Background
In the past decade, migraine research has identified novel drug targets. In this review, we discuss recent data on emerging anti-migraine therapies.
Main body
The development of ditans, ...gepants and anti-calcitonin gene-related peptide monoclonal antibodies for the treatment of migraine is one of the greatest advances in the migraine field. Lasmiditan, rimegepant and ubrogepant will extend our therapeutic armamentarium for managing acute migraine attacks when triptans are not effective or contraindicated due to cardiovascular disorders. The monoclonal antibodies are migraine specific prophylactic drugs with high responder rates and favorable adverse event profiles. Furthermore, they offer convenient treatment regimens of 4- or 12-week intervals.
Conclusion
Collectively, novel migraine therapies represent a major progress in migraine treatment and will undoubtedly transform headache medicine.
Objective
To narratively review the pathophysiological rationale of dual therapy with anti‐calcitonin gene‐related peptide monoclonal antibodies and botulinum toxin type A in treatment‐resistant ...chronic migraine prevention.
Background
For the prevention of chronic migraine, several pharmacological therapies are available, including oral medications, botulinum toxin type A, and the newly approved monoclonal antibodies targeting calcitonin gene‐related peptide or its receptor. However, monotherapy does not yield benefits in some affected individuals, which raises the question of whether dual therapy with monoclonal antibodies and botulinum toxin type A hold promise in patients with treatment‐resistant chronic migraine.
Method
We searched MEDLINE for articles published from database inception to December 31st, 2019. Publications were largely selected from the past 10 years but commonly referenced and highly regarded older publications were not excluded.
Results
Preclinical data suggest that anti‐calcitonin gene‐related peptide monoclonal antibodies and botulinum toxin type A have synergistic effects within the trigeminovascular system. Of note, findings indicate that fremanezumab – an antibody targeting the calcitonin gene‐related peptide – mainly prevents the activation of Aδ‐fibers, whereas botulinum toxin type A prevents the activation of C‐fibers.
Conclusion
There is currently only indirect preclinical evidence to support a rationale for dual therapy with anti‐calcitonin gene‐related peptide monoclonal antibodies and botulinum toxin type A for chronic migraine prevention. Rigorous studies evaluating clinical efficacy, safety, and cost‐effectiveness are needed.
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Acute myocardial infarction (MI) caused by ischemia is the most common cause of cardiac dysfunction. While growth factor therapy is promising, the retention in the highly vascularized ...myocardium is limited and prevents sustained activation needed for adequate cellular responses. Here, we demonstrated the use of polyethylene glycol-fibrinogen (PF) hydrogels for sustained dual delivery of vascular endothelial growth factor (VEGF) and angiopoietin-1 (ANG-1) to enhance myocardial repair and function. VEGF and ANG-1 were incorporated in PF hydrogels and their in vitro characteristics were studied. Acute MI was generated in a rodent model with rats randomly assigned to 4 groups; sham, saline, PF and PF-VEGF-ANG1 (n=10 each group). Saline or hydrogel was injected in infarct and peri-infarct areas of the myocardium. After 4weeks, myocardial function was assessed using echocardiography. Tissue samples were harvested for Hematoxylin and Eosin, Masson Trichrome and capillary staining to assess the extent of fibrotic scar and arteriogenesis. Both VEGF and ANG-1 were released in a sustained and controlled manner over 30days. PF-VEGF-ANG1 treated animals showed the best improvement in cardiac function, highest degree of cardiac muscle preservation, and arteriogenesis. This study demonstrates that PF hydrogels can simultaneously provide mechanical support to attenuate adverse myocardial remodelling, and a pro-angiogenic benefit from the sustained VEGF and ANG1 delivery that culminates in a restorative effect following MI. The utility of this synergistic, biomaterial-based growth factor delivery may have clinical implications in the prevention of post-MI cardiac dysfunction.
Acute myocardial infarction (MI) caused by ischemia is the most common cause of cardiac dysfunction. Here, we demonstrated the use of polyethylene glycol-fibrinogen (PF) hydrogels for sustained dual delivery of vascular endothelial growth factor (VEGF) and angiopoietin-1 (ANG-1) to enhance myocardial repair and function. Treated animals showed the best improvement in cardiac function, highest degree of cardiac muscle preservation, and arteriogenesis. This study demonstrates that PF hydrogels can simultaneously provide mechanical support to attenuate adverse myocardial remodelling, and a pro-angiogenic benefit from the sustained VEGF and ANG1 delivery that culminates in a restorative effect following MI.
In this study, the effect of coated hydrogel layer on characteristics of the whole gelatin/silver nanoparticles multi‐coated polycaprolactone membrane (PCLGelAg) was investigated through systematic ...and typical wound dressing characterizations to select the optimal number of layers for practical applications. Scanning electron microscopy, free swell absorptive capacity and tensile test in both wet and dry conditions were conducted to characterize all fabricated membranes of six coating times. In vitro cytotoxicity and agar diffusion evaluation were also carried out to assess the biocompatibility and antibacterial activity of the membranes. The findings illustrated that as the coated layers increase, the absorptive capacity, and degradation rate were higher, the membranes were stiffer in dry state while the tensile strength in wet state, elongation, and cell viability were significantly decreased. PCLGelAg3 was chosen to be the best fit for wound healing since it maintained quite sufficient maximum buffer uptake, elasticity, cell viability along with inducing abnormalities in bacterial morphology and preventing biofilm formation.
Large demands for water in industry and consumer markets have led to the development of seawater desalination plants worldwide. Electrodialysis allows the removal of ions at a much lower specific ...energy consumption than pressure-driven systems and holds the potential to move the desalination industry to greater water yields, lowering the degree of water wasted and energy required for separations. This study investigates the use of traditional electrodialysis as well as electrodeionization for the removal of contaminant ions from brackish water as well as samples from industrial sources. Results indicated that conventional electrodeionization can successfully remove ion contaminants from brackish water at specific energy consumptions of approximately 0.9–1.5kWh/m3 water recovered with high water productivity at 40–90L/m2h. Ion-exchange resin wafer electrodeionization showed greater promise with specific energy consumption levels between 0.6–1.1kWh/m3 water recovered and productivity levels between 10–40L/m2h. From these results, electrodialysis and electrodeionization have demonstrated viability as alternatives to pressure-driven membrane systems for brackish water desalination.
Comparison of SEC for ED, ED, and RO separation processes. At low inlet salinities, ED and EDI are favorable while at high salinities RO becomes favorable. This suggests two regimes where the ideal separation process can be determined from feed conditions. Display omitted
•Electrodialysis and electrodeionization of brackish water was conducted.•Systems demonstrated low specific energy consumption for low inlet salinity feeds.•Competitive electrodeionization techniques are discussed for desalination.
Background
Migraine aura (MA) is a common and disabling neurological condition, characterized by transient visual, and less frequently sensory and dysphasic aura disturbances.
MA is associated with ...an increased risk of cardiovascular disorders and is often clinically difficult to distinguish from other serious neurological disorders such as transient ischemic attacks and epilepsy. Optimal clinical classification of MA symptoms is important for more accurate diagnosis and improved understanding of the pathophysiology of MA through clinical studies.
Main body
A systematic review of previous prospective and retrospective systematic recordings of visual aura symptoms (VASs) was performed to provide an overview of the different types of visual phenomena occurring during MA and their respective frequencies in patients. We found 11 retrospective studies and three prospective studies systematically describing VASs. The number of different types of VASs reported by patients in the studies ranged from two to 23. The most common were flashes of bright light, “foggy” vision, zigzag lines, scotoma, small bright dots and ‘like looking through heat waves or water’.
Conclusions
We created a comprehensive list of VAS types reported by migraine patients based on all currently available data from clinical studies, which can be used for testing and validation in future studies. We propose that, based on this work, an official list of VAS types should be developed, preferably within the context of the International Classification of Headache Disorders of the International Headache Society.
The underlying causes of migraine headache remained enigmatic for most of the 20th century. In 1979, The Lancet published a novel hypothesis proposing an integral role for the neuropeptide-containing ...trigeminal nerve. This hypothesis led to a transformation in the migraine field and understanding of key concepts surrounding migraine, including the role of neuropeptides and their release from meningeal trigeminal nerve endings in the mechanism of migraine, blockade of neuropeptide release by anti-migraine drugs, and activation and sensitisation of trigeminal afferents by meningeal inflammatory stimuli and upstream role of intense brain activity. The study of neuropeptides provided the first evidence that antisera directed against calcitonin gene-related peptide (CGRP) and substance P could neutralise their actions. Successful therapeutic strategies using humanised monoclonal antibodies directed against CGRP and its receptor followed from these findings. Nowadays, 40 years after the initial proposal, the trigeminovascular system is widely accepted as having a fundamental role in this highly complex neurological disorder and provides a road map for future migraine therapies.
Summary
Background
Data on patients switched to tenofovir alafenamide (TAF) from nucleos(t)ide analogues (NUCs) other than tenofovir disoproxil fumarate are limited.
Aims
To assess the treatment and ...renal/bone safety outcomes following the switch to TAF.
Methods
We prospectively enrolled adult patients with chronic hepatitis B (CHB) who switched from any NUC to TAF at 14 centres in Japan, Korea, Taiwan and the U.S. Study outcomes were viral suppression (VR; HBV DNA < 20 IU/mL), biochemical response (BR; alanine aminotransferase normalisation), and changes in estimated glomerular filtration rate (eGFR) and T‐scores (L‐spine) by bone absorptiometry by 24 months after switch to TAF.
Results
We enrolled 270 eligible patients. Mean age was 58.1; 58.2% were male; 12.2% had cirrhosis and 73.3% previously received entecavir monotherapy. VR rate increased significantly from 95.2% to 98.8% by 24 months after the switch to TAF (p = 0.014). Between the switch and 24 months later, the mean spine T‐score improved significantly from −1.43 ± 1.36 to −1.17 ± 1.38 (p < 0.0001), while there was no significant change in mean eGFR (88.4 ± 16.9–89.5 ± 16.3 mL/min/1.73 m2, p = 0.13). On multivariable analysis adjusted for age, sex, baseline spine T‐score and prior TDF or adefovir dipivoxil use, male sex was significantly associated with lower risk of worsening spine T‐score (odds ratio: 0.29, p = 0.020), while age was significantly associated with a higher risk of worsening chronic kidney disease stage (OR: 1.07, p = 0.019).
Conclusions
At 24 months after the switch to TAF, VR rates and spine bone density improved significantly while renal function remained stable.
Sequential NUC treatment with a switch to TAF provided improvement of virological response rates and spine BMD without worsening of renal function.
Migraine: epidemiology and systems of care Ashina, Messoud; Katsarava, Zaza; Do, Thien Phu ...
The Lancet (British edition),
04/2021, Letnik:
397, Številka:
10283
Journal Article
Recenzirano
Migraine is a neurovascular disorder that affects over 1 billion people worldwide. Its widespread prevalence, and associated disability, have a range of negative and substantial effects not only on ...those immediately affected but also on their families, colleagues, employers, and society. To reduce this global burden, concerted efforts are needed to implement and improve migraine care that is supported by informed health-care policies. In this Series paper, we summarise the data on migraine epidemiology, including estimates of its very considerable burden on the global economy. First, we present the challenges that continue to obstruct provision of adequate care worldwide. Second, we outline the advantages of integrated and coordinated systems of care, in which primary and specialist care complement and support each other; the use of comprehensive referral and linkage protocols should enable continuity of care between these systems levels. Finally, we describe challenges in low and middle-income countries, including countries with poor public health education, inadequate access to medication, and insufficient formal education and training of health-care professionals resulting in misdiagnosis, mismanagement, and wastage of resources.
Nitrite (NO2−) production in chloraminated drinking water distribution systems (CDWDSs) is among the first bulk water indicators of a nitrification event and is typically quantified using ion ...chromatography (IC) or colorimetric techniques. NO2− can also be quantified using chemometric models (CMs) formulated using molar absorptivity (Ɛ) and/or ultraviolet absorbance (UVA) spectra, but concerns exist regarding their accuracy and generalizability because of varying source water natural organic matter (NOM), monochloramine (NH2Cl), bromide (Br−), and other species in CDWDSs. We demonstrate that the impact of NOM was mitigated in the second derivative molar absorptivity (Ɛ″) and UVA spectra (UVA″) between 200–300 nm and developed a generalizable CM for NO2− quantification. The Ɛ″+UVA″ CM was calibrated with daily NO2− measurements by IC from five biofilm annular reactor (BAR) tests with feedwater from Fayetteville, Arkansas, USA (FAY1, n = 275) and validated with eight BAR tests (n = 376) with another Fayetteville water (FAY2) and two waters from Dallas, Texas, USA (DAL1 and DAL2). The Ɛ″+UVA″ CM used Ɛ″ for NO2−, nitrate (NO3−), Br−, and NH2Cl at wavelengths of 213-, 225-, 229- and 253 nm, had an adjusted R2 of 0.992 for FAY1 and 0.987 for the other waters, and had a method detection limit (MDL) of 0.050 mg·L−1-N. NO2− challenge samples with three reconstituted NOM types and Br− indicated the Ɛ″+UVA″ CM was generalizable at NOM concentrations like those in the BAR tests (≤ 2.5 mg·L−1-C). The Ɛ″+UVA″ CM accurately simulated NO2− in field tests from two CDWDSs undergoing nitrification, including one with NOM at 3.5 mg·L−1-C, illustrating a practical application of the CM for identifying biological ammonia oxidation.
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