sequence reads, and linear mixed models were employed to identify significant microorganisms influencing treatment duration. Colwellia, Cryptococcus, and Citrobacter were found to significantly correlate with the duration of clinical treatment. Further analysis using propensity score matching (PSM) and rank-sum test identified clinical indicators significantly associated with the presence of these microorganisms. Using a linear mixed model after removed the outliers, we identified that the abundance of Colwellia, Cryptococcus, and Citrobacter significantly influences the treatment duration. The presence of these microorganisms is associated with a longer treatment duration for patients. Furthermore, these microorganisms were found to impact various clinical measures. Notably, an increase in hospitalization durations and medication costs was observed in patients with these microorganisms. In patients with Colwellia, Cryptococcus, and Citrobacter, we discover significant differences in platelets levels. We also find that in patients with Cryptococcus, white blood cells, hemoglobin, and neutrophils levels are lower. These findings suggest that Colwellia, Cryptococcus, and Citrobacter, particularly Cryptococcus, could potentially contribute to the severity of infections observed in this cohort, possibly as co-infections. These microorganisms warrant further investigation into their pathogenic roles and mechanisms of action, as their presence in combination with disease-causing organisms may have a synergistic effect on disease severity. Understanding the interplay between these microorganisms and pathogenic agents could provide valuable insights into the complex nature of severe pediatric infections and guide the development of targeted therapeutic strategies.

Efficacy and safety of alcohol reduction pharmacotherapy according to treatment duration in patients with alcohol dependence or alcohol use disorder: A systematic review and network meta-analysis.

Relapse is common in alcohol dependence (AD) and alcohol use disorder (AUD), so alcohol reduction therapy should be measured over as long a period as possible; however, existing reviews do not consider the duration of treatment and therefore alcohol reduction therapy may not have been appropriately evaluated. This review evaluated the efficacy and safety of alcohol reduction pharmacotherapy in patients with AD or AUD according to the duration of treatment. We conducted a systematic review and network meta-analysis of randomized controlled trials (RCTs) that assessed 15 pharmacological agents. MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Trials, the ClinicalTrials.gov and the International Clinical Trials Registry Platform were searched for eligible trials through to May 2021. Outcomes were heavy drinking days (HDD), total alcohol consumption (TAC), any adverse event and days without drinking. Fifty-five RCTs (n = 8891) were included. Nalmefene was superior to placebo for reducing HDD (standard mean difference [SMD] -0.28, 95% confidence interval [CI] -0.37, -0.18) and TAC (SMD -0.25, 95% CI -0.35, -0.16) in the long-term, but not in the short-term. Topiramate was superior to placebo for reducing HDD (SMD -0.35, 95% CI -0.59, -0.12) and days without drinking (SMD 0.46, 95% CI 0.11, 0.82), and baclofen was superior for reducing TAC (SMD -0.70, 95% CI -1.29, -0.11), in the short-term. The frequency of adverse events was higher with nalmefene and topiramate than with placebo. Nalmefene, topiramate and baclofen may be effective as alcohol reduction pharmacotherapy; however, only nalmefene has demonstrated long-term efficacy, and nalmefene and topiramate have a significantly higher frequency of adverse events compared with placebo.

Nivolumab Rechallenge After Prior Nivolumab Therapy in Advanced Gastric Cancer: A Single-Center Case Series and Literature Review.

Pivotal phase III trials indicated that the anti-PD-1 inhibitor nivolumab prolongs overall survival in patients with advanced gastric cancer. Nivolumab is currently used in the first- or later-line treatment of patients with advanced gastric cancer in Japan. The efficacy of immune check inhibitor rechallenge after progression has been reported in other cancers. Therefore, this study investigated the clinical outcome of nivolumab rechallenge in patients with advanced gastric cancer who received nivolumab in a previous systemic line. We retrospectively reviewed the medical records of six patients with advanced or recurrent gastric cancer who received nivolumab rechallenge. During initial nivolumab therapy, three patients experienced partial responses, and one patient achieved stable disease. The reasons for discontinuing initial nivolumab therapy were progressive disease in five patients and immune-related adverse events in one patient. The median interval duration of treatment for patients receiving both nivolumab regimens was 13.7 (range: 5.1-17.8) months. During nivolumab rechallenge, no patients achieved partial responses, whereas two patients had stable disease. Median progression-free survival was 2.5 (95% confidence interval [CI] = 1.6-not available [NA]) months, and median overall survival was 7.4 (95% CI = 2.3-NA) months. Although one patient had discontinued prior nivolumab therapy because of immune-related adverse events, there were no immune-related adverse events associated with nivolumab rechallenge. The benefit of nivolumab rechallenge in patients with advanced gastric cancer was limited. Rechallenge with the same immune check inhibitor might be ineffective in patients with advanced gastric cancer.

The usege of rigid fixation of dental splints in the treatment of patients with fractures of the lower jaw

The aim of our research was to study the effectiveness of rigid fixation in mandibular fractures. For this purpose, a study of 200 inpatients of the maxillofacial department was conducted. The study included 64 patients with jaw fractures who passed the criteria for inclusion in the study and the formation of the main group and the comparison group. The research methods were: assessment of the hygienic state of the oral cavity, clinical and radiological examination, electromyographic examination. The results of the study were evaluated at 3, 14, 22 days and after 3 months. After 3 months from the moment of hospitalization in all patients of the main group, a newly formed callus, complete bone radiological consolidation of fragments is clearly visible. In patients of the comparison group, a newly formed callus was clearly visible in the fracture gap. In 7 patients, complete bone radiological consolidation of fragments occurred. According to the results of electromyography, we found that in patients of the main group, whose treatment consisted in the imposition of rigid fixation of dental splints, a more complete recovery of the bioelectric activity of the masticatory muscles proper – 3 months after the injury, the comparison group – 380±10 μV, the main group – 510±10 µV. Conclusions: The use of rigid fixation in the treatment of mandibular fractures significantly reduces the duration of treatment in patients by 8 days of treatment compared with the traditional method.

COMPLEX TREATMENT OF INTERNAL TMJ DISORDERS IN PATIENTS WITH DIFFERENT BIT TYPES

Objective: To assess the impact of physiological and pathological types of occlusions on the effectiveness of the treatment of patients with internal disorders of the TMJ. Material and Methods: A comprehensive examination and treatment of 139 patients with internal TMJ disorders with subluxation and chronic dislocation of the articular disc was carried out. The patients were divided into three groups. All groups included patients with both physiological and pathological occlusion. The first group included 28 (20.1%) patients who were treated only with occlusal splint therapy; the second group included 95 (68.3%) patients who were treated with a combination of occlusal splint therapy and the use of arthrocentesis; in the third group (16 people (11.5%), along with splint therapy and arthrocentesis, TMJ arthroscopy was performed. The examination included a survey and examination of patients, a study of diagnostic models of the jaws to determine the types of occlusion and occlusal contacts, magnetic resonance imaging (MRI) and ultrasound examination (ultrasound) of the TMJ. Patients underwent a phased treatment, including occlusive splint therapy (stage I); with insufficient effectiveness - occlusive splint therapy and arthrocentesis (stage II); occlusive splint therapy and arthrocentesis in combination with arthroscopy (stage III of treatment). Results: As a result of the study, it turned out that the groups of patients differed significantly in the complexity and duration of the treatment. Thus, in patients with internal TMJ disorders and pathological type of occlusion, in 82.6% of cases, additional use of arthrocentesis was required and in 34.8% - arthroscopy (95 patients out of 139), while patients with physiological types of occlusions (orthognathic, progenic, biprogenic and direct) needed these treatments in 80.2% and 7.8% of cases, respectively In the groups of patients, the duration of therapy, as well as the number of arthrocentesis performed in patients at the second and third stages of treatment, significantly differed. In the first group, the duration of treatment was 6.2 months for patients with normal occlusion and 8.7 (p&lt;0.01) months for patients with pathological occlusion; additional methods of treatment (arthrocentesis and arthroscopy) were not used. In the second and third groups of patients, the duration of treatment for patients with occlusion pathology was also longer: in the second group 4.9 and 6.8 (p&lt;0.01) months for patients with physiological and pathological types of occlusions, respectively, in the third group with the use of splint therapy, arthrocentesis and arthroscopy in patients with normal occlusion was 13.1 (p&lt;0.05) months, and in patients with occlusion pathology 14.5 months Conclusion: Patients with internal TMJ disorders need a comprehensive examination for the timely detection of occlusion pathologies. The relationship between internal TMJ disorders and the type of occlusion must alway

Longitudinal assessment of the effects of passive training on stroke rehabilitation using fNIRS technology

For patients with severe conditions such as stroke, passive exercise is commonly used in the early stages of their rehabilitation training. This study aimed to assess the effect of passive training on stroke rehabilitation and track brain function changes and the patient's rehabilitation progress, by employing a robot glove to perform a passive flexion-extension task. Specifically, functional near-infrared spectroscopy data from 26 patients under resting and right-hand passive interactions (task state) were recorded before and after a one-week interval, respectively, to explore the variations in the brain network of the patients. The results showed a stronger functional connectivity in both states of the two experiments in the left and right homotopic brain regions (p < 0.01). The effective connectivity network between brain regions maintained a consistent trend during the same test. Changes in functional connectivity and effective connectivity networks may represent the advantages of motor rehabilitation tasks and patient treatment duration, providing a perspective for an easy understanding of the mechanisms of stroke-related brain changes. This study demonstrates the feasibility of passive training strategies in the field of intelligent rehabilitation by applying neuroscientific diagnostic methods based on physiological data to the field of human-computer interaction.

Applying Artificial Intelligence Machine Learning to Discover Factors That Shorten Duration of Treatment in Patients with Multiple Myeloma Using Real-World Patient-Level Longitudinal Data from Medical Data Vision Database

Introduction: To maximize the benefit of treatment in multiple myeloma (MM), it is important to continue treatment for appropriate duration . Our recent real-world study using the Medical Data Vision (MDV) claim database showed that median duration of treatment (DoT) of 1 line (L), 2L and 3L treatment was rather short (range: 6.7 to 8.6 months) in Japanese non-transplant patients with MM (Handa H, et al. Plos one. 2023). However, the broad range of treatment patterns in Japan makes it difficult to identify the cause of shortened DoT. Therefore, we assessed the predictive factors that shorten DoT at threshold of &amp;lt;3, &amp;lt;6 and &amp;lt;12 months by applying machine learning (ML) model using real-world clinical data of MM patients from the MDV database. Methods: This retrospective cohort study was conducted on 4848 individual treatments (2,762 patients; 1L for stem cell transplant-not conducted, 2L/3L) in patients (aged ≥18 years) with transplant-ineligible (newly diagnosed or relapsed/refractory) MM between 2003-21. An explainable deep learning model (point-wise linear model, PWL) was developed using 647 feature variables (evaluated before, during, and after treatment; Table) from the MDV database to identify the important predictors associated with DoT. The PWL model generated a custom-made logistic regression model for each sample, which was very familiar to medical researchers and allowed to analyze the importance of the feature variables. Predictive performance of the PWL model was compared with elastic-net regularized logistic regression and XGBoost models and calculated by area under the curve (AUC) and evaluated by 10-fold double cross validation. To stratify the patients with shorter DoT, a clustering analysis of 4848 individual treatment was conducted based on the similarity of coefficients of the custom-made logistic regression models generated from the PWL model. To understand characteristics of samples belonging to each cluster, the relationship between predicted DoT and MM treatment-related comorbidity management was investigated ( Table). Results: The AUC score of the PWL model to predict DoT of &amp;lt;3, &amp;lt;6 and &amp;lt;12 months was 0.61, 0.64 and 0.66, respectively ( Figure). As per clustering analysis, there were 2 clusters (cluster A and B) at DoT of &amp;lt;3 months and 3 clusters (cluster A, B and C) each at DoT of &amp;lt;6 and &amp;lt;12 months, respectively. At &amp;lt;3 months, cluster B showed lower median of prediction probability, and had a significantly (P&amp;lt;0.01) higher previous treatment lines, pre-treatment Charlson Comorbidity Index (CCI) versus cluster A. At &amp;lt;6 months, cluster C showed lower median of prediction probability, and had significantly (P&amp;lt;0.01) higher CCI and comorbidities, and cluster B had significantly (P&amp;lt;0.01) lower estimated glomerular filtration rate, among the clusters. At &amp;lt;12 months, cluster C showed lower median of prediction probability, and had significantly (P&amp;lt;0.01) higher lactate dehydrogenase (LD), previous treatment lines, pre-treatment CCI, degree of care requirement at diagnosis of MM, pre-treatment tube and parenteral nutrition, and comorbidities, among clusters. Additionally, in cluster B (at &amp;lt;3 months), and cluster C (at &amp;lt;6 and &amp;lt;12 months), use of immunomodulatory drugs (IMiDs) in treatment for MM was significantly higher in patients who met predicted DoT at each threshold versus the ones who were not. However, age and history of infectious diseases (antibacterial agents, γ globulin, etc.) was not affected. In addition, IMiDs and aspirin use at &amp;lt;3 and &amp;lt;6 months, and IMiDs use at &amp;lt;12 months had significant differences in events during and after treatment, which are important for considering treatment strategies for MM patients and may lead to the optimization of treatment plans. Study limitation included exclusion of important prognostic factors (cytogenetic profile, R-ISS stage, and presence of all plasmacytomas). Conclusions: TheML technique with PWL model yielded efficient results to understand the trend associated with event in treatment and characteristics of Japanese patients with MM whose DoT were shortened. Patient's condition and management related factors might have associated with shortened DoT, in consistent with clinical findings. These results are critical to continually improving MM management, achieving optimal patients care, and understanding the burden of disease and health services available to Japanese patients with MM in the real-world.

Some new aspects of the pathogenesis of venous trophic ulcers

Venous trophic ulcers are one of the most common in the population, and costly in terms of treatment costs for complications of chronic venous insufficiency. The prevalence of venous trophic ulcers ranges from 0.18 to 1%. Over the age of 65 it increases to 4%. The cause of the formation of venous trophic ulcers is chronic diseases of the veins of the lower extremities. Chronic disease of the veins is a term that includes a wide range of morphological and functional disorders affecting the venous system. At the same time, even after conservative treatment, the level of recurrence of venous trophic ulcers remains extremely high, which leads to an increase in the duration of treatment for patients in the hospital, in some cases causing permanent disability in patients of working age. The literature has accumulated a huge volume of both fundamental and clinical research on the etiology, pathogenesis, diagnosis and treatment of venous ulcers. However, despite the numerous studies, the number of patients with this disease continues to steadily increase, and a number of important aspects of the pathogenesis have not yet been studied. In addition, these works do not allow us to formulate a unified concept of the pathogenesis of venous ulcers, which in turn affects the effectiveness of treatment of venous trophic ulcers. Our study highlights modern aspects of the pathogenesis of venous trophic ulcers, which may be of key importance in the treatment of this pathology. Promising directions of scientific research in this area are determined. This requires a more in-depth study of aspects of intercellular interactions, and also opens up the prospect of searching for new methods of influencing the pathogenesis of venous trophic ulcers, taking into account the presence of microflora resistant to standard antibacterial agents.

Emulating a Target Trial of Shorter Compared to Longer Course of Antibiotic Therapy for Gram-Negative Bacteremia.

Despite the availability of antimicrobial therapies, gram-negative bacteremia remains a significant cause of morbidity and mortality on a global level. Recent randomized controlled trials support shorter antibiotic treatment duration for individuals with uncomplicated gram-negative bacteremia. The target trial framework using the cloning approach utilizes real-world data but eliminates the issue of immortal time bias seen in observational studies by emulating the analysis of randomized trials with full adherence. A hypothetical target trial allocating individuals with gram-negative bacteremia to either short antibiotic treatment duration (5-7 days) or longer antibiotic treatment duration (8-14 days) was specified and emulated using the cloning, censoring, and weighting approach. The primary outcome was 90-day all-cause mortality. Secondary outcome was a composite endpoint of clinical and microbiological relapse. The emulated trial included individuals from four hospitals in Copenhagen from 2018 through 2021. In sum, 1040 individuals were included. The median age of the cohort was 76 years, the majority were male (54%), had community-acquired gram-negative bacteremia (86%), urinary tract infection as the source of the infection (78%), and Escherichia coli as the pathogen of the infection (73%). The adjusted 90-day risk difference in all-cause mortality was 1.3% (95% confidence interval [CI]: -.7, 3.3), and the risk ratio was 1.12 (95% CI: .89, 1.37). The adjusted 90-day risk difference in relapse was 0.7% (95% CI: -2.3, 3.8), and the risk ratio was 1.07 (95% CI: .71, 1.45). We found comparative outcomes for shorter treatment duration compared to longer treatment duration in patients with gram-negative bacteremia.

Factors influencing pulmonary arterial pressure in three related patients with Cantú syndrome: glyburide may provide precision care

A range of pulmonary arterial pressures was observed in three related patients with Cantú syndrome. The incident patient developed a moderately high pulmonary vascular resistance. Several factors influenced the severity of his pulmonary vascular disease and the events, which ultimately resulted in his death. However, he had an acute improvement in blood pressure and respiratory support after a single dose of glyburide when he was critically ill. The father and sister of the incident patient have evidence of mildly increased pulmonary arterial pressure with normal pulmonary vascular resistance. They are being treated with glyburide to potentially decrease the high cardiac output associated with a gain in KATP channel function. Additional experience with glyburide or other KATP channel inhibitors is needed to determine the most appropriate agent, dose, time, and duration of treatment for patients with Cantú syndrome.

Monitoring of Plasma EGFR Mutations during Osimertinib Treatment for NSCLC Patients with Acquired T790M Mutation.

Osimertinib was first approved for the treatment of non-small cell lung cancer (NSCLC) in patients who have developed the epidermal growth factor receptor (EGFR) T790M mutation after treatment with EGFR tyrosine kinase inhibitors (TKIs). We routinely evaluated the plasma of NSCLC patients with the T790M mutation to more rapidly detect an increase in disease activity and resistance to treatment. Eligible patients received osimertinib after resistance to the first- or second-generation of EGFR-TKIs in NSCLC harboring T790M mutation detectable in tumor tissue or plasma. Plasma samples were collected every 8 weeks during osimertinib treatment. The plasma analysis was performed using an improved PNA-LNA PCR clamp method. We tested samples for a resistance mechanism, including EGFR-activating, T790M, and C797S mutations, and assessed the association between the mutations and osimertinib treatment. Of the 60 patients enrolled in the study, 58 were eligible for this analysis. In plasma collected before osimertinib treatment, activating mutations were detected in 47 of 58 patients (81.0%) and T790M was detected in 44 patients (75.9%). Activating mutations were cleared in 60.9% (28/46) and T790M was cleared in 93.0% (40/43). Of these, 71.4% (20/28) of activating mutations and 87.5% (35/40) of T790M mutation were cleared within 8 weeks of treatment. The total response rate (RR) was 53.4% (31/58). The median duration of treatment was 259 days, with a trend toward longer treatment duration in patients who experienced the clearance of activating mutations with osimertinib. At the time of disease progression during osimertinib treatment, C797S was detected in 3 of 37 patients (8.1%). Plasma EGFR mutation analysis was effective in predicting the effect of osimertinib treatment.

Risk Characterization of Treatment Histories and Comorbidities Regarding Tuberculosis Treatment Status in West Sumatra Province 2020-2021

Background: Tuberculosis (TB) is the leading cause of death among bacterial infectious diseases worldwide, and Indonesia is the second country with the highest TB burden.Objective: The treatment history and comorbidities of TB disease play a significant role in determining the appropriateness of therapy and the duration of treatment for patients. The objective is to identify the factors that influence the incidence of first molar caries.Methods: This study employs an analytic case-control design with a retrospective cohort methodology. 161 RO TB patients and 161 SO TB patients comprised the total sample size. Statistical analysis of this investigation utilizing R and R Studio.Result: In this study, there was a correlation between gender (p-value 0.006 and odds ratio 1.89), contact investigation (p-value 0.001 and odds ratio 0.23), new TB (p-value 0.001 and odds ratio 0.05), TB recurrence (p-value 0.001 and odds ratio 19.0), TB failed treatment (p-value 0.007 and odds ratio 16.4), and pH-saliva (p-value 0.0001 and odds ratio 21.250). In contrast, risk factors such as absenteeism, diabetes, and HIV were not associated with TB treatment status (p-value 0.05). Age, investigation of contact, and TB recurrence were the predominant factors associated with TB treatment status, as determined by multivariate analysis.Conclusions: Several factors, including gender and treatment history (new TB, Relapsed TB, Failed TB), influence the status of TB treatment in West Sumatra Province. These are important factors that must be considered and asked by TB officers at health facilities before the patient undergoes an examination of suspected samples and information to provide appropriate medical therapy to TB patients in health facilities.