Areas covered: This review focuses the BBB receptors/transporters to be exploited in regard to their overall structure and biologic function, as well as their role in the development of strategies envisaging drug delivery to the brain. Then, the interplay between the targeting of these BBB receptors/transporters and nanotechnology is explored, as they can increase by several-fold the effectiveness of brain-targeted therapies.
Expert opinion: Nanomedicine may be particularly useful in brain drug delivery, mainly due to the possibility of functionalizing nanoparticles to target specific receptors/transporters. Since the BBB is endowed with numerous receptors and transporters responsible for regulating the proper metabolic activity of the brain, their targeting can be a promising bypass strategy to circumvent the hurdle that the BBB represents for brain drug delivery. 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
Areas covered: We have tried to review the current status of nanotheranostic based approaches followed to manage neurological disorders. The focus has been majorly laid on to explore various theranostic nanoparticles and their application potential towards image-guided neurotherapies. Additionally, the usefulness of exceptional diagnostic, imaging techniques including magnetic resonance imaging and fluorescence imaging are being discussed by highlighting their promising opportunities in the detection, diagnosis, and treatment of the neurological disorders.
Expert opinion: Inimitable diagnostic and therapeutic potential of nanotheranostics have accomplished the aim of personalized therapies by governing the therapeutic efficacy of the system along with facilitating patient pre-selection grounded on non-invasive imaging, thereby predicting the responses of patients to nanomedicine treatments. While these accomplishments are encouraging, they are still the minority and demands for a continuous effort to improve sensitivity and precision in screening/diagnosis along with improving therapeutic efficacy in various neural disorders. 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
Methods: A randomized crossover study in healthy subjects (N = 161) examined the bioequivalence, safety, and tolerability of tocilizumab after a single subcutaneous injection by AI versus PFS. A nonrandomized observational, real-life human factors study in RA patients (N = 54) assessed user (RA patients, caregivers, health care providers) ability to administer tocilizumab effectively by AI.
Results: Bioequivalence criteria for tocilizumab AI versus PFS were met for key pharmacokinetic parameters. Safety was comparable between devices and consistent with the established tocilizumab profile. In the real-life human factors study, the proportion of users who successfully performed all essential tasks required to operate the AI to deliver the full dose was 92.3% at first assessment and 98.1% at second assessment, with no safety concerns.
Conclusions: Tocilizumab administration by AI was bioequivalent to administration by PFS. Intended users were successful in performing the tasks required to administer tocilizumab by AI. No new safety signals were observed in either study.
Clinical Trial Registration: NCT02678988, NCT02682823 相似文献
Method: Original data consists of personal interviews with 1163 substance misusers treated in inpatient units in Sweden during 1982-1983. The outcome variable is death retrieved from the National Cause of Death Register held by the National Board of Health and Welfare. Gender differences and similarities regarding predictors of mortality was estimated in univariate and multivariate models, using Cox proportional hazards models.
Results: School failure, imprisonment and being a parent without custody of the child seem to constitute risk factors for mortality among women, but not among men. A social network of friends seemed to be more important for men. Treatment-dropout was a significant risk factor for premature death among men, but not among women. Both gender reporting alcohol as their self-reported most dominant substance misuse showed higher mortality risks compared with those with stimulants as dominant substance misuse.
Conclusions: Imprisonment was highly predictive of mortality for the women, suggesting that this group is important to pay particular attention to. Suggested differences in the importance of social factors need to be investigated more thoroughly. The substantial hazard revealed for women with polydrug misuse including alcohol calls for attention to this in treatment for substance misuse. 相似文献
Research, design and methods: Three databases were searched for spontaneous AERs associated with celecoxib, submitted within the past 10 years: Australian Therapeutic Goods Administration Database of Adverse Event Notifications; Canada Vigilance Adverse Reaction Online Database; and the United States Food and Drug Administration Adverse Event Reporting System Database. Analysis of the AERs focussed on the identification of gastrointestinal, cardiovascular and renal adverse events and concomitant medications suspected of potentiating adverse event risks.
Results: A total of 24,232 celecoxib AERs were identified. Gastrointestinal disorders were the most frequently reported adverse events at the system organ class (SOC) level in the AERs. A large number of AERs documented the use of potentially inappropriate concomitant medicines which may have increased the risk of the reported adverse events.
Conclusions: The large number of reports that involved a concomitant medicine that was in contravention with prescribing guidelines indicates an increased need for efforts to support the safe prescribing of celecoxib. 相似文献
Areas covered: Herein, the authors review genetic, demographic, socioeconomic, nutritional and lifestyle risks associated with schizophrenia in pregnancy. They also cover specific risks associated with typical antipsychotic medications, specific risks associated with atypical antipsychotic medications, risks associated with polypharmacy and risks of developmental delay in children exposed to antipsychotic medications in utero.
Expert opinion: Our understanding of the risks that women with schizophrenia face in pregnancy from their illness and from the treatment they receive continues to evolve. As our ability to analyze data progresses, the risks conferred by antipsychotic medication treatment appear to lessen in clinical and statistical significance, whilst the true risks to these women and their babies from their experience of disadvantage continue to set them aside from the general population. Reducing polypharmacy and providing comprehensive and supportive care can minimize harm to women with schizophrenia and their babies. 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
Methods: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from 1966 to May 24, 2016 for randomized controlled trials. Two reviewers evaluated studies for eligibility, serially abstracted data, evaluated risk of bias, and graded strength of evidence (SOE) for critical outcomes (pain and quality-of-life).
Results: Twenty-three trials were included. For pain, alpha-lipoic acid was more effective than placebo (moderate SOE) and frequency-modulated electromagnetic stimulation was more effective than sham (low SOE) in the short-term but not the long-term. Electrical stimulation (including transcutaneous) was not effective for pain (low SOE). Spinal cord stimulation was more effective than usual care for pain (low SOE), but had serious complications, and studies had no sham arm. Evidence for cognitive behavioral therapy and acupuncture was insufficient; no exercise or physical therapy trials met inclusion criteria. No interventions reported sufficient evidence on quality-of-life. Most studies were short-term with unclear risk of bias.
Conclusions: Alpha-lipoic acid and spinal cord stimulation were effective for pain; studies were short-term with quality deficits. Spinal cord stimulation had serious adverse events. Further research should address long-term outcomes and other non-pharmacologic treatments. 相似文献
Methods: A cross-sectional, online survey using a validated questionnaire was administered to pharmacists working in community and hospital pharmacies in Saudi Arabia.
Results: 1,717 community and 153 hospital pharmacists participated in this study. Only 10.2% and 26.8% of community and hospital pharmacists, respectively, admitted ever reporting an ADR. The most reported factors that may facilitate ADRs reporting have included ongoing improvements in therapeutic knowledge about ADRs, attending educational programs with continuous medical education credits, the seriousness of the experienced ADRs and accessibility to patients’ medical profile. The impact of peers by seeing colleagues reporting ADRs and ADRs due to herbal or traditional medicine were the least important factors reported by pharmacists.
Conclusion: The study identified factors that can effectively address the under-reporting of ADRs by pharmacists. A multi-stakeholder, multi-pronged approach of ADR reporting is needed to develop greater awareness of this issue among pharmacists. 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: The purpose of this article is to survey the use of pharmacotherapy to treat different pathophysiological complications of burn injury. The author, herein, discusses the use of drug treatments for a number of systemic metabolic disturbances including hyperglycemia, elevated catabolism, and gluconeogenesis.
Expert opinion: Advancements in personalized and molecular medicine will make an impact on burn therapy. Similarities between severe burns and other critically ill patients will lead to cross-fertilization between different medical specialties. Furthermore, advances in stem cells and tissue regeneration will lead to improved healing and less lifelong disability. Indeed, research in new drug therapy for burns is actively progressing for many different complications. 相似文献
Methods: Relevant information was identified through a comprehensive literature search of several databases using the keywords pegvaliase, rAvPAL-PEG, and phenylketonuria. Additional information was gathered from the pegvaliase package insert, posters presented at scientific meetings, and materials provided from the manufacturer, BioMarin.
Results: Pegvaliase is effective in decreasing blood phenylalanine levels, and is associated with a manageable side-effect profile. Phase III clinical trial data demonstrated that 60.7% of patients were able to achieve blood phenylalanine levels less than the guideline recommended 360 µmol/L at 24 months. Brief sub-studies also showed the improvement in inattention symptoms in patients treated with pegvaliase, compared to placebo.
Conclusion: Pegvaliase is a promising new treatment option for adults living with PKU. Further studies are warranted to determine long-term safety and clinical efficacy in sub-populations. 相似文献
Methods: Ca-alginate beads were produced by electrostatic extrusion process. Gelatine/alginate coacervates were processed with coacervation. Carnauba wax microparticles were produced using melt dispersion process. Morphological properties, chemical, and thermal stabilities of encapsulates were tested by SEM, FTIR spectral, and thermogravimetric analysis.
Results: Alginate provided sufficient emulsion stability over 1?h. Ca-alginate showed higher encapsulation efficiency (EE) (98.4?±?4.3%) compared to carnauba wax (94.2?±?7.8%) and gelatine/alginate coacervates (13.2?±?1.2%). The presence of essential oil in all three types of encapsulates confirmed with FTIR. The encapsulation process ensured controlled release and thermal stability of the oil.
Conclusions: Ca-alginate matrix as the most suitable for peppermint essential oil encapsulation. The sensory analysis showed that ice cream incorporating encapsulates is a promising system for the consumption of health beneficial peppermint essential oil. 相似文献
Areas covered: This article reviews the principal pharmacological intervention studies for FTD. These are predominantly randomized clinical trials and include symptomatic treatments and potential disease-modifying drugs.
Expert opinion: There is insufficient evidence on effective treatments for FTD and studies with better methodological backgrounds are needed. Most studies reporting therapeutic benefits were conducted with selective serotonin reuptake inhibitors, while anti-dementia drugs have been ineffective in FTD. Since the underlying pathology of FTD mostly consists of abnormal tau protein or TDP-43 aggregates, treatments are being developed to interfere with their aggregation process or with the clearance of these proteins. Furthermore, disease-modifying treatments remain years away as demonstrated by the recent negative Phase III findings of a tau aggregation inhibitor (LMTM) for treating the behavioral variant of FTD. The results from current ongoing Phase I/II trials will hopefully give light to future treatment options. 相似文献
Methods: TD-MN system consisted of an array of tearable dissolving microneedles (TD-MN) and micro-pillars. The microneedle tips had a female part to integrate with the micro-pillars. The micro-pillars exerted a vertical force to cause the separation of the tips from the base. The separation force exerted by six TD-MN arrays with different thicknesses of separation region was measured. The TD-MN system with trypan blue was inserted into porcine skin to observe the separation of the microneedle tips, and then calcein was added separately to observe drug diffusion into the skin.
Results: The thickness of the tearable region and the depth of the female part were a function of the concentration and volume of the molding solution. The separation force increased as the thickness of the tearable region increased. Nine tips were successfully separated from the base by applying a force of through the micro-pillars.
Conclusions: The TD-MN system could provide immediate administration of a drug, resulting in improved patient convenience as well as delivery of the correct drug dose. 相似文献