Objective: The Greek Society of Migraine and Headache Patients conducted its third in-line population web-based survey in 2023 to ascertain if the burden of the disease and the patients\' satisfaction with conventional and novel migraine therapies are changing compared to our previous findings from 2018 and 2020. Methods: The sampling process was based on a random call to participants to reply to a specific migraine-focused self-administered questionnaire, including 83 questions in Greek, which was distributed nationwide through the online research software SurveyMonkey. Results: We eventually enrolled 2565 patients, the majority of which were females. Our findings clearly demonstrate that migraine is still a burdensome condition. The degree of its impact on all aspects of productivity depends on the monthly frequency of migraine and the response rates to acute and prophylactic treatments. A total of 1029 (42.4%) of the patients had visited the emergency room mainly for unresponsiveness to acute treatments or aura-related symptoms. Triptans seem to be partly effective as acute therapies. OnabotulinumtoxinA seems to be effective for almost half of chronic migraine patients (43.9%) to report adequate satisfaction with this treatment (27.8% were \"fairly happy\", 10.6% were \"very happy\", and 5.5% were \"extremely happy\"). Due to their high rates of preventative effectiveness, most respondents treated with anti-CGRP Mabs expressed their optimism concerning their future while living with their migraine (88.25%), as well as towards further improvements in their quality of life (82.8%) status, mostly with fremanezumab. Conclusions: The patients recognize the usefulness of anti-CGRP Mabs in migraine prevention and consequently seem to be more optimistic than before about living with migraine. Considering the market change that is anticipated with the use of gepants and ditans, larger longitudinal population-based studies are warranted to further explore if the new era of migraine therapeutics might further lessen the burden of the disease.

BACKGROUND:  Early childhood caries (ECC) is a widespread dental problem that impacts children below the age of six years. Traditional restorative treatments like fillings are often challenging and invasive for young children. Silver diamine fluoride (SDF) offers a minimally invasive and cost-effective alternative for managing ECC. However, the effects, acceptance, and understanding of this treatment by parents remain crucial for its successful implementation.
OBJECTIVE: To evaluate the impact and level of acceptance of SDF treatment in ECC.
METHODS: Thirty-two children from an Anganwadi center aged between two to five years suffering from ECC were selected. A 38% SDF was applied for 3 minutes on the identified carious lesion, and the arrest percentage was checked after a recall period of three weeks and three months. The Likert scale was used for the questionnaire regarding parental feedback about the ease of application procedure, tooth discoloration, possible pain associated with the procedure, and the taste of SDF.
RESULTS: In the present study, a total of 75 surfaces were subjected to the application of SDF. After a period of three weeks, it was observed that 64 of these surfaces had successfully undergone the process of caries arrest. This finding was deemed to be statistically significant, with a P value of 0.021. Furthermore, the remaining surfaces that had not achieved caries arrest were subsequently treated at three months. The results of this subsequent treatment were also found to be statistically significant, with a P value of 0.027. These findings highlight the efficacy of both caries treatment and caries arrest in relation to the utilization of SDF.
CONCLUSIONS: SDF was found to be minimally invasive, easy to administer, inexpensive, highly efficient, and effective treatment in arresting caries in the primary dentition of young children, particularly in patients lacking cooperation.

Eptinezumab, a monoclonal antibody that targets calcitonin gene-related peptide (CGRP), was recently approved in Europe for the prophylactic treatment of migraine in adults who have at least four migraine days a month. Eptinezumab is administered by intravenous infusion every 12 weeks. During recent months, a considerable amount of evidence from eptinezumab trials has been published. The aim of this review is to describe the existing evidence on the tolerability, safety and efficacy of eptinezumab in patients with migraine. Data from randomized (PROMISE-1, PROMISE-2, RELIEF and DELIVER) and open-label (PREVAIL) phase 3 clinical trials have demonstrated the favorable effect of eptinezumab in migraine symptoms from first day of treatment. These studies showed that eptinezumab results in an overall reduction in mean monthly migraine days (MMDs), increases in the ≥50% and ≥ 75% migraine responder rates (MRRs) and improvements in patient-reported outcome measures in both patients with episodic migraine (EM) and with chronic migraine (CM), including patients who failed previous preventive treatments. The RELIEF trial also showed that eptinezumab, within 2 h of administration, reduced headache pain, migraine-associated symptoms and acute medication use when administered during a migraine attack. Eptinezumab benefits manifested as early as day 1 after dosing and with the subsequent doses lasted up to at least 2 years. Treatment-emergent adverse events reported by ≥2% of patients included upper respiratory tract infection and fatigue. Current evidence demonstrates that eptinezumab has a potent, fast-acting, sustained migraine preventive effect in patients with EM and CM. Eptinezumab has also shown to be well tolerated, supporting its use in the treatment of patients with migraine and inclusion in the current migraine therapeutic options.

Preventive treatment for people with latent Tuberculosis infection (LTBI) has aroused our great interest. In this paper, we propose and analyze a novel mathematical model of TB considering preventive treatment with media impact. The basic reproduction number R0 is defined by the next generation matrix method. In the case without media impact, we prove that the disease-free equilibrium is globally asymptotically stable (unstable) if R0<1(R0>1). Furthermore, we obtain that a unique endemic equilibrium exists when R0>1, which is globally asymptotically stable in the case of permanent immunity and no media impact. We fit the model to the newly reported TB cases data from 2009 to 2019 of four regions in China and estimate the parameters. And we estimated R0=0.5013<1 in Hubei indicating that TB in Hubei will be eliminated in the future. However, the estimated R0=1.015>1 in Henan, R0=1.282>1 in Jiangxi and R0=1.930>1 in Xinjiang imply that TB will continue to persist in these three regions without further prevention and control measures. Besides, sensitivity analysis is carried out to illustrate the role of model parameters for TB control. Our finding reveals that appropriately improving the rate of timely treatment for actively infected people and increasing the rate of individuals with LTBI seeking preventive treatment could achieve the goal of TB elimination. In addition, another interesting finding shows that media impact can only reduce the number of active infections to a limited extent, but cannot change the prevalence of TB.

BACKGROUND: In the DELIVER study, eptinezumab reduced monthly migraine days (MMDs) more than placebo in patients with 2-4 prior preventive migraine treatment failures. This post hoc analysis evaluated the efficacy of eptinezumab across the 24-week placebo-controlled period of the DELIVER study in subgroups defined by prior treatment failure type.
METHODS: DELIVER (NCT04418765) randomized adults with migraine to eptinezumab 100 mg, 300 mg, or placebo, administered intravenously every 12 weeks. Changes from baseline in MMDs and percentages of patients with ≥ 50% reduction from baseline in MMDs (≥ 50% migraine responder rates [MRRs]) were summarized in subgroups of patients defined by prior treatment failure type. Subgroups were not mutually exclusive and included patients for whom topiramate, beta blockers (metoprolol, propranolol), amitriptyline, and/or flunarizine had failed.
RESULTS: Across Weeks 1-12 in all subgroups, patients treated with eptinezumab experienced greater reductions from baseline in MMDs than those receiving placebo (reductions ranged from 4.5-5.5 vs 1.6-2.4, respectively), with larger reductions over Weeks 13-24. Similarly, ≥ 50% MRRs were consistently higher with eptinezumab than placebo and increased following a second infusion.
CONCLUSIONS: In all subgroups, regardless of prior preventive treatment failure type, eptinezumab demonstrated greater reductions in MMDs and higher MRRs compared with placebo.
BACKGROUND: ClinicalTrials.gov (Identifier: NCT04418765).

Objectives: We compared and ranked the efficacy and tolerability of multiple prophylactic treatments for vestibular migraine (VM), including β-blockers, calcium channel blockers, antiseizure medications, and antidepressants such as tricyclics and serotonin-noradrenaline reuptake inhibitors. Methods: PubMed, Web of Science, Embase, and Cochrane Center for Clinical Trials were systematically searched for relevant randomized clinical trials (RCTs) from March 2023 to May 2023. Studies on the efficacy and tolerability of prophylactic treatments for VM were included. Efficacy was measured using the average vertigo frequency per month and dizziness handicap inventory (DHI) improvement after 3-6 months of treatment. Tolerability was measured by the number of patients reporting at least one adverse event (AE). Network meta-analyses were performed according to a Bayesian framework and a random-effects model based on odds ratios or mean differences (MDs) and 95% confidence intervals (CIs). A sequence of ranking probability was calculated according to the surface under the cumulative ranking (SUCRA) curve. This network meta-analysis was previously registered with PROSPERO (CRD42023422258). Results: Five RCTs comprising 334 patients were analyzed by synthesizing the published evidence. Considering the examined prophylactic therapies, there is significant evidence that valproate acid (VPA) is superior to placebo or abortive treatment alone (MD = -4.12, 95% CI = -8.09, -0.15) in reducing the frequency of vertigo. Flunarizine (MD = 20.00, 95% CI = 10.90, 29.10), valproate acid (MD = 18.88, 95% CI = 10.42, 27.34), and venlafaxine (MD = 11.48, 95% CI = 9.84, 13.12) were significantly more effective than placebo or abortive treatment in reducing DHI. VPA most strongly reduced the frequency of vertigo according to SUCRA, but it ranked third-to-last in tolerability. Flunarizine ranked best in DHI improvement but worst in tolerability. Metoprolol ranked worst for efficacy but best for tolerability. Conclusion: VPA and flunarizine reduced the frequency of vertigo and improved DHI, but they had unfavorable tolerability. The effects of metoprolol on vertigo require further study. Given the low certainty and limited sample, additional head-to-head RCTs are warranted to further confirm efficacy. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/; Identifier CRD42023422258.

BACKGROUND: Tuberculosis (TB) preventive treatment (TPT) substantially reduces the risk of developing active TB for people living with HIV (PLHIV). We utilized a novel implementation strategy based on choice architecture (CAT) which makes TPT prescribing the default option. Through CAT, health care workers (HCWs) need to \"opt-out\" when choosing not to prescribe TPT to PLHIV. We assessed the prospective, concurrent, and retrospective acceptability of TPT prescribing among HCWs in Malawi who worked in clinics participating in a cluster randomized trial of the CAT intervention.
METHODS: 28 in-depth semi-structured interviews were conducted with HCWs from control (standard prescribing approach) and intervention (CAT approach) clinics. The CAT approach was facilitated in intervention clinics using a default prescribing module built into the point-of-care HIV Electronic Medical Record (EMR) system. An interview guide for the qualitative CAT assessment was developed based on the theoretical framework of acceptability and on the normalization process theory. Thematic analysis was used to code the data, using NVivo 12 software.
RESULTS: We identified eight themes belonging to the three chronological constructs of acceptability. HCWs expressed no tension for changing the standard approach to TPT prescribing (prospective acceptability); however, those exposed to CAT described several advantages, including that it served as a reminder to prescribe TPT and routinized TPT prescribing (concurrent acceptability). Some felt that CAT may reduce HCW´s autonomy and might lead to inappropriate TPT prescribing (retrospective acceptability).
CONCLUSIONS: The default prescribing module for TPT has now been incorporated into the point-of-care EMR system nationally in Malawi. This seems to fit the acceptability of the HCWs. Moving forward, it is important to train HCWs on how the EMR can be leveraged to determine who is eligible for TPT and who is not, while acknowledging the autonomy of HCWs.

BACKGROUND: Monoclonal antibodies (mAbs) targeting the Calcitonin Gene-Related Peptide (CGRP) pathway are safe and effective treatments for migraine prevention. However, the high cost of these novel therapies has led to reimbursement policies requiring patients to try multiple traditional preventives before access. In Germany, a recent change in insurance policy significantly expanded coverage for the CGRP receptor mAb erenumab, enabling migraine patients who failed just one prior prophylactic medication to receive this mAb. Here, we compare the clinical response to treatment with erenumab in migraine patients treated using the old and new coverage policy.
METHODS: In this retrospective cohort study, we included CGRP-mAb naïve patients with episodic or chronic migraine, who started erenumab at our headache center according to either the old or the new insurance policy and received at least 3 consecutive injections. Headache diaries and electronic documentation were used to evaluate reductions in monthly headache and migraine days (MHD and MMD) and ≥ 50% and ≥ 30% responder rates at month 3 (weeks 9-12) of treatment.
RESULTS: We included 146 patients who received erenumab according to the old policy and 63 patients that were treated using the new policy. At weeks 9-12 of treatment, 37.7% of the old policy group had a 50% or greater reduction in MHD, compared to 63.5% of the new policy group (P < 0.001). Mean reduction in MHD was 5.02 days (SD = 5.46) and 6.67 days (SD = 5.32, P = 0.045) in the old and new policy cohort, respectively. After propensity score matching, the marginal effect of the new policy on treatment outcome was 2.29 days (standard error, SE: 0.715, P = 0.001) more reduction in MHD, and 30.1% (SE: 10.6%, P = 0.005) increase in ≥ 50% response rate for MHD.
CONCLUSIONS: Starting erenumab earlier in the course of migraine progression in a real-world setting may lead to a better response than starting after multiple failed prophylactic attempts. Continually gathering real-world evidence may help policymakers in deciding how readily to cover CGRP-targeted therapies in migraine prevention.

BACKGROUND: Cluster headache is a severe and disabling primary headache disorder. Galcanezumab is a monoclonal antibody against calcitonin gene-related peptide and a preventive therapy for episodic cluster headache. However, the approval and insurance coverage for episodic cluster headache differ in each country. Additionally, the consistency of efficacy of galcanezumab therapy has not yet been evaluated. This study aimed to assess the efficacy and safety of 240 mg of galcanezumab therapy for consecutive cluster bouts in patients with episodic cluster headache.
METHODS: The study enrolled patients with episodic cluster headache who received two courses of galcanezumab therapy at three university hospitals in Republic of Korea between February 2020 and April 2022. The efficacy and safety of galcanezumab were analyzed by comparing daily headache frequency, the number of headache days, and headache intensity and adverse effects during the one-week period before and the third week after galcanezumab injection for each episode of cluster bouts. Paired t-test was used for comparing repeated data from different episodes of cluster bout.
RESULTS: Sixteen patients were enrolled in this study. Fourteen patients received galcanezumab therapy for two consecutive cluster bouts. Galcanezumab was administered 24 days and 11 days after the first and second cluster bouts, respectively. The proportion of patients with 50% or more reduction in frequency of daily headache at week 3 from baseline was 86% and 64% during the first and second episodes, respectively. The proportion of patients who received transitional therapy before galcanezumab therapy was higher in the first episode of cluster bout than that in the second episode of cluster bout. No serious adverse reactions or significant differences in adverse effects between cluster bouts were noticed. Two patients received a second galcanezumab therapy during the pre-cluster period, and their cluster periods ended without typical cluster headache attacks 10-60 days after galcanezumab therapy.
CONCLUSIONS: This exploratory analysis suggests that galcanezumab may be effective as a preventive therapy in subsequent cluster bouts. Patients with episodic cluster headaches who underwent galcanezumab therapy tended to receive a second round of treatment in the early stages of their next cluster bout without transitional therapy.

BACKGROUND: There is increasing research interest in the development of preventive treatment for individuals at risk of rheumatoid arthritis (RA). Previous studies have explored the perceptions of at-risk groups and patients about predictive and preventive strategies for RA, but little is known about health care professionals\' (HCPs) perspectives.
METHODS: One-to-one semi-structured qualitative interviews were conducted (face-to-face or by telephone) with HCPs. Audio recordings of the interviews were transcribed, and the data were analysed by thematic analysis.
RESULTS: Nineteen HCPs (11 female) were interviewed, including ten GPs, six rheumatologists and three rheumatology nurse specialists. The thematic analysis identified four organising themes: 1) Attributes of predictive and preventive approaches; 2) Ethical and psychological concerns; 3) Implementation issues and 4) Learning from management of other conditions. Theme 1 described necessary attributes of predictive and preventive approaches, including the type and performance of predictive tools, the need for a sound evidence base and consideration of risks and benefits associated with preventive treatment. Theme 2 described the ethical and psycho-social concerns that interviewees raised, including the potential negative economic, financial and psychological effects of risk disclosure for \'at-risk\' individuals, uncertainty around the development of RA and the potential for benefit associated with the treatments being considered. Theme 3 describes the implementation issues considered, including knowledge and training needs, costs and resource implications of implementing predictive and preventive approaches, the role of different types of HCPs, guidelines and tools needed, and patient characteristics relating to the appropriateness of preventive treatments. Theme 4 describes lessons that could be learned from interviewees\' experiences of prediction and prevention in other disease areas, including how preventive treatment is prescribed, existing guidelines and tools for other diseases and issues relating to risk communication.
CONCLUSIONS: For successful implementation of predictive and preventative approaches in RA, HCPs need appropriate training about use and interpretation of predictive tools, communication of results to at-risk individuals, and options for intervention. Evidence of cost-efficiency, appropriate resource allocation, adaptation of official guidelines and careful consideration of the at-risk individuals\' psycho-social needs are also needed.