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Migraine is one of top 5 medical conditions that contribute to Years Lived with Disability and affects approximately 1 billion people from around the world. To date, preventive treatment and acute therapies for migraine are limited, have undesirable side effects and are poorly tolerated in patients. In the last few decades, considerable advances in our understanding of migraine and its pathophysiology have paved the way for the development of targeted treatment options. Calcitonin gene-related peptide (CGRP) plays an integral role in the neurobiology of migraine, and new classes of drugs that target the CGRP pathway have included gepants and CGRP pathway monoclonal antibodies. Serotonin 5-HT1F receptor agonists—namely ditans—have also been developed to treat acute migraine. Lastly, non-invasive neuromodulation offers another treatment option for migraine patients who prefer treatments that have fewer side effects and are well tolerated. In this review, we discussed emerging treatment options for migraine that were made available in recent years. Ann Acad Med Singapore 2020;49:226–35 Key words: Calcitonin gene-related peptide monoclonal antibody, Gepants, Headache, Lasmiditan, Neuromodulation

Management of migraine in adolescents poses a great challenge, as many of the approved pharmacological migraine preventive agents have age restrictions. Following favorable safety and efficacy reports of the new class agent calcitonin gene-related peptide (CGRP) monoclonal antibody for use in migraine prevention, there is growing interest in its application in pediatric migraine. We present here a case series detailing our experience of using erenumab, a CGRP monoclonal antibody, in six adolescent patients. Two patients had a reduction of at least 50% in the mean number of monthly migraine days, one patient reported subjective improvement, while three patients did not respond to the first dose of erenumab and discontinued treatment. One patient reported constipation associated with erenumab use. We speculate that CGRP monoclonal antibody could potentially be a viable option in adolescent patients with migraine. Further evidences that support efficacy and safety of erenumab in this group is needed.

Background: Hand-foot-and-mouth disease (HFMD) is a common childhood illness caused by enteroviruses. Oseltamivir (OS), a neuraminidase inhibitor, has been frequently used as an adjunctive therapy for the treatment of HFMD. Solid evidence, however, is lacking regarding the efficacy of such adjunctive therapy. This work is to conduct a meta-analysis of randomized clinical trials (RCTs) to assess the efficacy of oseltamivir for HFMD in children.Methods: Eligible studies from inception to October 10, 2020 were identified by searching six databases (PubMed, Embase, CENTRAL, CNKI, Wanfang, and VIP database). Quality of evidence was assessed using the Cochrane Collaboration tool.Results: Of a total of 91 entries, 11 RCTs involving 977 HFMD children were included in the final analysis. The results showed that the therapy combined with oseltamivir was more effective, with higher effective rate (RR, 0.84; 95% CI, 0.80 to 0.87; p < 0.01), shorter fever clearance time (days) (SMD, −0.74; 95% CI, −1.12 to −0.35; p < 0.01), shorter rash regression time (days) (MD, −0.89; 95% CI, −1.05 to −0.72; p < 0.01) and shorter clinical cure time (SMD, −1.08; 95% CI, −1.55 to −0.61; p < 0.01). No significant difference was observed in the risk of adverse reactions between the groups with and without oseltamivir.Conclusion: The use of oseltamivir as adjunctive therapy shows effectiveness and no increased risk of adverse reactions for the treatment of HFMD in children.

Metabolomics offers a noninvasive methodology to identify metabolic markers for pathogenesis and diagnosis of diseases. This work aimed to characterize circulating metabolic signatures of benign thyroid nodule (BTN) and papillary thyroid carcinoma (PTC) via serum-plasma matched metabolomics. A cohort of 1,540 serum-plasma matched samples and 114 tissues were obtained from healthy volunteers, BTN and PTC patients enrolled from 6 independent centers. Untargeted metabolomics was determined by liquid chromatography-quadrupole time-of-flight mass spectrometric and multivariate statistical analyses. The use of serum-plasma matched samples afforded a broad-scope detection of 1,570 metabolic features. Metabolic phenotypes revealed significant pattern differences for healthy versus BTN and healthy versus PTC. Perturbed metabolic pathways related mainly to amino acid and lipid metabolism. It is worth noting that, BTN and PTC showed no significant differences but rather overlap in circulating metabolic signatures, and this observation was replicated in all study centers. For differential diagnosis of healthy versus thyroid nodules (BTN + PTC), a panel of 6 metabolic markers, namely myo-inositol, α-N-phenylacetyl-L-glutamine, proline betaine, L-glutamic acid, LysoPC(18:0) and LysoPC(18:1) provided area under the curve of 97.68% in the discovery phase and predictive accuracies of 84.78-98.18% in the 4 validation centers. Taken together, serum-plasma matched metabolomics showed significant differences in circulating metabolites for healthy versus nodules but not for BTN versus PTC. Our results highlight the true metabolic nature of thyroid nodules, and potentially decrease overtreatment that exposes patients to unnecessary risks.

Background Pathogenesis and diagnostic biomarkers for diseases can be discovered by metabolomic profiling of human fluids. If the various types of coronary artery disease (CAD) can be accurately characterized by metabolomics, effective treatment may be targeted without using unnecessary therapies and resources. Objectives The authors studied disturbed metabolic pathways to assess the diagnostic value of metabolomics-based biomarkers in different types of CAD. Methods A cohort of 2,324 patients from 4 independent centers was studied. Patients underwent coronary angiography for suspected CAD. Groups were divided as follows: normal coronary artery (NCA), nonobstructive coronary atherosclerosis (NOCA), stable angina (SA), unstable angina (UA), and acute myocardial infarction (AMI). Plasma metabolomic profiles were determined by liquid chromatography–quadrupole time-of-flight mass spectrometry and were analyzed by multivariate statistics. Results We made 12 cross-comparisons to and within CAD to characterize metabolic disturbances. We focused on comparisons of NOCA versus NCA, SA versus NOCA, UA versus SA, and AMI versus UA. Other comparisons were made, including SA versus NCA, UA versus NCA, AMI versus NCA, UA versus NOCA, AMI versus NOCA, AMI versus SA, significant CAD (SA/UA/AMI) versus nonsignificant CAD (NCA/NOCA), and acute coronary syndrome (UA/AMI) versus SA. A total of 89 differential metabolites were identified. The altered metabolic pathways included reduced phospholipid catabolism, increased amino acid metabolism, increased short-chain acylcarnitines, decrease in tricarboxylic acid cycle, and less biosynthesis of primary bile acid. For differential diagnosis, 12 panels of specific metabolomics-based biomarkers provided areas under the curve of 0.938 to 0.996 in the discovery phase (n = 1,086), predictive values of 89.2% to 96.0% in the test phase (n = 933), and 85.3% to 96.4% in the 3-center external sets (n = 305). Conclusions Plasma metabolomics are powerful for characterizing metabolic disturbances. Differences in small-molecule metabolites may reflect underlying CAD and serve as biomarkers for CAD progression.