Prednisone Group Research Articles

Comparison of changes of fatigue and psycho-physical wellbeing in rheumatoid arthritis patients during add-on treatment with alfacalcidol or prednisolone

The aim of this study was to investigate and compare effects of vitamin D analogue alfacalcidol (1αD3) or prednisolone add-on treatment to fatigue and psycho-physical well-being in patients with active RA. The study included 67 RA patients with active disease (DAS28 >3,2), despite standard methotrexate (MTX) therapy. We collected data on disease activity based on joints examination and erythrocyte sedimentation rate (DAS28 ESR). Psycho-psychical wellbeing assessed by patient reported outcomes (PRO): health assessment questionnaire (HAQ), short form 36 quality of life (SF-36Qol) and functional assessment of chronic illness therapy (FACIT F) questionnaires. At enrolment, patients were randomly assigned to three-month supplementation with 1 μg (group A1) or 2 μg (group A2) or 3 μg (group A3) of 1αD3 daily or prednisone (group C) 20 mg daily, for the first month and 10 mg afterwards, in addition to MTX. We found significantly improved functional status-HAQ-DI (p<0,05) and physical components of quality of life - PCSQol (p<0,05), in A2 group (N=19). Subscales of quality of life such as vitality, general health (p<0,01), social, pain and mental components of quality of life - MCSQol (p<0,05) significantly improved only in the same, A2 group, while fatigue improved in all 1αD3 treated patients, in contrast to negative change in group C. Upon completed treatment, we found disease activity highly significantly reduced in all four treatment groups (DAS28 p<0,01). Alfacalcidol add-on treatment has positive impact on fatigue and psycho-physical wellbeing in RA patients, particularly 2 μg daily, which was as effective as prednisolone in disease control with significant multifaceted favourable impact on fatigue and wellbeing.

Comparison of alfacalcidol or prednisone effects as an add-on treatment to methotrexate in active rheumatoid arthritis

Objectives: To compare efficacy of alfacalcidol (1αD3) or prednisone as an add-on treatment for patients with active Rheumatoid Arthritis (RA). Methods: Sixty-seven RA patients on maximum tolerated stable methotrexate (MTX) dose, yet with moderate/high RA activity were included. Written consent, demographic data and blood samples for inflammatory biomarkers, calcium and lipid metabolism, cytokine testing were obtained, and disease activity was calculated (DAS28). They were randomly assigned to either three-month treatment with 1 μg (group A1), 2 μg (group A2), 3 μg (group A3) 1αD3 daily or prednisone (group C) 20 mg daily, for the first month and 10 mg afterwards, in addition to MTX. At the end of each treatment period, disease activity and laboratory tests were reassessed. Results: Out of 67 patients, 68% females, average age 56.24 ± 12.423, disease duration 7.71 ± 6.68 years, MTX dose 15.41 ± 3.28 mg/week, average RA activity DAS28 5.58 ± 0.905. Patients randomized to four different study treatments were fully comparable. After three-month treatment, we found highly significantly reduced disease activity in all groups as per DAS28 and patient visual assessment scale - PVAS (p<0.01). Group A2 and C in term of ΔDAS28 and ΔPVAS (pE‚0.05) did not differ. In 1αD3 2 μg (A2) treated patients (N=19), C-Reactive Protein (CRP) (pE‚0.01), erythrocyte sedimentation rate (ESR) and interleukin-6 (IL6) levels (pE‚0.05) were significantly reduced, while High-Density Lipoprotein (HDL) increased (pE‚0.05). Serum calcidiol in prednisone users (N=16) significantly decreased (pE‚0.01). Conclusion: Addition of either 1 μg, 2 μg, 3 μg 1αD3 or prednisone to MTX for three months, led to a significant reduction of disease activity in active RAy.

Abiraterone acetate for chemotherapy-naive metastatic castration-resistant prostate cancer: a single-centre prospective study of efficacy, safety, and prognostic factors

BackgroundTo evaluate the efficacy and safety of abiraterone acetate (AA) plus prednisone compared with prednisone alone in Asian patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC), and to identify predictive factors.MethodsWe reviewed the medical records of 60 patients with chemotherapy-naive mCRPC at Renji Hospital who were treated with AA plus prednisone (n = 43) or prednisone alone (n = 17). All patients were assessed for prostate-specific antigen (PSA) response, PSA progression-free survival (PSA PFS), radiographic progression-free survival (rPFS), and overall survival (OS). The ability of several parameters to predict PSA PFS, rPFS, and OS was studied.ResultsThe median follow-up time was 14.0 months (range 7.0–18.5 months), at which time 19 death events had been reported: 11 in the AA + prednisone group and 8 in the prednisone group. The AA + prednisone group had significantly longer median PSA PFS (10.3 vs 3.0 months, P < 0.001), rPFS (13.9 vs 3.9 months, P < 0.001), and OS (23.3 vs 17.5 months, P = 0.016) than the prednisone-alone group. The most frequently reported grade 3 or 4 adverse event in both the AA + prednisone and prednisone-alone groups was elevated alanine aminotransferase level in 5 of 43 patients (11.6%) and 2 of 17 patients (11.8%), respectively. No adverse events led to discontinuation of therapy. In multivariate analysis, time from androgen deprivation therapy (ADT) to castration resistance of ≤18 months was a determinant of shorter OS (P = 0.007).ConclusionsThese results support the favourable safety and efficacy profile of AA for the treatment of Asian patients with chemotherapy-naive mCRPC. Longer duration of ADT response was significantly associated with longer survival.

Prednisone for the Prevention of Paradoxical Tuberculosis-Associated IRIS

BackgroundEarly initiation of antiretroviral therapy (ART) in human immunodeficiency virus (HIV)–infected patients who have tuberculosis reduces mortality among patients with low CD4 counts, but it increases the risk of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (IRIS).MethodsWe conducted this randomized, double-blind, placebo-controlled trial to assess whether prophylactic prednisone can safely reduce the incidence of paradoxical tuberculosis-associated IRIS in patients at high risk for the syndrome. We enrolled HIV-infected patients who were initiating ART (and had not previously received ART), had started tuberculosis treatment within 30 days before initiating ART, and had a CD4 count of 100 cells or fewer per microliter. Patients received either prednisone (at a dose of 40 mg per day for 14 days, then 20 mg per day for 14 days) or placebo. The primary end point was the development of tuberculosis-associated IRIS within 12 weeks after initiating ART, as adjudicated by an independent committee.ResultsAmong the 240 patients who were enrolled, the median age was 36 (interquartile range, 30 to 42), 60% were men, and 73% had microbiologically confirmed tuberculosis; the median CD4 count was 49 cells per microliter (interquartile range, 24 to 86), and the median HIV type 1 RNA viral load was 5.5 log10 copies per milliliter (interquartile range, 5.2 to 5.9). A total of 120 patients were assigned to each group, and 18 patients were lost to follow-up or withdrew. Tuberculosis-associated IRIS was diagnosed in 39 patients (32.5%) in the prednisone group and in 56 (46.7%) in the placebo group (relative risk, 0.70; 95% confidence interval [CI], 0.51 to 0.96; P=0.03). Open-label glucocorticoids were prescribed to treat tuberculosis-associated IRIS in 16 patients (13.3%) in the prednisone group and in 34 (28.3%) in the placebo group (relative risk, 0.47; 95% CI, 0.27 to 0.81). There were five deaths in the prednisone group and four in the placebo group (P=1.00). Severe infections (acquired immunodeficiency syndrome–defining illnesses or invasive bacterial infections) occurred in 11 patients in the prednisone group and in 18 patients in the placebo group (P=0.23). One case of Kaposi’s sarcoma occurred in the placebo group.ConclusionsPrednisone treatment during the first 4 weeks after the initiation of ART for HIV infection resulted in a lower incidence of tuberculosis-associated IRIS than placebo, without evidence of an increased risk of severe infections or cancers. (Funded by the European and Developing Countries Clinical Trials Partnership and others; PredART ClinicalTrials.gov number, NCT01924286.)

Identification of subgroups of metastatic castrate-resistant prostate cancer (mCRPC) patients treated with abiraterone plus prednisone at low- vs. high-risk of radiographic progression: An analysis of COU-AA-302.

Radiographic imaging is used to monitor disease progression for men with metastatic castrate-resistant prostate cancer (mCRPC). The optimal frequency of imaging, a costly and limited resource, is not known. Our objective was to identify predictors of radiographic progression to inform the frequency of imaging for men with mCRPC. We accessed data for men with chemotherapy-naive mCRPC in the abiraterone acetate plus prednisone (AA-P) group of a randomized trial (COU-AA-302) (n=546). We used Cox proportional hazards modelling to identify predictors of time to progression. We divided patients into groups based on the most important predictors and estimated the probability of radiographic progression-free survival (RPFS) at six and 12 months. Baseline disease and change in prostate-specific antigen (PSA) at eight weeks were the strongest determinants of RPFS. The probability of RPFS for men with bone-only disease and a ≥50% fall in PSA was 93% (95% confidence interval [CI] 87-96) at six months and 80% (95% CI 72-86) at 12 months. In contrast, the probability of RPFS for men with bone and soft tissue metastasis and <50% fall in PSA was 55% (95% CI 41-67) at six months and 34% (95% CI 22-47) at 12 months. These findings should be externally validated. Patients with chemotherapy-naive mCRPC treated with first-line AA-P can be divided into groups with significantly different risks of radiographic progression based on a few clinically available variables, suggesting that imaging schedules could be individualized.

Study on the effect of Huangqi-Gegen decoction and Peiyuan-Guben powder on autoimmune myasthenia gravis rats

Objective Experimental model of experimental autoimmune Myasthenia Gravis (EAMG) were established to explore the effect of Zini-Huangqi-Gegen decoction and Peiyuan-Guben powder on EAMG rats model. Methods Experimental animals were randomly divided into the control group (n=10) and the model group (n=30). The model rats were induced by murine AChR-α97-116 peptide immunostaining for EAMG rats model. After the first immunization, the general condictions and body weight of rats were observed, and the Lennon score was used to evaluate the rats. The second immunization was performed on the 11th day after the first immunization. On the 15th day after the first immunization, the rats were randomly divided into the model group(n=8), Huangqi-Gegen decoction and Peiyuan-Guben powder group (abbreviated Huangpei group, n=8) and Prednisone group (n=8) according to the Lennon score. Huangpi group rats were treated with Huangqi-Gegen decoction (21.5 g/kg) combined with Peiyuan-Guben powder (0.8 g/kg), prednisone group with 0.005 4 g/kg prednisone aqueous solution, the control group and the model group oral volume of distilled water. The rats were administered with a body weight of 10 ml/kg once a day for a total of 56 days. At the 70th day after the first immunization, serum was extracted from the rats. The Anti-AChR-α97-116 IgG and its subtype in serum were detected by ELISA. The IL-4, IL-10, IL-17 in serum were detected by ELISA. Results Compared with the model group, the weight of the rats in the Huangpei group and the prednisone group significantly increased after the 28th day of the first immunization (P<0.05). After the 36nd day of the first immunization, the Lennon score of the Huangpei group significantly decreased (P<0.05). At the end of the administration, the amplitude of EMG amplitude attenuation (41.83% ± 7.45% vs. 67.76% ± 4.32%) in the Huangpei group significantly decreased (P<0.05), and the serum IgG (1.15 ± 0.07 vs. 1.24 ± 0.08), IgG1 (0.17 ± 0.01 vs. 0.25 ± 0.03), IL-4 (16.54 ± 1.66 pg/ml vs. 25.64 ± 1.74 pg/ml), IL-10 ( 113.65 ± 12.87 pg/ml vs. 121.54 ± 10.44 pg/ml), IL-17 (43.58 ± 3.54 pg/ml vs. 65.76 ± 3.59 pg/ml) in the rat serum significantly decreased (P<0.05). Conclusions Huangqi-Gegen decoction and Peiyuan-Guben powder can increase the body weight of rats, decrease the concentration of AChR-Ab in serum, the concentrations of IL-4, IL-10 and IL-17 in serum, and effectively improve the symptoms of EAMG rats. Key words: Myasthenia gravis, autoimmune, experimental; Huangqi-Gegen decoction and Peiyuan-Guben powder; Inflammation; Rats

Calcineurin Inhibitors With Reduced-Dose Steroids as First-Line Therapy for Focal Segmental Glomerulosclerosis

IntroductionHigh-dose corticosteroids remain the first-line therapy for focal and segmental glomerulosclerosis (FSGS), whereas calcineurin inhibitors (CNIs) are reserved for those patients resistant to corticosteroid therapy.MethodsThis is a retrospective cohort analysis in patients with primary FSGS diagnosed between 2007 and 2014. According to the administered treatment, patients were segregated into 3 groups: high-dose prednisone, first-line CNIs plus low-dose prednisone, and rescue CNIs. Cumulative corticosteroid doses were compared as well as response to therapy and long-term renal survival by Cox regression analysis.ResultsA total of 66 patients were included (39 treated with high-dose prednisone, 11 treated with first-line CNI, 16 treated with high-dose prednisone followed by rescue CNI). Cumulative doses of prednisone in the high-dose group were 9.3 g (interquartile range [IQR] = 7.5−12.5 g), compared to 2.5 g (IQR = 1.82−3.12 g) in the first-line CNI plus low-dose corticosteroid group and 13.8 g (IQR = 9.2−15.8 g) rescue CNI groups, respectively (P < 0.001). Time under corticosteroid management was also higher in the high-dose prednisone group compared to the first-line CNI group. There was a response to treatment in 76.9%, 72.7%, and 87.5% of high-dose prednisone, first-line CNI and rescue CNI groups, with complete remission in 48.7%, 36.4%, and 31.3% respectively. There was no difference in relapse incidence after treatment (48.4%, 44.4%, and 46.7%) or in 5-year renal survival (87.2%, 81.8%, and 87.5%). Baseline proteinuria, biopsy chronicity score, and response to therapy were independent predictors of renal survival.ConclusionAn initial CNI plus low-dose corticosteroid approach in primary FSGS reduces corticosteroid exposure with a response-to-therapy rate similar to that of the currently recommended high-dose corticosteroid regimen. These findings justify a randomized trial to formally test this hypothesis.

Combined prednisone and levothyroxine improve treatment of severe thrombocytopenia in hepatitis B with compensatory cirrhosis accompanied by subclinical and overt hypothyroidism.

The aim of the present study was to investigate the relationship between hypothyroidism and thrombocytopenia in hepatitis B-related compensatory liver cirrhosis and to determine whether treatment with levothyroxine and prednisone is superior in a multicenter, open-label, observational study in China. In total, 125 consecutive hepatitis B-related compensated liver cirrhosis patients with severe thrombocytopenia accompanied by hypothyroidism were included. The patients were divided into four groups according to treatment strategy: a control group (n=29), a prednisone group (n=25), a levothyroxine group (n=32) and a prednisone plus levothyroxine group (n=39). Severe thrombocytopenia was more prevalent in hepatitis B-associated compensatory liver cirrhosis patients with hypothyroidism than in euthyroid patients (29.6% vs. 14.7%, P<0.05). Combination treatment with prednisone and levothyroxine decreased the risk of bleeding and improved platelet recovery compared to control treatment and treatment with either prednisone or levothyroxine alone. The platelet count before therapy, serum thyroid stimulating hormone and combination treatment with prednisone and levothyroxine were associated with bleeding events. Therefore, the present study suggests that hypothyroidism is associated with severe thrombocytopenia in hepatitis B-associated compensatory liver cirrhosis. Treatment with prednisone plus levothyroxine may present a novel approach in these patients.

The effect of medical treatments on the bacterial microbiome in patients with chronic rhinosinusitis: a pilot study.

Antibiotics and corticosteroids are prescribed to patients with chronic rhinosinusitis (CRS) to reduce bacterial burden and mucosal inflammation. Unfortunately, clinical improvement is often short-lived and symptoms frequently recur following cessation of treatment. The impact of these systemic therapies on bacterial communities is not well understood. Improved knowledge of how medical therapies influence the intranasal ecosystem may allow for more effective prescribing and the development of more targeted treatments. Twenty patients with CRS were randomized to receive either doxycycline 100 mg twice daily or prednisone 30 mg once daily for 7 days. A further 6 patients with CRS were recruited as untreated controls. Swabs were taken immediately before and after the study period. Symptom scores (22-item Sino-Nasal Outcome Test [SNOT-22]) were recorded. Bacterial communities were characterized using 16S ribosomal RNA (rRNA) gene-targeted amplicon sequencing. Bacterial abundance was estimated using quantitative polymerase chain reaction (PCR) of 16S rRNA gene copies. Bacterial profiles were dominated by members of the genera Corynebacterium and Staphylococcus. Patients treated with either doxycycline or prednisone had variable and unpredictable changes in communities. The average relative abundance of Propionibacterium increased after treatment in the doxycycline treatment group, and Corynebacterium reduced in the prednisone group. Significant differences in clinical scores, bacterial community richness, diversity, and bacterial abundance were not seen after treatment. The short-term response of bacterial communities to antibiotic or corticosteroid therapy is unpredictable. This study suggests that the use of systemic therapy in patients with stable CRS should be rationalized to minimize antibiotic-associated morbidity and bacterial dysbiosis.

Feixian Recipe inhibits pulmonary fibrosis by targeting pulmonary microvascular endothelial cells and VEGF/VEGFR2 signaling pathway

Objective: To investigate the regulatory mechanism of PMVECs and vascular endothelial growth factor VEGF/vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathway in pulmonary fibrosis and the inhibitory effect of Feixian Recipe (FXR) in pulmonary fibrosis by targeting VEGF/VEGFR2 signal pathway. Methods: In this study, pulmonary microvascular endothelial cells (PMVECs) were successfully isolated from rats with pulmonary fibrosis. Cells were divided into six groups: model group, prednisone group, losartan group and three different concentrated (100[Formula: see text]ug/mL, 60[Formula: see text]ug/mL, 20[Formula: see text]ug/mL) FXR groups. The adhesion rate, migration and closed blood vessels of each PMVECs group were detected. The mRNA expression of VEGF, VEGFR2, phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinases 38 (P38 MAPK) and activin receptor-like kinase (ALK) were detected by SYBR Green I real-time fluorescence quantitative PCR. Results: Compared with the model group, the adhesion rate, migration and angiogenesis of PMVECs were decreased in FXR groups ([Formula: see text]). Compared with prednisone and losartan groups, the mRNA expressions of VEGF, VEGFR2, PI3K and P38 MAPK were down-regulated significantly by FXR ([Formula: see text]). Conclution: FXR can inhibit the migration, adhesion and angiogenesis of PMVECs in rats with pulmonary fibrosis by targeting VEGF/VEGFR2 signal pathway, and inhibit the progress of pulmonary fibrosis.

Thymectomy lowers the myasthenia gravis biomarker miR-150-5p.

ObjectiveThe aim of the study was to analyze the effect of thymectomy on the proposed disease-specific microRNA (miRNA) biomarkers miR-150-5p and miR-21-5p in patients from the prospective randomized trial of thymectomy in myasthenia gravis (MGTX trial) and to evaluate the longitudinal changes in clinical patterns compared with these miRNA levels.MethodsSerum samples were obtained from 80 patients with MG who were included in the MGTX trial. Thirty-eight patients were randomized to thymectomy plus prednisone treatment, and 42 patients were randomized to prednisone treatment. Serum samples were analyzed for the expression of miR-150-5p and miR-21-5p, with quantitative reverse transcriptase PCR at baseline and at 12, 24, and 36 months after randomization. The inclusion criteria for participation in the MGTX trial were age 18–65 years, generalized myasthenia gravis (Myasthenia Gravis Foundation of America Class II–IV), disease duration of less than 5 years, and seropositivity for acetylcholine receptor antibodies (AChR+).ResultsPatients treated with thymectomy had lower levels of miR-150-5p at 24 months, both compared with baseline values (p = 0.0011) and the prednisone group (p = 0.04). No change in miRNA levels was found in the prednisone group. Levels of miR-21-5p displayed a negative correlation with the prednisone dose within the prednisone-only group (p ≤ 0.001).ConclusionsThymectomy lowers the levels of the proposed biomarker miR-150-5p, which strengthens its position as a potential disease-specific biomarker for AChR+ MG.

Effects of Tongbi capsule on joint lesions in rabbits with rheumatoid arthritis

The purpose of this experiment is to observe the effects of Tongbi capsule on joint lesions in rabbit with rheumatoid arthritis induced by ovalbumin and explore the mechanism in order to provide reference for clinical application of Tongbi capsule. Rheumatoid arthritis in rabbits was induced by subcutaneous injection of emulsions of ovalbumin and Freund's complete adjuvant and intra articular injection of ovalbumin. After successful modeling, 30 New Zealand rabbits with arthritis were randomly divided into model control group, the high, medium and low dose groups of Tongbi capsule (90, 45, 22.5 mg·kg⁻¹) and prednisone group (5 mg·kg⁻¹). Another six normal rabbits were used as normal control group. After 24 hours of modeling, the rabbits in Tongbi capsule groups received intragastric (i.g.) administrations of Tongbi capsule at 90, 45, 22.5 mg·kg⁻¹·d⁻¹, and the rabbits of prednisone group received i.g. administrations of prednisone at 5 mg·kg⁻¹·d⁻¹ for 2 weeks. The rabbits in normal and model groups received the same volume of distilled water at the same time. The swelling degree of rabbit knee joint and local skin temperature were observed daily. After two weeks of administration, pathological changes of rabbit knee joint were examined by magnetic resonance imaging (MRI); the morphological changes of articular cartilage and synovial membrane were observed by microscope; and the contents of interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α) in serum were detected by enzyme linked immunosorbent assay (ELISA).The results showed that 24 h after modeling, the knee joints of the rabbits were swollen, with red or dark redlocal skin, and fever, elevated local skin temperature and increased diameters of knee joints. Two weeks after modeling, the swelling of rabbit knee joints was obvious in model group; the joint cavities were filled with purulent fluid; joint synovial membranes were obviously thickened, and even joint cavities were fibrotic and cartilage surfaces showed slight defect; the surface of articular cartilage was obvious fibrosis; synovial epithelial cell proliferation was obvious and accompanied by extensive inflammatory cell infiltration; the levels of IL-1 and TNF-α were significantly higher as compared with those seen in model rabbits (P<0.05, P<0.01). After 1 and 2 weeks of administration, knee joint diameters and local skin temperatures were smaller or lower than thosein model group (P<0.05, P<0.01); The lesions of joint cartilage and synovial of all rabbits in each group were less than those in model group; IL-1 and TNF-α levels in serum were also lower than those in model group (P<0.05, P<0.01). The results reveal that high and medium doses of Tongbi capsule can suppress rheumatoid arthritis induced by ovalbumin in rabbits, reduce joint swelling, inhibit synovial epithelial and fiber hyperplasia and inflammatory cell infiltration, and alleviate articular cartilage damage. The mechanism may be associated with decreasing IL-1 and TNF-α levels in serum.

Therapeutic effects of rutaecarpine on dextran sodium sulfate-induced experimental colitis in mice

Objective: To determine the therapic effects of rutaecarpine in dextran sodium sulfate (DSS)induced experimental colitis and explore whether the protective role of rutaecarpine is related to the synthesis and release of CGRP. Methods: Fifty female BABL/c strain mice were randomly divided into untreated model control group and DSS-exposed groups.DSS-exposed groups were given administration of 5% DSS for 7 days and respectively treated with vehicle, rutacarpine(30 mg/kg, 100 mg/kg) , prednisone by intragastric administration from day 8 to day 14.The disease activity index (DAI) scores, the histological scores, the mRNA and protein concentrations of CGRP in colonic tissues were measured. Results: On day 7, the DAI scores of the DSS-exposed groups[vehicle group (8.9±0.9), low-dose Rut group(8.9±0.6), high-dose Rut group(8.2±0.8), prednisone group(8.7±1.6)] were much higher, compared with the untreated model control group(0±0)(P<0.01). The DAI scores on day 14 of the vehicle, rutaecarpine or prednisone treated groups were respectively markedly lower than on day 7(3.2±0.6, 0.9±0.6, 3.1±0.7 vs 8.9±0.6, 8.2±0.8, 8.7±1.6, P<0.05). The DAI score of mice treated with high-dose rutaecarpine was significantly lower, compared with those treated with low-dose rutaecarpine and prednisone.Compared to the untreated model control group, the histological scores in other four groups significantly increased.Comparisons of values among the post-treatment groups had statistical significance (0.2±0.4 vs 6.9±0.9, 4.5±0.9, 2.8±0.8, 5.7±0.7, P<0.01), while the high-dose rutaecarpine group presented the lowest score.The colonic mucosal CGRP mRNA and CGRP protein expressions in groups receiving vehicle, low-dose rutaecarpine and prednisone were significantly reduced than those in the untreated model control group(0.32±0.03 vs 0.15±0.02, 0.18±0.01, 0.22±0.01, P<0.01). The CGRP mRNA and CGRP protein expressions in the untreated model control group was similar to those in the DSS+ high-dose rutaecarpine group with no statistic significance between them(0.32±0.03 vs 0.31±0.02, P>0.05). Pearson correlation analysis between CGRP mRNA levels, CGRP immunohistochemisty levels and DAI, histological scores showed a statistically negative relationship respectively(r=-0.797, -0.819, -0.863, -0.845, all P<0.01). Conclusions: Rutaecarpine can ameliorate the DAI scores and histological scores of ulcerative colitis in mice.Rutaecarpine can upregulate the expressions of CGRP mRNA and CGRP protein.Correlation between CGRP mRNA, CGRP protein levels and DAI scores, histological scores respectively showed a statistically negative relationship.

Patient-reported outcomes following abiraterone acetate plus prednisone added to androgen deprivation therapy in patients with newly diagnosed metastatic castration-naive prostate cancer (LATITUDE): an international, randomised phase 3 trial

In the LATITUDE trial, addition of abiraterone acetate plus prednisone to androgen deprivation therapy (ADT) improved overall survival compared with placebos plus ADT in patients with newly diagnosed, high-risk, metastatic castration-naive prostate cancer. Understanding the effects of treatments on patient-reported outcomes (PROs) and health-related quality of life (HRQOL) is important for treatment decisions; therefore we aimed to analyse the effects of ADT plus abiraterone acetate and prednisone versus ADT plus placebos on PROs and HRQOL in patients in the LATITUDE study. In the multicentre, international, randomised, phase 3 LATITUDE trial, eligible patients were aged 18 years or older, had newly diagnosed, high-risk, metastatic castration-naive prostate cancer confirmed by bone scan (bone metastases) or by CT or MRI (visceral, soft tissue, or nodal metastases), and an Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less. Patients from 235 clinical sites in 34 countries were randomly assigned (1:1) following a country-by-country scheme done by permuted block randomisation (with two blocks) and stratified by the presence of visceral metastasis and ECOG performance status to receive ADT plus 1000 mg oral abiraterone acetate and 5 mg oral prednisone once daily or ADT plus placebos. Selection of ADT, chemical or surgical, was at the investigator's discretion. The co-primary endpoints of the trial, overall survival and radiographic progression-free survival, have been published. PRO data were collected directly on electronic tablet devices at the clinical sites during screening and before any other visit procedure on day 1 of cycles 1-3, monthly during cycles 4-13, and then every 2 months until the end of treatment, by use of the Brief Pain Inventory-Short Form (BPI-SF), Brief Fatigue Inventory (BFI), Functional Assessment of Cancer Therapy Prostate scale (FACT-P), and the EuroQol (EQ-5D-5L) questionnaires. PRO analyses were an exploratory endpoint. Analyses were by intention-to-treat. Results from the first pre-planned interim analysis (Oct 31, 2016), are presented here. This ongoing study is registered with Clinicaltrials.gov, number NCT01715285. Between Feb 12, 2013, and Dec 11, 2014, 1199 patients were randomly assigned: 597 to ADT plus abiraterone acetate and prednisone and 602 to ADT plus placebos. Median follow-up was 30·9 months (IQR 21·2-33·2) in the ADT plus abiraterone acetate and prednisone group versus 29·7 months (1·4-43·5; 16·1-31·3) in the ADT plus placebos group. Median time to worst pain intensity progression assessed by the BPI-SF score was not reached in either group (ADT plus abiraterone acetate and prednisone, not reached [95% CI not reached to not reached]; 25th percentile 11·07 months [95% CI 9·23-18·43]; ADT plus placebos group, not reached [95% CI not reached to not reached]; 25th percentile 5·62 [95% CI 4·63-7·39]; hazard ratio [HR] 0·63 [95% CI 0·52-0·77]; p<0·0001). Median time to worst fatigue intensity was not reached in either the ADT plus abiraterone acetate and prednisone group (not reached [95% CI not reached to not reached]; 25th percentile 18·4 months [95% CI 12·9-27·7]) or the ADT plus placebos group (not reached [95% CI not reached to not reached]; 25th percentile 6·5 months [95% CI 5·6-9·2]; HR 0·65 [95% CI 0·53-0·81], p=0·0001). Median time to deterioration of functional status assessed by the FACT-P total score scale was 12·9 months (95% CI 9·0-16·6) in the ADT plus abiraterone acetate and prednisone group versus 8·3 months (7·4-11·1) in the ADT plus placebos group (HR 0·85 [95% CI 0·74-0·99]; p=0·032). The addition of abiraterone acetate plus prednisone to ADT in patients with newly diagnosed, high-risk metastatic castration-naive prostate cancer improved overall PROs by consistently showing a clinical benefit in the progression of pain, prostate cancer symptoms, fatigue, functional decline, and overall HRQOL. Janssen Research & Development.

Effect of daily low dose prednisone, divided or single daily dose, in the treatment of African Americans with early rheumatoid arthritis.

Determine the effect of daily low divided or single daily dose of prednisone on the longitudinal change in the number of tender and swollen joints and HAQ scores in African Americans (AA) with early rheumatoid arthritis (RA) from the Consortium for the Longitudinal Evaluation of African Americans with Early Rheumatoid Arthritis (CLEAR) 1 Registry. In a prospective, multicenter observational cohort study, AA with early RA were enrolled and followed longitudinally for up to 5years. 345 were enrolled. The mean age at enrollment was 51years and 82% were women. At baseline, the prevalence of low dose prednisone use was 77% and median prednisone dose was 10mg. At enrollment 238 patients were on single daily and 107 on divided daily doses of prednisone. There was a significant reduction during follow-up in the number of tender and swollen joints and in the HAQ scores in all patients. Cohort retention was 54%. The adjusted mean number of tender joints was approximately 2-3 joints lower for patients on divided daily dose compared to a single daily dose in follow up. The rate of osteopenia and osteoporosis at 5years remained similar to baseline prevalence and no difference in the treatment groups. At 5years the percentage of patients with hypertension was lower in the divided daily prednisone group. During the 5years of follow-up, clinical outcomes improved in all AA patients with early RA. Reduced number of tender joints was associated with divided daily low doses of prednisone. Hypertension was less in those treated with divided daily doses of prednisone.

Effect of Single-agent Daily Prednisone on Outcomes and Toxicities in Metastatic Castration-resistant Prostate Cancer: Pooled Analysis of Prospective Studies.

The clinical effect of prednisone in metastatic castration-resistant prostate cancer (mCRPC) is unknown. We performed a pooled analysis of control arms of randomized controlled trials that had or had not administered single-agent prednisone. Randomized controlled trials with a control arm that included single-agent placebo (or no anticancer therapy) or single-agent prednisone (with or without placebo) were eligible for analysis. Patients receiving prednisone combined with other agents in the control arm were excluded. The trial characteristics, baseline demographic data, overall survival (OS), progression-free survival (PFS), prostate-specific antigen (PSA) response, Response Evaluation Criteria In Solid Tumors response, and toxicities were recorded. The effect of prednisone was investigated for significance in bivariate models, adjusting for age, pre- and post-docetaxel status, Eastern Cooperative Oncology Group performance status, and trial publication year. Eighteen trials were included; 9 had control arms that contained prednisone (n= 2831) and 9 did not (n= 2784). No significant differences were identified for OS or toxicities of anygrade. A significantly greater PSA response rate (18.8% vs. 2.5%; P= .023) and a trend toward more frequent grade≥ 3 fluid retention (1.0% vs. 0.4%; P= .097) was seen in the prednisone group. Prednisone was also significantly associated with PFS after adjusting for docetaxel status. Single-agent prednisone for mCRPC did not improve OS but was associated with a greater PSA response rate and PFS. Overall and grade≥ 3 toxicities were not significantly different with prednisone. With the exception of concurrent use with abiraterone or for palliative purposes, the routine use of prednisone for mCRPC appears unnecessary.

Analysis for the effect of different regimens on ocular myasthenia gravis in children

To evaluate the efficacy, recurrent risk factors and transferable ratio of treatments with 3 different regiments on children with systematic myasthenia gravis (MG). Methods: The data of 104 children with ocular MG from June 2010 to March 2014 were collected from Department of Pediatric Neurology of Xiangya Hospital and they were retrospectively studied. The patients were divided into 3 groups: a methylprednisolone group (n=44), a prednisone group (n=48) and a bromine pyridostigmine group (n=12). Evaluative system from American MG foundation was used to evaluate the efficacy of treatment and the ratio of ocular MG transformed into systematic MG. Results: The efficacy in the methylprednisolone group was better than that in the prednisone group, and both of them were better than that in the bromine pyridostigmine group (both P<0.05).Methylprednisolone, prednisone combined with bromine pyridostigmine could reach a better long-term efficacy in children with ocular MG. Early treatment with glucocorticoid could reduce clinical relapse. Conclusion: A treatment with high-dose methylprednisolone pulse can improve early clinical remission in children with ocular MG. However, there is a similar efficacy in the long run of different glucocorticoid therapeutic regiments. A relatively order onset age, infection and thyroid dysfunction are recurrent risk factors in children with ocular MG.

Custirsen (OGX-011) combined with cabazitaxel and prednisone versus cabazitaxel and prednisone alone in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel (AFFINITY): a randomised, open-label, international, phase 3 trial

Docetaxel and cabazitaxel improve overall survival compared with mitoxantrone in patients with metastatic castration-resistant prostate cancer. Custirsen (OGX011) is a second generation highly specific antisense oligonucleotide that inhibits the production of clusterin, an antiapoptotic protein that is upregulated in response to chemotherapy and that confers treatment resistance. We aimed to assess whether custirsen in combination with cabazitaxel and prednisone increases overall survival in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel. In this randomised, open-label, international, phase 3 trial, men with radiographically documented metastatic castration-resistant prostate cancer that had progressed after docetaxel treatment with a Karnofsky performance status of more than 70% and who were fit for chemotherapy, were recruited from 95 cancer treatment centres in eight countries. Patients were randomly assigned (1:1) centrally using permuted blocks (block size 8) to receive cabazitaxel plus prednisone (cabazitaxel 25 mg/m2 intravenously every 21 days plus oral prednisone 10 mg daily) with or without custirsen (640 mg intravenously on days 1, 8, and 15, plus three previous loading doses) until disease progression, unacceptable toxicity, or the completion of ten treatment cycles. Randomisation was stratified by use of opioids for prostate cancer-related pain at screening, disease progression following first-line docetaxel treatment established by radiographic evidence, and previous treatment with abiraterone or enzalutamide. The co-primary endpoints were overall survival in all randomly assigned patients and in a poor-prognosis subgroup. All analyses were intention to treat with the exception of safety, which was reported for patients who received any assigned treatment. The trial has been completed and the results presented here are the final analysis. This trial is registered with Clinicaltrials.gov, number NCT01578655. Between Sept 9, 2012, and Sept 29, 2014, 795 patients were screened for enrolment. 635 men were eligible for inclusion and were randomly assigned (n=317 in the cabazitaxel and prednisone plus custirsen group and n=318 in the cabazitaxel and prednisone group). Median follow up was 28·3 months (IQR 24·4-34·5) for the custirsen group and 29·8 months (IQR 25·3-35·2) for the control group. Median overall survival in all randomly assigned patients did not differ between the two groups (14·1 months [95% CI 12·7-15·9] in the curtisen group vs 13·4 months [12·1-14·9] in the control group; hazard ratio [HR] 0·95 [95% CI 0·80-1·12]; log-rank p=0·53). In the poor prognosis subgroup, median overall survival also did not differ between the two treatment groups (11·0 months [95% CI 9·3-13·3] in the custursin group vs 10·9 months [8·2-12·4] in the control group; HR 0·97 [95% CI 0·80-1·21]; two-sided p=0·80). The most frequently reported grade 3 or worse adverse events in the custirsen versus control groups were neutropenia (70 [22%] of 315 vs 61 [20%] of 312), anaemia (68 [22%] vs 49 [16%]), fatigue (23 [7%] vs 18 [6%]), asthenia (16 [5%] vs 8 [3%]), bone pain (16 [5%] vs 5 [2%]), and febrile neutropenia (16 [5%] vs 9 [3%]). Serious adverse events were reported in 155 (49%) versus 132 (42%). 27 patients died within 30 days of treatment in the cabazitaxel and prednisone plus custirsen group, seven of which were deemed to be treatment related, versus 17 in the cabazitaxel and prednisone group, eight of which were deemed to be treatment related. Of the 21 deaths reported, 15 were reported as complications related to study treatment, either chemotherapy (eight and three, respectively) or study drug (none and four, respectively). We noted no survival benefit in men with metastatic castration-resistant prostate cancer with the addition of custirsen to cabazitaxel and prednisone treatment. Cabazitaxel and prednisone remains the standard of care for patients with metastatic castration-resistant prostate cancer progressing after docetaxel chemotherapy. OncoGenex Pharmaceuticals.

Preventive effects of Polygonum multiflorum on glucocorticoid-induced osteoporosis in rats.

In Traditional Chinese Medicine, Polygonum multiflorum (PM) is known for its anti-aging properties. A previous study by our group showed that extracts of PM were able to prevent and treat bone loss in vivo, and the active components emodin and 2,3,5,4,-tetrahydroxystilbene-2-O-β-glucoside (TSG) promoted the osteogenic differentiation of mesenchymal stem cells in vitro. The aim of the present study was to investigate the preventive effects of PM on glucocorticoid-induced osteoporosis (GIO) in rats. A crude extract of PM was prepared with 75% ethanol, purified and enriched using a D-101 macroresin column and elution with 30% ethanol, and the material obtained was assessed by high-performance liquid chromatography. Male or female Sprague Dawley rats (n=180) were randomly divided into nine groups: Control, prednisone, prednisone plus calcitriol (CAL), prednisone plus 30% ethanolic eluate of PM [high (H), medium (M) and low (L) dose] and prednisone plus crude extract of PM (H, M and L dose). Prednisone was orally administered to the osteoporosis model rats for 21 weeks, alongside which they received PM extracts. The weight of the viscera, anterior tibial muscle and other tissues was recorded at the end of the experiment. The femur and lumbar vertebra were collected for the measurement of three-dimensional microarchitecture by micro-computed tomography scanning, assessment of biomechanical properties and determination of bone mineral density (BMD). In the 30% ethanolic eluate of the PM extract, the content of TSG and combined anthraquinone was 9.20 and 0.15%, respectively, and that in the crude extract of PM was 2.23 and 0.03%, respectively. Over 6 weeks, the weight of the rats the in prednisone group decreased (P<0.05), while the weight of rats treated with M and H doses of 30% ethanolic eluate was increased compared with that in the prednisone group (P<0.05). Rats exposed to prednisone exhibited a deteriorated bone microarchitecture, low BMD, decreased bone volume/total volume and poor biomechanical properties. Furthermore, the weight of the adrenal gland and the anterior tibial muscle was decreased. 30% ethanolic eluate of PM at M and L doses and crude extract of PM at the H dose counteracted the alterations of skeletal and other characteristics induced by prednisone in rats, as did CAL. In conclusion, extracts of PM exerted a protective effect on bone tissue in GIO rats.

Levocetirizine and Prednisone Are Not Superior to Levocetirizine Alone for the Treatment of Acute Urticaria: A Randomized Double-Blind Clinical Trial

We evaluate the efficacy of a 4-day course of prednisone added to antihistamine for the management of acute urticaria in an emergency department (ED). In this double-blind randomized clinical trial, patients were eligible for inclusion if aged 18 years or older and with acute urticaria of no more than 24 hours' duration. Patients with anaphylaxis or who had received antihistamines or glucocorticoids during the previous 5 days were not included. In addition to levocetirizine (5 mg orally for 5 days), patients were assigned to receive prednisone (40 mg orally for 4 days) or placebo. The primary endpoint of the study was itching relief 2 days after the ED visit, rated on a numeric scale of 0 to 10. Secondary endpoints were rash resolution, relapses, and adverse events. A total of 100 patients were included, 50 in each group. Seven patients in the prednisone group and 8 in the placebo group discontinued treatment. At 2-day follow-up, 62% of patients in the prednisone group had an itch score of 0 versus 76% of those in the placebo group (Δ 14%; 95% confidence interval -31% to 4%). Thirty percent of patients in the prednisone group and 24% in the placebo group reported relapses (Δ 6%; 95% confidence interval -23% to 11%). Mild adverse events were reported by 12% of patients in the prednisone group and 14% in the placebo group. The addition of a prednisone burst did not improve the symptomatic and clinical response of acute urticaria to levocetirizine. This study does not support the addition of corticosteroid to H1 antihistamine as first-line treatment of acute urticaria without angioedema.