Overall Efficacy Of Treatment Research Articles

Immunotherapy in liver cancer: overcoming the tolerogenic liver microenvironment.

Liver cancer is a major global health concern, ranking among the top causes of cancer-related deaths worldwide. Despite advances in medical research, the prognosis for liver cancer remains poor, largely due to the inherent limitations of current therapies. Traditional treatments like surgery, radiation, and chemotherapy often fail to provide long-term remission and are associated with significant side effects. Immunotherapy has emerged as a promising avenue for cancer treatment, leveraging the body's immune system to target and destroy cancer cells. However, its application in liver cancer has been limited. One of the primary challenges is the liver's unique immune microenvironment, which can inhibit the effectiveness of immunotherapeutic agents. This immune microenvironment creates a barrier, leading to drug resistance and reducing the overall efficacy of treatment. Recent studies have focused on understanding the immunological landscape of liver cancer to develop strategies that can overcome these obstacles. By identifying the specific factors within the liver that contribute to immune suppression and drug resistance, researchers aim to enhance the effectiveness of immunotherapy. Prospective strategies include combining immunotherapy with other treatments, using targeted therapies to modulate the immune microenvironment, and developing new agents that can bypass or counteract the inhibitory mechanisms in the liver. These advancements hold promise for improving outcomes in liver cancer treatment.

Long-Term Vonoprazan and Acotiamide-Refractory Patients With Functional Dyspepsia Partly Exhibit Pancreatic Enzyme Abnormalities.

Although a new potassium-competitive acid blocker (P-CAB)vonoprazan has been developed in Japan, no data are available regarding long-term vonoprazan or vonoprazan and acotiamide combination treatment in patients with functional dyspepsia (FD). A total of 73 consecutive patients with FD diagnosed according to the Rome III classification were enrolled. Forty-two patients with FD were treated with vonoprazan monotherapy and thirty-one patients with FD were treated with vonoprazan and acotiamide combination therapy for 24 weeks. The levels of five pancreatic enzymes were measured, and the overall treatment efficacy (OTE) was defined as the ratio of FD patients with improved or unchanged in all items of GSRS and FD symptom scores after the treatment. Treatment with vonoprazan monotherapy and vonoprazan and acotiamide combination therapy significantly improved FD symptoms. There were no significant differences in OTE between patients treated with vonoprazan monotherapy (42.9%) and those treated with vonoprazan and acotiamide combination therapy (52%). There were no significant differences in duodenal eosinophilic infiltration between the improved and unimproved groups treated with vonoprazan alone and vonoprazan and acotiamide combination therapy, respectively. In contrast, there was a significant difference (P = 0.004) in the ratio of pancreatic enzyme abnormalities between the improved and unimproved patients treated with vonoprazan monotherapy and those treated with vonoprazan and acotiamide combination therapy. Long-term vonoprazan alone or vonoprazan and acotiamide combination therapy significantly improved each FD symptom. The OTE in patients treated with vonoprazan alone or vonoprazan and acotiamide combination therapy was only 50%. Long-term vonoprazan and acotiamide combination therapy may differentiate patients with pancreatic enzyme abnormalities from those with FD.

Acute BRCAness Induction and AR Signaling Blockage through CDK12/7/9 Degradation Enhances PARP Inhibitor Sensitivity in Prostate Cancer.

This study introduces BSJ-5-63, a triple degrader designed to target CDK12, CDK7, and CDK9, making a significant advancement in CRPC therapy. The distinctive mechanism of BSJ-5-63 involves downregulating HRR genes and inhibiting AR signaling, thereby inducing a BRCAness state. This enhances sensitivity to PARP inhibition, effectively addressing ARSI resistance and improving the overall efficacy of treatment. The development of BSJ-5-63 represents a promising therapeutic approach, with the potential to benefit a broad spectrum of CRPC patients.

Effects of comprehensive nursing intervention in patients with diabetic foot ulcers: A meta‐analysis

AbstractThis study systematically evaluates the impact of comprehensive nursing interventions on the treatment efficacy for patients with diabetic foot ulcers. Utilizing computerized searches of databases including PubMed, Embase, Google Scholar, Cochrane Library, China National Knowledge Infrastructure and Wanfang databases, we identified randomized controlled trials pertaining to this topic, with the search timeframe extending to May 2023. Two independent researchers screened the literature, extracted data and conducted a quality assessment. Data analysis was performed using Stata 17.0 software. A total of 17 randomized controlled trials, encompassing 1306 patients with diabetic foot ulcers, were included in this analysis. The analysis revealed that the application of comprehensive nursing interventions significantly reduced the wound healing time in patients with diabetic foot ulcers (standard mean difference [SMD] = −2.44, 95% confidence interval [CI]: −3.05 to −1.83, P < 0.001). Additionally, there was a notable enhancement in nursing satisfaction (odds ratio [OR] = 7.54, 95% CI: 3.99–14.26, P < 0.001) and the overall treatment efficacy rate (OR = 6.97, 95% CI: 3.32–14.60, P < 0.001). This study demonstrates that comprehensive nursing interventions significantly shorten the wound healing time in patients with diabetic foot ulcers, enhance clinical nursing satisfaction and improve the overall efficacy of treatment. These findings underscore the value of such interventions for widespread clinical application.

Efficacy and Safety of Prophylaxis with a Plasma-Derived Von Willebrand Factor/ Factor VIII Concentrate in Previously Treated Patients with Von Willebrand Disease

Introduction: Long-term prophylaxis with a von Willebrand factor (VWF) concentrate is recommended in von Willebrand disease (VWD) patients with a history of severe and frequent bleeds, regardless of age or VWD type. Data on the efficacy and safety of prophylaxis with a human plasma-derived VWF/factor VIII concentrate (pdVWF/FVIII; wilate®) that contains the two factors in a physiological 1:1 activity ratio have been collected previously from 19 VWD patients in four prospective, multicenter phase 2 and 3 trials. In these patients, bleeding rates were significantly reduced compared with previous treatment. Aims: To investigate the efficacy and safety of regular prophylaxis with a pdVWF/FVIII concentratein previously treated patients with VWD. Methods: WIL-31 (NCT04052698) was a prospective, non-controlled, international, multicenter phase 3 trial that enrolled patients of any gender with VWD type 1 (VWF:RCo <30 IU/dL), type 2 (except 2N) or type 3, who were at least 6 years old. Prior to entering the WIL-31 study, all patients had received on-demand treatment with pdVWF/FVIII during a 6-month, prospective, observational, run-in study (WIL-29); patients who experienced at least 6 bleeding episodes (BEs), excluding menstrual bleeds, with at least 2 of these BEs treated with a VWF-containing product, were eligible to enter WIL-31. Patients in WIL-31 received regular pdVWF/FVIIIprophylaxis, 2-3 times per week at a dose of 20-40 IU/kg, for 12 months. The primary endpoint of the study was to demonstrate that prophylaxis with pdVWF/FVIII lowered the mean total annualized bleeding rate (ABR) compared with that during 6 months of on-demand treatment by more than 50%. Secondary outcomes included spontaneous ABR and treatment-emergent adverse events. Results: Thirty-three patients were included in the modified full analysis set, with a median (range) age of 18 years (7-61). Fourteen (42.4%) patients were female, 9 (27.3%) patients were <12 years old. Six (18.2%) patients had severe Type 1 VWD, 7 (21.2%) had type 2, and 20 (60.6%) patients had type 3 VWD. Mean (median, range) total ABR in the on-demand run-in period and during pdVWF/FVIII prophylaxis was 33.4 (24.5, 11-115) and 5.2 (1.9, 0-35.8), respectively (Figure 1), meeting the primary endpoint of a ≥50% reduction in mean ABR. Mean (median, range) spontaneous ABR in the on-demand run-in period and during pdVWF/FVIII prophylaxis was 24.4 (18.7, 5-93) and 3.2 (1.0, 0-24.6), respectively. Of the 33 patients, 10 (30.3%) and 15 (45.5%) patients had zero total or spontaneous BEs during the study period, respectively. A total of 173 BEs occurred, the majority of which (146 BEs; 84.4%) were classified as minor. Of the 173 BEs, 121 (69.9%) were treated with pdVWF/FVIII. The overall efficacy of treatment was assessed as "excellent” or "good” for 120 (99.2%) BEs and "moderate” for 1 (0.8%) BE. Five serious adverse events were reported, none of which were assessed as related to the study treatment. Two patients had adverse events assessed as probably or possibly related to the study treatment by the investigator, and both patients discontinued from the study. One patient developed mild chest tightness (3 events), the other had hypersensitivity reactions of moderate severity (2 events). No thrombotic events occurred. Conclusions: Prophylaxis with a pdVWF/FVIII containing VWF and FVIII in a 1:1 activity ratio was effective in pediatric and adult patients with VWD of all types. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Efficacy of Rikkunshito for Functional Heartburn: A Prospective Pilot Study.

Although rikkunshito was reported to be effective for treatment-resistant nonerosive gastroesophageal reflux disease (NERD), it is unclear which Rome IV subgroups of NERD patients benefit fromrikkunshito. This study investigated the efficacy of rikkunshito in patients with functional heartburn. Ten patients with functional heartburn who experienced symptoms of dyspepsia were enrolled and received rikkunshito for 8 weeks. The Frequency Scale for Symptoms of GERD (FSSG), the Japanese translation of the Quality of Life in Reflux and Dyspepsia (QOLRAD-J) questionnaire, and the Hospital Anxiety and Depression Scale (HADS) before, and 4 and 8 weeks after, administration were evaluated. Overall treatment efficacy (OTE) was evaluated at 8 weeks after administration. One patient voluntarily withdrew from treatment at 4 weeks. Total FSSG score was significantly (P = 0.039) lower 8 weeks after treatment or at discontinuation (13.2 ± 8.0) than before treatment (18.3 ± 10.7). Although QOLRAD-J score was higher 8 weeks after treatment or at discontinuation than before treatment, the difference was not significant different. HADS score was not significantly lower 8 weeks after treatment or at discontinuation, as compared with before treatment. However, total FSSG and HADS anxiety scores were positively correlated (correlation coefficient: 0.684, P = 0.027). The findings from this first study of the efficacy of rikkunshito for functional heartburn suggest that it might be effective in such patients.

Comparative efficacy and acceptability of psychotherapies for panic disorder with or without agoraphobia: systematic review and network meta-analysis of randomised controlled trials.

Psychotherapies are the treatment of choice for panic disorder, but which should be considered as first-line treatment is yet to be substantiated by evidence. To examine the most effective and accepted psychotherapy for the acute phase of panic disorder with or without agoraphobia via a network meta-analysis. We conducted a systematic review and network meta-analysis of randomised controlled trials (RCTs) to examine the most effective and accepted psychotherapy for the acute phase of panic disorder. We searched MEDLINE, Embase, PsycInfo and CENTRAL, from inception to 1 Jan 2021 for RCTs. Cochrane and PRISMA guidelines were used. Pairwise and network meta-analyses were conducted using a random-effects model. Confidence in the evidence was assessed using Confidence in Network Meta-Analysis (CINeMA). The protocol was published in a peer-reviewed journal and in PROSPERO (CRD42020206258). We included 136 RCTs in the systematic review. Taking into consideration efficacy (7352 participants), acceptability (6862 participants) and the CINeMA confidence in evidence appraisal, the best interventions in comparison with treatment as usual (TAU) were cognitive-behavioural therapy (CBT) (for efficacy: standardised mean differences s.m.d. = -0.67, 95% CI -0.95 to -0.39; CINeMA: moderate; for acceptability: relative risk RR = 1.21, 95% CI -0.94 to 1.56; CINeMA: moderate) and short-term psychodynamic therapy (for efficacy: s.m.d. = -0.61, 95% CI -1.15 to -0.07; CINeMA: low; for acceptability: RR = 0.92, 95% CI 0.54-1.54; CINeMA: moderate). After removing RCTs at high risk of bias only CBT remained more efficacious than TAU. CBT and short-term psychodynamic therapy are reasonable first-line choices. Studies with high risk of bias tend to inflate the overall efficacy of treatments. Results from this systematic review and network meta-analysis should inform clinicians and guidelines.

47982 Reversing the resistance to chemotherapy in White and Black patients with triple negative breast cancer (TNBC).

ABSTRACT IMPACT: Reversing tumor microenvironment (TME) immunosuppression will help to increase the overall efficacy of treatment of chemo-resistant triple negative breast cancer (TNBC) and mitigate racial disparities in treatment response. OBJECTIVES/GOALS: We have developed an ex-vivo whole tissue culture model to test the feasibility of reversing local immunosuppression in TME by chemokine modulatory (CKM) regimen. Our current objective is to analyze the molecular changes in CKM-treated chemoresistant TNBC from White and Black women and identify factors determining response to CKM. METHODS/STUDY POPULATION: Freshly resected residual TNBC from 20 White and 20 Black women ≥18 yrs old treated with neoadjuvant chemotherapy (NAC) will be procured. Tumor explants will be prepared &amp; cultured in the absence and presence of CKM (Interferon-ð 〉1/4, TLR3 agonist rintatolimod and COX-2 inhibitor celecoxib). Chemokines implicated in cytotoxic T-lymphocyte (CTL)- &amp; MDSC/ Treg attraction will be analyzed using Taqman &amp; ELISA. We will have 80% power to detect a 0.7 standard deviation difference in chemokines between untreated &amp; treated samples within and between cohorts using ANCOVA. Bulk RNA sequencing will be performed on both untreated &amp; treated samples from CKM responding (highest aggregate increase in CTL- and highest decrease in Treg/MDSC-favoring chemokines in the top quartile) and non-responding (bottom quartile) tissues. RESULTS/ANTICIPATED RESULTS: Our preliminary data show that Black patients (pts) with breast cancer (BC) have an immunosuppressive TME associated with poor outcomes. This is similar to other existing literature showing that Black pts with BC have less favorable and more unfavorable chemokines in the TME. We anticipate the chemokine changes with CKM treatment will be larger in the Black cohort given their ability to elicit a robust inflammatory response. Therefore, we expect that CKM treatment will result in favorable TME in both groups and improve outcomes in TNBC, which has the worst prognosis of all subtypes, eliminating a key area of disparity in BC. The proposed transcriptome analysis will help identify key gene networks involved in response to CKM treatment and guide modulating the targets for non-responsiveness to improve efficacy of CKM. DISCUSSION/SIGNIFICANCE OF FINDINGS: Pts with residual disease (RD) after NAC have a 3-yr overall survival 68% vs. 94% for pts with complete response. Blacks have a higher incidence of TNBC with more likelihood of RD &amp; mortality. We anticipate that the existing TME differences can be abrogated by our current CKM regimen or via developing an alternative CKM regimen optimized for Black pts.

A Randomized, Double-Blind, Placebo Controlled, Parallel-Group, Comparative Clinical Study to Evaluate the Efficacy and Safety of OLNP-06 versus Placebo in Subjects with Functional Dyspepsia

OLNP-06 is ginger extract product standardized to higher amount of total gingerols formulated with proprietary Aqueosome technology. The safety and efficacy of OLNP-06 were evaluated in a randomized, double blind, placebo controlled, parallel group comparative clinical study in subjects with functional dyspepsia (FD). Significant improvements in clinical endpoints were observed during the trial along with excellent safety profile. Fifty subjects aged between 18 and 55 years suffering from FD as per ROME III criteria were enrolled into the study. They were randomized into two treatment groups, one group received OLNP-06, 200 mg twice daily and other group received placebo 200 mg twice daily. The primary efficacy end point was global assessment of overall treatment efficacy (OTE). Secondary efficacy endpoints were elimination rate of three major symptoms (postprandial fullness, upper abdominal bloating and early satiation) and elimination rate for each individual symptom scores. Biochemical and hematological parameters including urine analysis were performed to evaluate the safety of OLNP-06. Out of 50 subjects, 48subjects completed the study. Total 79% of the subjects receiving OLNP-06 and 21% of the subjects receiving placebo (p < .05) were classified as responders according to the assessment of OTE. Elimination rate (score 0) of postprandial fullness, upper abdominal bloating and early satiation was 64% in subjects receiving ONLP-06 compared with 13% in the placebo group (p < .05). OLNP-06 was found to be safe and well tolerated as there was no incidence of treatment-related AE’s. Supplementation of OLNP-06 for 4 weeks significantly reduced dyspeptic symptoms in subjects suffering from FD. Trial Registration: Clinical Trial Registry-India, CTRI/2019/09/021019, Registered on 2 Sep 2019.

Randomized trial of telehealth delivery of cognitive-behavioral treatment for insomnia vs. in-person treatment in veterans with PTSD

• Insomnia is common in veterans with PTSD. • Cognitive behavioral treatment for insomnia can effectively treat insomnia in this population. • Cognitive behavioral treatment can be delivered via telemedicine without losing clinical effectiveness. Insomnia is prevalent in veterans with PTSD but often goes untreated. Cognitive behavioral therapy for insomnia (CBT-I) is an efficacious treatment but many patients do not have access to this intervention. Clinical video telehealth provides a means of increasing access to care but there is a need to understand the effectiveness of care delivered using this modality. Randomized non-inferiority trial comparing group CBT-I delivered between VA clinics over video telehealth to in-person treatment. 116 Veterans with PTSD received CBT-I over six weeks in a group format at a VA healthcare facility. The Insomnia Severity Index (ISI) was the primary outcome measure. Secondary outcomes included measures of sleep, PTSD severity and quality of life. The non-inferiority margin was defined as a difference in ISI change scores between groups ≥1.67 points. The mean(SD) improvement in the ISI was 6.48 (0.90) points for in-person treatment and 4.45 (0.98) points for telehealth treatment in intent-to-treat analyses. In both intent-to-treat and per-protocol analyses, the difference between these change scores of 2.03 had a confidence interval that included the non-inferiority margin of 1.67, supporting the hypothesis of non-inferiority. On secondary outcomes, there were significant improvements after treatment only in sleep quality and no between-group differences. The eligibility criteria were intentionally broad, so there were several potential confounding factors. Drop-out was also considerable, with only 54.3% of subjects in the in-person group and 46.9% in the telehealth group completing treatment. Delivery of group CBT-I by clinical video telehealth to veterans with PTSD is non-inferior to in-person treatment, although overall efficacy of treatment was modest. Telehealth technology can increase access to care without sacrificing clinical gains.

Effect of Vestibular Exercises Associated With Repositioning Maneuvers in Patients With Benign Paroxysmal Positional Vertigo: A Randomized Controlled Clinical Trial.

It was to evaluate the additional effects of vestibular rehabilitation exercises as a therapeutic resource in the treatment of BPPV, to improve symptoms and reduce recurrence. This was an experimental, prospective, randomized, controlled study. Instituto Brasiliense de Otorrinolaringologia (IBORL) from August 2016 to September 2017. Thirty-two individuals, both men and women, over 18 years of age with BPPV. They were randomly assigned to two groups: the control group (n = 15) performing only the maneuver technique as treatment and the experimental group (n = 17) performing the maneuvers and vestibular rehabilitation exercises. Patients underwent treatment and responded to the dizziness handicap inventory (DHI) and visual analog scale (VAS) questionnaires for comparison between groups. Participants were followed up for 6 months to observe recurrence of symptoms. To investigate the additional effects of vestibular exercises in the treatment of BPPV. The experimental group had a lower level of dizziness in the posttreatment period (p < 0.05) and a lower incidence of recurrences (p = 0.038) than the control group. Vestibular exercises performed after repositioning treatments for BPPV increased the overall efficacy of treatment by improving symptoms with a lower rate of recurrence.

Abstract 296: Trastuzumab sensitizes HER2+ breast cancer to increase efficacy of chemotherapy in vitro and in vivo

Abstract Purpose: Optimization of drug synergy has potential to improve efficacy of combination treatments. Breast cancer that overexpresses the human epidermal growth factor receptor (HER2) has a higher chance of metastasis and recurrence compared to HER2- patients. Standard-of-care treatment typically includes chemotherapy (i.e., paclitaxel, doxorubicin) followed by or in combination with targeted antibody treatments (i.e., trastuzumab, pertuzumab). The purpose of this study is to investigate, the timing, order, and dosage of standard-of-care combination therapies and how they affect the overall efficacy of treatment in HER2+ breast cancer in vitro and in vivo. Experimental Procedure: BT474, HER2+ breast cancer cells were longitudinally evaluated with time resolved microscopy to measure changes in cell confluence (Incucyte). Cells were treated with combinations of trastuzumab (10-50 ug/ml) and paclitaxel (10-150 nmol/L) with alternating sequencing and timing (24, 48 hrs) of the therapies (N=8 replicates per combination). Cellular confluence was measured over 4 days and normalized percent changes were calculated. BT474 tumor-bearing mice (N=42) were treated singularly or in combination with alternating sequencing of trastuzumab (10 mg/kg) and doxorubicin (1.5 mg/kg). Tumors were evaluated for changes in tumor size and survival. An unpaired t-test was used for statistical comparisons for in vitro and in vivo studies. Assessment of cellular and tumor microenvironment influences on drug synergy are ongoing. Results: Experimental outcomes indicate that alternating order and dose play a crucial role in the anticancer efficacy and synergistic drug effects. Trastuzumab (25 ug/ml) dosing prior to paclitaxel (50 nmol) significantly decreased cell confluence compared to the same total therapeutic dose where paclitaxel was introduced first in vitro (p &amp;lt; 0.001). Similarly, trastuzumab dosing in vivo prior to a one dose of chemotherapy achieves the same tumor response as a two doses of chemotherapy administered simultaneously with trastuzumab (p &amp;lt; 0.001). Discussion and Conclusions: Sequencing of targeted and chemotherapies altered treatment response both in vivo and in vitro, resulting in differences in overall cancer cell death. In vitro longitudinal imaging can provide numerous combinations of treatments can be tested to ultimately find optimal treatments to test in vivo. Recent evidence also shows that targeted anti-HER2 therapy can alter vascularity, oxygenation, and immune cell infiltration in HER2+ breast cancer tumors; therefore, further investigations in the temporal effects of the tumor microenvironment are warranted. Improved temporal windows of anticancer effects for standard-of-care combination therapies could improve breast cancer treatment regimens and potentially minimize toxic side effects. Funding was provided by CPRIT RR160005 and ACS-RSG-18-006-01-CCE. Citation Format: Alay Shah, Angela Jarrett, Anum Syed, Thomas Yankeelov, Anna Sorace. Trastuzumab sensitizes HER2+ breast cancer to increase efficacy of chemotherapy in vitro and in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 296.

Re-Irradiation with Stereotactic Radiosurgery/Radiotherapy for Recurrent High-Grade Gliomas: Improved Survival in the Modern Era

Objective: The aim of this study was to evaluate the efficacy of stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) as salvage therapy for recurrent high-grade glioma and to look at the overall efficacy of treatment with linear accelerator (LINAC)-based radiosurgery and fractionated radiotherapy. Methods: From 2010 to 2017, a total of 25 patients aged 23–74 years were re-irradiated with LINAC-based SRS and fSRT. Patients were treated to a median dose of 25 Gy in 5 fractions. Results: The median overall survival (OS) after (initial) diagnosis was 39 months with an actuarial 1-, 3-, and 5-year OS rate of 88, 56, and 30%, respectively. After treatment with SRS or fSRT, the median OS was 9 months with an actuarial 1-year OS rate of 29%. Local control, assessed for 28 tumors, after 6 months was 57%, while local control after 1 year was 39%. Three patients experienced local failure. There was no evidence of toxicity noted after SRS or fSRT throughout the follow-up period. Conclusion: SRS and fSRT remain a safe, reasonable, effective treatment option for re-irradiation following recurrent glioblastoma. Additionally, treatment volume may predict local control in the salvage setting.

Impact of new DAA therapy on real clinical practice: a multicenter region-wide cohort study

BackgroundManagement of chronic hepatitis C (CHC) has significantly accelerated in the last few years. Currently, second generation direct acting antivirals (DAAs) promise clearance of infection in most of patients. Here we present the results of the first analysis carried out on data of Lazio clinical network for DAAs.MethodsThe study was designed as a multicenter cohort: a) to assess the evolution of treatment during the first 24 months of the activity of the Clinical Network; b) to report overall efficacy of treatments; c) to analyze potential factors associated with lack of virological response at 12 weeks after therapy (SVR12); d) to evaluate the variation of ALT at baseline and 12 weeks after therapy in those who achieved SVR12 in comparison to those who did not. Analyses of efficacy were carried out with multilevel mixed effect logistic regression model. ALT temporal variation was assessed by mixed effect model mixed models with random intercept at patient’s level and random slope at the level of the time; i.e. either before or after therapy.ResultsBetween 30 December 2014 and 31 December 2016 5279 patients started a DAA treatment; of those, 5127 (in 14 clinical centers) had completed the 12-week follow-up. Overall proportion of SVR12 was 93.41% (N = 4780) with no heterogeneity between the 14 clinical centers. Interruption as the consequence of severe side effect was very low (only 23 patients). Unadjusted analysis indicates that proportion of SVR12 significantly changes according to patient’s baseline characteristics, however after adjusting for potential confounders only adherence to current guidelines, stage of liver diseases, gender, transplant and HIV status were independently associated with the response to therapy. Analysis of ALT temporal variation showed that ALT level normalized in most, but not, all patients who achieved SVR12.ConclusionOur study confirmed the extraordinary efficacy of DAAs outside clinical trials. The advantage of DAAs was particularly significant for those patients who were previously considered as difficult-to-treat and did not have treatment options before DAAs era. Intervention based on network of select centers and prioritization of patients according to diseases severity was successful. Further studies are needed to establish whether clearance of HCV after DAAs therapy can arrest or even revert liver fibrosis in non-cirrhotic patients and/or improve life quality and expectancy in those who achieve SVR12 with cirrhosis.

Rikkunshito simultaneously improves dyspepsia correlated with anxiety in patients with functional dyspepsia: A randomized clinical trial (the DREAM study).

Functional dyspepsia (FD), a heterogeneous disorder, involves multiple pathogenetic mechanisms. Developing treatments for FD has been challenging. We performed a randomized, placebo-controlled, double-blind clinical trial to determine the efficacy of rikkunshito, a Japanese herbal medicine, in FD patients. FD patients (n=192) who met the Rome III criteria without Helicobacter pylori infection, predominant heartburn, and depression were enrolled at 56 hospitals in Japan. After 2weeks of single-blind placebo treatment, 128 patients with continuous symptoms were randomly assigned to 8weeks of rikkunshito (n=64) or placebo (n=61). The primary efficacy endpoint was global assessment of overall treatment efficacy (OTE). The secondary efficacy endpoints were improvements in upper gastrointestinal symptoms evaluated by the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM), the Global Overall Symptom scale (GOS), and the modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (m-FSSG), and psychological symptoms evaluated by the Hospital Anxiety and Depression Scale (HADS). Rikkunshito increased OTE compared to placebo at 8weeks (P=.019). Rikkunshito improved upper gastrointestinal symptoms (PAGI-SYM, GOS, and m-FSSG) at 8weeks, especially postprandial fullness/early satiety (P=.015 and P=.001) and bloating (P=.007 and P=.002) of the PAGI-SYM subscales at 4weeks and 8weeks. Improvement of HADS at 8weeks (P=.027) correlated with those of PAGI-SYM (r=.302, P=.001), GOS (r=.186, P=.044), and m-FSSG (r=.462, P<.001), postprandial fullness/early satiety (r=.226, P=.014), dyspepsia (r=.215, P=.019), and PDS (r=.221, P=.016). Rikkunshito may be beneficial for FD patients to simultaneously treat gastrointestinal and psychological symptoms.

Efficacy of 8 Gy Single Fraction Palliative Radiation Therapy in Painful Bone Metastases: A Single Institution Experience.

IntroductionBone metastasis (BM) is a major complication of many solid tumors like breast, prostate, lung and renal cancers. BM leads to serious sequelae of pain, fractures, spinal cord compression and hypercalcemia. Radiotherapy has an established role in relieving pain caused by BM. Worldwide different radiotherapy schedules are being used for BM. The aim of this study is to determine the efficacy of single fraction palliative radiotherapy for painful bone metastases.MethodsBetween April 2014 and April 2017, single fraction radiotherapy was used to treat 73 patients in our institution. They had pathologically proven breast, prostate, lung or renal cancer with radiological evidence of bone metastases. There were 39 males (53%) and 34 females (47%). The median age was 58 years (range 33–87 years). 39% patients (n = 28) had breast cancer, 35% had prostate cancer (n = 26), 23% had lung cancer (n = 17), and 3% had renal cancer (n = 2). On presentation, all the patients had a pain score of more than five on Brief Pain Inventory (BPI).ResultsResponse assessment to pain after three months from single fraction radiotherapy was found to be complete response (CR) in 23% patients (n = 17), partial response (PR) in 38% patients (n = 28), stable disease (SD) in 26% patients (n = 19) and progressive disease (PD) in 12% patients (n = 9). The overall efficacy of treatment was 62%, with CR 23% and PR 38%. Pre-treatment mean pain score was 8.15 compared to 4.68 post-treatment (p < 0.001).ConclusionsSingle fraction palliative radiotherapy of 8 Gy showed significant efficacy in painful bone metastases in our setting and merits further investigation in our population.

Применение элтромбопага у детей и молодых взрослых с приобретенной апластической анемией

The standard immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine in treatment of acquired aplastic anemia (AA) results to hematologic response in two thirds of patients, and approximately one third of the responding patients is relapsed. One third of patients have disease that is refractory to IST, with persistent severe cytopenia and a profound deficit in hematopoietic stem cells. In patients with refractory or recurrent disease, the use of alternative immunosuppressive drugs is possible, but the efficacy of the latter does not high. Recent studies have demonstrated the efficacy of eltrombopag in refractory aplastic anemia and in the first line of therapy in combination with IST. It has been shown eltrombopag not only restored the level of platelets, but was associated with multilineage clinical responses. In this study we analyzed the use of eltrombopag in 15 children and young adults with AA: 11 patients in refractory disease, one patient in relapse and three patients in the first line of therapy in combination with IST. The overall efficacy of treatment was 40% (6/15). The main adverse event was moderate and reversible increase of hepatic transaminases (3/15, 20%). A complete hematologic response was achieved in 3/15 patients (20%), and in 2 patients the response is continued after drug withdrawal. Eltrombopag is effective in patients with refractory AA, and it may be an alternative option in patients who do not have suitable donors for hematopoietic stem cells transplantation (HSCT). The first-line treatment with eltrombopag in combination with standard IST in our small group of patients also showed efficacy (60%) and safety.

Effect of administration of vitamin E, selenium and antimicrobial therapy on incidence of mastitis, productive and reproductive performances in dairy cows

Administration of vitamin, mineral and antimicrobials at the end of lactation plays potential role in preventing mastitis in dairy cows. A total of 255 cows dividing into five groups (A=50, B=50, C=50, D=50 and E=55) at their late gestation period were selected to explore the effect of vitamin E, selenium and antimicrobial therapy on mastitis incidence, their productive and reproductive performances. Each cow of group A received α-tocopherol+sodium selenite orally daily for last 30days before calving, while each cow of group B, C and D was treated with α-tocopherol+sodium selenite intramuscular injection, procaine penicillin+neomycin sulfate, and dicloxacillin sodium intramammary infusions at Day 30–20 before calving, respectively. Group E cows served as untreated control. California mastitis test (CMT) revealed that 70.0%, 76.0%, 84.0% and 100.0% cows in group A, B, C and D, respectively were free from new intramammary infections (IMIs) during early lactation period. The bacteriological results showed highest IMIs rates (76.3%) in group E and lowest IMIs (2.0%) in group D (P<0.05). Staphylococcus aureus and Escherichia coli were the most predominant udder pathogens in all groups except group D (only CNS). The mean IMIs incidence (20.5%) was significantly lower in treated cows (P<0.001). The treated cows had higher cure rates (81.9%) than control cows (23.1%) and overall efficacy of treatments on cure rates was 71.8% for all mastitis pathogens (P<0.0001). The productive and reproductive performances of the treated cows at postpartum and early lactation period remained always higher than their non-treated counterparts (P<0.001). A number of cow and herd related factors were identified to be significantly associated with mastitis (P<0.001). The results concluded that antimicrobial therapy had more beneficial effect in preventing mastitis over vitamin–mineral administration and intramammary infusion with dicloxacillin sodium remained as the best effective preventive strategies for mastitis in dairy cows.

Benzimidazole resistance in Nematodirus spathiger and N. filicollis in New Zealand

AIM: To determine the prevalence of benzimidazole resistance in Nematodirus spathiger and N. filicollis from a sample of New Zealand farms.METHODS: The efficacy of albendazole (ABZ) against Nematodirus spp. was assessed by faecal nematode egg count reduction (FECR) tests undertaken in lambs aged 3–8 months old on 27 sheep farms throughout New Zealand. On each farm, groups of 10–16 lambs were either treated with ABZ (4.75 mg/kg) or remained as untreated controls. Faecal samples were collected from all animals at the time of treatment and 7–10 days later. Faecal nematode egg counts (FEC) were performed using a modified McMaster technique. Larvae were cultured from pooled faecal samples, collected 7–10 days after treatment from each group, by incubation at 20°C for 6 weeks, 4°C for 26 weeks then 13°C for 2 weeks. The resulting third stage larvae were identified to species using a multiplex PCR assay, that identified species-specific sequences in the second internal transcribed spacer region of ribosomal DNA. The efficacy of ABZ for N. spathiger and N. filicollis was calculated from the proportion of the two species in culture and the group mean FEC before and after treatment. Only farms with a mean of 10 epg for each species in untreated samples were included for analysis. Resistance was defined as an efficacy <95%.RESULTS: On farms that met the threshold of 10 epg in faecal samples, benzimidazole resistance was found on 20/21 (95%) farms for N. spathiger compared with 4/10 (40%) farms for N. filicollis (p<0.05). In samples collected following treatment, a mean of 83 (min 46, max 100)% of Nematodirus spp. larvae recovered from the untreated groups were N. spathiger, compared with 94 (min 45, max 100)% in the ABZ treated groups (p=0.03). This change in percentage was not influenced by the overall efficacy of treatment based on the FECR test (p=0.324).CONCLUSION: The results confirm the high level of resistance in N. spathiger in New Zealand and that benzimidazole resistance was more common in N. spathiger than N. filicollis. While resistance to benzimidazole anthelmintics has been reported previously in New Zealand, this is the first report of N. filicollis being resistant to benzimidazole anthelmintics.

Emerging treatments in neurogastroenterology: Acotiamade, a novel treatment option for functional dyspepsia.

Acotiamide hydrochloride (Z-338) is a new therapeutic agent for functional dyspepsia (FD). In 2013, the use of acotiamide was approved by the Japanese health insurance system. The aim of this review is to summarize the present staus of basic and clinical approach to acotiamide for the treatment of functional dyspepsia. The agent inhibits acetylcholinesterase in vitro and enhances muscle motility ex vivo. In phase-II studies, 100 mg three times daily (t.i.d.) was determined to be the optimal dose for the treatment of FD. In phase-III studies, overall treatment efficacy (OTE) was significantly better in the acotiamide group (52.2%) than in the placebo group (34.8%). However, the mechanism of its efficacy needs to be further elucidated. Acotiamide effectively improved FD symptoms, particularly postprandial distress syndrome symptoms, without causing major adverse effects.