Improvement In Effectiveness Of Treatment Research Articles

ТУБЕРКУЛЕЗ ЛЕГКИХ У БОЛЬНЫХ ВИЧ-ИНФЕКЦИЕЙ НА ПОЗДНИХ СТАДИЯХ И ПСИХИЧЕСКИМИ ЗАБОЛЕВАНИЯМИ

According to the data of a retrospective assessment of the medical histories of 238 patients, the features of the clinical course of pulmonary tuberculosis in patients with late-stage HIV infection and mental pathology in various morbid variants are considered in a comparative aspect. The data on age-sex and social characteristics, clinical, radiological and bacteriologicalfeatures of the course of the disease in the observed patients are presented. It was found that disseminated (39.4%) and generalized (24.5%) forms of the disease prevailed in patients with pulmonary tuberculosis and late-stage HIV infection in combination with mental illnesses. Bacterioexcretion was observed in 60.6% of patients, including 70.2% of patients with multidrug-resistant tuberculosis and 44.7% of patients with cavities. Distinctive clinical and radiological signs of the course of tuberculosis in patients with various comorbid variants of these nosologies are presented, which is essential for the development of patient-oriented management programs and improvement of treatment effectiveness in these severe categories of patients.

Extraction method of nanoparticles concentration distribution from magnetic particle image and its application in thermal damage of magnetic hyperthermia

Magnetic particle imaging (MPI) technology can generate a real-time magnetic nanoparticle (MNP) distribution image for biological tissues, and its use can overcome the limitations imposed in magnetic hyperthermia treatments by the unpredictable MNP distribution after the intratumoral injection of nanofluid. However, the MNP concentration distribution is generally difficult to be extracted from MPI images. This study proposes an approach to extract the corresponding concentration value of each pixel from an MPI image by a least squares method (LSM), which is then translated as MNP concentration distribution by an interpolation function. The resulting MPI-based concentration distribution is used to evaluate the treatment effect and the results are compared with the ones of two baseline cases under the same dose: uniform distribution and MPI-based distribution considering diffusion. Additionally, the treatment effect for all these cases is affected by the blood perfusion rate, which is also investigated deeply in this study. The results demonstrate that the proposed method can be used to effectively reconstruct the concentration distribution from MPI images, and that the weighted LSM considering a quartic polynomial for interpolation provides the best results with respect to other cases considered. Furthermore, the results show that the uniformity of MNP distribution has a positive correlation with both therapeutic temperature distribution and thermal damage degree for the same dose and a critical power dissipation value in the MNPs. The MNPs uniformity inside biological tissue can be improved by the diffusion behavior after the nanofluid injection, which can ultimately reflect as an improvement of treatment effect. In addition, the blood perfusion rate considering local temperature can have a positive effect on the treatment compared to the case which considers a constant value during magnetic hyperthermia.

Research Progress of Cytokines in the Prognosis of Acute Myeloid Leukemia --Review

At present, acute myeloid leukemia (AML) is mainly treated with combination medication, high-dose, and early intensification. The treatment has achieved good results, but the long-term treatment effect is still not satisfactory. Studies have shown that the different levels of cytokine expression in AML patients can help AML risk stratification, search for treatment directions and predict the prognosis. It has been confirmed that the expression of IL-1β, IL-6, TNF-α, and TGF-β1 are increased in AML patients, and they all indicate a poor prognosis. However, IL-8, IFN-γ, and CCL5 have great research value in chemotherapy resistance and improvement of treatment effect. This article reviews the research progress of cytokine biomarkers in the prognosis of AML patients.

Acupoint herbal patching for bronchitis: A systematic review and meta-analysis.

Background:Acupoint herbal patching (AHP) has long been used to treat patients with bronchitis in East Asia. This review assessed the efficacy and safety of AHP as a treatment for bronchitis.Methods:We performed a literature search using the 9 databases and included randomized controlled trials (RCTs) or quasi-RCTs that used AHP for bronchitis. The methodological quality of each RCT was assessed using the Cochrane Handbook version 5.3, the risk of bias tool, and Grading of Recommendations Assessment, Development and Evaluation (GRADE).Results:Seven RCTs were included based on the inclusion criteria. All RCTs were published in China and had a high risk of bias. Three RCTs compared AHP with conventional drug therapy for the treatment of bronchitis. The meta-analysis also showed a significant improvement in treatment effectiveness (relative risk [RR] 1.28, 95% confidence interval [CI] 1.15, 1.42; P < .00001; I2 = 0%). Two RCTs investigated AHP combined with conventional drug therapy versus conventional drug therapy. The meta-analysis showed that AHP was significantly more effective than conventional therapy in terms of treatment effective rate (RR 1.16, 95% CI 1.03, 1.29; P = .01; I2 = 0%). Three RCTs reported adverse events, and none reported severe adverse events.Conclusions:AHP appears to be more effective than conventional drug therapy alone or a placebo. Furthermore, the AHP appears to be a safe treatment option. However, due to the small number of included trials and their poor methodological quality, future studies should include larger sample sizes and well-designed RCTs.Trial registration number:PROSPERO: CRD 42018110380.

P-203: EXCALIBER: a phase 3 study comparing iberdomide, daratumumab, and dexamethasone (IberDd) with daratumumab, bortezomib, and dexamethasone (DVd) in patients with relapsed or refractory multiple myeloma

<h3>Background</h3> Despite recent advances, new therapies are needed to deepen and extend remissions in early-line relapsed/refractory multiple myeloma (RRMM). Iberdomide (IBER) is a novel, potent oral cereblon E3 ligase modulator (CELMoD®) compound with enhanced tumoricidal and immune-stimulatory effects when compared with IMiD® agents. Preclinically, IBER overcomes IMiD resistance and has synergy with dexamethasone (DEX), daratumumab (DARA), and bortezomib (BORT). In a phase 1/2 trial in patients (pts) with RRMM, IberDd showed efficacy with favorable tolerability, and pharmacodynamic data demonstrated increased NK and T cell proliferation (Lonial S, et al. HemaSphere 2021; 5(S2):49). The EXCALIBER trial was initiated to compare efficacy and safety of IberDd with that of DVd, a globally approved regimen, in pts with early-line RRMM. <h3>Methods</h3> In this multicenter, open-label, phase 3 study ≈742 pts will be randomized 1:1 to receive IberDd or DVd. Pts will be stratified within each cohort by number of prior lines of therapy (1 vs 2), age (≤70 years vs >70 years), and ISS staging at study entry (I–II vs III). Key eligibility criteria include age (≥18 years), measurable disease treated with 1–2 prior lines of antimyeloma therapy where a partial response or better to ≥1 prior therapy was achieved, and disease progression during or after the last regimen. Prior treatment with anti-CD38 monoclonal antibodies and/or BORT is permitted under stringent conditions. Treatment in the IberDd arm will consist of 28-day (D) cycles (C) with 1.6 mg IBER on D1–21; 1,800 mg subcutaneous (SC) DARA on D1, 8, 15, and 22 of C1–2, D1 and 15 of C3–6, and D1 of ≥C7; and 40 mg oral DEX (20 mg if ≥75 years) on D1, 8, 15, and 22. Treatment in the DVd arm will consist of 21-D cycles for C1–8 and 28-D cycles for ≥C9; 1,800 mg SC DARA on D1, 8, and 15 for C1–3, D1 for C4–8, and D1 for ≥C9; 1.3 mg/m2 SC BORT on D1, 4, 8, and 11 for C1–8; and 20 mg oral DEX (10 mg if ≥75 years) on D1, 2, 4, 5, 8, 9, 11, and 12 for C1–8. Treatment will continue until confirmed progressive disease, unacceptable toxicity, or consent withdrawal. Primary efficacy endpoint is PFS, calculated as the time from randomization to progressive disease, or death. Assuming a decrease in the PFS risk by 25% (HR=0.75) with IberDd, under exponential distribution assumption of PFS (one-sided α=0.025) and adjusted for the 2 interim analyses, 441 PFS events will have 85% power to detect an improvement in treatment effect. Secondary efficacy endpoints include OS, duration of response, time to progression, overall response rate, measurable residual disease, and quality of life. Safety evaluations include treatment-emergent adverse events, laboratory parameters, and vital signs. Two interim analyses are planned for PFS, when ≈134 (30%) and ≈334 (75%) events have been accumulated, to examine futility and superiority, respectively. Enrollment is expected to begin in Q3, 2021. NCT number is pending.

PROSPECTIVE ANALYSIS OF IMPACT OF PHARMCOTHERAPY ADHERENCE ON TREATMENT EFFECTIVENESS IN POST OPERATIVE HEART PATIENTS

Myocardial infarction is the irreversible damage of myocardial tissue caused by prolonged ischemia and hypoxia. This most commonly occurs when a coronary artery becomese blocked following the rupture of an atherosclerotic plaque, which then leads to the formation of a blood clot (coronary thrombosis). This event can also trigger coronary vasospasm. Ischemia induces profound metabolic and ionic perturbations in the affected myocardium and causes rapid depression of systolic function. Prolonged myocardial ischemia activates a "wavefront" of cardiomyocyte death that extends from the subendocardium to the subepicardium. Mitochondrial alterations are prominently involved in apoptosis and necrosis of cardiomyocytes in the infarcted heart.&#x0D; This prospective, pilot, observational study performed confirmed the hypothesis that systematic identifications and interventions administered through continued physician follow-up and patients counselling will improve adherence to therapy and therefore improvement in treatment effectiveness by lowering especially Troponin level ,CPK and quality of life in MI patients.&#x0D; Study was shown that lack of proper knowledge about disease and patients counseling and chronic treatment, most of patients takes disease and its treatment lightly and shows lower adherence attitude. The study analysis shown that female are generally more aware than males for adherence. Study analysis concluded that there was significant reduction in their Troponin level and CPK values in different comparison groups after each level of follow up.&#x0D; Statistical analysis concluded that patients with adherence ˃ 95% showed significant reduction in Troponin level and CPK values and patients with age group ≤50 shows more adherence than older.&#x0D; Most heart patients recorded with hypertension and Coronary Artery Diseases only few ones with diabetic complications. During study patients shows good control over their blood pressure and only few adverse events but no complications occur during study period.

Optimization of rituximab dosing schedule in R-CHOP therapy for diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype, and nearly 70% of patients may be cured by administering R-CHOP therapy. However, R-CHOP is found to be inadequate in approximately one-third of the DLBCL cases, and refractory disease to R-CHOP is usually associated with a major cause of mortality. Therefore, it is essential to improve the efficacy of initial treatment in order to avoid unfavorable outcomes in patients with refractory DLBCL. In general, R-CHOP comprises of CHOP regimen that is repeated every 3 weeks and adding one-dose rituximab in each cycle. Although this combination method of rituximab with CHOP is effective and convenient, it does not contain enough scientific rationale and the schedule of rituximab administration has not been optimized. The pharmacokinetics of rituximab differs substantially among individuals and its serum half-life is approximately more than 500 hours; therefore, the peak concentration increases cumulatively by weekly infusion. A previous study revealed that patients with high blood concentration of rituximab showed higher response rate and longer progression-free survival. These findings suggest that the retention of higher levels of rituximab concentration and combination with chemotherapy during an early treatment period may bring about improvement of treatment effect. The HOVON group and Japan Clinical Oncology Group conducted randomized phase III studies to evaluate the efficacy of the dose-dense rituximab strategy for untreated DLBCL.

PND9 NOVEL METHOD OF ADJUSTMENT FOR HETEROGENEOUS ROUTES OF ADMINISTRATION WITHIN A COST-EFFECTIVENESS ANALYSIS: A CASE STUDY IN MIGRAINE

Placebo can affect subjective outcomes like pain. Cost-effectiveness analyses (CEAs) that compare interventions versus no intervention (rather than “sham intervention/placebo”) should account for the placebo effect. We demonstrate a method to adjust network meta-analysis (NMA) for placebo effects (specifically, by route of treatment administration [ROA]). A Cochrane review of pain treatments estimated a standardized mean placebo effect, which was assumed to reflect the difference between no treatment and mean placebo effect. Bannuru 2015 estimated differences in placebo effect between three ROAs. It was assumed that three levels of placebo in Bannuru 2015 center around the mean placebo effect as estimated by Cochrane and that distribution of these ROAs correspond to the differences between subcutaneous (SC), intramuscular (IM), and intravenous (IV) ROAs. We applied these to an NMA of change in monthly migraine days (MMDs) informing a CEA of monoclonal antibody calcitonin gene-related peptide inhibitors (both IV and SC) or onabotulinumtoxinA (IM) over weeks 1-4 in patients with chronic migraine. We evaluated the impact of placebo adjustment on observed outcomes modeled as the additive effect of placebo and treatment. Compared to no adjustment, estimates for SC treatments with adjustment had decreased treatment effect (increase in MMDs) over weeks 1-4, ranging from 0.59 to 1.51 days depending on the specific treatment. Results over weeks 1-4 for IM treatment showed an improvement in treatment effect of -0.74 days, while IV treatment showed an improved treatment effect of -1.92 days. When added to the treatment effect, inclusion of the adjustment resulted in IV treatment having higher absolute improvements over all other treatments. Results were consistent with an analysis of weeks 9-12. This case study illustrates the importance of addressing varying placebo responses in indirect treatment comparisons informing CEAs.

Long-term efficacy of specific subcutaneous, short-term MPL adjuvant immunotherapy over three treatment and three follow-up years, as measured by quality of life

Apart from allergen avoidance, specific immunotherapy (SIT) is the only causal treatment for pollen allergy diseases. Its efficacy and tolerability have been demonstrated in numerous studies on adults and children. There are fewer studies, however, evidencing a long-term treatment effect and the effect of treatment on patients’ quality of life (QoL). The aim of this prospective, noninterventional postmarketing surveillance (PMS) study was to document QoL with, and long-term effect of, an MPL (monophosphoryl lipid A)-adjuvanted allergoid involving four injections over 3 treatment years and 3 follow-up years. In the period from 2006–2012, 223 pollen-allergic individuals from 12 centers were evaluated annually. The patients completed standardized questionnaires on QoL for each pollen season. Symptoms documented in the QoL questionnaire were temporally aligned with data from regional pollen traps. Patients with allergy to pollen from early bloomers (birch, alder, hazel), as well as patients with grass/rye allergy, showed a continuous improvement in treatment effect over the 3 treatment years and a good carry-over effect in follow-up years 1–3. Short-term MPL adjuvant therapy showed good efficacy at 3 years following treatment completion and is suited to the long-term improvement of patient QoL.

Optimization of Radiation Therapy Fractionation Schedules in the Presence of Tumor Repopulation

We analyze the effect of tumor repopulation on optimal dose delivery in radiation therapy. We are primarily motivated by accelerated tumor repopulation toward the end of radiation treatment, which is believed to play a role in treatment failure for some tumor sites. A dynamic programming framework is developed to determine an optimal fractionation scheme based on a model of cell kill from radiation and tumor growth in between treatment days. We find that faster tumor growth suggests shorter overall treatment duration. In addition, the presence of accelerated repopulation suggests larger dose fractions later in the treatment to compensate for the increased tumor proliferation. We prove that the optimal dose fractions are increasing over time. Numerical simulations indicate a potential for improvement in treatment effectiveness.

Influence Factors of Cu-Fe-La/FSC Catalyst Applications in CWAO Technology

Catalytic Wet Air Oxidation (CWAO) is one of advanced oxidation methods about organic wastewater treatment, and the treatment effect of high concentration organic wastewater is remarkable with this method. In this study, the influence factors of the reaction temperature, the reaction pressure and the influent pH were researched on the treatment of the printing and dyeing wastewater with Cu-Fe-La/FSC catalyst, by the single factor experiments and Catalytic Wet Air Oxidation (CWAO) method. Then the catalysts were evaluated by two aspects of the activity and stability. The results show that: with the increase of the reaction temperatures and the reaction pressures, and with the decrease of the influent pH, the CODCrremoval rate improved and the effluent pH reduced. However, the amount of dissolution catalyst components increased with the improvement of treatment effect and the extension of reaction time. By weighing the activity and stability of the catalysts, the optimized reaction temperature, the reaction pressure and the influent pH are 180 °C, 2.5 MPa and 7.25, respectively. Under the optimized operating conditions, the printing and dyeing wastewater with CODCrof 2000 mg/L reaches the CODCrremoval rate of 78.2%, and the dissolvedC[Cu] andC[Fe] of the catalysts are 12.2 and 10.9 mg/L, respectively. Therefore, the catalyst Cu-Fe-La/FSC presents the high activity and stability.

How prepared are our future doctors for HIV/AIDS?

Three cohorts (n=391) of final-year medical students in Hong Kong were evaluated on their preparedness to provide HIV care. Through a self-administered questionnaire, half (53%) were assessed to be better prepared and had a lower perceived risk of infection at work, though unwillingness to manage HIV patients was reported in a minority (4.6%). For a majority of medical students (72.8%), a specially-designed clinic attachment offered the only opportunity to come face-to-face with HIV patients for the first time. With continued improvement in treatment effectiveness, HIV/AIDS is evolving to become a new chronic disease in most societies. Curriculum development in HIV medicine remains a challenge in this HAART era.

Efficacy of interventions in improving adherence to antiretroviral therapy

The aim of this paper is to perform a critical review of the effectiveness of interventions for the purpose of enhancing adherence to antiretroviral therapy. The overall evaluation indicates that research is in its early stages. Although pilot studies provide support for the feasibility of their protocols, and preliminary results also suggest their capacity to improve adherence, only three major trials have reported significant improvement in adherence. The issues that will have to be addressed by future studies include: (a) the need for a theoretical and empirical understanding of the phenomena; (b) adoption of a format that fits the attributes of the population; (c) the use of multiple strategies involving key providers; (d) a concise and precise schedule governing the frequency and intensity of the intervention; (e) a careful selection of direct outcome; and (f) appropriate time measurement. In sum, greater efforts to design and evaluate interventions are needed to lead to an increase in adherence and improvement in treatment effectiveness.

Sources of variability on the estimate of treatment effect in the PROWESS trial: Implications for the design and conduct of future studies in severe sepsis*

To elucidate sources of variability in the estimate of treatment effects in a successful phase 3 trial in severe sepsis and to assess their implications on the design of future clinical trials. Retrospective evaluation of prospectively defined subgroups from a large phase 3, placebo-controlled clinical trial (PROWESS). The study involved 164 medical centers. Patients were 1,690 patients with severe sepsis. Drotrecogin alfa (activated) (Xigris) 24 microg/kg/hr for 96 hrs, or placebo. All prospectively defined subgroups were examined to identify treatment effects that potentially differed across subgroup strata (assessed by Breslow-Day p < .10). Potential interactions were identified for subgroups defined by a) presence vs. absence of a significant protocol violation (p = .07); b) original vs. amended protocol (p = .08); and c) Acute Physiology and Chronic Health Evaluation (APACHE) II quartile at baseline (p = .09). No treatment benefit was observed in patients having a protocol violation, regardless of type. There appeared to be less treatment effect in patients enrolled under the original vs. amended protocol. The risk ratio exceeded 1.0 for patients in the lowest APACHE II score quartile. A highly significant correlation was observed between the sequence of enrollment at a site, the frequency of protocol violations, and the observed treatment effect. As enrollment increased, frequency of protocol violations decreased (p < .0001) and the treatment effect improved. The correlation between the sequence of enrollment and improvement in treatment effect remained even after removal of patients with protocol violations. Removal of the first block of patients at each site from the analysis reduced the extent of interaction by protocol version and APACHE II score. A learning curve appeared to be present within the PROWESS trial such that the ability to demonstrate efficacy improved with increasing site experience. This potential learning curve may have implications for design of future trials. Investigational sites may need to require a minimum level of protocol-specific experience to appropriately implement a given trial. This experience should be an important consideration in designing trials and analysis plans. Diligence by coordinating centers, site investigators, study coordinators, and sponsors is necessary to ensure that the protocol is executed as designed such that a treatment benefit, if present, will be evident.

Strategies to Decrease Tuberculosis in US Homeless Populations

The rate of tuberculosis (TB) among US homeless persons may be 20 times that of the general adult population. Studies suggest that the majority of urban homeless TB cases are attributable to ongoing transmission of TB. Optimal TB-control strategies in both chronically and transiently homeless populations are not known. To examine the effects of TB-control strategies on projected TB cases and deaths in US homeless populations using a computer-based simulation model. The US general population and a theoretical population of 2 million homeless individuals in 1995 were divided into 18 clinical states based on the risk for or presence of TB and human immunodeficiency virus (HIV) infection in a semi-Markov model. Prevalence of transiently and chronically homeless individuals with active TB and deaths from TB as a function of public health measures taken to control and eliminate TB, including improvement of treatment effectiveness, improvement in access to treatment, and vaccination with BCG. A 10% increase in access to treatment among homeless persons with active TB produced larger declines in predicted TB cases and deaths after 10 years (cases and deaths among chronically homeless persons decreased 12.5% and 19.8% and among transiently homeless persons dropped 35.9% and 32.4%, respectively) than improvements in the effectiveness of treatment programs (cases and deaths among chronically homeless persons declined 7.2% and 3.1% and among transiently homeless persons dropped 10.9% and 4.1%, respectively). A 10% increase in access to treatment among homeless persons with latent TB infection led to a 6.7% decline in TB among chronically homeless persons and a 5.7% decline among transiently homeless persons, while a 10% improvement in effectiveness of treatment for latent TB infection was associated with declines of 3.0% and 3.3%, respectively. When treatment for latent TB infection was modeled to be the same in vaccinated and nonvaccinated populations, BCG vaccination led to TB case declines of 15.4% and 21.5% in chronically and transiently homeless populations, respectively. Overcoming barriers faced by homeless individuals in accessing TB treatment programs will be crucial to reducing the burden of TB in this high-risk group. Increased treatment access, improvement in the effectiveness of treatment programs, and BCG vaccination of HIV-negative homeless individuals have the best chance to markedly decrease TB morbidity and mortality.