MicroRNA profiling in women with migraine: effects of CGRP-targeting treatment.

BACKGROUND: Migraine lacks biomarkers that can trace the biological pathways of the disease and predict the effectiveness of treatments. Monoclonal antibodies targeting calcitonin gene-related peptide pathway - including erenumab - offer the opportunity of investigating potential migraine biomarkers due to their specific mechanism of action in preventing both episodic (EM) and chronic (CM) migraine. Our study aims at evaluating the expression levels of circulating microRNAs (miRNAs) according to migraine type, before and after treatment with erenumab and based on treatment response, in order to identify miRNAs with potential role as epigenetic biomarkers. METHODS: The study included women aged 25-50 years with EM or CM treated with erenumab according to clinical indications. MiRNAs expression levels were assessed before (baseline) and after a 16-week treatment with erenumab, 140 mg every four weeks (post-treatment). An extensive miRNAs profiling was performed by qRT-PCR in small, pooled groups of ≤ 8 women each, classified according to migraine frequency (EM and CM) and the degree of response to erenumab. The expression levels of selected miRNAs were also validated using single miRNA assays in each woman with EM and CM. RESULTS: During the study, 36 women with migraine (19 with EM and 17 with CM) out of 40 who were initially screened, performed the assessment of miRNA expression at baseline and post-treatment, Erenumab treatment significantly improved migraine burden in both EM and CM. MiRNA profiling revealed differential expression levels of a wide set of miRNAs (hsa-let-7d-3p, hsa-miR-106b-3p, hsa-miR-122-5p, hsa-miR-143-3p, hsa-miR-144-3p, hsa-miR-16-5p, hsa-miR-181a-5p, hsa-miR-221-3p, hsa-miR-25-3p, hsa-miR-29b-2-5p, hsa-miR-326, miR-363-3p, hsa-miR-424-5p, hsa-miR-485-3p, hsa-miR-532-5p, hsa-miR-543, hsa-miR-629-5p, hsa-miR-660-5p, hsa-miR-92a-3p) depending on treatment response. Among them, single miRNA assays confirmed the progressive decrease of hsa-miR-143-3p expression levels in relation to increasing response to erenumab in women with EM (7 with low, 6 with medium, and 6 with high response; p = 0.02). Additionally, single assays showed higher hsa-miR-34a-5p and hsa-miR-382-5p expression levels at baseline in women with CM compared with those with EM (p = 0.0002 and p = 0.0007, respectively), as well as their expression level decrease in women with CM from baseline to follow-up (p = 0.04 and p = 0.02, respectively). CONCLUSIONS: Our study suggests that targeting the CGRP pathway in migraine changes the expression levels of certain miRNAs. These miRNA levels are linked to the levels of response to CGRP receptor blockage. Future research challenges include assigning specific functions to the modulated miRNAs to unravel pathways modulated by the disease and the treatment. TRIAL REGISTRATION: The study was registered in clinicaltrials.gov with code NCT04659226 and in the Novartis database with code CAMG334AIT05T.

Monoclonal antibodies targeting the calcitonin gene-related peptide pathway improve the effectiveness of acute medication-a real-world study.

BACKGROUND: One of the aims of migraine prevention is to improve response to acute migraine treatments. The aim of the present study was to assess whether monoclonal antibodies targeting the CGRP pathway (CGRP-mAbs) can improve the perceived efficacy of acute treatments. METHODS: We included and followed up patients with chronic or episodic migraine from the Headache Centers of Avezzano-L'Aquila and Naples treated with CGRP-mAbs from March 2021 to December 2022. All patients filled out the Migraine Treatment Optimization Questionnaire (MTOQ), the Headache Impact Test (HIT-6), and the Migraine Impact and Disability Assessment Scale (MIDAS) at baseline and 3-6 months after the start of treatment with CGRP-mAbs. RESULTS: Sixty-five patients (81.3%) completed the 6-month follow-up. Most patients were female (55, 84.6%), with a median age of 46 years (IQR 39-56). Median MTOQ score increased from 8 (interquartile range [IQR] 4-13) at baseline to 15 (IQR 11-17) at 3 months (p < 0.001) and 16 (IQR 13-17) at the 6-month follow-up (p < 0.001). Median migraine days over 90-day periods decreased from 40 (IQR 24-60) to 24 (IQR 15-30) at 3 months (p < 0.001) and to 20 (IQR 12-24) at 6 months (p < 0.001). Median monthly intake of acute medication decreased from 55 doses (IQR 29-80.5) to 24 doses (IQR 15-40) at 3 months and 18 doses (IQR 11-30) at 6 months (p < 0.001). CONCLUSIONS: We showed that 6 months of preventive treatment with CGRP-mAbs led to a significantly better effectiveness of acute treatments, paralleled by decreased monthly migraine days and acute treatment intake.

Telehealth care and remote monitoring strategies in heart failure patients: A systematic review and meta-analysis.

BACKGROUND: Heart failure (HF) is a cardiac clinical syndrome that involves complex pathological aetiologies. It represents a growing public health issue and affects a significant number of people worldwide. OBJECTIVES: To synthesize evidence related to the impact of telemonitoring strategies on mortality and hospital readmissions of heart failure patients. METHODS: A systematic literature review was conducted using PubMed, Scopus, CINAHL, IEEE Xplore Digital Library, Engineering Source, and INSPEC. To be included, studies had to be in English or Italian and involve heart failure patients of any NYHA class, receiving care through any telecare, remote monitoring, telemonitoring, or telehealth programmes. Articles had to contain data on both mortality and number of patients who underwent rehospitalizations during follow-ups. To explore the effectiveness of telemonitoring strategies in reducing both one-year all-cause mortality and one-year rehospitalizations, studies were synthesized through meta-analyses, while those excluded from meta-analyses were summarized narratively. RESULTS: Sixty-one studies were included in the review. Narrative synthesis of data suggests a trend towards a reduction in deaths among monitored patients, but the number of rehospitalized patients was higher in this group. Meta-analysis of studies reporting one-year all-cause mortality outlined the protective power of care models based on telemonitoring in reducing one-year all-cause mortality. Meta-analysis of studies reporting the number of rehospitalized patients in one-year outlined that telemonitoring is effective in reducing the number of rehospitalized patients when compared with usual care strategies. CONCLUSION: Evidence from this review confirms the benefits of telemonitoring in reducing mortality and rehospitalizations of HF patients. Further research is needed to reduce the heterogeneity of the studies.

Nursing Diagnosis Accuracy in Nursing Education: Clinical Decision Support System Compared With Paper-Based Documentation-A Before and After Study.

Computer-based technologies have been widely used in nursing education, although the best educational modality to improve documentation and nursing diagnostic accuracy using electronic health records is still under investigation. It is important to address this gap and seek an effective way to address increased accuracy around nursing diagnoses identification. Nursing diagnoses are judgments that represent a synthesis of data collected by the nurse and used to guide interventions and to achieve desirable patients' outcomes. This current investigation is aimed at comparing the nursing diagnostic accuracy, satisfaction, and usability of a computerized system versus a traditional paper-based approach. A total of 66 nursing students solved three validated clinical scenarios using the NANDA-International terminologies traditional paper-based approach and then the computer-based Clinical Decision Support System. Study findings indicated a significantly higher nursing diagnostic accuracy ( P < .001) in solving cancer and stroke clinical scenarios, whereas there was no significant difference in acute myocardial infarction scenario. The use of the electronic system increased the number of correct diagnostic indicators ( P < .05); however, the level of students' satisfaction was similar. The usability scores highlighted the need to make the electronic documentation systems more user-friendly.

Long-Term Treatment Over 52 Weeks with Monthly Fremanezumab in Drug-Resistant Migraine: A Prospective Multicenter Cohort Study.

BACKGROUND: Real-world studies on fremanezumab, an anti-calcitonin gene-related peptide monoclonal antibody for migraine prevention, are few and with limited follow-up. OBJECTIVE: We aimed to evaluate the long-term (up to 52 weeks) effectiveness and tolerability of fremanezumab in high-frequency episodic migraine and chronic migraine. METHODS: This s an independent, prospective, multicenter cohort study enrolling outpatients in 17 Italian Headache Centers with high-frequency episodic migraine or chronic migraine and multiple preventive treatment failures. Patients were treated with fremanezumab 225 mg monthly. The primary outcomes included changes from baseline (1 month before treatment) in monthly headache days, response rates (reduction in monthly headache days from baseline), and persistence in medication overuse at months 3, 6, and 12 (all outcome timeframes refer to the stated month). Secondary outcomes included changes from baseline in acute medication intake and disability questionnaires scores at the same timepoints. A last observation carried forward analysis was also performed. RESULTS: A total of 90 patients who received at least one dose of fremanezumab and with a potential 12-month follow-up were included. Among them, 15 (18.0%) patients discontinued treatment for the entire population, a reduction in monthly headache days compared with baseline was reported at month 3, with a significant median [interquartile range] reduction in monthly headache days (- 9.0 [11.5], p < 0.001). A statistically different reduction was also reported at month 6 compared with baseline (- 10.0 [12.0]; p < 0.001) and at 12 months of treatment (- 10.0 [14.0]; p < 0.001). The percentage of patients with medication overuse was significantly reduced compared with baseline from 68.7% (57/83) to 29.6% (24/81), 25.3% (19/75), and 14.7% (10/68) at 3, 6, and 12 months of treatment, respectively (p < 0.001). Acute medication use (days and total number) and disability scores were also significantly reduced (p < 0.001). A ≥ 50% response rate was achieved for 51.9, 67.9, and 76.5% of all patients at 3, 6, and 12 months, respectively. Last observation carried forward analyses confirmed these findings. Fremanezumab was well tolerated, with just one patient discontinuing treatment because of adverse events. CONCLUSIONS: This study provides evidence for the real-world effectiveness of fremanezumab in treating both high-frequency episodic migraine and chronic migraine, with meaningful and sustained improvements in multiple migraine-related variables. No new safety issue was identified.

Long-Term Effect of Switching From an Anti-CGRP Receptor to an Anti-CGRP Ligand Antibody in Treatment-Refractory Chronic Migraine: A Prospective Real-World Analysis.

In migraine patients with a poor response to a calcitonin gene-related peptide monoclonal antibody against the receptor, switching to a calcitonin gene-related peptide monoclonal antibodies against the ligand may be beneficial. This was a long-term real-world prospective analysis conducted in treatment-refractory chronic migraine patients coming from two large tertiary referral headache centres, who did not achieve a meaningful response to erenumab and were switched to fremanezumab. Responders to fremanezumab were considered those who achieved at least 30% reduction in monthly migraine days by month 3, compared to the post-erenumab baseline. Secondary efficacy and disability outcomes were analysed. Thirty-nine patients (female n = 32, 82.1%; median age: 49 years old, IQR = 29.0-56.0) were included. After three months of treatment with fremanezumab, ten out of 39 patients (25.6%) were considered responders. Four of the 11 patients who continued fremanezumab became responders at month 6, increasing the number of responders to 14 patients (35.9%). Responders received a median of 12 injections (IQR = 9.0-18.0) at the time of the analysis. After the last treatment, 13 patients (33.3%) remained responders. The number of mean monthly migraine days significantly decreased from 21.4 at baseline (IQR = 10.7-30.0) to 8.6 (IQR = 3.8-13.9) at the last follow-up. Painkillers intake and HIT-6 score were significantly reduced at the last follow-up. About 1/3 of patients with treatment refractory chronic migraine who have a disappointing response to erenumab and switch to fremanezumab, obtained a meaningful and sustained improvement of their migraine load over time, supporting the appropriateness of this therapeutic approach in clinical practice.

Two-year effectiveness of erenumab in resistant chronic migraine: a prospective real-world analysis.

BACKGROUND: Controlled and real-world evidence have demonstrated the efficacy of calcitonin gene related peptide (CGRP) monoclonal antibodies (MABs) in migraine. However, data on the over-one-year sustained effectiveness of CGRP MABs in resistant chronic migraine (CM) is sparse.  METHODS: This is a two-year real-world prospective analysis of an ongoing single centre audit conducted in patients with resistant CM. Patients received monthly erenumab for six months before assessing its effectiveness. Responders were considered those who achieved at least 30% reduction in monthly migraine days (MMD) by month 6, compared to baseline. Secondary outcomes were also analysed, including changes of the Headache Impact Test version 6 (HIT-6). RESULTS: One hundred sixty-four patients [135 (82.3%) females; mean age 46 SD 14) years] were included in the audit and 160 patients analysed. Patients had failed a mean of 8.4 preventive treatments at baseline. At month 6, 76 patients (48%) were 30% responders to erenumab, 50 patients (31%) were 50% responders and 25 (15%) were 75% responders. The mean reduction in MMD at month 6 was 7.5 days compared to baseline (P < 0.001). At month 12 and month 18, 61 patients (38%) and 52 patients (33%) remained 30% responders respectively. At month 24, 36 patients (23%) remained 30% responders, 25 patients (16%) and 13 patients (8%) were respectively 50% and 75% responders. Compared to 95% of patients at baseline, at months 6, 12 and 24, 46%, 29% and 16% of responders respectively had severe disability. At least one adverse event at month 6, 12, 18 and 24 was reported by 49%, 19%, 11% and 3% of patients. By month 6, 13% of patients discontinued the treatment because of side effects, often constipation. CONCLUSIONS: Long-term sustained effectiveness of erenumab was reported only by a minority of resistant CM patients. Although more research in resistant migraine is needed, Erenumab can provide long-term meaningful reduction in migraine load and migraine-related disability in some patients.

Cranial autonomic symptoms and response to monoclonal antibodies targeting the Calcitonin gene-related peptide pathway: A real-world study.

Objective: Cranial autonomic symptoms (CAS), including conjunctival injection, tearing, nasal congestion or rhinorrhea, eyelid edema, miosis or ptosis, and forehead or facial sweating ipsilateral to headache, are often reported by patients with migraine during headache attacks. CAS is a consequence of the activation of the trigeminovascular system, which is the target of monoclonal antibodies acting on the CGRP pathway. Therefore, we hypothesized that patients with CAS might have higher trigeminovascular activation than those without CAS leading to a better response to anti-CGRP treatments. Methods: We performed a prospective analysis including patients with episodic or chronic migraine treated with anti-CGRP monoclonal antibodies (i.e., erenumab, fremanezumab, and galcanezumab) between 2019 and 2021. The observation period included a 12-week baseline before treatment with anti-CGRP antibodies and a 12-week treatment follow-up. We evaluated the prevalence of CAS in our cohort and compared disease characteristics and treatment response (i.e., 12-week monthly headache days and 0-29, 30-49, 50-74, 75-99, and 100% monthly headache days reduction from baseline) among patients with and without CAS using the χ2 test, Kruskal-Wallis test, and Mann-Whitney U-test. Results: Out of 136 patients, 88 (65%) had CAS. Both patients with and without CAS reported a significant decrease in monthly headache days from baseline. During the 12-week follow-up, the median difference in monthly headache days from baseline was higher in patients with CAS (-10, IQR-15 to-6) than in those without CAS (6, IQR 12 to 3; P = 0.009). However, the proportions of patients with 0 to 29, 30 to 49, 50 to 74, 75 to 99, and 100% response rates did not differ between the two groups. Conclusions: In our cohort, the presence of CAS was associated with a greater response to monoclonal antibodies targeting the CGRP pathway. CAS could be a clinical marker of trigeminovascular activation and thus be related to a better response to CGRP treatments.

Applying a biopsychosocial model to migraine: rationale and clinical implications.

Migraine is a complex condition in which genetic predisposition interacts with other biological and environmental factors determining its course. A hyperresponsive brain cortex, peripheral and central alterations in pain processing, and comorbidities play a role from an individual biological standpoint. Besides, dysfunctional psychological mechanisms, social and lifestyle factors may intervene and impact on the clinical phenotype of the disease, promote its transformation from episodic into chronic migraine and may increase migraine-related disability.Thus, given the multifactorial origin of the condition, the application of a biopsychosocial approach in the management of migraine could favor therapeutic success. While in chronic pain conditions the biopsychosocial approach is already a mainstay of treatment, in migraine the biomedical approach is still dominant. It is instead advisable to carefully consider the individual with migraine as a whole, in order to plan a tailored treatment. In this review, we first reported an analytical and critical discussion of the biological, psychological, and social factors involved in migraine. Then, we addressed the management implications of the application of a biopsychosocial model discussing how the integration between non-pharmacological management and conventional biomedical treatment may provide advantages to migraine care.

Effectiveness of Transcranial Direct Current Stimulation and Monoclonal Antibodies Acting on the CGRP as a Combined Treatment for Migraine (TACTIC): Protocol for a Randomized, Double-Blind, Sham-Controlled Trial.

Background: Migraine is a recurrent headache disorder that has a still unclear pathophysiology, involving several circuits of both the central and peripheral nervous system. Monoclonal antibodies acting on the calcitonin gene-related (CGRP) pathway (CGRP-MAbs) are the first drugs specifically designed for migraine; those drugs act peripherally on the trigeminal ganglion without entering the blood-brain barrier. Conversely, neuromodulation techniques such as transcranial direct current stimulation (tDCS) act centrally by increasing or decreasing the neuronal firing rate of brain cortical areas. The aim of the study will be to evaluate whether tDCS, in addition to CGRP-MAbs, is an effective add-on treatment in reducing headache frequency, intensity and acute medication use in patients with migraine. To demonstrate the biological effects of tDCS, the electroencephalographic (EEG) power changes after tDCS will be assessed. Methods: We will include patients with migraine on treatment with CGRP-MAbs and reporting ≥8 monthly migraine days. During a prospective 28-day baseline period, patients will fill in a headache diary and questionnaires to evaluate migraine-related disability, anxiety and depressive symptoms, sleep quality, and health-related quality of life. Subjects will be randomly assigned in a 1:1 ratio to active or sham tDCS. The stimulation protocol will consist in five daily sessions, the cathodes will be applied bilaterally above the occipital areas, with the reference anode electrodes positioned above the primary motor areas. Before the first, and immediately after the last stimulation session, patients will perform a 10-min resting EEG recording. During a 28-day follow-up period following tDCS, patients will have to fill in a headache diary and questionnaires identical to those of the baseline period. Discussion: This trial will evaluate the efficacy of an add-on treatment acting on the brain in patients with migraine, who are already treated with peripherally acting drugs, showing how tDCS acts in restoring the dysfunctional brain networks typical of the migraine patient. Clinical Trial Registration: NCT05161871.

Acute Medication Use in Patients With Migraine Treated With Monoclonal Antibodies Acting on the CGRP Pathway: Results From a Multicenter Study and Proposal of a New Index.

Introduction: Assessing the impact of migraine preventive treatments on acute medication consumption is important in clinical evaluation. The number of acute medication intakes per each monthly migraine day (MMD) could provide insights on migraine burden and represent a new proxy of treatment effectiveness in clinical trials and real-life studies. We evaluated the effect of monoclonal antibodies acting on calcitonin gene-related peptide (CGRP) pathway on the consumption of migraine acute medication in real-life. Methods: In two headache centers in Prague (CZ), we included and followed up to 6 months consecutive patients treated with MoAbs acting on CGRP (erenumab or fremanezumab). For each month of treatment, we reported monthly drug intake (MDI) in doses of any medication, migraine-specific (MS), and non-migraine-specific (non-MS) medications, and computed a ratio between MMDs and MDI, i.e., Migraine Medication Index (MMI) for MS and non-MS medications. Results: We included 90 patients (91.1% women) with a median age of 47 [interquartile range (IQR) 42-51] years; 81 (90.0%) treated with erenumab and 9 (10.0%) with fremanezumab. Median MMDs decreased from 11 (IQR 8-14) at baseline to 4 (IQR 2-5) at Month 3 (p < 0.001 vs. baseline) and 3 (IQR 2-6) at Month 6 (p < 0.001 vs. baseline). Median MDI decreased from 15 drug intakes (IQR 11-20) at baseline to four drug intakes (IQR 2-7) at Month 3 (p < 0.001) and four drug intakes (IQR 2-7) at Month 6 (p < 0.001).The corresponding MDIs for MS medications were 10 (IQR 6-14) at baseline, 3 (IQR 1-5, p < 0.001) at Month 3, and 2 (IQR 0-4, p < 0.001) at Month 6. Monthly drug intakes for non-MS medications were 4 (IQR 0-9) at baseline, 1 (IQR 0-3, p < 0.001) at Month 3 and at Month 6.Median MMI decreased from 1.32 (IQR 1.11-1.68) at baseline to 1.00 (IQR 1.00-1.50, p < 0.001) at Month 3 and 1.00 (IQR 1.00-1.34, p < 0.001) at Month 6. Conclusions: We confirmed that MoAbs acting on CGRP pathway decrease acute migraine medication consumption. We proposed a new index that can be easily applied in clinical practice to quantify migraine burden and its response to acute medication. Our index could help optimizing migraine acute treatment in clinical practice.

Dose-Response Relationship between High-Fidelity Simulation and Intensive Care Nursing Students' Learning Outcomes: An Italian Multimethod Study.

Background: The best application modality of high-fidelity simulation in graduate critical care nursing courses is still rarely investigated in nursing research. This is an important issue since advanced nursing skills are necessary to effectively respond to critically ill patients' care needs. The aim of the study was to examine the influence of a modified teaching model based on multiple exposures to high-fidelity simulations on both the learning outcomes and the perceptions of graduate students enrolled in a critical care nursing course. Methods: A multimethod study involving a sample of graduate critical care nursing students was conducted. A theoretical teaching model focused on multiple exposures to high-fidelity simulations is currently applied as a teaching method in an Italian critical care nursing course. According to the Kirkpatrick model for evaluating training programs, the performance, self-efficacy, and self-confidence in managing critically ill patients were considered learning outcomes, while satisfaction with learning and students' lived experiences during the experimental phases were considered students' perceptions. Results: Multiple exposures to high-fidelity simulations significantly improved performance, self-efficacy, and self-confidence in managing virtual critically ill patients' care needs. The satisfaction level was high, while lived experiences of participants were positive and allowed for better explanation of quantitative results of this study. Conclusions: Multiple exposures to high-fidelity simulations can be considered a valuable teaching method that can improve the learning outcomes of graduate nurses enrolled in an intensive care course.

Different effects of air microembolism through patent foramen ovale in patients with migraine: A quantitative electroencephalogram case series.

Background: Literature suggests an association between patent foramen ovale (PFO) and migraine, mostly migraine with aura (MA). Previous data suggest that air microembolism through PFO can lead to bioelectrical abnormalities detectable at electroencephalogram (EEG) in patients with MA, thus suggesting a pathophysiological mechanism for the MA-PFO association. However, those data lack replication. Methods: Patients with MA or migraine without aura (MO) and large PFO underwent a 19-channel EEG recording before and after injection of air microbubbles. We compared EEG power before and after microbubble injection for each electrode location, for each frequency band (theta: 5-7 Hz; alpha: 8-12 Hz; beta: 13-30 Hz; lower gamma: 31-45 Hz), and for total global power (the average of EEG power at each location and frequency band). Results: We included 10 patients, four with MA and six with MO; six patients had medium-to-high migraine frequency (four or more monthly migraine days), while four had low frequency (one monthly migraine day). EEG power changes after air microembolism varied across patients. Considering the overall group, total global EEG power did not change; however, EEG power in the higher frequency ranges (beta and lower gamma) increased in patients with MA. Conclusions: We did not replicate the effects of air microembolism previously reported in patients with migraine. Aura status, migraine frequency, and medications might influence patients' response to microembolism. More refined EEG measurements are needed to clarify the dynamic role of PFO on migraine occurrence.

The COVID-19 Pandemic as an Opportunity to Improve Health Care Through a Nurse-Coordinated Multidisciplinary Model in a Headache Specialist Center: The Implementation of a Telemedicine Protocol.

Background: Due to coronavirus disease-19 (COVID-19) pandemic, Italian outpatient clinics were suspended in March-April 2020 and subsequently slowed down. Telemedicine was shown to be useful in headache clinics, despite absence of a detailed protocol for its development. Objective: To describe the implementation of a structured telemedicine protocol during COVID-19 pandemic. Materials and Methods: Since May 2020, we performed a quality improvement study in a Headache Specialist Center in central Italy. We involved patients who had in-person follow-up visits scheduled during suspension and initial reopening of clinics. Patients had two appointments with a nurse specialized in headache care and a headache physician, respectively, using Microsoft Teams®. The service is still active. We collected sociodemographic and clinical characteristics of patients, technical details of telemedicine visits, patient feedback, medical judgment about complexity of clinical decisions, and need for in-person re-evaluation. We also performed a Strengths-Weaknesses-Opportunities-Threats analysis to provide a realistic picture of the service. Results: We performed 207 telemedicine visits involving 100 patients with a median age of 44 (interquartile range [IQR]: 35-56) years; 76.0% were women and lived at a median of 68 (IQR: 24-109) km from the Center. Thirty-nine (39.0%) were visited for migraine without aura. Patients mostly used a computer (68.1% visits) with high audio-video quality in 93.2% of visits. First and second appointments lasted in median 20 (IQR: 14-25) minutes and 9 (IQR: 7-13) minutes, respectively. Interacting with patients was very easy in 66.7% of visits. Patients reported no difficulty in sharing documents and high satisfaction in 78.6% and 93.5% of visits, respectively. Perceived complexity of clinical decisions was generally low (86.5%), whereas 8.2% of cases required in-person re-evaluation. Conclusions: Telemedicine facilitated follow-ups, ensuring multidisciplinary care and high patient satisfaction, justifying its wider adoption in headache care.

Multi-Center Randomized Phase II Clinical Trial on Remote Ischemic Conditioning in Acute Ischemic Stroke Within 9 Hours of Onset in Patients Ineligible to Recanalization Therapies (TRICS-9): Study Design and Protocol.

Aim: To assess the efficacy of remote ischemic conditioning (RIC) in patients with ischemic stroke within 9 h of onset, that are not candidates for recanalization therapies. Sample Size Estimates: A sample size of 80 patients (40 in each arm) should yield 80% power to detect a 20% difference in early neurological improvement at 72 h at p = 0.05, two sided. Methods and Design: TRICS-9 is a phase II, multicenter, controlled, block randomized, open-label, interventional clinical trial. Patients recruited in Italian academic hospitals will be randomized 1:1 to either RIC plus standard medical therapy or standard medical therapy alone. After randomization, RIC will be applied manually by four alternating cycles of inflation/deflation 5 min each, using a blood pressure cuff around the non-paretic arm. Study Outcomes: The primary efficacy outcome is early neurological improvement, defined as the percent change in the National Institute of Health Stroke Scale (NIHSS) at 72 h in each arm. Secondary outcomes include early neurologic improvement at 24 and 48 h, disability at 3 months, rate of symptomatic intracerebral hemorrhage, feasibility (proportion of patients completing RIC), tolerability after RIC and at 72 h, blood levels of HIF-1α, and HSP27 at 24 h and 72 h. Discussion/Conclusion: RIC in combination with recanalization therapies appears to add no clinical benefit to patients, but whether it is beneficial to those that are not candidates for recanalization therapies is still to be demonstrated. TRICS-9 has been developed to elucidate this issue. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04400981.

Which is the best transcranial direct current stimulation protocol for migraine prevention? A systematic review and critical appraisal of randomized controlled trials.

BACKGROUND: Transcranial direct current stimulation (tDCS) could counteract the pathophysiological triggers of migraine attacks by modulating cortical excitability. Several pilot randomized controlled trials (RCTs) assessed the efficacy of tDCS for migraine prevention. We reviewed and summarized the state of the art of tDCS protocols for migraine prevention, discussing study results according to the stimulations parameters and patients' populations. MAIN BODY: We combined the keywords 'migraine', 'headache', 'transcranial direct current stimulation', and 'tDCS' and searched Pubmed, Scopus, and Web of Science, from the beginning of indexing to June 22, 2021. We only included RCTs comparing the efficacy of active tDCS with sham tDCS to decrease migraine frequency, intensity, and/or acute drug utilization. The risk of bias of each RCT was assessed by using the RoB-2 tool (Cochrane Collaboration). Thirteen RCTs (from 2011 to 2021) were included in the review. The included patients ranged from 13 to 135. RCTs included patients with any migraine (n=3), chronic migraine (n=6), episodic migraine (n=3) or menstrual migraine (n=1). Six RCTs used cathodal and five anodal tDCS, while two RCTs compared the efficacy of both cathodal and anodal tDCS with that of sham. In most of the cathodal stimulation trials, the target areas were the occipital regions, with reference on central or supraorbital areas. In anodal RCTs, the anode was usually placed above the motor cortical areas and the cathode on supraorbital areas. All RCTs adopted repeated sessions (from 5 to 28) at variable intervals, while the follow-up length spanned from 1 day up to 12 months. Efficacy results were variable but overall positive. According to the RoB-2 tool, only four of the 13 RCTs had a low risk of bias, while the others presented some concerns. CONCLUSIONS: Both anodal and cathodal tDCS are promising for migraine prevention. However, there is a need for larger and rigorous RCTs and standardized procedures. Additionally, the potential benefits and targeted neurostimulation protocols should be assessed for specific subgroups of patients.

Detailed data about a forty-year systematic review and meta-analysis on nursing student academic outcomes.

Data were extracted from observational studies describing undergraduate nursing students' academic outcomes that were included in a systematic review and meta-analysis conducted in 2019 and updated in 2020 [1]. Data were extracted by two researchers independently through a previously tested electronic spreadsheet; any disagreement about data extraction was discussed with a third author. Extracted data were studies' general information, characteristics (i.e., country, study design, involved centers, number of cohort of students involved, duration (years) and denomination of the program attended, sample (N), sociodemographic characteristics of the sample, and methods utilized for data collection), and data related to the research question(s) of the review, i.e., nursing students' academic outcomes occurrence and associated factors. Raw data for each included study are reported, along with meta-analyses that were performed using ProMeta free software utilizing Odds Ratio (OR) and Cohen's d as principal effect sizes. The random-effect model was used for all studies, while the level of heterogeneity was explored and quantified through the Cochran's Q-test and I2 , respectively. Substantial or considerable heterogeneity (i.e., I2 ≥ 50%) was explored through a subgroup analysis based on the study design, when feasible [2]. A sensitivity analysis was also performed to detect the possible influence of single studies on meta-analyses results [2]. Publication bias was assessed through funnel plots and the testsf for their asymmetry, i.e., Begg and Mazumdar's rank correlation and Egger's linear regression method [2]. These data provide for an updated state of the art about nursing students' outcomes and associated factors. Therefore, they could ease future literature summaries about the topic, other than allow a comparison of the literature with future research results.

The lived experiences of intensive care nursing students exposed to a new model of high-fidelity simulation training: a phenomenological study.

BACKGROUND: In postgraduate intensive care nursing courses, high-fidelity simulation is useful to prepare students to guarantee safe and quality care of critically ill patients. Surprisingly, this issue has not attracted sufficient attention in the literature, and it is not clear whether the linear application of the traditional high-fidelity simulation method based on prebriefing, the simulation session and debriefing, can serve as empirical reference in postgraduate students' education. The aim of this study was to investigate the lived experiences of postgraduate students receiving multiple exposures to an innovative high-fidelity simulation design based on Kolb's Experiential Learning Theory. METHODS: A phenomenological study was conducted at an Italian University involving a purposive sample of 15 nursing students attending the postgraduate intensive care course. Audio-recorded face-to-face in-depth interviews were held by a researcher in a dedicated room complemented with non-verbal communication outlined in the field notes. Thematic analysis was used to analyse the transcribed data. RESULTS: Three themes and ten categories were derived from the data analysis. The themes included pragmatic learning experience, the emotional path, and confidence. CONCLUSIONS: Multiple exposure to high-fidelity simulation was lived as a pragmatic learning experience enhancing the students' ability to apply theory into practice. This novel approach also contributed to the transition from negative to positive feelings and improved students' confidence about technical and non-technical skills when caring for a critically ill patient.

Evaluating the interchangeability of infrared and digital devices with the traditional mercury thermometer in hospitalized pediatric patients: an observational study.

Gradual replacement of the mercury thermometers with alternative devices is ongoing around the world in a bid to protect human health and the environment from the adverse effects of mercury. However, to reduce the risks of misdiagnosis, unnecessary treatments, and omission of care in pediatric populations, more evidence on the reliability of alternative thermometers is needed. The aim of this comparative observational study was to detect any differences in temperature measurements between the use of the axillary mercury thermometer and the alternative techniques. Temperature values in degree Celsius (°C) were measured in a group of Albanian children aged up to 14 years using mercury and digital axillary thermometers, as well as forehead and tympanic infrared thermometers. The digital axillary device, compared with the mercury one, showed no clinically significant difference in the mean values (- 0.04 ± 0.29 °C) and the narrowest 95% level of agreement (+ 0.53 °C to - 0.62 °C) in the paired comparisons. For cut-off point of 37.5 °C, the digital axillary thermometer showed the highest levels of sensitivity (72.5%) and specificity (99.1%) in detecting fever. This study indicates that the digital axillary thermometer may be the better option since it adequately balances accuracy, safety, and children's comfort.