Dataset Information

Gepants - a long way to cure: a narrative review.

ABSTRACT: Calcitonin gene-related peptide (CGRP) is probably the most potent vasodilator in cerebral circulation. Forty years after its discovery, the new CGRP-targeted therapy monoclonal antibodies, and the small molecule gepants, are now available for clinical practice. While randomized controlled trials and real-world experience consistently demonstrated the high efficacy and tolerability of monoclonal antibodies, limited evidence is available to characterize gepants fully. Depending on pharmacokinetics, these CGRP receptor antagonists can be used for acute (ubrogepant, rimegepant, and the not yet approved zavegepant) or preventive (atogepant and rimegepant) migraine treatment. Randomized placebo-controlled trials demonstrated gepants efficacy in treating acute attacks to obtain 2 h pain freedom in about 20% of patients and pain relief in about 60%, while up to 60% of treated patients with episodic migraine may experience a 50% reduction in monthly migraine days. The most common treatment-related emergent adverse events were gastrointestinal (nausea, constipation) for the acute or preventive use. No vascular or hepatic concerns have emerged so far. More studies are ongoing to investigate gepant tolerability and safety also if associated with monoclonal antibodies targeting CGRP and other therapeutic classes. Gepants are also under investigation to treat other painful and non-painful conditions. Real-life studies are necessary to confirm the trials' findings and investigate more practical clinical aspects.

SUBMITTER: Altamura C

PROVIDER: S-EPMC9159895 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Tendinopathy can be resistant to treatment and often recurs, implying that current treatment approaches are suboptimal. Rehabilitation programmes that have been successful in terms of pain reduction and return to sport outcomes usually include strength training. Muscle activation can induce analgesia, improving self-efficacy associated with reducing one's own pain. Furthermore, strength training is beneficial for tendon matrix structure, muscle properties and limb biomechanics. However, current tendon rehabilitation may not adequately address the corticospinal control of the muscle, which may result in altered control of muscle recruitment and the consequent tendon load, and this may contribute to recalcitrance or symptom recurrence. Outcomes of interest include the effect of strength training on tendon pain, corticospinal excitability and short interval cortical inhibition. The aims of this concept paper are to: (1) review what is known about changes to the primary motor cortex and motor control in tendinopathy, (2) identify the parameters shown to induce neuroplasticity in strength training and (3) align these principles with tendon rehabilitation loading protocols to introduce a combination approach termed as tendon neuroplastic training. Strength training is a powerful modulator of the central nervous system. In particular, corticospinal inputs are essential for motor unit recruitment and activation; however, specific strength training parameters are important for neuroplasticity. Strength training that is externally paced and akin to a skilled movement task has been shown to not only reduce tendon pain, but modulate excitatory and inhibitory control of the muscle and therefore, potentially tendon load. An improved understanding of the methods that maximise the opportunity for neuroplasticity may be an important progression in how we prescribe exercise-based rehabilitation in tendinopathy for pain modulation and potentially restoration of the corticospinal control of the muscle-tendon complex.

Project description:IntroductionThe increasing emergence of bacterial strains with new resistance determinants has become a threat to current antibiotic therapies in recent years. This has prompted research for innovative options with improved efficacy and safety profiles: long-acting glycopeptides, such as dalbavancin and oritavancin, are currently approved for the treatment of acute bacterial skin and skin structure infections (ABSSSI). Their efficacy, microbiological profile, and ease of administration may provide an answer to this challenge, as well as reducing length of stay and hospital costs. This narrative review aims to explore the current evidence on the real-word use of dalbavancin and oritavancin, in labelled and off-label indications in clinical practice.MethodsA PubMed library database search with no time limits was performed using the following terms: long-acting antibiotics, dalbavancin, oritavancin.DiscussionRegistration studies confirmed non-inferiority of long-acting glycopeptides to standard of care in ABSSSI (dalbavancin DISCOVER 1 and 2: 79.7% clinical success in the dalbavancin group and 79.8% in the vancomycin-linezolid group; oritavancin SOLO I: 82,3% clinical success in the oritavancin group versus 78,9% for the vancomycin group; SOLO II: 80,1% clinical success versus 82,9%). Large cohorts have confirmed similar success rates in ABSSSI treatment in real-world practice. Evidence for off-label indications is still rather scarce but promising, especially in bone and joint infections therapy for both dalbavancin and oritavancin, and infective endocarditis for dalbavancin. Moreover, these drugs may have their place in non-adherent patients, in setting of addition or difficult access to healthcare. Another potential use of these drugs is in patients with oral intake impairment or reduced gastro-intestinal absorption. However, the low penetration in cerebrospinal fluid of dalbavancin and the unfavourable outcomes in the only case report of oritavancin treatment in human meningitis despite encouraging animal models would seem to make these molecules unsuitable for central nervous system infection therapy. Most of the available evidence is based on small retrospective cohorts, so robust prospective studies investigating off-label indications are needed.

Project description:The immune system is complex: it involves many cell types and numerous chemical mediators. An immature immune response increases susceptibility to infection, whilst imbalances amongst immune components leading to loss of tolerance can result in immune-mediated diseases including food allergies. Babies are born with an immature immune response. The immune system develops in early life and breast feeding promotes immune maturation and protects against infections and may protect against allergies. The long-chain polyunsaturated fatty acids (LCPUFAs) arachidonic acid (AA) and docosahexaenoic acid (DHA) are considered to be important components of breast milk. AA, eicosapentaenoic acid (EPA) and DHA are also present in the membranes of cells of the immune system and act through multiple interacting mechanisms to influence immune function. The effects of AA and of mediators derived from AA are often different from the effects of the n-3 LCPUFAs (i.e., EPA and DHA) and of mediators derived from them. Studies of supplemental n-3 LCPUFAs in pregnant women show some effects on cord blood immune cells and their responses. These studies also demonstrate reduced sensitisation of infants to egg, reduced risk and severity of atopic dermatitis in the first year of life, and reduced persistent wheeze and asthma at ages 3 to 5 years, especially in children of mothers with low habitual intake of n-3 LCPUFAs. Immune markers in preterm and term infants fed formula with AA and DHA were similar to those in infants fed human milk, whereas those in infants fed formula without LCPUFAs were not. Infants who received formula plus LCPUFAs (both AA and DHA) showed a reduced risk of allergic disease and respiratory illness than infants who received standard formula. Studies in which infants received n-3 LCPUFAs report immune differences from controls that suggest better immune maturation and they show lower risk of allergic disease and respiratory illness over the first years of life. Taken together, these findings suggest that LCPUFAs play a role in immune development that is of clinical significance, particularly with regard to allergic sensitisation and allergic manifestations including wheeze and asthma.

Dataset Information

Gepants - a long way to cure: a narrative review.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets