Investigation Of Treatment Effects Research Articles

Application of Natural Products in Radiotherapy-Induced Dermatitis: A Comprehensive Review

Radiodermatitis (RD) is experienced by many cancer patients ‎receiving radiotherapy. An increasing number of these patients demand alternative natural therapies. This study aimed to review the natural products application in cancer patients who experience RD.‎ A search of studies published from 1990 to ‎‎2020 in the ‎databases including PubMed, Scopus, and Google Scholar was performed with the keywords relevant to “Radiotherapy” “Dermatitis” and “Natural Products”. Out of 73 papers obtained, 40 papers were excluded which described only protocols or were non-clinical, non-English language, or without full text. The obtained studies were ‎discussed in detail according to the outcomes and potential mechanisms of action for each natural ‎product.‎ Clinically studied natural products were found to show several outcomes from non-effective to effective in diminishing various items of RD. Outcomes on the effectiveness of Aloe vera were diverse. Some trials suggest that Silybum marianum, Boswellia, Nigella sativa, olive oil, Lianbai, and Hypericum perforatum as well as some multi-ingredient products might be effective prophylactic treatments for RD. Potential mechanisms of these natural products included topical hydrating, anti-inflammatory, antioxidant, and wound ‎healing activities. Results from this review shows that there are some promising natural product options for the prevention and treatment of RD via their multifactorial bioactivities. However, additional research is needed before any definitive conclusions. A larger sample size, optimum doses and duration of intervention as well as investigation of treatment effects in diverse populations and comorbid complications would also be essential in future studies.

Frequent follow-up of suicidal youth assessed in the emergency room: Long-term trajectory and predictors of suicidality

Suicide was the second‑leading cause of US deaths in 2018 among 15–24-year-olds. Suicide attempts, a risk factor for completions, and suicide ideation have doubled among pediatric emergency room (ER) patients during the past decade. Borderline Personality Disorder (BPD), a comorbid condition, has a 10% suicide rate. We examined the 4-year outcome of a cohort of suicidal adolescents, many also suffering from BPD and having undergone some form of treatment, to identify baseline factors which could inform intervention that would minimize suicidality 4 years post-discharge. MethodsWe conducted a prospective longitudinal study of suicidality at twelve points (four assessment occasions) for 286 suicidal youth presenting to a pediatric ER, most suffering from BPD, with 36 suicide ratings from baseline to 2-, 6- and 48-month follow-up evaluations. We examined the trajectory and predictors of persisting suicidality. ResultsSuicidality rapidly decreased within 2 months post-ER-discharge, subsequently remaining low throughout 48 months. Baseline functioning, female sex, stressful life events and BPD impulsiveness were most predictive of persisting suicidality at 48-month follow-up. ConclusionMost suicidal youth, many meeting BPD criteria, no longer feel suicidal 2 months after ER discharge. Management of participants' baseline poor functioning stressful life events and the impulsiveness component of BPD specifically in females could impact suicidality 4 years later, and guide treatment options. The absence of the BPD cognitive and affective subscales as predictors of suicidality at 4-year follow-up may reflect treatment received. Further investigation of treatment effects is warranted and under way.

The Investigation of Treatment Effects on Serum Biochemical Parameters in Bladder Cancer Diseases

The Investigation of Treatment Effects on Serum Biochemical Parameters in Bladder Cancer Diseases

The challenges in data integration \u2013 heterogeneity and complexity in clinical trials and patient registries of Systemic Lupus Erythematosus

BackgroundIndividual clinical trials and cohort studies are a useful source of data, often under-utilised once a study has ended. Pooling data from multiple sources could increase sample sizes and allow for further investigation of treatment effects; even if the original trial did not meet its primary goals. Through the MASTERPLANS (MAximizing Sle ThERapeutic PotentiaL by Application of Novel and Stratified approaches) national consortium, focused on Systemic Lupus Erythematosus (SLE), we have gained valuable real-world experiences in aligning, harmonising and combining data from multiple studies and trials, specifically where standards for data capture, representation and documentation, were not used or were unavailable. This was not without challenges arising both from the inherent complexity of the disease and from differences in the way data were captured and represented across different studies.Main bodyData were, unavoidably, aligned by hand, matching up equivalent or similar patient variables across the different studies. Heterogeneity-related issues were tackled and data were cleaned, organised and combined, resulting in a single large dataset ready for analysis. Overcoming these hurdles, often seen in large-scale data harmonization and integration endeavours of legacy datasets, was made possible within a realistic timescale and limited resource by focusing on specific research questions driven by the aims of MASTERPLANS. Here we describe our experiences tackling the complexities in the integration of large, diverse datasets, and the lessons learned.ConclusionsHarmonising data across studies can be complex, and time and resource consuming. The work carried out here highlights the importance of using standards for data capture, recording, and representation, to facilitate both the integration of large datasets and comparison between studies. Where standards are not implemented at the source harmonisation is still possible by taking a flexible approach, with systematic preparation, and a focus on specific research questions.

Reactions to Multiple Ascending Doses of the Microtubule Stabilizer TPI-287 in Patients With Alzheimer Disease, Progressive Supranuclear Palsy, and Corticobasal Syndrome

Basket-design clinical trials that allow investigation of treatment effects on different clinical syndromes that share the same molecular pathophysiology have not previously been attempted in neurodegenerative disease. To assess the safety, tolerability, and pharmacodynamics of the microtubule stabilizer TPI-287 (abeotaxane) in Alzheimer disease (AD) or the 4-repeat tauopathies (4RT) progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). Two parallel-design, double-blind, placebo-controlled phase 1 randomized clinical trials in AD and 4RT were conducted from December 20, 2013, through May 4, 2017, at the University of California, San Francisco, and University of Alabama at Birmingham. A total of 94 patients with clinically diagnosed AD (n = 39) and 4RT (n = 55) were screened; of these, 3 refused to participate, and 10 with AD and 11 with 4RT did not meet inclusion criteria. A total of 29 patients with AD, 14 with PSP, and 30 with β-amyloid-negative CBS (determined on positron emission tomography findings) were enrolled. Data were analyzed from December 20, 2013, through May 4, 2017, based on modified intention to treat. Randomization was 8:3 drug to placebo in 3 sequential dose cohorts receiving 2.0, 6.3, or 20.0 mg/m2 of intravenous TPI-287 once every 3 weeks for 9 weeks, with an optional 6-week open-label extension. Primary end points were safety and tolerability (maximal tolerated dose) of TPI-287. Secondary and exploratory end points included TPI-287 levels in cerebrospinal fluid (CSF) and changes on biomarker, clinical, and neuropsychology measures. A total of 68 participants (38 men [56%]; median age, 65 [range, 50-85] years) were included in the modified intention-to-treat analysis, of whom 26 had AD (14 women [54%]; median age, 63 [range, 50-76] years), and 42 had 4RT (16 women [38%]; median age, 69 [range, 54-83] years). Three severe anaphylactoid reactions occurred in TPI-287-treated patients with AD, whereas none were seen in patients with 4RT, leading to a maximal tolerated dose of 6.3 mg/m2 for AD and 20.0 mg/m2 for 4RT. More falls (3 in the placebo group vs 11 in the TPI-287 group) and a dose-related worsening of dementia symptoms (mean [SD] in the CDR plus NACC FTLD-SB [Clinical Dementia Rating scale sum of boxes with frontotemporal dementia measures], 0.5 [1.8] in the placebo group vs 0.7 [1.6] in the TPI-287 group; median difference, 1.5 [95% CI, 0-2.5]; P = .03) were seen in patients with 4RT. Despite undetectable TPI-287 levels in CSF, CSF biomarkers demonstrated decreased chitinase-3-like protein-1 (YKL-40) levels in the 4RT treatment arm (mean [SD], -8.4 [26.0] ng/mL) compared with placebo (mean [SD], 10.4 [42.3] ng/mL; median difference, -14.6 [95% CI, -30.0 to 0.2] ng/mL; P = .048, Mann-Whitney test). In this randomized clinical trial, TPI-287 was less tolerated in patients with AD than in those with 4RT owing to the presence of anaphylactoid reactions. The ability to reveal different tau therapeutic effects in various tauopathy syndromes suggests that basket trials are a valuable approach to tau therapeutic early clinical development. ClinicalTrials.gov identifiers: NCT019666666 and NCT02133846.

Microproteome of dentoalveolar tissues

Proteomic analysis of extracellular matrices (ECM) of dentoalveolar tissues can provide insights into developmental, pathological, and reparative processes. However, targeted dissection of mineralized tissues, dental cementum (DC), alveolar bone (AB), and dentin (DE), presents technical difficulties. We demonstrate an approach combining EDTA decalcification and laser capture microdissection (LCM), followed by liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS), to analyze proteome profiles of these tissues. Using the LCM-LC-MS/MS approach, a total of 243 proteins was identified from all tissues, 193 proteins in DC, 147 in AB, and 135 proteins DE. Ninety proteins (37% of total) were common to all tissues, whereas 52 proteins (21%) were overlapping in only two. Also, 101 (42%) proteins were exclusively detected in DC (60), AB (15), or DE (26). Identification in all tissues of expected ECM proteins including collagen alpha-1(I) chain (COL1A1), collagen alpha-1(XII) chain (COL12A1), biglycan (BGN), asporin (ASPN), lumican (LUM), and fibromodulin (FMOD), served to validate the approach. Principal component analysis (PCA) and hierarchical clustering identified a high degree of similarity in DC and AB proteomes, whereas DE presented a distinct dataset. Exclusively and differentially identified proteins were detected from all three tissues. The protein-protein interaction network (interactome) of DC was notable for its inclusion of several indicators of metabolic function (e.g. mitochondrial proteins, protein synthesis, and calcium transport), possibly reflecting cementocyte activity. The DE proteome included known and novel mineralization regulators, including matrix metalloproteinase 20 (MMP-20), 5′ nucleotidase (NT5E), and secreted phosphoprotein 24 (SPP-24 or SPP-2). Application of the LCM-LC-MS/MS approach to dentoalveolar tissues would be of value in many experimental designs, including developmental studies of transgenic animals, investigation of treatment effects, and identification of novel regenerative factors.

Analysis of Variance of Integro-Differential Equations with Application to Population Dynamics of Cotton Aphids

The population dynamics of cotton aphids is usually described by mechanistic models, in the form of integro-differential equations (IDEs), with the IDE parameters representing some key properties of the dynamics. Investigation of treatment effects on the population dynamics of cotton aphids is a central issue in developing successful chemical and biological controls for cotton aphids. Motivated by this important agricultural problem, we propose a framework of analysis of variance (ANOVA) of IDEs. The main challenge in estimating the IDE-based ANOVA model is that IDEs usually have no analytic solution, and repeatedly solving IDEs numerically leads to a high computational cost. We propose a penalized spline method in which spline functions are used to estimate the IDE solutions and the penalty function is defined by the IDEs. The estimated IDE solutions, as implicit functions of the parameters, are inputs in a nonlinear least squares criterion, which in turn is minimized by a Gauss–Newton algorithm. The proposed method is illustrated using simulation and an observed cotton aphid data set.

Abstract CN03-04: Gastrointestinal and liver toxicities related to targeted therapies

Abstract CN03-04: Gastrointestinal and liver toxicities related to targeted therapies

Clinical Outcomes Associated with Bevacizumab-Containing Treatment of Metastatic Colorectal Cancer: The BRiTE Observational Cohort Study

The Bevacizumab Regimens' Investigation of Treatment Effects (BRiTE) study is a prospective, observational cohort study designed to elucidate safety and effectiveness outcomes associated with bevacizumab combined with chemotherapy as used in clinical practice for first-line treatment of metastatic colorectal cancer (mCRC). Baseline characteristics, prespecified bevacizumab-related adverse events, and effectiveness data were collected from 1,953 mCRC patients who were receiving first-line treatment including bevacizumab at 248 U.S. sites. At database lock, the median follow-up was 20.1 months. At baseline, 46% of patients were aged >or=65 years and 49% had an Eastern Cooperative Oncology Group performance status score >or=1. Fluorouracil, leucovorin, and oxaliplatin was the most common first-line chemotherapy regimen (56%). Overall rates of bevacizumab-related adverse events in the BRiTE study, such as gastrointestinal perforation (1.9%), arterial thromboembolic events (2%), grade 3-4 bleeding (2.2%), and de novo hypertension requiring medication (22%), were consistent with those reported in randomized clinical trials (RCTs) of bevacizumab in first-line mCRC treatment. The median progression-free survival (PFS) and overall survival (OS) times were 9.9 (95% confidence interval [CI], 9.5-10.3) months and 22.9 (95% CI, 21.9-24.4) months, respectively. The median PFS and OS durations and safety profile of bevacizumab in the BRiTE study were similar to those in RCTs of bevacizumab plus chemotherapy in first-line mCRC patients. The observations from the BRiTE study complement and expand upon RCT data, providing clinical information in a large cohort of bevacizumab-treated patients and subgroups such as the elderly.

Bevacizumab Beyond First Progression Is Associated With Prolonged Overall Survival in Metastatic Colorectal Cancer: Results From a Large Observational Cohort Study (BRiTE)

Bevacizumab provides a survival benefit in first- and second-line metastatic colorectal cancer (mCRC). In a large, observational, bevacizumab treatment study (Bevacizumab Regimens: Investigation of Treatment Effects and Safety [BRiTE]) in patients who had mCRC, a longer-than-expected overall survival (OS) of 25.1 months was reported. The association between various pre- and post-treatment factors (including the use of bevacizumab beyond first progression [BBP]) and survival was examined. The 1,445 of 1,953 previously untreated patients with mCRC who were enrolled in BRiTE and who experienced disease progression (PD) were classified into three groups: no post-PD treatment (n = 253), post-PD treatment without bevacizumab (no BBP; n = 531), and BBP (n = 642). Relevant baseline and on-study variables, including BBP, were analyzed with a Cox model with respect to their independent effect on survival beyond first PD. Median OS was 25.1 months (95% CI, 23.4 to 27.5 months), and median progression-free survival was 10.0 months in the overall BRiTE population. Baseline and postbaseline factors were well balanced between the BBP and no-BBP groups. Median OS rates were 12.6, 19.9, and 31.8 months in the no post-PD treatment, no-BBP, and BBP groups, respectively. In multivariate analyses, compared with no BBP, BBP was strongly and independently associated with improved survival (HR, 0.48; P < .001). Hypertension that required medication was the only bevacizumab-related safety event that occurred more frequently in the BBP group (24.6% v 19.2%). These results from a large, prospective, observational study suggest that continued vascular endothelial growth factor inhibition with bevacizumab beyond initial PD could play an important role improving the overall success of therapy for patients who have mCRC.

Preliminary Treatment Patterns and Safety Outcomes for Non—Small-Cell Lung Cancer from ARIES, a Bevacizumab Treatment Observational Cohort Study

BackgroundBevacizumab, a monoclonal antibody against vascular endothelial growth factor, provides benefit in advanced non—smallcell lung cancer (NSCLC), prolonging progression-free and overall survival. Observational cohort studies such as ARIES (“Avastin® Regimens: Investigation of Treatment Effects and Safety”) provide valuable safety and effectiveness data for a broader patient population than controlled trials, such as Eastern Cooperative Oncology Group (ECOG) 4599, which have strict eligibility criteria required for study participation. The ARIES study objective is to further delineate clinical outcomes associated with bevacizumab use in a real-world setting in patients with advanced NSCLC. Patients and MethodsPatients with locally advanced/metastatic nonsquamous NSCLC, whose first therapy includes bevacizumab, may enroll. There are no protocol-specified treatments or assessments. Data are collected at baseline, then quarterly, including targeted safety events, until death, consent withdrawal, loss to follow-up, or study closure. ARIES is conducted at 276 US sites. Planned NSCLC accrual is 2000 patients. ResultsAs of February 14, 2008, 996 evaluable patients with NSCLC have been enrolled. Median follow-up is 6.1 months; 84% of patients have ≥ 1 quarterly update. Key demographics are shown in Table 1. Targeted serious adverse events (SAEs) to date include venous thromboembolic events and other events, 2%; grade 3/4 bleeding and arterial thromboembolic events, 1% each; gastrointestinal perforation, reversible posterior leukoencephalopathy syndrome, pulmonary hemorrhage, hypertension, and wound complications, < 1% each. The most common chemotherapy regimens are carboplatin/paclitaxel, 63%; carboplatin/docetaxel, 11%; non—platin-based, 10%. ConclusionLow rates of targeted SAEs were preliminarily observed despite the inclusion of patients underrepresented in E4599, including those with ECOG performance status ≥ 2, brain metastasis, therapeutic anticoagulation at baseline, and older age. Updated safety data, treatment patterns (with bevacizumab dose and duration), and demographics will be provided at the meeting, based on > 1300 patients.

Randomized Controlled Trial of a Cognitive-Behavioral Intervention for HIV-Positive Persons: An Investigation of Treatment Effects on Psychosocial Adjustment

Questions remain regarding the clinical utility of psychological interventions for HIV-positive persons because randomized controlled trials have utilized stringent inclusion criteria and focused extensively on gay men. The present randomized controlled trial examined the efficacy of a 15-session, individually delivered cognitive-behavioral intervention (n = 467) compared to a wait-list control (n = 469) in a diverse sample of HIV-positive persons who reported HIV transmission risk behavior. Five intervention sessions that dealt with executing effective coping responses were delivered between baseline and the 5 months post-randomization. Additional assessments were completed through 25 months post-randomization. Despite previously documented reductions in HIV transmission risk, no intervention-related changes in psychosocial adjustment were observed across the 25-month investigation period. In addition, there were no intervention effects on psychosocial adjustment among individuals who presented with mild to moderate depressive symptoms. More intensive mental health interventions may be necessary to improve psychosocial adjustment among HIV-positive individuals.