Favorable Treatment Effect Research Articles

Pharmacological Therapy for Apathy in Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Apathy is highly prevalent in Alzheimer's disease (AD), but whether pharmacotherapy is effective in managing apathy is unclear. To assess the efficacy of pharmacotherapy for apathy in AD we searched for randomized controlled trials (RCT) and aggregate data reporting on apathy in several search engines, reference lists of articles, and reviews. Demographic characteristics and relevant data were extracted to assess apathy. Fifteen RCTs' were examined, and 11 were used in aggregate meta-analytic statistics. Drugs included were cholinesterase inhibitors, memantine, and psycho-stimulants. We found no significant treatment effect in favour of any of the drugs, and the effect-size estimates under a random effect model were heterogeneous. Most RCTs had a high attrition rate and used the NPI apathy subscale to measure apathy. The lack of an effect could be explained by methodological limitations, publication bias, and heterogeneity.

Fatty acid and non-alcoholic fatty liver disease: Meta-analyses of case-control and randomized controlled trials

Blood and/or liver fatty acid contents of healthy subjects and non-alcoholic fatty liver disease (NAFLD) patients have shown inconsistent associations. In addition, the results of randomized controlled trials (RCTs) in relation to the effects of n-3 polyunsaturated fatty acid (PUFA) supplementation on alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver fat, triglyceride (TAG) and fasting glucose levels are inconsistent. The present study aimed to investigate the differences of fatty acid content in the blood and/or liver tissue between healthy subjects and NAFLD patients, and to quantify the benefits of n-3 PUFA therapy in NAFLD patients. A systematic literature search was performed up to November 2016 using PubMed and Scopus databases. The differences of fatty acid content between cases and controls were calculated as weighted mean differences (WMD) by using a random-effects model. The intervention effects of RCTs were calculated as WMD for net changes in ALT, AST, liver fat, TAG and fasting glucose levels, respectively. Meta-regression with restricted maximum likelihood estimation was used to evaluate a potential linear relationship between confounding factors and effect sizes. Generalized least square was performed for dose-response analysis. Ten eligible case-control studies and 11 RCTs were included. The pooled estimates of case-control studies showed that blood and/or liver docosahexaenoic acid (DHA) content was significantly higher in the controls compared with cases. The pooled estimates of RCTs showed that n-3 PUFA supplementation significantly reduced the ALT (-7.53U/L; 95% CI:-9.98,-5.08U/L), ASL (-7.10U/L, 95% CI:-11.67,-2.52U/L) and TAG (-36.16mg/dL, 95% CI:-49.15,-23.18mg/dL) concentrations, and marginally reduced the liver fat content (-5.11%, 95% CI:-10.24, 0.02%, P=0.051), but not fasting glucose. Dose-response analysis of RCTs showed that 1g per day increment of eicosapentaenoic acid (EPA)+DHA was associated with a 3.14U/L, 2.43U/L, 2.74% and 9.97mg/dL reduction in ALT (95% CI:-5.25,-1.02U/L), AST (95% CI:-3.90,-0.90U/L), liver fat (95% CI:-4.32,-1.16%) and TAG (95% CI:-14.47,-5.48mg/dL) levels, respectively. The present meta-analysis provides substantial evidence that n-3 PUFA supplementation, especially DHA, has a favorable effect in treatment of NAFLD.

Effectiveness of Measuring Genetic Polymorphisms in Metabolizing Enzymes of Tacrolimus within One Medical Facility.

Because genetic polymorphisms cause diverse activity in drug metabolizing enzymes, drug concentrations in the blood may be variable among patients. We analyzed the genotypes of CYP3A5 and MDR1, and investigated their relationship with whole blood drug concentrations. Eight patients were administered an oral dose of tacrolimus for one week or longer prior to enrollment in this study. Whole blood concentrations for tacrolimus were measured 12 hours post oral administration, on the same day as genotyping, within our hospital using a fully automated gene analyzer. The procedures became so rapid that collection of blood samples could be completed within the same day (approximately one hour). The genotype frequency of CYP3A5 was *3/*3 in five patients, *1/*3 in two patients, and *1/*1 in one patient. All five patients with *3/*3 showed favorable increases in tacrolimus blood concentrations. In the two patients with *1/*3, an increase in tacrolimus blood concentration was not readily achieved in one patient, but increased favorably in the other patient. In the patient with *1/*1, tacrolimus was not detectable in the patient's blood. A favorable treatment effect was obtained by changing tacrolimus to cyclosporine. It is notable that genotypes in patients where tacrolimus was not detected in the blood were wild types: 2677G/G and 3435C/C in MDR1. The measurement of genetic polymorphisms in metabolizing enzymes of tacrolimus, within one medical facility, is applicable for the selection of immunosuppressants and individual dosing for the treatment of autoimmune disease.

Early efficacy observation of generic imatinib for treatment of chronic myeloid leukemia in chronic phase

Objective To evaluate the cytogenetic, molecular responses and safety of generic imatinib in newly diagnosed patients with chronic myelogenous leukemia in chronic phase (CML-CP) in 1-year at different stages. Methods From January 2014 to November 2014, 50 CML-CP patients received oral generic imatinib 400 mg/d. The cytogenetic examinations, bcr-abl transcript levels and safety were monitored after 3, 6, 9 and 12 months respectively. Results 46 of 50 patients insisted on oral generic imatinib and followed up 1 year. At 3-month, 52.0 % (26/50) patients reached the complete hematologic responses(CHR) rate, and patients at least achieved minor cytogenetic response (mCyR) and bcr-ablIS≤10 % were 84.0 % (42/50) and 42.0 % (21/50). At 6-month, patients at least achieved part cytogenetic response (PCyR) and bcr-ablIS≤10 % were 73.5 % (36/49) and 59.2 % (29/49). At 12-month, patients achieved complete cytogenetic response (CCyR), bcr-ablIS≤1 % and bcr-ablIS≤0.1 % were 60.9 % (28/46), 63.1 % (29/46) and 45.7 % (21/46). The grade 3 leukopenia, thrombocytopenia and anemia rates were 34 % (17/50), 40 % (20/50) and 30 % (15/50), respectively. No grade 4 hematologic toxicity occurred. The common non-hematologic toxicities included edema [84 % (42/50)], nausea [46 % (40/50)], muscle pain [20 % (10/50)], rash [16 % (8/50)], and impaired liver function [8 % (4/50)]. Conclusion Generic imatinib has a favorable effect in treatment of patients with CML-CP, and without serious adverse reactions. Key words: Leukemia, myeloid, chronic; Cytogenetics; Bcr-abl; Generic imatinib

Patient-reported outcomes with sofosbuvir and velpatasvir with or without ribavirin for hepatitis C virus-related decompensated cirrhosis: an exploratory analysis from the randomised, open-label ASTRAL-4 phase 3 trial

Hepatitis C virus (HCV) treatment regimens with direct-acting antivirals have not been extensively studied in patients with decompensated cirrhosis. We assessed patient-reported outcomes (PROs) in patients with decompensated cirrhosis given a fixed-dose combination of sofosbuvir and velpatasvir with and without ribavirin. This study was an exploratory analysis of data collected in a randomised, open-label phase 3 trial (ASTRAL-4) in which patients with HCV-related decompensated cirrhosis were randomly assigned to an all-oral fixed-dose combination of sofosbuvir (400 mg) and velpatasvir (100 mg) once daily for 12 weeks, sofosbuvir and velpatasvir plus oral ribavirin (weight-based 1000 mg or 1200 mg) for 12 weeks, or sofosbuvir and velpatasvir for 24 weeks. Eligible patients were aged 18 years or older with any HCV genotype and decompensated cirrhosis at screening. PROs were collected for the intention-to-treat population using four questionnaires, Short Form (36) Health Survey version 2 (SF-36v2), the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), the Chronic Liver Disease Questionnaire-HCV Version (CLDQ-HCV), and the Work Productivity Activity Index:HCV (WPAI), which were given prospectively to patients before, during, and after treatment. The ASTRAL-4 study is registered with ClinicalTrials.gov, number NCT02201901. Patients were enrolled at 47 hepatology outpatient practices in the USA from Aug 19, 2014, to Dec 19, 2014. 267 patients with HCV-related decompensated cirrhosis were included. In patients given sofosbuvir and velpatasvir for 12 weeks (n=90), clinically significant improvements in PROs started 4 weeks after treatment initiation (+4·4 to +7·5 points on a 0-100 scale at treatment week 4). By the end of treatment, mean improvements in PROs of +5·3 to +16·0 points were noted in all PROs except for role emotional, mental component summary, and social wellbeing scores and work productivity metrics by WPAI:HCV. Similar end-of-treatment improvements (+3·8 to +17·0 points) were observed in patients given sofosbuvir and velpatasvir for 24 weeks (n=90). In patients given sofosbuvir and velpatasvir plus ribavirin (n=87), PRO scores decreased within 4 weeks of treatment (-3·6 to -6·9 points), although scores returned to the baseline levels by the end of treatment. After treatment cessation, significant improvements in all PROs were similar between the treatment groups (all p>0·01) and, by post-treatment week 24, improvements were between +4·9 and +21·2 points. In multivariate analysis, predictors of PRO impairment were treatment naivety, anxiety, use of anxiolytics, use of antidepressants, use of opioids, ribavirin use, the presence of ascites, encephalopathy, insomnia, and depression. A clinically significant early (within 4 weeks) and sustained improvement in PROs was observed in patients with HCV-related decompensated cirrhosis who were given sofosbuvir and velpatasvir without ribavirin. A similar regimen with ribavirin resulted in a temporary decrease in PROs, which completely resolved after 8 weeks of treatment. Accompanied by high efficacy, the favourable effect of treatment on PROs improves patients' experience in this difficult-to-treat population with HCV. Gilead Sciences.

Cancer cachexia-when proteasomal inhibition is not enough.

Cachexia is a life threatening syndrome associated with several diseases, such as end‐stage heart failure, end‐stage renal disease, chronic obstructive pulmonary disease, chronic inflammation (i.e. rheumatoid arthritis), acquired immune deficiency syndrome, and cancer.1, 2 Cachexia is found in 31–87% of cancer patients especially in advanced disease stages.3 It is characterized by progressive weight loss, metabolic alterations, fatigue, and persistent reduction of body cell mass in response to a malignant tumour.2, 4, 5, 6 The incidence of cachexia in cancer patients is dependent on the type and site of the tumour. While patients with non‐Hodgkin's lymphoma, breast cancer, and sarcomas show low incidences, rates up to 83% in pancreatic cancer patients, and over 85% in patients with gastric cancer have been found. Additionally, around 60% of small‐cell and non‐small‐cell lung cancer patients develop cachexia.7, 8, 9 Cancer cachexia affects the function of several organs such as muscle, adipose tissue, liver, brain, immune system, and heart, collectively decreasing patients' quality of life and worsening their prognosis. Therefore, cachexia must be considered as a true multi‐organ syndrome.10 Because cancer cachexia leads to a decrease in physical performance and quality of life,11 and is associated with poor survival (accounting for more than 20% of cancer deaths,7, 12, 13, 14, 15) it is of major clinical relevance. Even more so since cachectic patients show lower response rates to chemotherapy7 and a reduced tolerance to anticancer treatment.16 Despite its importance, weight loss in cancer patients is rarely recognized, assessed,17 or treated actively.18, 19 Thus, cancer cachexia represents an important underappreciated clinical syndrome.

Effects of Allopurinol on Arterial Stiffness: A Meta-Analysis of Randomized Controlled Trials.

BackgroundSeveral studies have tested the effects of allopurinol on arterial stiffness, but the results have been inconclusive. We aimed to conduct a meta-analysis to investigate the impacts of allopurinol treatment on arterial stiffness, as measured by pulse wave velocity (PWV) and augmentation index (AIx).Material/MethodsRandomized controlled trials (RCTs) assessing the effects of allopurinol on arterial stiffness were identified through searching PubMed, Web of Science, EMBASE, the Cochrane Library for Central Register of Clinical Trials, and China National Knowledge Infrastructure up to December 2015. The primary endpoints were the change of PWV and AIx after allopurinol treatment. The weighted mean difference (WMD) or standardized mean difference (SMD) and the 95% confidence interval (CI) of each study were pooled for meta-analysis.ResultsA total of 11 RCTs met the inclusion criteria and were included in the final meta-analysis. Eight RCTs with 1,111 patients were pooled for PWV; eight RCTs with 397 patients were pooled for PWV. Allopurinol administration did not significantly change PWV (WMD=−0.19 m/s, 95% CI: −0.49 to 0.12, Z=1.21, p=0.23), but significantly reduced AIx (SMD=−0.34, 95% CI: −0.54 to −0.14, Z=3.35, p=0.0008).ConclusionsAlthough our meta-analysis showed some favorable effects of allopurinol treatment on improving AIx, its impact on arterial stiffness must be tested in more large-scale RCTs.

Efficacy and Safety of a Novel Endothelin Receptor Antagonist, Macitentan, in Japanese Patients With Pulmonary Arterial Hypertension.

Macitentan is a novel, dual endothelin receptor antagonist with sustained receptor binding, used for the long-term treatment of pulmonary arterial hypertension (PAH). In the present study, we assessed the efficacy and safety of macitentan in Japanese patients with PAH. Macitentan was administered at a once-daily dose of 10 mg in 30 patients. The primary endpoint was change in pulmonary vascular resistance (PVR) from baseline to week 24. Change to week 24 in the other hemodynamic parameters, 6-min walk distance (6MWD), World Health Organization (WHO) functional class, and plasmaN-terminal pro-brain natriuretic peptide (NT-pro-BNP), as well as time to clinical deterioration up to week 52 were also assessed as secondary endpoints. In the 28 patients on per-protocol analysis, PVR decreased from 667±293 to 417±214 dyn·sec·cm(-5)(P<0.0001). 6MWD increased from 427±128 to 494±116 m (P<0.0001). WHO functional class improved in 13 patients (46.4%) and was maintained in 15 patients (53.6%), and NT-pro-BNP was reduced by 18% (P<0.0001). The favorable treatment effect on PVR was apparent regardless of concomitant therapy for PAH. Macitentan was efficacious and well tolerated and improved the hemodynamic parameters, exercise capacity, symptoms, and clinical biomarkers in Japanese PAH patients. Macitentan can be a valuable therapeutic option for Japanese patients with PAH. ( JAPIC Clinical Trials Information [JapicCTI-121986].) (Circ J 2016; 80: 1478-1483).

The Favorable Effect of Mesenchymal Stem Cell Treatment on the Antioxidant Protective Mechanism in the Corneal Epithelium and Renewal of Corneal Optical Properties Changed after Alkali Burns.

The aim of this study was to examine whether mesenchymal stem cells (MSCs) and/or corneal limbal epithelial stem cells (LSCs) influence restoration of an antioxidant protective mechanism in the corneal epithelium and renewal of corneal optical properties changed after alkali burns. The injured rabbit corneas (with 0.25 N NaOH) were untreated or treated with nanofiber scaffolds free of stem cells, with nanofiber scaffolds seeded with bone marrow MSCs (BM-MSCs), with adipose tissue MSCs (Ad-MSCs), or with LSCs. On day 15 following the injury, after BM-MSCs or LSCs nanofiber treatment (less after Ad-MSCs treatment) the expression of antioxidant enzymes was restored in the regenerated corneal epithelium and the expressions of matrix metalloproteinase 9 (MMP9), inducible nitric oxide synthase (iNOS), α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and vascular endothelial factor (VEGF) were low. The central corneal thickness (taken as an index of corneal hydration) increased after the injury and returned to levels before the injury. In injured untreated corneas the epithelium was absent and numerous cells revealed the expressions of iNOS, MMP9, α-SMA, TGF-β1, and VEGF. In conclusion, stem cell treatment accelerated regeneration of the corneal epithelium, restored the antioxidant protective mechanism, and renewed corneal optical properties.

Porous tantalum rods improve the hip joint function of patients with avascular necrosis of the femoral head after femoral neck fracture surgery: study protocol of a randomized controlled trial

Background: After femoral neck fracture, insufficient blood supply to the femoral head can cause avascular necrosis of this region. This can lead to increased treatment difficulty, and may greatly influence the recovery of hip joint function. Core decompression with bone grafting is a common treatment for avascular necrosis of the femoral head. An implanted porous tantalum rod, which is a bone trabecula-like metal implant that is used to support the weight-bearing area of necrotic bone, can prevent further collapse of the necrotic area. This strategy has led to favorable effects in the early treatment of avascular necrosis of the femoral head. However, few randomized controlled studies have reported on porous tantalum rod implantation for treatment of avascular necrosis of the femoral head after femoral neck fracture surgery. We hypothesized that, compared with core decompression alone, core decompression with porous tantalum rod implantation would have a more beneficial effect of the hip joint function of patients with avascular necrosis of the femoral head after femoral neck fracture surgery. Methods/Design: This is a prospective, single-center, randomized controlled, open-label trial, which will be performed in the Department of Orthopedic Trauma, Qinghai University Affiliated Hospital, China. A total of 100 patients with avascular necrosis of the femoral head after femoral neck fracture surgery will be randomly assigned to undergo core decompression and porous tantalum rod implantation (experimental group, n = 50) or core decompression only (control group, n = 50). All patients will be followed up for 1 year. The primary outcome measure is the percentage of patients (of the total number of patients in each group) whose hip joint function is graded as excellent as per Harris hip scores 12 months after surgery. This value will be used to evaluate the recovery of hip joint function. Secondary outcome measures include (1) the percentage of patients with excellent hip joint function, prior to and 1 and 6 months after surgery (of the total number of patients in each group); (2) hip joint pain score on a Visual Analogue Scale prior to and 1, 6, and 12 months after surgery, which will be used to evaluate the severity of pain; (3) the percentage of patients presenting with femoral head collapse, prosthesis loosening, and peri-prosthesis infection 6 and 12 months after surgery, which will be used to evaluate the biocompatibility of the biomaterial with the host site; (4) incidence of complications 6 and 12 months after surgery, which will be used to evaluate the safety of porous tantalum rod implantation. Discussion: This study is powered to validate the biocompatibility and therapeutic effects of porous tantalum rods in the treatment of avascular necrosis of the femoral head after femoral neck fracture, with the hopes that this novel surgical method represents a superior treatment for this disease. Trial registration: ClinicalTrial.gov identifier: NCT02877472; registered on 19 August 2016. Ethics: This study protocol has been approved by the Medical Ethics Committee of Qinghai University Affiliated Hospital of China (approval number: QHY1016B) and will be performed in accordance with the guidelines of the Declaration of Helsinki, formulated by the World Medical Association. Informed consent: Signed informed consent regarding trial procedure and treatment will be obtained from each patient.

Successful endovascular stroke therapy in a 103-year-old woman

People older than 80 years of age constitute the most rapidly growing age group in the world. Several trials confirming superior efficacy of endovascular therapy did not have an upper...

Atrial Fibrillation and Cognition: Epidemiological Data and Possible Mechanisms.

Dementia is one of the most disabling conditions in older people. Incidence of dementia steeply increases with age, doubling approximately every 5 years, and ranging from 4.0 per 1000 person-years in the group aged 65 to 69 years to 33.5 per 1000 person-years in the group aged 80 to 84 years.1 The most frequent type of dementia is Alzheimer’s disease (AD), followed by vascular dementia, a category encompassing different subtypes among which cerebral small vessel disease (SVD) and multi-infarct dementia are the most common.2 In both AD and vascular dementia, vascular risk factors play an important role, suggesting a possible favorable effect of treatment on the onset and progression of cognitive decline. Atrial fibrillation (AF) is a supraventricular tachyarrhythmia characterized by uncoordinated atrial activation and ineffective atrial contraction and may be detected on ECG when distinct P waves are absent, and R–R intervals and atrial activity are irregular.3 AF is the most common arrhythmia encountered in clinical practice, and, similarly to dementia, its prevalence increases with age. Approximately 1% of AF patients are 7 days).3 Interest has emerged concerning the possible role of AF in relation to cognitive decline and dementia. More than 40 years ago, the term cardiogenic dementia had been introduced in support of a possible link between cardiac arrhythmias and cognitive impairment in elderly subjects.4 Only recently the relation between AF and cognitive impairment has become the object of investigations, reviews, and meta-analyses.5–11 …

Locoregional treatment versus no treatment of the primary tumour in metastatic breast cancer: an open-label randomised controlled trial

The role of locoregional treatment in women with metastatic breast cancer at first presentation is unclear. Preclinical evidence suggests that such treatment might help the growth of metastatic disease, whereas many retrospective analyses in clinical cohorts have suggested a favourable effect of locoregional treatment in these patients. We aimed to compare the effect of locoregional treatment with no treatment on outcome in women with metastatic breast cancer at initial presentation. In this open-label, randomised controlled trial, we recruited previously untreated patients (≤65 years of age with an estimated remaining life expectancy of at least 1 year) presenting with de-novo metastatic breast cancer from Tata Memorial Centre, Mumbai, India. Patients were randomly assigned (1:1) to receive locoregional treatment directed at their primary breast tumour and axillary lymph nodes, or no locoregional treatment, by a computer-generated block randomisation sequence (block size of four). Randomisation was stratified by site of distant metastases, number of metastatic lesions, and hormone receptor status. Patients with resectable primary tumour in the breast that could be treated with endocrine therapy were randomly assigned upfront, whereas those with an unresectable primary tumour were planned for chemotherapy before randomisation. Of the patients who had chemotherapy before randomisation, we randomly assigned patients who had an objective tumour response after six to eight cycles of chemotherapy. The primary endpoint was overall survival analysed by intention to treat. This study is registered with ClinicalTrials.gov, NCT00193778. Between Feb 7, 2005, and Jan 18, 2013, of the 716 women presenting with de-novo metastatic breast cancer, we randomly assigned 350 patients: 173 to locoregional treatment and 177 to no locoregional treatment. At data cut-off of Nov 1, 2013, median follow-up was 23 months (IQR 12·2-38·7) with 235 deaths (locoregional treatment n=118, no locoregional treatment n=117). Median overall survival was 19·2 months (95% CI 15·98-22·46) in the locoregional treatment group and 20·5 months (16·96-23·98) in the no-locoregional treatment group (HR 1·04, 95% CI 0·81-1·34; p=0·79), and the corresponding 2-year overall survival was 41·9% (95% CI 33·9-49·7) in the locoregional treatment group and 43·0% (35·2-50·8) in the no locoregional treatment group. The only adverse event noted was wound infection related to surgery in one patient in the locoregional treatment group. There is no evidence to suggest that locoregional treatment of the primary tumour affects overall survival in patients with metastatic breast cancer at initial presentation who have responded to front-line chemotherapy, and this procedure should not be part of routine practice.

Telephone Consultation as a Substitute for Routine Out-patient Face-to-face Consultation for Children With Inflammatory Bowel Disease: Randomised Controlled Trial and Economic Evaluation

BackgroundEvidence for the use of telephone consultation in childhood inflammatory bowel disease (IBD) is lacking. We aimed to assess the effectiveness and cost consequences of telephone consultation compared with the usual out-patient face-to-face consultation for young people with IBD. MethodsWe conducted a randomised-controlled trial in Manchester, UK, between July 12, 2010 and June 30, 2013. Young people (aged 8–16years) with IBD were randomized to receive telephone consultation or face-to-face consultation for 24months. The primary outcome measure was the paediatric IBD-specific IMPACT quality of life (QOL) score at 12months. Secondary outcome measures included patient satisfaction with consultations, disease course, anthropometric measures, proportion of consultations attended, duration of consultations, and costs to the UK National Health Service (NHS). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02319798. FindingsEighty six patients were randomised to receive either telephone consultation (n=44) or face-to-face consultation (n=42). Baseline characteristics of the two groups were well balanced. At 12months, there was no evidence of difference in QOL scores (estimated treatment effect in favour of the telephone consultation group was 5.7 points, 95% CI −2.9 to 14.3; p=0.19). Mean consultation times were 9.8min (IQR 8 to 12.3) for telephone consultation, and 14.3min (11.6 to 17.0) for face-to-face consultation with an estimated reduction (95% CI) of 4.3 (2.8 to 5.7) min in consultation times (p<0.001). Telephone consultation had a mean cost of UK£35.41 per patient consultation compared with £51.12 for face-face consultation, difference £15.71 (95% CI 11.8–19.6; P<0.001). InterpretationWe found no suggestion of inferiority of telephone consultation compared with face-to-face consultation with regard to improvements in QOL scores, and telephone consultation reduced consultation time and NHS costs. Telephone consultation is a cost-effective alternative to face-to-face consultation for the routine outpatient follow-up of children and adolescents with IBD. FundingResearch for Patient Benefit Programme, UK National Institute for Health Research.

Antitumor action of the peroxisome proliferator-activated receptor-γ agonist rosiglitazone in hepatocellular carcinoma.

The inhibition of apoptosis in cancer cells is the major pathological feature of hepatic carcinoma. Rosiglitazone (RGZ), a ligand for peroxisome proliferator-activated receptor γ (PPAR-γ), has been shown to induce apoptosis in hepatic carcinoma cells. However, the mechanism underlying this effect remains to be elucidated. The present study aimed to investigate the effect of RGZ on cell viability and apoptosis, and its mechanisms in cultured HepG2 cells using MTT assay, flow cytometry and western blotting. The results revealed that treatment with RGZ may attenuate HepG2 cell viability and induce the apoptosis of the cells. The mechanism of RGZ-induced apoptosis involves an increase in the level of activated PPAR-γ (p-PPAR-γ) and a decrease in p85 and Akt expression. In addition, the PPAR-γ antagonist GW9662 suppressed the effect of RGZ in the HepG2 cells. Taken together, the results suggest that RGZ induces the apoptosis of HepG2 cells through the activation of PPAR-γ, suppressing the activation of the PI3K/Akt signaling pathway. Such mechanisms may contribute to the favorable effects of treatment using RGZ in HepG2 cells.

Treat Phoenix River Water by Constructed Rapid Infiltration System

Xu, W.; Yang, Y.; Cheng, C., Pei, X., and Luo, J., 2015. Treat phoenix river water by constructed rapid infiltration system.CRI system is a new technology of sewage disposal which involves less investment, low operating cost, favorable treatment effects and so on. In 2007, a CRI system was built to improve the water quality of Phoenix River. The practical operation shows that: the layout of the CRI system is appropriate and in accord with the practical situation of pollutant sources. Operation results show that CRI system is good at removing the NH3, COD, SS and so on, effluent water is stable in CRI system, and the CRI system has stronger ability to resist impact load. The effluent NH3, COD and SS concentrations can meet the A-level of primary standard of plant emission standards (GB 18918-2002) in Municipal wastewater treatment. But the removal efficiency is bad for TP and TN and the ultimate effluent is not qualified for the A-level of primary standard of plant emission standards (GB 18918-2002) in Municipal wastewater treatment. When improving the CRI system, it must consider changing the structure of the pool filter layer, filter material composition and operation mode to improve the removal efficiency of TN and TP in CRI system.

Effects of Aerobic Exercise On Negative Symptoms in Schizophrenia: a Meta-analysis

Introduction Negative symptoms in patients with schizophrenia are strongly associated to disease burden. Aerobic exercise might be beneficial in treating negative symptoms. Objective The meta-analysis aims to evaluate the effect of aerobic exercise on negative symptoms in schizophrenia. Methods The Cochrane Library, Medline, Embase, PsycINFO and CINAHL were searched from their inception until 16 March 2014. Randomised controlled trials (RCT's) comparing aerobic exercise with other psychosocial interventions in schizophrenia were included if negative symptoms were assessed. The methodological quality of the studies was assessed with the Clinical Trial Assessment Measure (CTAM). Results Nine studies were included (N= 488). Seven out of nine studies had poor methodological quality as measured with the CTAM. The meta-analysis showed a small non-significant treatment effect in favour of exercise interventions (Hedges’ g = -0.310, CI -0.787 0.168) with a power of 75%. The analysis indicates high heterogeneity (Q(8)=37.163 (P 20 sessions (Hedges’ g = 0.640, CI -1.281 0.000, Q(5)=24.214 (P A large significant effect of exercise was found in five studies comparing exercise to TAU (Hedges’ g=-1.370, CI -2.352 -0.389, Q(4)=29.278 (P Conclusions This meta-analysis demonstrated a significant effect of aerobic exercise on negative symptoms in schizophrenia compared to TAU, but no effect compared to any other (active) control condition. The quality of the included studies was low.

A Systematic and Narrative Review of Acupuncture Point Application Therapies in the Treatment of Allergic Rhinitis and Asthma during Dog Days.

Acupuncture point application therapies, including San-Fu-Tie and San-Fu-Jiu, have been widely employed to treat diseases with attacks in winter during dog days in China. The therapies combine Chinese herbal medicine and acupuncture points with the nature. However, the previous studies were reported to be unsystematic and incomplete. To develop a more comprehensive understanding of the effects of acupuncture point application therapies on allergic rhinitis and asthma, a systematic review of the literature up to 2015 was conducted. After filtering, eighteen randomized controlled trials (RCTs) involving 1,785 subjects were included. This systematic and narrative review shows that acupuncture point application therapies have been extensively applied in the treatment of allergic rhinitis and asthma with advantages of favorable treatment effect, convenient operation, receiving patients' good acceptability and compliance, and few side effects. Meanwhile, the study elaborated the operating process of San-Fu-Tie and San-Fu-Jiu in detail. The review may provide a reference for clinical application in future. However, the efficacy, safety, and mechanisms of San-Fu-Tie and San-Fu-Jiu in treating the above diseases need to be validated by more well-designed and fully powered RCTs in a larger population of patients.

Platelet derivatives in regenerative medicine: an update.

Prior preclinical and clinical studies support the use of platelet-derived products for the treatment of soft and hard tissue lesions. These regenerative effects are controlled by autocrine and paracrine biomolecules including growth factors and cytokines contained in platelet alpha granules. Each growth factor is involved in a phase of the healing process, such as inflammation, collagen synthesis, tissue granulation, and angiogenesis collectively promoting tissue restitution. Platelet derivatives have been prepared as platelet-rich plasma, platelet gel, platelet-rich fibrin, and platelet eye drops. These products vary in their structure, growth factors, composition, and cytokine concentrations. Here, we review the current use of platelet-derived biological products focusing on the rationale for their use and the main requirements for their preparation. Variation in the apparent therapeutic efficacy may have resulted from a lack of reproducible, standardized protocols for preparation. Despite several individual studies showing favorable treatment effects, some randomized controlled trials as well as meta-analyses have found no constant clinical benefit from the application of platelet-derived products for prevention of tissue lesions. Recently, 3 published studies in dentistry showed an improvement in bone density. Seven published studies showed positive results in joint regeneration. Five published studies demonstrated an improvement in the wound healing, and an improvement of eye epithelial healing was observed in 2 reports. Currently, at least 14 ongoing clinical trials in phase 3 or 4 have been designed with large groups of treated patients (n > 100). Because the rationale of the therapy with platelet-derived compounds is still debated, a definitive insight can be acquired only when these large randomized trials will be completed.

Effects of acute and chronic exercise in patients with essential hypertension: benefits and risks.

The importance of regular physical activity in essential hypertension has been extensively investigated over the last decades and has emerged as a major modifiable factor contributing to optimal blood pressure control. Aerobic exercise exerts its beneficial effects on the cardiovascular system by promoting traditional cardiovascular risk factor regulation, as well as by favorably regulating sympathetic nervous system (SNS) activity, molecular effects, cardiac, and vascular function. Benefits of resistance exercise need further validation. On the other hand, acute exercise is now an established trigger of acute cardiac events. A number of possible pathophysiological links have been proposed, including SNS, vascular function, coagulation, fibrinolysis, and platelet function. In order to fully interpret this knowledge into clinical practice, we need to better understand the role of exercise intensity and duration in this pathophysiological cascade and in special populations. Further studies in hypertensive patients are also warranted in order to clarify the possibly favorable effect of antihypertensive treatment on exercise-induced effects.