Methods: In this phase 2, open-label study (NCT02565810; EudraCT Number 2014-004887-39), adult RA patients self-administered 40?mg SB5 subcutaneously via PFS at weeks 0 and 2, followed by AI at weeks 4, 6, 8, and 10. Patients rated injection site pain from 0 (no pain) to 10 (severe pain) using a visual numeric scale immediately and 15–30?min post-injection at weeks 0, 2, 4, and 6. Equivalence between PFS and AI was concluded if the 97.5% confidence interval (CI) of the difference in the injection site pain scores at weeks 2 and 6 was contained within the equivalence margin of ±5. Overall impression and preference for PFS and AI were also evaluated. Safety was assessed up to 20?weeks after the first injection.
Results: Of 49 patients enrolled, 48 completed the study. Mean injection site pain scores were equivalent between PFS and AI immediately (2.3 vs 2.0; 97.5% CI = ?0.99–0.30) and 15–30?min post-injection (0.8 vs 0.7; 97.5% CI = ?0.47–0.25). The overall impression of both devices was comparable. The overall preference of AI was higher than PFS. Treatment-emergent adverse events (TEAE) were mild-to-moderate. There were no severe or serious TEAEs reported during the study.
Conclusions: In RA patients, SB5 showed equivalent injection site pain and comparable safety when administered via PFS and AI. 相似文献
Objective: Evaluation of the peripapillary choroidal layer in the patients receiving oral isotretinoin therapy may aid in explaining the pathophysiology of ocular side effects.
Methods: In this study, peripapillary choroidal thickness was assessed in the patients receiving oral isotretinoin treatment via optical coherent tomography technique.
Results: Significant difference was found in the superotemporal and temporal areas.
Conclusion: Oral isotretinoin treatment may affect the thickness of the peripapillary choroidal layer. 相似文献
Aim: Microencapsulate lavender oil by spray drying using a biocompatible polymeric blend of gum acacia and maltodextrin to protect the oil components. Effect of total polymer content, oil loading, gum acacia, and maltodextrin proportions on the size, yield, loading, and encapsulation efficiency of the microparticles was investigated.
Methods: Morphology and oil localisation within microparticles were assessed by confocal laser scanning electron microscope. Structural preservation and compatibility were assessed using Fourier transform infra-red spectroscopy, differential scanning calorimetry, and gas chromatography–mass spectrometry.
Results: Lavender microparticles of size 12.42?±?1.79?µm prepared at 30 w/w% polymer concentration, 16.67 w/w% oil loading, and 25w/w% gum acacia showed maximum oil protection at high loading (12?mg w/w%), and encapsulation efficiency (77.89 w/w%).
Conclusion: Lavender oil was successfully microencapsulated into stable microparticles by spray drying using gum acacia/maltodextrin polymeric blend. 相似文献
Research design and methods: This multicenter, open-label, single-group, prospective interventional study evaluated changes in total gait-related scores of the Part II/III Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and Freezing of Gait Questionnaire (FOG-Q) in 31 Parkinson’s disease patients treated with istradefylline. Gait analysis by portable gait rhythmogram was performed.
Results: MDS-UPDRS Part III gait-related total scores significantly decreased at Weeks 4–12 from baseline with significant improvements in gait, freezing of gait, and postural stability. Significant decreases in MDS-UPDRS Part II total scores and individual item scores at Week 12 indicated improved daily living activities. At Week 12, there were significant improvements in FOG-Q, new FOG-Q, and overall movement per 48 h measured by portable gait rhythmogram. Adverse events occurred in 7/31 patients.
Conclusions: Istradefylline improved gait disorders in Parkinson’s disease patients complicated with freezing of gait, improving their quality of life. No unexpected adverse drug reactions were identified.
Trial registration: UMIN-CTR (UMIN000020288). 相似文献
Methods: We evaluated a historical cohort composed of users of the Brazilian National Health System in the period between 2006 January and 2014 December. The endpoint was the medication persistence at 12 months.
Results: A population composed of 66,787 individuals started the first line of biological drug. Out of such individuals, 34,595 (51.80%) persisted in the treatment at 12 months. Abatacept was the drug that presented higher persistence, followed by golimumab, tocilizumab, etanercept, and adalimumab and, with lower persistence certolizumab and infliximab. Younger individuals, living in regions with higher social inequality by Gini coefficient, using certolizumab and infliximab in comparison with adalimumab presented a higher risk of non-persistence to treatment. Individuals from the Southeastern region were more persistent than Northeastern, Central-western, Northern and Southern regions.
Conclusion: The medication persistence was different between biological drugs. The rigorous follow-up of patients, by a multidisciplinary team, is important to enable the development of strategies for the adequate use of such drugs. 相似文献
2. Mass balance of a single intravenous WTX101 dose, measured as molybdenum (Mo), was assessed over 168?h in control (Long Evans Agouti [LEA]) and Long-Evans Cinnamon (LEC) rats, a WD model.
3. In LEC rats, Mo was partially excreted (up to 45%); 29% by renal clearance, and faecal clearance, still ongoing at 168?h, accounted for 16%. In contrast, in LEA rats, Mo was almost fully excreted (~87%); 79% was renally cleared with only 7% faecal excretion.
4. In LEC rats, the proportion of faecal to renal Mo excretion was enhanced (4:6) compared to controls (1:9).
5. Substantially more Mo was found in LEC liver and kidney compared with LEA tissues, in line with tissue Cu distribution.
6. These findings are consistent with the WTX101 mechanism of action: in the WD model, excess Cu is removed from hepatic metallothionein and retained within the stable tetrathiomolybdate-Cu-albumin tripartite complex, preventing tetrathiomolybdate degradation and resulting in less urinary elimination and greater faecal excretion than in controls. 相似文献
Areas covered: This paper focuses on the pathophysiology of transplantation-related AKI and recent findings on cellular stress responses at the intersection of 1. The Unfolded protein response; 2. Mitochondrial dysfunction; 3. The benefits of mineralocorticoid receptor antagonists. Lastly, perspectives are offered to the readers.
Expert opinion: Renal IRI is caused by a sudden and temporary impairment of blood flow to the organ.
Defining the underlying cellular cascades involved in IRI will assist us in the identification of novel interventional targets to attenuate IRI with the potential to improve transplantation outcomes. Targeting mitochondrial function and cellular bioenergetics upstream of cellular damage may offer several advantages compared to targeting downstream inflammatory and fibrosis processes.
An improved understanding of the cellular pathophysiological mechanisms leading to kidney injury will hopefully offer improved targeted therapies to prevent and treat the injury in the future. 相似文献
Materials and methods: The study was developed in an installed additive manufacturing machine, having controlled temperature and humidity in an industrial unit where metal parts were being produced using stainless steel powders of granulometry of 10 to 35?μm.
Results and discussion: Monitoring of airborne nanoparticles emission was made using adequate equipment, which showed considerable number of nanoparticles over the baseline, having the same composition as the steel powder used.
Conclusion: It is concluded that the values of professional exposure to nanoparticles are high in these workstations and that the nanoparticles to which the workers are exposed are small in size (around 15?nm), thus having a strong capacity for alveolar penetration and, consequently, with a strong possibility of passing to the bloodstream, accumulating in the body. 相似文献
Methods: We studied 200 patients: 100 hypertensive and 100 normotensive. The parameters we evaluated included: patient age, ABI, IMT, PWV, serum uric acid and serum C-reactive protein (CRP). In addition, the cardiovascular risk according to the SCORE and Framingham scales was assessed.
Results: In the hypertensive group, there were significant correlations between ABI and the Framingham scale in both sexes. In hypertensive women, there were also significant correlations between IMT and the SCORE scale risk, and IMT and the Framingham scale risk.
In normotensive women, there were significant correlations between ABI and the SCORE scale risk, and between ABI and the Framingham scale risk. In normotensive men, there were significant correlations between PWV and the SCORE scale risk, and between PWV and the Framingham scale risk. Lastly, in the group of normotensive men, there were significant correlations between IMT and the SCORE scale risk, and IMT and the Framingham scale risk.
The possibility of correctly classifying a patient into the high-risk category by a logistic regression model using synchronous ABI, IMT and PWV was high – 74% for the risk according to the SCORE scale (66% in men, 88% in women), and 98% for the Framingham scale.
Conclusions: The addition of recognized subclinical target organ damage tests to the estimation of cardiovascular risk can significantly strengthen the prevention of cardiovascular disease.
Cardiovascular risk estimation follow-up with ABI, PWV and IMT increased the probability of correctly classifying people, especially women, into an at least high-risk category according to the SCORE scale, which has valuable therapeutic implications. 相似文献
Methods: Poly (lactic-co-glycolic acid) (PLGA) MPs loaded with pIGF-1 were prepared, characterised and evaluated using double emulsion solvent evaporation method.
Results: Spherical MPs showed an average particle size of 2?µm, encapsulation efficiency (EE) of 67% and 50% degradation over 15?days. With a view to enhancing retention in the myocardium, the MP formulation was encapsulated in a cross-linked hyaluronic acid hydrogel. pIGF-1 released from MPs and from MPs suspended in hyaluronic acid hydrogel remained bioactive, determined by a significant increase in cellular proliferation of c-kit+ cells.
Conclusion: This formulation has potential for loco-regional delivery to damaged myocardium to promote the survival of cardiomyocytes. 相似文献
Design and methods: Inductive content analysis was used to analyze the experiences of 31 Greek addiction professionals who participated in focus groups.
Findings: Professionals adopted various interventions which included (a) respond to parents quest for help, (b) involvement of the distant parent in treatment, (c) boundary setting, (d) facilitation of parent-child communication, and (e) support of parental changes. These interventions were perceived as necessary, both for motivating and sustaining the client’s change, and for alleviating the parents’ chronic grief and distress over their child’s addiction.
Conclusion: Overall, addiction professionals perceived low intensity interventions, information giving, and non- judgmental informal interactions as catalysts for the parents involvement in addiction treatment. 相似文献
Purpose: Characteristics of the main safety parameters of biosimilar hormone preparations licensed by EMA.
Methods: This paper analyzes the results demonstrating the similarities and differences between biosimilar and reference hormone products indicated in the EPAR (public assessment report) for the examination of materials presented for the licensing of biosimilar products.
Results: During the development of biosimilar hormone medicines, differences in the glycosylation profile between biosimilar and reference preparations are revealed. As biotherapeutical preparations are produced by cells, the differences in glycosylation profile between biosimilar and referent preparation are predictable. While carrying out clinical studies, a high similarity of biosimilar and reference product effectiveness is shown, but some differences between them in the safety profile are revealed.
Conclusions: The study of biosimilar product safety has shown the necessity of further improvement in safety and standard approaches for the assessment of the immunogenicity of biosimilar products. 相似文献
Objectives: To investigate levels of secondary cannabis use among drug treatment clients and perceived need for support addressing this use among clients and staff.
Methods: Cross-sectional surveys of clients (N?=?295) and staff (N?=?33) were conducted in 2015 at four London drug and alcohol treatment services. Client measures included recent drug use, type of cannabis used, Severity of Dependence Scale for cannabis, and views on secondary cannabis use treatment. Staff measures included definition of problem cannabis use, importance and timing for addressing secondary cannabis use.
Results: Among clients, 39.7% reported recent secondary cannabis use, with 30.8% of these clients meeting criteria for problem use. Problem users were more likely to be interested in receiving treatment for cannabis use than non-problem users (51.4% versus 10.8%, p?<?.001). Nearly half of staff (48.5%) thought secondary cannabis use should be addressed early in treatment.
Conclusions: Two out of five drug treatment clients used cannabis and a third experienced cannabis-related problems. Many are willing to address cannabis use, but defined treatment pathways are needed. 相似文献
Methods: A matching-adjusted indirect comparison method was implemented to adjust for cross-trial differences in patient characteristics between ASCEND-4 and PROFILE 1014 trials. Patient-level data from ASCEND-4 and published summary data from PROFILE 1014 were used. Patients in ASCEND-4 were reweighted to match average baseline characteristics (i.e. age, sex, race, tumor histology, ECOG score, smoking status, extent of disease, and presence of brain metastases) reported for PROFILE 1014 patients using propensity score weighting. PFS and OS were then compared between balanced populations.
Results: ASCEND-4 included more current smokers (8.0% vs 4.4%) and fewer patients under the age of 65 years (78.5% vs 84.0%) compared to PROFILE 1014. After matching, these and all other patient characteristics were balanced between the two trial populations. Compared to crizotinib, ceritinib was associated with a significantly longer PFS (hazard ratio [95% confidence interval] (HR [CI])?=?0.64 [0.47–0.87]; median PFS: 25.2 vs 10.8 months, log-rank p-value?=?0.003). OS did not differ significantly, with a HR of 0.82 [0.54–1.27] for ceritinib compared to crizotinib.
Conclusions: In the adjusted indirect comparison with external controls, the second generation ALK inhibitor, ceritinib, was associated with a significantly prolonged PFS compared to crizotinib as first-line treatment for ALK-positive NSCLC. 相似文献
2. Serum concentrations of ADC and total antibody were detected using validated ELISA methods. The results showed low systemic clearance of both ADC and total antibody in all three species as reflected by gradual decrease in serum concentrations. Half-life (t1/2) of ADC ranged from 4.6 to 11.3?days in the three species.
3. Tissue distribution study in tumor-bearing mice showed high accumulation of 125I-SHR-A1403 in tumor tissues over the other organs/tissues, indicating the favorable safety of SHR-A1403 and characteristics of an ADC drug.
4. Relatively low grade of anti-drug antibody (ADA) in monkeys had no impact on PK profile of the ADC.
5. During discovery stage, undesirable exposure and/or ADA incidence were observed for SHR-A1403 with high or low drug-antibody ratio (DAR), which was DAR?=?5 to 6 and DAR?=?1, respectively, and therefore prompted selection of an appropriate DAR value (DAR?=?2) for SHR-A1403 used in preclinical development and clinical trials.
6. In conclusion, our work demonstrated favorable PK characterization of SHR-A1403, and supported for investigational new drug application (IND) and the ongoing first-in-human trial in the US. 相似文献
Research design and methods: Three Phase I trials were conducted: a single rising-dose study and a multiple rising-dose study to evaluate the safety, tolerability, and pharmacokinetics of BI 653048, and a multiple parallel-arm-dose study with intravenous lipopolysaccharide challenge to assess in vivo pharmacodynamics. The pharmacodynamics, efficacy, and safety of BI 653048 and prednisolone were compared.
Results: Treatment with 200 mg BI 653048 was associated with a reduced expression of IL1R2, ITGB3, and SDPR versus 20 mg prednisolone; comparable levels of FKBP5, ZBTB16, and DDIT4 expression were observed. Changes in C-peptide, glucose, insulin, and cortisol were moderate compared with prednisolone. A greater reduction of osteocalcin was observed with 200 mg BI 653048 versus 20 mg prednisolone. Comparable anti-inflammatory efficacy was demonstrated for 200 mg BI 653048 and 20 mg prednisolone. BI 653048 was well tolerated in healthy subjects.
Conclusion: BI 653048 demonstrated the desired anti-inflammatory effects of the nonsteroidal GC; however, the undesirable side-effect profile associated with GC steroids could not be disassociated from BI 653048.
Trial registration: ClinicalTrials.gov identifiers NCT02217644, NCT02217631, and NCT02224105. 相似文献
Areas covered: A literature search on ‘HDAC inhibitors’ and ‘multiple myeloma’ was carried out using PubMed and Google Scholar in the preparation of this overview on clinical efficacy and safety data.
Expert opinion: First-generation non-selective HDAC inhibitors have demonstrated minimal single-agent activity in refractory MM. Subsequently, combination therapy has proven an improvement in progression-free survival (PFS) but not response rates. The main concerns are associated with toxicities. Ongoing studies on new and more selective agents, i.e. Romidepsin or Ricolinostat, are promising in terms of better efficacy and less toxicity. 相似文献
Methods: MAIC is a propensity score-type method that adjusts for differences in baseline characteristics between trials to estimate relative efficacy. Analyses were based on patient-level data from the ALTA trial for brigatinib and published summary-level trial data from ASCEND-1 and ASCEND-2 for ceritinib and NP28761 and NP28673 for alectinib. Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were compared.
Results: After matching, all key baseline characteristics were balanced between trials. Compared with ceritinib, brigatinib was associated with longer PFS (ASCEND-1: median 15.7 vs 6.9 months, hazard ratio (HR) [95% confidence interval]?=?0.38 [0.26–0.57]; ASCEND-2: median?=?18.3 vs 7.2 months, HR?=?0.33 [0.20–0.56]) and OS (ASCEND-1: not available; ASCEND-2: median 27.6 vs 14.9 months, HR?=?0.33 [0.17–0.63]). Versus alectinib, brigatinib was associated with longer PFS (NP28761: median?=?17.6 vs 8.2 months, HR?=?0.56 [0.36–0.86]; NP28673: median?=?17.6 vs 8.9 months, HR?=?0.61 [0.40–0.93]); results for OS were inconclusive (NP28761: median?=?27.6 vs 22.7 months, HR?=?0.70 [0.42–1.16]; NP28673: median?=?27.6 vs 26.0 months, HR?=?0.66 [0.39–1.09]). ORR was similar.
Conclusion: In crizotinib-refractory ALK?+?NSCLC patients, relative efficacy estimates suggest brigatinib may have prolonged PFS and OS vs ceritinib and prolonged PFS vs alectinib. 相似文献