Unmet Needs in the Acute Treatment of Migraine.

Migraine represents the most common neurologic disorder, ranking second among the world's causes of disability [expressed as years lived with disability (YLDs)]. Patients often do not receive the best therapy because of safety issues, tolerance, and prescription accessibility. General practitioners are not always educated about the disease, and specialists are few and often difficult to reach. Therapies are limited and have many side effects that can impede the prescription. Prophylactic therapy is recommended in case of four or more headaches a month, eight or more headache days a month, debilitating headaches, and medication-overuse headaches. The available therapeutic options are in constant development. The classic one consists of non-specific drugs: ß-blockers, tricyclics, antiepileptics, and botulinum toxin. Monoclonal antibodies targeting the calcitonin gene receptor (CGRP) peptide or its receptor are the only ones specifically designed to treat migraine. Their efficiency and convenient safety profile have been demonstrated in a number of trials versus both placebo and classic therapies. The treatment of acute migraine attack consists of medications designed to affect the painful symptoms. For over 30 years, the cornerstones of treatment in clinical practice have continued to be represented by triptans and non-steroidal anti-inflammatory drugs (NSAIDs), with the well-know related adverse effects. Opioids are used inappropriately and overprescribed. Polytherapy is strongly not recommended but is still a common practice because treatment is not optimized and thus not efficient. Great promise comes from gepants, also targeting CGRP, and ditans, 5-HT1F receptor agonists. They seem to outweigh the risk of medication overuse headache because of their efficacy and rapid onset and have no cardiovascular contraindications. Nonetheless, these points remain to be confirmed. Although therapies have been implemented in the last years, significant unmet treatment needs remain a reality in patients' lives. This commentary aims to identify the most important unmet needs in the acute treatment of migraine, analyzing the current status of available therapies and their limits. We also analyzed some of the prophylactic therapies available, especially focusing on anti-CGRP monoclonal antibodies, to better understand the importance of setting a therapeutic strategy that includes the two modes, both acute and prophylactic, to reach the best result. We hope that having an overview of the shortcomings will help to provide constructive ideas for improvement.

Unmet Needs in Preventive Treatment of Migraine.

Migraine represents the most common cause of work disability in young women and the second one in the general population. Preventive treatment can reduce the frequency of attacks and their intensity, consequently improving the quality of life. Despite this, global health systems have shown important gaps in addressing optimal management of preventive therapy. Despite numerous adverse effects of traditional medications for migraine prevention being well known, these medications continue to be considered the standard of care for prophylaxis of this disease in many contexts. On the other hand, the widespread use of calcitonin gene-related peptide (CGRP) receptor antagonists, which have marked a breakthrough in prophylactic therapy of migraine, has been limited because of their high cost. We also highlight important shortcomings in migraine management by general practitioners (GPs) and poor patient education on the disease with a consequent delay in referring selected patients to dedicated headache centres. Over the next few years, we expect the headache medicine community to mobilize to address these gaps in preventive treatment of migraine.

Lessons Learned from the Lessons Learned in Public Health during the First Years of COVID-19 Pandemic.

(1) Objectives: to investigate the main lessons learned from the public health (PH) response to COVID-19, using the global perspective endorsed by the WHO pillars, and understand what countries have learned from their practical actions. (2) Methods: we searched for articles in PubMed and CINAHL from 1 January 2020 to 31 January 2022. 455 articles were included. Inclusion criteria were PH themes and lessons learned from the COVID-19 pandemic. One hundred and forty-four articles were finally included in a detailed scoping review. (3) Findings: 78 lessons learned were available, cited 928 times in the 144 articles. Our review highlighted 5 main lessons learned among the WHO regions: need for continuous coordination between PH institutions and organisations (1); importance of assessment and evaluation of risk factors for the diffusion of COVID-19, identifying vulnerable populations (2); establishment of evaluation systems to assess the impact of planned PH measures (3); extensive application of digital technologies, telecommunications and electronic health records (4); need for periodic scientific reviews to provide regular updates on the most effective PH management strategies (5). (4) Conclusion: lessons found in this review could be essential for the future, providing recommendations for an increasingly flexible, fast and efficient PH response to a healthcare emergency such as the COVID-19 pandemic.

New Migraine Drugs for Older Adults.

Migraine is one of the most widespread and burdensome diseases, affecting one in every seven individuals in the world, for an estimated global prevalence of 14%. Until recently, therapeutic choices for older migraineurs have been limited by safety concerns and such patients have typically been excluded from clinical trials. However, randomized controlled trials (RCTs) of new migraine drugs have begun to include participants aged over 65 years, offering clinicians relevant safety and efficacy data to be able to treat older patients with the newest drug classes, including monoclonal antibodies for CGRP (r), CGRP antagonists, and drugs targeting the serotonin 5-HT1F receptor. RCT inclusion criteria nonetheless select the most appropriate older patients, usually excluding polymorbid participants. In a real-life setting, older patients may have several comorbidities, and this reduces the clinical applicability of the new drugs to these patients. Two main points should be addressed to solve this barrier: the inclusion of a sufficient number of migraineurs aged over 65 years in RCTs and the publication of appropriate guidelines for a tailored treatment that considers the existence of multimorbid pathologies in this population of individuals.

A bedside ultrasound protocol to the measurement of the systemic vascular resistances: Preliminary results in the patients with sepsis.

BACKGROUND: The use of the ultrasound (US) bedside examination is increasing for the detailed evaluation of the hemodynamic parameters, allowing the physicians to set the appropriate therapeutic strategies with greater precision. OBJECTIVE: The aim of this study is to evaluate the hemodynamic parameters (the cardiac output or CO, the central venous pressure or CVP and the systemic vascular resistance or SVR) in the patients with sepsis, by using a bedside US approach. METHODS: We consecutively enrolled n.82 patients of S.Andrea Hospital (n.47 with sepsis and n.35 without sepsis), examining the hemodynamic parameters by a bedside US evaluation. RESULTS: The incidence of sepsis was more than 50% of cases. The patients with sepsis presented higher comorbidity and polypharmacy (p < 0.01, p < 0.001), with increased creatinine (p < 0.001) and consequent esteemed glomerular filtration rate (p < 0.01), C-reactive protein (p < 0.01), SOFA (Sepsis-related Organ Failure Assessment) score (p < 1.58×10-7) and reduced SVR (p < 0.05). The SOFA score was inversely related to the SVR (p < 0.05). CONCLUSIONS: To our best knowledge, this is the first study with a bedside US protocol to measure SVR, beyond the abdominal and cardiac qualitative evaluation.

The Point-of-Care Ultrasound (POCUS) by the Handheld Ultrasound Devices (HUDs) in the COVID-19 Scenario: a Review of the Literature.

The use of portable ultrasound (US) devices is increasing, due to its accessibility, versatility, non-invasiveness, and its significant support in the patient management, extending the traditional physical examination through the POCUS (point-of-care ultrasound). The pocket-size or handheld ultrasound devices (HUDs) can easily perform focused exams, not aiming to substitute for the high-end US systems (gold standard), since the HUDs usually have more limited functions. The HUDs are promising tools for the diagnosis, prognosis, and monitoring of the COVID-19 infection and its related disorders. In conclusion, the routine use of HUDs may ameliorate the management of COVID-19 pandemic, according to the guidelines for the POCUS approach and the procedures for the protection of the patients and the professionals.

Long COVID headache.

Headache is among the most frequent symptoms persisting or newly developing after coronavirus disease 2019 (COVID-19) as part of the so-called long COVID syndrome. The knowledge on long COVID headache is still limited, however growing evidence is defining the features of this novel condition, in particular regarding clinical characteristics, some pathophysiological mechanisms and first treatment recommendations. Long COVID headache can present in the form of worsening of a preexisting primary headache, or, more specifically, in the form of a new (intermittent or daily) headache starting during the acute infection or after a delay. It often presents together with other long COVID symptoms, most frequently with hyposmia. It can manifest with a migrainous or, more frequently, with a tension-type-like phenotype. Persistent activation of the immune system and trigeminovascular activation are thought to play a role. As there are virtually no treatment studies, treatment currently is largely guided by the existing guidelines for primary headaches with the corresponding phenotype. The present report, a collaborative work of the international group of the Junior Editorial Board of The Journal of Headache and Pain aims to summarize the most recent evidence about long COVID headache and suggests approaches to the diagnosis and treatment of this disorder.

Recently approved and emerging drug options for migraine prophylaxis.

INTRODUCTION: Migraine occupies the first position regarding the disability caused in female working population (15-49 years). Research in the field of prophylaxis in this pathology has made enormous strides in recent years. AREAS COVERED: In this narrative review, we retrace the most important scientific evidence regarding recently approved and emerging drugs for the prophylactic treatment of migraine. The purpose of this article is in fact to evaluate currently approved or emerging pharmacological agents for migraine prophylaxis. This review is based on the literature published in the peer review journal obtained through PubMed, Cochrane library, Clinicaltrials.gov, and US FDA. EXPERT OPINION: Monoclonal antibodies (mAbs) that target the calcitonin gene-related peptide signaling pathway (CGRP) have marked an innovation in prophylactic migraine therapy. The combination of Onabotulinumtoxin-A (OBTA) and mAbs appears to be an effective, but costly, therapeutic option for resistant cases. New classes of molecules like gepants and ditans seem to give exceptional results. In addition, new prophylactic drugs are emerging with several targets: the pituitary adenylate cyclase-activating polypeptide (PACAP), ion channels, several receptors coupled to G proteins, orexin, and glutamate. All these therapies will implement and improve migraine management, as well as personalized medicine for each patient.

Novel Migraine Therapies May Reduce Public and Personal Disadvantages for People with Migraine.

The introduction of new drug classes for migraine, such as monoclonal antibodies that target the calcitonin gene-related peptide (CGRP) or its receptor and small-molecule antagonists of CGRP, have opened a new scenario in a large population of individuals suffering from migraines. The provision of an effective and safe therapy can help overcome the high social and personal costs together with the burden of this disease by offering social, work and economic recovery to the people affected by migraine. Whether the satisfaction of personal and collective unmet needs will be achieved in the vast majority of migraine sufferers now depends only on the efficiency of the organizational care structures dedicated to this socially impactful disease. This path will offer personal benefits and significant psychosocial relief that will help to reduce the enormous current healthcare expenditure necessary for the management of the huge number of individuals suffering from migraines. The new pharmacological classes for prevention must be applied as an interdiction to the chronic phase to express their full rehabilitation potential.

Tele-healthcare in migraine medicine: from diagnosis to monitoring treatment outcomes.

INTRODUCTION: Primary headaches represent a huge cost in terms of decreased productivity and migraine occupies the first position among disabilities in working population. Migraine has a high incidence, disproportionate to the available primary care centers. In most cases, migraine can be managed through the simple and accurate collection of clinical history, which makes it an ideal candidate for tele-healthcare. AREAS COVERED: In this narrative review, we retrace the most important scientific evidence regarding use of tele-healthcare in headache medicine. Over the last few years, it has proved to be a valid and useful tool for the management of migraine. Furthermore, current pandemic has imposed a drastic change in the way of thinking and setting up medicine, forcing clinicians and patients to a huge expansion of telemedicine. EXPERT OPINION: We should permanently insert the culture of telemedicine in the headache care not only in academies and scientific societies, but extend it to specialized hospitals for the treatment of headaches. Only by broadening the old book-based strategy, we will be able to open the door to the multidimensional culture of headache medicine. Experts of excellence centers should set an example and pave the way for the rest of the clinicians.

Access to COVID-19 Vaccination during the Pandemic in the Informal Settlements of Rome.

With the advent of vaccines, the world has a chance to see a real end to the COVID-19 pandemic. To make this possible, however, it is necessary that all groups of people are considered. Contexts of informal settlements and populations such as the homeless and migrants are often forgotten by vaccination campaigns. In this study, carried out as a result of a collaboration with MEDU, a non-profit association aimed at bringing healthcare to vulnerable populations, we provide important data related to the vaccination campaign carried out in the informal settlements of Rome. The objectives of this work are to (1) evaluate vaccination coverage in these contexts, (2) assess the gap with the vaccination coverage of the Italian population and try to hypothesize the causes, and (3) provide recommendations for how humanitarian associations can respond to reduce this gap. We observed important differences in vaccination coverage depending on the type of settlement. The percentage of vaccinated people in these contexts at the beginning of October range between 14.4% and 55.5%, underlining an important gap with the vaccination rate of Italy's population, which is close to 80%. The data also show that particular attention must be paid to the transiting and irregular people as they are more at risk for a lack of access to vaccination. With this study, in which we provide recommendations that integrate MEDU's fieldwork experience with the advice of the Framework report, we hope we can help those who work in similar contexts, to carry out a fair and effective vaccination campaign.

CHA2DS2-VASc score in patients with COVID-19 pneumonia and its relationship with biomarkers of thrombosis, inflammation and myocardial injury.

CHA2DS2-VASC score associates with worse prognosis in coronavirus-disease-19 (COVID-19). This study investigated laboratory correlates of increasing CHA2DS2- VASc in patients with COVID-19. Patients with COVID-19 were stratified by CHA2DS2-VASc (Group 1: CHA2DS2-VASc 0-1; Group 2: CHA2DS2-VASc 2-3; Group 3: CHA2DS2-VASc ≥4). We found stepwise increase of D-dimer, hs-Troponin and in-hospital mortality across groups (all P < 0.01). D-dimer and hs-Troponin remained independently associated with CHA2DS2-VASc (B = 0.145, P = 0.03; B = 0.320, P < 0.001, respectively). We found significant correlations between D-dimer and C-reactive protein (CRP) in Group 1 and 2, not in Group 3 (r2 = 0.103, P = 0.005; r2 = 0.226, P = 0.001; r2 = 0.021, P = 0.253 respectively), and between D-dimer and hs-Troponin in group 2 and 3, not in Group 1 (r2 = 0.122, P = 0.003; r2 = 0.120, P = 0.007; r2 = 0.006, P = 0.514 respectively). In our cohort, CHA2DS2- VASc was independently associated with D-dimer and hs- Troponin increase. Variable relationships of D-dimer with hs-Troponin and CRP within different CHA2DS2-VASc strata suggest multiple mechanisms to be responsible for D-dimer increase in COVID-19.

OnabotulinumtoxinA Treatment in Chronic Migraine: Investigation of Its Effects on Disability, Headache and Neck Pain Intensity.

Neck disability and pain are frequently encountered problems in patients with chronic migraine (CM). The long-term stimuli of neurons in the trigeminocervical junction may explain this situation. OnabotulinumtoxinA (ONA) treatment is one of the proven treatments for CM; however, there is no study data on the efficacy of ONA treatment on neck disability and pain in CM patients. Therefore, we aimed to investigate the effect of ONA treatment on disability, neck pain and headache intensity in CM patients. One hundred thirty-four patients who met the inclusion criteria were included in the study. ONA treatment was administered at a dose of 195 U to 39 sites in total as per Follow-the-Pain PREEMPT protocol. The disability was evaluated with the Neck Disability Index and the Migraine Disability Assessment; pain intensity was evaluated with the Visual Analogue Scale; the monthly number of headache days were recorded; quality of life was evaluated with the Headache Impact Test. All assessments were recorded at baseline and 3 months after treatment. After the treatment, neck−migraine disabilities decreased from severe to mild for neck and moderate for migraine (p < 0.001). Neck pain and headache intensities decreased by almost half (p < 0.001). The median number of monthly headache days decreased from 20 days to 6 days (p < 0.000). The quality-of-life level decreased significantly from severe to substantial level (p < 0.001). According to our results, ONA treatment was effective in reducing neck-related problems in CM patients. Long-term follow-up results may provide researchers with more comprehensive results in terms of the treatment of chronic migraine−neck-related problems.

How Does COVID-19 Pandemic Impact on Incidence of Clostridioides difficile Infection and Exacerbation of Its Gastrointestinal Symptoms?

Coronavirus disease 2019 (COVID-19) has rapidly spread all over the world with a very high rate of mortality. Different symptoms developed by COVID-19 infection and its impacts on various organs of the human body have highlighted the importance of both coinfections and superinfections with other pathogens. The gastrointestinal (GI) tract is vulnerable to infection with COVID-19 and can be exploited as an alternative transmission route and target for virus entry and pathogenesis. The GI manifestations of COVID-19 disease are associated with severe disease outcomes and death in all age groups, in particular, elderly patients. Empiric antibiotic treatments for microbial infections in hospitalized patients with COVID-19 in addition to experimental antiviral and immunomodulatory drugs may increase the risk of antibiotic-associated diarrhea (AAD) and Clostridioides difficile infection (CDI). Alterations of gut microbiota are associated with depletion of beneficial commensals and enrichment of opportunistic pathogens such as C. difficile. Hence, the main purpose of this review is to explain the likely risk factors contributing to higher incidence of CDI in patients with COVID-19. In addition to lung involvement, common symptoms observed in COVID-19 and CDI such as diarrhea, highlight the significance of bacterial infections in COVID-19 patients. In particular, hospitalized elderly patients who are receiving antibiotics might be more prone to CDI. Indeed, widespread use of broad-spectrum antibiotics such as clindamycin, cephalosporins, penicillin, and fluoroquinolones can affect the composition and function of the gut microbiota of patients with COVID-19, leading to reduced colonization resistance capacity against opportunistic pathogens such as C. difficile, and subsequently develop CDI. Moreover, patients with CDI possibly may have facilitated the persistence of SARS-CoV-2 viral particles in their feces for approximately one month, even though the nasopharyngeal test turned negative. This coinfection may increase the potential transmissibility of both SARS-CoV-2 and C. difficile by fecal materials. Also, CDI can complicate the outcome of COVID-19 patients, especially in the presence of comorbidities or for those patients with prior exposure to the healthcare setting. Finally, physicians should remain vigilant for possible SARS-CoV-2 and CDI coinfection during the ongoing COVID-19 pandemic and the excessive use of antimicrobials and biocides.

Hormonal therapies in migraine management: current perspectives on patient selection and risk management.

INTRODUCTION: The link between sex hormones and migraines has long been investigated but the mechanisms underlying this altered interaction are not yet fully understood. Herein, we retrace the knowledge on this association in relationship with risk of stroke. AREAS COVERED: Estrogens fluctuations could trigger migraine attacks and exogenous estrogens intake could be a risk factor for venous thromboembolism (VTE) and stroke. At the same time, ischemic heart diseases and stroke share a common substrate with migraine and other mood disorders, depression, and anxiety. EXPERT OPINION: The use of hormonal therapies in the context of contraception or replacement therapy must be closely evaluated in a careful risk assessment. We highlight the complex interaction of hormone/neuroinflammation pathways underlying the pathophysiology of migraine glimpsing in mood disorders a possible common denominator of link between hormonal and neuronal systems.

Coronavirus disease 2019 in patients with cardiovascular disease: clinical features and implications on cardiac biomarkers assessment.

INTRODUCTION: Previous cardiovascular disease (CVD) and myocardial involvement are common in coronavirus disease-19 (COVID-19). We investigated relationships between CVD, cardiac biomarkers and outcome in COVID-19. METHODS: We analyzed n = 252 patients from a multicenter study and provided comparison according to the presence or absence of underlying CVD. Cardiac biomarkers high-sensitivity Troponin [upper reference of normality (URN) 35 pg/ml for Troponin I and 14 pg/ml for Troponin T] and natriuretic peptides (Nt-pro-B-type natriuretic peptide, URN 300 pg/ml and B-type natriuretic peptide, URN 100 pg/ml) were both available in n = 136. RESULTS: Mean age was 69 ±â€Š16 years (56% men, 31% with previous CVD). Raised hs-Troponin and natriuretic peptides were detected in 36 and 50% of the cases respectively. Age, chronic obstructive pulmonary disease, hemoglobin, hs-Troponin and natriuretic peptides were independently associated with underlying CVD (P < 0.05 for all). Compared with the normal biomarkers subgroups, patients with isolated hs-Troponin elevation had higher in-hospital mortality (31 vs. 4%, P < 0.05), similar CVD prevalence (15 vs. 11%) and trend towards higher D-dimer (930 vs. 397 ng/ml, P = 0.140). Patients with both biomarkers elevated had higher age, D-dimer, CVD and in-hospital mortality prevalence compared with other subgroups (all P < 0.05 for trend). Outcome analysis revealed previous CVD [model 1: OR 2.72 (95% CI 1.14-6.49), P = 0.024. model 2: OR 2.65 (95% CI 1.05-6.71), P = 0.039], hs-Troponin (log10) [OR 2.61 (95% CI 1.21-5.66), P = 0.015] and natriuretic peptides (log10) [OR 5.84 (95%CI 2.43-14), P < 0.001] to be independently associated with in-hospital mortality. CONCLUSION: In our population, previous CVD was part of a vulnerable phenotype including older age, comorbidities, increased cardiac biomarkers and worse prognosis. Patients with isolated increase in hs-Troponin suffered higher mortality rates despite low prevalence of CVD, possibly explained by higher COVID-19-related systemic involvement.

Recent advancements in tension-type headache: a narrative review.

INTRODUCTION: Tension-type headache (TTH) is the most common primary headache disorder with a prevalence of up to 78% in general population and huge expenses in terms of health service. Despite its high incidence and impact on life's quality the knowledge on the pathophysiology and efficacious treatment of TTH was still limited. AREAS COVERED: In recent years, a series of studies highlighted the heterogeneous nature of this pathology that seems to be determined by a complex interaction between genetic, environmental, and neuromuscular factors, which result in nociceptive system activation. In this setting, alongside the simple analgesic therapies used during the acute attack, a series of therapeutic options based on newly acquired experiences have taken hold. EXPERT REVIEW: Not having a single substrate or a typical site of pathophysiology, TTH must be analyzed in a global and multidisciplinary way. Herein, we perform a narrative review of the most recent advancement stimulating the concept of this disease as the tip of the iceberg of a more complex individual malaise secondary to different alterations. Strategies based solely on symptomatic drugs should therefore be avoided by experienced personnel and treatment should aim at taking charge of the patient considering the processes behind this complex pathology.

Migrants' Quarantine and COVID-19 Pandemic in Italy: a Medico-anthropological View.

The COVID-19 pandemic represents an important risk factor for migrants' health. Paul Farmer highlighted the risk of global health response in emergency conditions exacerbating global and social inequalities. We argue that this is the case for quarantine ships and migrants' management during the pandemic. Every aspect of infection-control and prevention measures acquires detention characteristics in these situations. With emphasis to the evolution of the doctor-patient relationship and to the anthropological and cultural aspects that were established during the pandemic, this article aims to provide an integrated view where physicians and anthropologists collaborate to deepen the understanding of the topic.