Real-world experience with calcitonin gene-related peptide-targeted antibodies for migraine prevention: a retrospective observational cohort study at two Japanese headache centers.

BACKGROUND: Although randomized controlled trials (RCTs) have shown that calcitonin gene-related peptide (CGRP)-targeted monoclonal antibodies (CGRP mAbs) are an efficacious and safe therapeutic modality for migraine prevention, their clinical benefits have not been well validated in Japanese patients in the real-world setting. The present study aimed to evaluate the real-world efficacy and safety of galcanezumab, fremanezumab, and erenumab in Japanese patients with migraine. METHODS: This observational retrospective cohort study was conducted at two headache centers in Japan. Patients with migraine who had experienced treatment failure with at least one traditional oral migraine preventive agent were treated with a CGRP mAb de novo. The primary efficacy endpoints were the changes from baseline in monthly migraine days (MMDs) and Headache Impact Test-6 (HIT-6) score after 3 dosing intervals (V3). We explored whether demographic and clinical characteristics predicted therapeutic outcomes at V3. RESULTS: Sixty-eight patients who completed three doses of a CGRP mAb (85.3% female [58/68], mean age: 46.2 ± 13.1 years) were included in the analysis. There were 19 patients with chronic migraine. The baseline MMDs were 13.4 ± 6.0. After 3 doses, the MMDs significantly decreased to 7.4 ± 5.5 (p < 0.0001), and the 50% response rate was 50.0%. HIT-6 score was significantly reduced from 66.7 ± 5.4 to 56.2 ± 8.7 after 3 doses (P = 0.0001). There was a positive correlation between the changes in MMDs and HIT-6 score from baseline after 2 doses (p = 0.0189). Those who achieved a ≥ 50% therapeutic response after the first and second doses were significantly more likely to do so at V3 (crude odds ratio: 3.474 [95% CI: 1.037 to 10.4], p = 0.0467). The most frequent adverse event was constipation (7.4%). None of the adverse events were serious, and there was no need for treatment discontinuation. CONCLUSIONS: This real-world study demonstrated that CGRP mAbs conferred Japanese patients with efficacious and safe migraine prevention, and an initial positive therapeutic response was predictive of subsequent favorable outcomes. Concomitant measurement of MMDs and HIT-6 score was useful in evaluating the efficacy of CGRP mAbs in migraine prevention.

Reliability, validity, and responsiveness of the Arabic version of HIT-6 questionnaire in patients with migraine indicated for preventive therapy: A multi-center study.

BACKGROUND: The Headache Impact Test (HIT-6) is an important patient-reported outcome measure (PROM) in migraine prevention trials. OBJECTIVES: This study aimed to (i) assess the reliability and validity of the Arabic version of HIT-6 in Arabic-speaking patients experiencing migraine, and (ii) evaluate the responsiveness of HIT-6 following migraine preventive therapy. METHODS: In this prospective study, patients with migraine (n = 145) were requested to fill out a headache diary, the Arabic version of HIT-6, and Migraine Disability Assessment Scale (MIDAS) at two time points (baseline and 3 months after initiation of prophylactic treatment). Some respondents (n = 73) were requested to fill out HIT-6 again 1 week from the baseline for test-retest reliability. The intensity of migraine headache attacks was evaluated using the Visual Analogue Scale (VAS). An anchor-based method was used to establish the minimal important change (MIC) value and responsiveness of HIT-6. RESULTS: The total scores of HIT-6 were significantly correlated to a fair degree with MIDAS (r = 0.41), as well as VAS (r = 0.53), and monthly migraine days (r = 0.38) at the baseline while at the follow-up (after 3 months), the correlations were of moderate degree with MIDAS scores (r = 0.62) and monthly migraine days (r = 0.60; convergent validity). Reliability estimates of the Arabic HIT-6 were excellent (Cronbach's α = 0.91 at baseline and 0.89 at follow-up). The average measure interclass correlation coefficient (ICC) value for the test-retest reliability was 0.96 (95% confidence interval = 0.94-0.98, p < 0.001). The HIT-6 total score is sensitive to change, being significantly reduced after prophylactic treatment compared to before (effect size = 1.5, standardized response mean = 1.3). A reduction from baseline of 4.5 on HIT-6 showed the highest responsiveness to predict improvement with an area under the curve equal to 0.66, sensitivity of 80%, specificity of 45%, and significance at 0.021. Changes in the HIT-6 total score were positively correlated with changes in monthly migraine days (r = 0.40) and VAS scores (r = 0.69) but not with changes in the score of MIDAS (r = 0.07). CONCLUSION: The Arabic version of HIT-6 is valid, reliable, and sensitive to detect clinical changes following migraine prophylactic treatment with a MIC of 4.5 points.

Experimental periprosthetic fractures with collarless polished tapered cemented stems.

PURPOSE: After cemented total hip arthroplasty, the risk of periprosthetic fracture (PPF) of taper-slip stems is higher than that of composite-beam stems. We aimed to assess the conditions resulting in PPFs of taper-slip stems using a falling weight. METHODS: Taper-slip stems were fixed to five types of simulated bone models using bone cement, and the fractures were evaluated by dropping stainless-steel weights from a predetermined height onto the heads. The periprosthetic fracture height in 50% of the bone models (PPFH50) was calculated using the staircase method. RESULTS: For the fixation with 0° of flexion, the values for PPFH50 were 61 ± 11, 60 ± 13, above 110, 108 ± 49, and 78 ± 12 cm for the cobalt-chromium-molybdenum alloy, stainless steel alloy (SUS), titanium alloy (Ti), smooth surface, and thick cement mantle models, respectively; for the fixation with 10° of flexion (considering flexure), the PPFH50 values were 77 ± 5, 85 ± 9, 90 ± 2, 89 ± 5, and 81 ± 11 cm, respectively. The fracture rates of the polished-surface stems were 78.6 and 35.7% at the proximal and distal sites, respectively (p < 0.05); the fracture rates of the smooth-surface stems were 14.2 and 100%, respectively (p < 0.05). CONCLUSION: The impact tests demonstrated that the conditions that were less likely to cause PPFs were use of Ti, a smooth surface, a thick cement mantle, and probably, use of SUS.

Quantitative analysis of the protective performance of bicycle helmet with multi-direction impact protection system in oblique impact tests.

PURPOSE: The current study aimed to assess the protective performance of helmets equipped with multi-directional impact protection system (MIPS) under various oblique impact loads. METHODS: Initially, a finite element model of a bicycle helmet with MIPS was developed based on the scanned geometric parameters of an actual bicycle helmet. Subsequently, the validity of model was confirmed using the KASK WG11 oblique impact test method. Three different impact angles (30°, 45°, and 60°) and 2 varying impact speeds (5 m/s and 8 m/s) were employed in oblique tests to evaluate protective performance of MIPS in helmets, focusing on injury assessment parameters such as peak linear acceleration (PLA) and peak angular acceleration (PAA) of the head. RESULTS: The results demonstrated that in all impact simulations, both assessment parameters were lower during impact for helmets equipped with MIPS compared to those without. The PAA was consistently lower in the MIPS helmet group, whereas the difference in PLA was not significant in the no-MIPS helmet group. For instance, at an impact velocity of 8 m/s and a 30° inclined anvil, the MIPS helmet group exhibited a PAA of 3225 rad/s2 and a PLA of 281 g. In contrast, the no-MIPS helmet group displayed a PAA of 8243 rad/s2 and a PLA of 292 g. Generally, both PAA and PLA parameters decreased with the increase of anvil angles. At a 60° anvil angles, PAA and PLA values were 664 rad/s2 and 20.7 g, respectively, reaching their minimum. CONCLUSION: The findings indicated that helmets incorporating MIPS offer enhanced protection against various oblique impact loads. When assessing helmets for oblique impacts, the utilization of larger angle anvils and rear impacts might not adequately evaluate protective performance during an impact event. These findings will guide advancements in helmet design and the refinement of oblique impact test protocols.

Dynamic changes in glymphatic function in reversible cerebral vasoconstriction syndrome.

BACKGROUND: The pathophysiology of the reversible cerebral vasoconstriction syndrome (RCVS) remains enigmatic and the role of glymphatics in RCVS pathophysiology has not been evaluated. We aimed to investigate RCVS glymphatic dynamics and its clinical correlates. METHODS: We prospectively evaluated the glymphatic function in RCVS patients, with RCVS subjects and healthy controls (HCs) recruited between August 2020 and November 2023, by calculating diffusion-tensor imaging along the perivascular space (DTI-ALPS) index under a 3-T MRI. Clinical and vascular (transcranial color-coded duplex sonography) investigations were conducted in RCVS subjects. RCVS participants were separated into acute (≤ 30 days) and remission (≥ 90 days) groups by disease onset to MRI interval. The time-trend, acute stage and longitudinal analyses of the DTI-ALPS index were conducted. Correlations between DTI-ALPS index and vascular and clinical parameters were performed. Bonferroni correction was applied to vascular investigations (q = 0.05/11). RESULTS: A total of 138 RCVS patients (mean age, 46.8 years ± 11.8; 128 women) and 42 HCs (mean age, 46.0 years ± 4.5; 35 women) were evaluated. Acute RCVS demonstrated lower DTI-ALPS index than HCs (p < 0.001) and remission RCVS (p < 0.001). A continuously increasing DTI-ALPS trend after disease onset was demonstrated. The DTI-ALPS was lower when the internal carotid arteries resistance index and six-item Headache Impact test scores were higher. In contrast, during 50-100 days after disease onset, the DTI-ALPS index was higher when the middle cerebral artery flow velocity was higher. CONCLUSIONS: Glymphatic function in patients with RCVS exhibited a unique dynamic evolution that was temporally coupled to different vascular indices and headache-related disabilities along the disease course. These findings may provide novel insights into the complex interactions between glymphatic transport, vasomotor control and pain modulation.

Two-year, real-world erenumab persistence and quality of life data in 82 pooled patients with abrupt onset, unremitting, treatment refractory headache and a migraine phenotype: New daily persistent headache or persistent post-traumatic headache in the majority of cases.

BACKGROUND: Patients diagnosed with New Daily Persistent Headache and Persistent Post-Traumatic Headache belong to a heterogeneous group of primary and secondary headache disorders, with the common clinical feature that these conditions start abruptly, continue unabated, and are refractory to conventional migraine preventive treatments. OBJECTIVE: This is a real-world, medium-term audit to explore whether erenumab improves quality of life in a pooled group of 82 abrupt-onset, unremitting and treatment refractory patients, where the diagnosis is new daily persistent headache and persistent post-traumatic headache in the majority of cases. METHODS: Eighty-two patients were treated with erenumab every 28 days over a two to three-year period, beginning in December 2018. These patients were "longstanding chronic" and refractory with a median of eight (IQR 4-12) prior failed migraine preventive treatments and median duration of disease of seven (IQR 3-11) years. The starting dose of erenumab was 70 mg in 79% of cases and 140 mg in the remaining patients (individuals with a BMI of more than 30). All patients were asked to complete three migraine specific Quality of Life questionnaires or Patient Reported Outcome Measures before starting treatment and typically at 3-12 intervals until the end of June 2021 or cessation of treatment. The Patient Reported Outcome Measures included: Headache Impact Test-6, Migraine Associated Disability Assessment test and Migraine-Specific Quality-of-Life Questionnaire. Patients generally only stayed on treatment after 6-12 months if there was deemed to be an improvement of at least 30% and there were no significant side effects. The longest treated cases have quality of life data for 30 months after starting erenumab. RESULTS: Of the 82 patients, 29 (35%) had improvement in Quality of Life scores, with no significant side effects, and wished to stay on treatment. Fifty-three patients (65%) stopped treatment during the first 6-25 months due to lack of efficacy and/or patient reported side effects (n = 33 and n = 17, respectively) or a combination of both, pregnancy planning (n = 2), and lost to follow up (n = 1). CONCLUSION: Significant improvements in Quality of Life scores were recorded by one-third of patients over a period of 11-30 months, with a 35% persistence after a median of 26 months of treatment. This contrasts with our recently published, treatment resistant, chronic migraine cohort where the persistence with erenumab treatment was almost 55% after a median time of 25 months.

The value of right heart contrast echocardiography combined with migraine rating scale in evaluating the efficacy of patent foramen ovale closure.

OBJECTIVES: To investigate the clinical values of right heart contrast transthoracic echocardiography (cTTE) combined with migraine rating scale in evaluating the efficacy of patent foramen ovale (PFO) closure. METHODS: From January 2018 to December 2021, a total of 68 hospitalized patients, 21 males and 47 females, who were treated with transcatheter closure of PFO-induced migraine in the Heart Center of the First Affiliated Hospital of Tsinghua University were selected, with the age of 38.4 ± 11.9 years old. The changes of right heart contrast transthoracic echocardiography (cTTE), visual analogue pain score(VAS), headache impact test-6(HIT-6) and migraine disability assessment questionnaire(MIDAS) before and 6 months after PFO occlusion were compared. RESULTS: Pre-operative cTTE data show that 36 patients (52.9%) had moderate right-to-left shunt (RLS), and 32 patients (47.1%) had massive RLS. cTTE was reexamined 6 months after operation and 1 case in the moderate RLS group had minimal RLS, 2 cases in the large RLS group had minimal RLS, and no shunts were seen for the rest. The VAS, HIT-6 and MIDAS scores before and 6 months after the operation were 7.65 ± 1.39 vs. 1.28 ± 1.53, 70.78 ± 6.82 vs. 41.53 ± 6.07, and 30.60 ± 13.24 vs. 1.93 ± 3.87, respectively. All the indexes 6 months after the operation significantly improved compared with the preoperative baseline (P < 0.05). CONCLUSIONS: cTTE combined with migraine evaluation scale could be used as an objective index to evaluate the clinical effect of PFO occlusion.

The pattern of primary headache in the North India population: a hospital-based study.

BACKGROUND: The aim of the study was to investigate the clinical profile, disease burden, quality of life, and treatment patterns of various headache subtypes. METHOD: In this prospective observational study, 815 patients presenting with chief complaints of headache between January 2020 to September 2021 were registered. After a detailed history, clinical examination, and subtyping, they were assessed at baseline with well-validated scales for severity (Visual Analogue Scale-VAS), disability burden (Migraine Disability Assessment- MIDAS), Humanistic burden (Headache Impact Test-HIT-6), and quality of life (World health organization-quality of life-WHO-QoL-8) scores. After initiating adequate management, parameters were reassessed at 3 and 6 months. RESULTS: 549 (67.7%) patients had migraine (395-episodic migraine, 144-chronic migraine), 266 (32.2%) patients had tension-type headache (TTH). Loss of sleep, prolonged working hours, and stress were common triggers. Disease burden, severity, and poor life quality was quite high in migraine patients (76.5% with moderate to severe disability, 61.7% with severe headache at onset, and 72% with poor life quality). All parameters had statistically significant improvement with preventive medication and lifestyle changes. CONCLUSION: In our study, we found migraine was the most common primary headache followed by TTH. Migraine patients had more severity, disease burdens, and inferior quality of life at onset compared to other headaches. With early and proper diagnosis as well as preventive treatment (including lifestyle modifications), all parameters could be reversed positively in a brief time. This is the first study on headache burden and its effect on the quality of life in the north Indian population.

Pedestrian Safety in Frontal Tram Collision, Part 2: Laminated Glass as a Crucial Part of the Absorption and Deformation Zone-Its Impact Test and Analysis.

As was shown in the previous part of the study, windshields are an important part of the passive safety means of modern low-floor trams with an extraordinary effect on pedestrian safety in a pedestrian-tram collisions. Therefore, maximum attention must be paid to the definition of tram windshield characteristics. This article describes a windshield crash test, from which data are obtained to verify the feasibility of the applied computational approaches. A developed analytical model is utilised for a simple description of the energy balance during collision with an illustrative definition of the important parameters of laminated glass as well as their clear physical interpretations. The finite element analysis (FEA) performed in Ansys software using two versions of material definition, namely a simpler (*MAT_ELASTIC with nonlocal failure criterion) and a more complex (*MAT_GLASS with brittle stress-state-dependent failure) material model, which are presented as suitable for obtaining a detailed description of the shattering process of laminated glass, which can also be used effectively in windshield engineering.

Medium-term real-world data for erenumab in 177 treatment resistant or difficult to treat chronic migraine patients: persistence and patient reported outcome measures after 17-30 months.

BACKGROUND: Many migraine patients do not respond adequately to conventional preventive treatments and are therefore described as treatment/medically resistant or difficult to treat cases. Calcitonin gene-related peptide monoclonal antibodies are a relatively novel molecular treatment for episodic and chronic migraine that have been shown to be effective in short duration clinical trials in approximately 40-50% of all chronic migraine patients. Patient Related Outcome Measures (PROM) or Quality of Life (QoL) questionnaires are used to help measure response to treatment in migraine. Although some open label extension studies have become available for erenumab, there is a lack of real-world data pertaining to quality of life in the medium to long-term for chronic and treatment resistant migraine patients. METHODS: A total of 177 treatment resistant CM patients were started on erenumab (70 mg or 140 mg subcutaneous injection every 4 weeks) in our three specialist Headache Clinics. Of these, 174 had their first injection between December 2018 and October 2019. All patients were evaluated with the following PROM: the Headache Impact Test- 6, Migraine Associated Disability Assessment test and Migraine-Specific QoL Questionnaire, before starting treatment with erenumab and at intervals of 3-12 months after starting treatment. The decision to continue treatment was based on subjective clinical improvement of at least 30% (as reported by the patient), supported with diaries and QoL questionnaires. We present here the QoL measurements for this group of 177 patients. Prior preventive migraine treatments included conventional oral prophylactic medications (such as topiramate, candesartan, propranolol, or amitriptyline), at least two cycles of PREEMPT protocol onabotulinumtoxin A or (in a small number of cases) neuromodulation with single pulse Transcranial Magnetic Stimulation. RESULTS: Of the 177 patients who started treatment with erenumab, 68/177 (38.4%) stopped during the first year, either due to lack of efficacy (no significant benefit or only minimal improvement) and/or possible side effects. 109/177 (61.6%) patients reported clinically significant improvement after 6-12 months and wished to stay on treatment. Twelve of these 109 patients subsequently stopped treatment in the period between 1 year and up to June 2021 (mainly due to a worsening of their migraine). Therefore, a total of 97/177 patients (54.8%) remained on treatment as of June 2021 (duration of treatment 17-30 months, median of 25 months). CONCLUSION: Approximately 55% of treatment resistant or difficult to treat CM patients who trialled erenumab in our clinics reported a subjective benefit and were still on treatment after 17-30 months.

The potential impact of insulin resistance and metabolic syndrome on migraine headache characteristics.

BACKGROUND & OBJECTIVES: Studying comorbidities with migraine aids in a better understanding of its pathophysiology and potential therapeutic targets. This case-control study aimed to study the impact of insulin resistance and metabolic syndrome on the characteristics of migraine headache attacks. METHODS: A case-control study was conducted on 30 migraine patients and 30 healthy controls. The following data were assessed in migraine patients: type of migraine, duration of attacks, Migraine Severity Scale (MIGSEV), and Headache Impact Test-6 (HIT-6). Both groups were assessed for waist circumference and underwent the following tests: fasting blood glucose, fasting insulin, high-density lipoprotein cholesterol level, and triglycerides, and homeostasis model assessment-insulin resistance (HOMA-IR) was applied. RESULTS: This study included age and sex-matched patients and controls. Migraine patients had significantly higher waist circumference, higher mean values of serum insulin, HOMA-IR and higher frequency of insulin resistance and metabolic syndrome than the control group (P-value = 0.005, 0.049, 0.01, 0.012, 0.024, respectively). Migraine patients with insulin resistance had significantly higher intensity and tolerability scores, MIGSEV total score, and HIT-6 total score compared to those without (P-value = 0.005, 0.005, 0.002, 0.018, respectively). There was a significantly positive correlation between the MIGSEV and HIT-6 scores and fasting insulin levels, and HOMA-IR value (P-value = 0.006, ≤ 0.001, 0.017, ≤ 0.001, respectively). CONCLUSION: Insulin resistance and metabolic syndrome are more common in migraine patients than in healthy controls. The severity and impact of migraine attacks are higher in patients with insulin resistance than in those without.

Measuring health-related quality of life in chronic headache: A comparative evaluation of the Chronic Headache Quality of Life Questionnaire and Headache Impact Test (HIT-6).

OBJECTIVE: To compare the quality and acceptability of a new headache-specific patient-reported measure, the Chronic Headache Quality of Life Questionnaire (CHQLQ) with the six-item Headache Impact Test (HIT-6), in people meeting an epidemiological definition of chronic headaches. METHODS: Participants in the feasibility stage of the Chronic Headache Education and Self-management Study (CHESS) (n = 130) completed measures three times during a 12-week prospective cohort study. Data quality, measurement acceptability, reliability, validity, responsiveness to change, and score interpretation were determined. Semi-structured cognitive interviews explored measurement relevance, acceptability, clarity, and comprehensiveness. RESULTS: Both measures were well completed with few missing items. The CHQLQ's inclusion of emotional wellbeing items increased its relevance to participant's experience of chronic headache. End effects were present at item level only for both measures. Structural assessment supported the three and one-factor solutions of the CHQLQ and HIT-6, respectively. Both the CHQLQ (range 0.87 to 0.94) and HIT-6 (0.90) were internally consistent, with acceptable temporal stability over 2 weeks (CHQLQ range 0.74 to 0.80; HIT-6 0.86). Both measures responded to change in headache-specific health at 12 weeks (CHQLQ smallest detectable change (improvement) range 3 to 5; HIT-6 2.1). CONCLUSIONS: While both measures are structurally valid, internally consistent, temporally stable, and responsive to change, the CHQLQ has greater relevance to the patient experience of chronic headache.Trial registration number: ISRCTN79708100. Registered 16th December 2015, http://www.isrctn.com/ISRCTN79708100.

The synergistic effects of nano-curcumin and coenzyme Q10 supplementation in migraine prophylaxis: a randomized, placebo-controlled, double-blind trial.

Introduction: Migraine is a disabling neurovascular disorder characterized by increasing levels of pro-inflammatory cytokines and oxidative stress biomarkers. Curcumin and coenzyme Q10 (CoQ10) can exert neuroprotective effects through modulation of inflammation and oxidative stress. The aim of the present study was to evaluate the combined effects of nano-curcumin and CoQ10 supplementation on migraine symptoms and quality of life in migraine patients.Methods: One-hundred men and women (mean age 32 years) with episodic migraine based on the International Headache Society (IHS) criteria participated in this study. The subjects were randomly divided into four groups as (1) combination of nano-curcumin (80 mg) plus CoQ10 (300 mg), (2) nano-curcumin (80 mg), (3) CoQ10 (300 mg) and (4) the control (nano-curcumin and CoQ10 placebo included oral paraffin oil) beside usual prophylactic drugs for 8 weeks. Frequency, severity, duration of headache attacks, the headache diary results (HDR) and headache disability based on migraine-specific questionnaires were assessed at the baseline and end of the study.Results: Ninety-one of 100 patients completed the study. The results showed a significant effect of nano-curcumin and CoQ10 supplementation on frequency, severity, duration of migraine attacks and HDR compared to other groups (All P < 0.001). Nano-curcumin and CoQ10 group also had better scores in migraine-specific questionnaires at the end of the study compared to other groups (All P < 0.001). There were no side effects reported by the participants.Conclusions: These findings suggest a possible synergistic effect of nano-curcumin and CoQ10 on clinical features of migraine.Trial registration number: IRCT2017080135444N1.

Content Validity of HIT-6 as a Measure of Headache Impact in People With Migraine: A Narrative Review.

BACKGROUND: The short-form Headache Impact Test (HIT-6) is a widely used patient-reported outcome measure that assesses the negative effects of headaches on normal activity. It was developed using the general headache population and prior to the establishment of the now well-accepted FDA patient-reported guidance. OBJECTIVE: The objective of this narrative review was to examine existing qualitative research in patients with migraine and headache, providing insight into the relevance and meaningfulness of HIT-6 items to the lives of migraine patients. METHODS: Articles were identified through database searches (National Library of Medicine and Google Scholar) and review of reference lists of candidate articles. RESULTS: A total of 3227 articles were identified through database and hand searching. Of these, 12 contained patient- or expert-generated qualitative information regarding headache patients' experience (8 specific to migraine [episodic and chronic] patients and 4 citing general headache patients). The combined publications described a total of 283 patient interviews. Overarching themes and specific information were identified that provide support of the relevance of content for each HIT-6 item to migraine patients' lives. Identified effects of headaches on patients with migraine included limitations in daily activities, needing to lie down during headaches, feeling tired, being irritated by headaches, difficulty concentrating, and the experience of pain. Further, previous research specific to the HIT-6 indicated that patients understood the instructions, items, and response scales as intended by the instrument authors. CONCLUSIONS: This narrative literature review demonstrates qualitative research support for the relevance of the items of the HIT-6 in migraine patients, supporting its ongoing use in clinical migraine research and practice.

Determining Thresholds for Meaningful Change for the Headache Impact Test (HIT-6) Total and Item-Specific Scores in Chronic Migraine.

OBJECTIVE: The objective of the analyses described here was to develop thresholds defining clinically meaningful response on the total and item scores of the 6-item short-form Headache Impact Test (HIT-6) in a population of patients with chronic migraine (CM). BACKGROUND: The HIT-6 is a short, easily understood, and useful measure of the impact of headache on daily life. Though widely used, limited literature supports a threshold value for clinically meaningful response within individuals over time for the HIT-6 total score and for the item scores, especially in the CM population. METHODS: PROMISE-2 is a randomized, double-blind, multicenter study comparing intravenous eptinezumab 100 and 300 mg with placebo for the preventive treatment of CM. Responder definitions for HIT-6 total and items scores using data from PROMISE-2 study were calculated via distribution-based and anchor-based methods. Distribution-based methods included half of the baseline standard deviation and baseline standard error of measurement. The change from baseline to week 12 in HIT-6 scores was assessed using the following anchors: patient global impression of change, reduction in migraine frequency, and change in EuroQol 5 dimensions 5 levels visual analog scale. Values from the literature and PROMISE-2 analyses were plotted against the cumulative distribution function of change values (baseline to week 12) and used to triangulate to empirically support clinically meaningful change definitions for the HIT-6 total and item scores in patients with CM. RESULTS: From the literature, 5 articles provided 7 candidate values for a responder threshold for the HIT-6 total score. From distribution- and anchor-based methods, 5 candidate values were derived from PROMISE-2 data. Using the median of all candidate values, a HIT-6 total score responder definition estimate of -6 (ie, ≥6-point improvement in the total score) appears most appropriate for discriminating between individuals with CM who have experienced meaningful change over time and those who have not. For item-level analyses using anchor-based methods, the responder definition for items 1-3 ("severe pain," "limits daily activities," and "lie down") was a 1-category improvement in response (eg, from Sometimes to Rarely); for items 4-6 ("too tired," "felt fed up or irritated," and "limits concentration"), a 2-category improvement in response (eg, from Always to Sometimes) was clinically meaningful. CONCLUSIONS: Using a multifaceted, statistically-based approach, the recommended responder definition for the HIT-6 total score in the CM population is a ≥6-point decrease, consistent with previous literature. Anchor-based item-level responder thresholds were defined as a decrease of 1 or 2 categories, depending on the item. These CM-specific values will provide researchers and clinicians a means to interpret clinically meaningful change in the HIT-6 total and item scores and may facilitate the measurement of treatment benefits in specific functional domains of the HIT-6.

An Approach to Characterize the Impact Absorption Performance of Construction Helmets in Top Impact.

The helmets used by construction site workers are mainly designed for head protection when objects are dropped from heights. Construction helmets are also casually called "hard hats" in industries. Common construction helmets are mostly categorized as type 1 according to different standards. All type 1 helmets have to pass type 1 standard impact tests, which are top impact tests-the helmet is fixed and is impacted by a free falling impactor on the top crown of the helmet shell. The purpose of this study was to develop an approach that can determine the performance characterization of a helmet. A total of 31 drop impact tests using a representative type 1 helmet model were performed at drop heights from 0.30 to 2.23 m, which were estimated to result in impact speeds from 2.4 to 6.6 m/s. Based on our results, we identified a critical drop height that was used to evaluate the performance of helmets. The peak impact forces and peak accelerations varied nonproportionally with the drop height. When the drop height is less than the critical height, the peak force and peak acceleration increase gradually and slowly with increasing drop height. When the drop height is greater than the critical height, the peak force and peak acceleration increase steeply with even a slight increase in drop height. Based on the critical drop height, we proposed an approach to determine the safety margin of a helmet. The proposed approach would make it possible to determine the performance characteristics of a helmet and to estimate the safety margin afforded by the helmet, if the helmet first passes the existing standardized tests. The proposed test approach would provide supplementary information for consumers to make knowledgeable decisions when selecting construction helmets.

Application of a Novel Long-Gauge Fiber BraggGrating Sensor for Corrosion Detection via aTwo-level Strategy.

Corrosion of main steel reinforcement is one of the most significant causes of structuraldeterioration and durability reduction. This research proposes a two-level detection strategy tolocate and quantify corrosion damage via a new kind of long-gauge fiber Bragg grating (FBG) sensor.Compared with the traditional point strain gauges, this new sensor has been developed for bothlocal and global structural monitoring by measuring the averaged strain within a long gauge length.Based on the dynamic macrostrain responses of FBG sensors, the strain flexibility of structures areidentified for corrosion locating (Level 1), and then the corrosion is quantified (Level 2) in terms ofreduction of sectional stiffness of reinforcement through the sensitivity analysis of strain flexibility.The two-level strategy has the merit of reducing the number of unknown structural parametersthrough corrosion damage location (Level 1), which guarantees that the corrosion quantification(Level 2) can be performed efficiently in a reduced domain. Both numerical and experimentalexamples have been studied to reveal the ability of distributed long-gauge FBG sensors for corrosionlocalization and quantification.

A PVDF-Based Sensor for Internal Stress Monitoring of a Concrete-Filled Steel Tubular (CFST) Column Subject to Impact Loads.

Impact loads can have major adverse effects on the safety of civil engineering structures, such as concrete-filled steel tubular (CFST) columns. The study of mechanical behavior and stress analysis of CFST columns under impact loads is very important to ensure their safety against such loads. At present, the internal stress monitoring of the concrete cores CFST columns under impact loads is still a very challenging subject. In this paper, a PVDF (Polyvinylidene Fluoride) piezoelectric smart sensor was developed and successfully applied to the monitoring of the internal stress of the concrete core of a CFST column under impact loads. The smart sensor consists of a PVDF piezoelectric film sandwiched between two thin steel plates through epoxy. The protection not only prevents the PVDF film from impact damages but also ensures insulation and waterproofing. The smart sensors were embedded into the circular concrete-filled steel tube specimen during concrete pouring. The specimen was tested against impact loads, and testing data were collected. The time history of the stress obtained from the PVDF smart sensor revealed the evolution of core concrete internal stress under impact loads when compared with the impact force⁻time curve of the hammer. Nonlinear finite element simulations of the impact process were also carried out. The results of FEM simulations had good agreement with the test results. The results showed that the proposed PVDF piezoelectric smart sensors can effectively monitor the internal stress of concrete-filled steel tubular columns under impact loads.

Headache in Idiopathic Intracranial Hypertension: Findings From the Idiopathic Intracranial Hypertension Treatment Trial.

OBJECTIVE: To characterize the phenotype, headache-related disability, medical co-morbidities, use of symptomatic headache medications, and headache response to study interventions in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). METHODS: Patients with untreated IIH and mild vision loss enrolled in the IIHTT and randomized to acetazolamide (ACZ) and weight loss or placebo (PLB) and weight loss had prospective assessment of headache disability using the Headache Impact Test-6 (HIT-6) questionnaire. Subjects with headache at the baseline visit were assigned a headache phenotype using the International Classification for Headache Disorders version 3 beta (ICHD-3b). Medication overuse was determined using the participants' reported medication use for the preceding month and ICHD-3b thresholds for diagnosing medication overuse headache. We investigated relationships between headache disability and various other clinical characteristics at baseline and at 6 months. RESULTS: Headache was present in 139 (84%) of the 165 enrollees at baseline. The most common headache phenotypes were migraine (52%), tension-type headache (22%), probable migraine (16%), and probable tension-type headache (4%). Fifty-one (37%) participants overused symptomatic medications at baseline, most frequently simple analgesics. A similar amount of improvement in the adjusted mean (± standard error) HIT-6 score occurred in the ACZ (-9.56 ± 1.05) and PLB groups (-9.11 ± 1.14) at 6 months (group difference -0.45, 95% CI -3.50 to 2.60, P = .77). Headache disability did not correlate with any of the studies, variables of interest, which included: the lumbar puncture opening pressure at baseline or at 6 months, body mass index, the amount of weight lost, papilledema grade, perimetric mean deviation, or the use of hormonal contraception. Headache disability was significantly associated with patient-reported quality of life in the physical, mental, and visual domains. CONCLUSIONS: Headache was common, of varied character, disabling, and associated with poorer quality of life in our cohort of patients with mild visual impairment. The lack of correlation between headache disability and cerebrospinal fluid (CSF) pressure at baseline and at the end of the randomized phase of the study implies that headache in IIH may be related to factors other than intracranial hypertension, and that specific headache treatment is needed in addition to therapies directed at lowering CSF pressure.

Experimental Assessment of the Equivalent Strain Rate for an Instrumented Charpy Test.

Instrumented Charpy test data can be used to obtain estimates of dynamic yield strength, by means of a well-established relationship published by W. Server in 1978. A fundamental issue in comparing measured dynamic tensile properties and Charpy-based estimations is establishing the equivalent uniaxial strain rate for an instrumented Charpy test, typically conducted at ≈ 5.5 m/s. In this investigation, by performing tensile tests at various strain rates and instrumented Charpy tests for 10 different materials, we compared values of dynamic yield strength both measured from tensile tests and estimated by means of Server's equation. The obtained equivalent Charpy strain rates were found to vary significantly from material to material, and to correlate reasonably with specific values of absorbed energy measured during the impact tests.