Situational prevention: Pharmacotherapy during periods of increased risk for migraine attacks.

The small molecule calcitonin gene-related peptide receptor antagonists (gepants) are the only drug class with medicines indicated for both the acute and preventive treatment of migraine. Given this dual capacity to both treat and prevent, along with their favorable tolerability profiles and lack of an association with medication-overuse headache, headache specialists have begun to use gepants in ways that transcend the traditional categories of acute and preventive treatment. One approach, called situational prevention, directs patients to treat during the interictal phase, before symptoms develop, in situations of increased risk for migraine attacks. Herein, we present three patients to illustrate scenarios of gepant use for situational prevention. In each case, a gepant was started in anticipation of a period of increased headache probability (vulnerability) and continued for a duration of 1 day to 5 consecutive days. Although this approach may expose patients to medication when headache may not have developed, the tolerability and safety profile and preventive effect of gepants may represent a feasible approach for some patients. Situational prevention is an emerging strategy for managing migraine before symptoms develop in individuals who can identify periods when the probability of headache is high. This paper is intended to increase awareness of this strategy and stimulate future randomized, placebo-controlled trials to rigorously assess this strategy.

Enlarged Breast Size (Macromastia) and Associated Neurologic Risks: A Scoping Review.

BACKGROUND AND OBJECTIVES: Symptomatic macromastia (enlarged breasts) is a syndrome of persistent headache, neck and shoulder pain, thoracic kyphosis, painful shoulder grooving from bra straps, inframammary rash, backache, and upper extremity paresthesias. Up to 89% of the 100,000 US women undergoing breast reduction surgery (reduction mammoplasty) annually report headache preoperatively with many endorsing postoperative headache improvement. Headache is one insurance indication to cover surgical reduction, and peak prevalence of migraine matches the average age of women with macromastia at time of surgery. Little is known about the influence of macromastia on headache. The goal of our narrative review is to understand the evidence for and potential mechanisms underlying macromastia-related headache. METHODS: A literature search was performed in PubMed Medline using concepts "breast hypertrophy," "macromastia," "headache," "migraine," "breast reduction," and "reduction mammoplasty" excluding limits on age, language, publication date, or study type. Supplemental literature searches were performed to provide a comprehensive understanding of potential mechanisms underlying macromastia-related headache. RESULTS: We identified 25 studies describing macromastia-associated headache in the setting of reduction mammoplasty, with 23 original research studies (retrospective, n = 12, prospective, n = 11) totaling 3,799 patients, 1 systematic review, and 1 meta-analysis. Most (24/25) were published in Plastic Surgery, one in Internal Medicine, and none in Neurology. Wide ranges were identified for preoperative headache prevalence (2%-89%) and postoperative headache improvement (34%-100%). Studies described headache as "myofascial" or "tension-type" without detailing headache definitions, chronicity, headache screening method, or neurologic examination. Potential pathophysiologic mechanisms of macromastia-associated headache include structural, mechanical, psychosocial, and hormonal. DISCUSSION: No studies on macromastia-associated headache and reduction mammoplasty are published in Neurology. This important women's health topic remains unexplored in fields outside Plastic Surgery. Many questions remain unanswered that are important for neurologists to understand, including which headache type(s) women with macromastia experience and which headache type(s) respond to surgical intervention.

Advances in the Applications of Clinoptilolite-Rich Tuffs.

Adsorptive, catalytic, and antibacterial properties of clinoptilolite-rich tuffs (ZT) are presented here. ZT transformed into Fe-containing ZT (Fe-ZT) removes various organic and inorganic anions from water. Fe-ZT, which contains selenium, is beneficial for growing Pleurotus ostreatus mushrooms. The fungi convert inorganic Se from Fe-ZT into a more useful organically bonded form. ZT and Fe-ZT as supplements retain nitrogen and potassium in sandy, silty loam and silty clay soils. ZT shows an affinity toward toxic metal cations, which are essential for cleaning contaminated water. The adsorption of atenolol, acetylsalicylic, and salicylic acid onto M-ZT (M-Cu2+, Mn2+, Ni2+, or Zn2+) from water solutions suggests that both the natures of M and pharmaceuticals have a significant impact on the adsorption mechanism and determine the adsorption capability of the ZT. ZT is an excellent carrier for ultrafine (2-5 nm) nano oxide particles, which have been shown to have catalytic activity in different chemical processes and photodegradation reactions of organic pollutants. ZT can also be transformed into SO4-SnO2-ZT, which is catalytically active as a solid acid. M-ZT is an effective carrier of valuable bacteria. Ag-ZT possesses beneficial bactericidal activity in disinfecting water and soil remediation.

The Importance of Natural and Acquired Immunity to SARS-CoV-2 Infection in Patients on Peritoneal Dialysis.

The pandemic caused by the SARS-CoV-2 virus had a great impact on the population of patients treated with peritoneal dialysis (PD). This study demonstrates the impact of infection and vaccination in 66 patients treated with PD and their outcomes during a 6-month follow-up. This is the first research that has studied the dynamics of anti-SARS-CoV-2 IgG in serum and effluent. In our research, 57.6% of PD patients were vaccinated, predominantly with Sinopharm (81.6%), which was also the most frequently administered vaccine in the Republic of Serbia at the beginning of immunization. During the monitoring period, the level of anti-SARS-CoV-2 IgG antibodies in the PD patients had an increasing trend in serum. In the group of vaccinated patients with PD, anti-SARS-CoV-2 IgG antibodies had an increasing trend in both serum and effluent, in contrast to non-vaccinated patients, where they decreased in effluent regardless of the trend of increase in serum, but statistical significance was not reached. In contrast to vaccinated (immunized) patients who did not acquire infection, the patients who only underwent the COVID-19 infection, but were not immunized, were more prone to reinfection upon the outbreak of a new viral strain, yet without severe clinical presentation and with no need for hospital treatment.

Effect of galcanezumab in women with episodic migraine meeting criteria for menstrually related migraine: A post hoc analysis of EVOLVE-1 and EVOLVE-2.

BACKGROUND: We evaluated galcanezumab for migraine prevention in patients who met International Classification of Headache Disorders, 3rd edition criteria for menstrually related migraine (MRM). METHODS: Patients were identified post hoc from three double-blind, randomized, phase 3 clinical trials in patients with episodic migraine. Patients completed a 1-month prospective baseline period and up to 6 months (EVOLVE-1 and -2, studies pooled) of double-blind treatment with galcanezumab (120 mg/month) or placebo. Menses and headache information were recorded by electronic daily diary. Patients with a migraine attack starting during the 5-day perimenstrual interval (first day of bleeding ± 2 days) for ≥2 of their first three diary-recorded menstrual cycles were categorized as having MRM. The primary efficacy measure was mean change in monthly migraine headache days from baseline, averaged over Months 4 through 6. Response rates, change in monthly perimenstrual migraine headache days, monthly non-perimenstrual migraine headache days, and quality of life were also assessed. RESULTS: Post hoc MRM analysis criteria were met by 462/1133 women (41%). Mean (standard deviation) baseline monthly migraine headache days were 9.7 (±3.1; n = 146) for galcanezumab-treated patients and 9.6 (±2.8; n = 316) for placebo-treated patients. The mean change (standard error [SE]) in migraine headache days over Months 4 through 6 was -5.1 days (±0.39) for galcanezumab versus -3.2 (±0.35) for placebo (p < 0.001). The mean change (SE) in perimenstrual migraine headache days over Months 4 through 6 was -0.75 days (±0.08) for galcanezumab versus -0.49 (±0.07) for placebo (p = 0.004). For migraine headache days outside the perimenstrual period, the mean change in migraine headache days was -4.6 (±0.38) for galcanezumab and -2.8 (±0.33) for placebo (p < 0.001). Improvements in response rates and the Migraine-Specific Quality of Life Questionnaire were also observed over Months 4 through 6. CONCLUSION: Galcanezumab was effective for migraine prevention in women with MRM.

Association of Migraine and Blood Pressure-Does Obesity Severity Have a Moderating Role?

BACKGROUND: The relationship between migraine and blood pressure (BP) is equivocal, warranting exploration of potential moderators. Obesity associates with both migraine and BP in a dose-dependent fashion, although its role as a moderator has not been evaluated. We examined the relation between migraine and BP in women with comorbid migraine and obesity, and whether this relation was influenced by obesity severity. METHODS: Women with migraine and obesity (n = 134) completed a 28-day headache diary before randomization to lifestyle intervention or migraine education. BP (systolic (SBP)/diastolic (DBP)), body mass index (BMI), and waist circumference (WC) were measured before diary completion. Hierarchical linear regression assessed associations between BP and migraine characteristics (headache frequency, duration, and pain intensity), and obesity severity (both total (BMI) and abdominal (WC)) as moderators of these associations. RESULTS: Participants (BMI = 35.4 ± 6.5 kg/m2; WC = 105.4 ± 15.6 cm, SBP = 113.1 ± 12.1/DPB = 68.1 ± 8.0 mmHg) reported 8.4 ± 4.5 migraine days that lasted 20.2 ± 15.9 h with mean pain intensity of 5.9 ± 1.6 on a 10-point scale. DBP inversely related to migraine days in both total (ß = - 0.226, p = .010) and abdominal (ß = 0.214, p = .015) obesity severity models. SBP and obesity severity did not relate to migraine characteristics. Obesity severity did not moderate relations between migraine characteristics and BP (p's > .05). CONCLUSION: Among women with comorbid migraine and obesity, DBP inversely related to migraine frequency; however, obesity severity did not affect the strength of this or other examined associations. Future studies including healthy weight controls and men and women with continuous BP measures are needed to confirm these findings and identify mechanisms and moderators.

Silicon modifies leaf nutriome and improves growth of oak seedlings exposed to phosphorus deficiency and Phytophthora plurivora infection.

Beneficial effects of silicon (Si) on plants have primarily been studied in crop species under single stress. Moreover, nutrient acquisition-based responses to combination of biotic and abiotic stresses (a common situation in natural habitats) have rarely been reported, in particular in conjunction with soil amendments with Si. Pedunculate oak (Quercus robur L.), one of the ecologically and economically most important tree species in Europe, is facing a severe decline due to combined stresses, but also problems in assisted regeneration in nurseries. Here, we studied the effect of Si supply on the leaf nutriome, root traits and overall growth of 12-weeks-old oak seedlings exposed to abiotic stress [low phosphorus (P) supply], biotic stress (Phytophthora plurivora root infection), and their combination. The application of Si had the strongest ameliorative effect on growth, root health and root phenome under the most severe stress conditions (i.e., combination of P deficiency and P. plurivora root infection), where it differentially affected the uptake and leaf accumulation in 11 out of 13 analysed nutrients. Silicon supply tended to reverse the pattern of change of some, but not all, leaf nutrients affected by stresses: P, boron (B) and magnesium (Mg) under P deficiency, and P, B and sulphur (S) under pathogen attack, but also nickel (Ni) and molybdenum (Mo) under all three stresses. Surprisingly, Si affected some nutrients that were not changed by a particular stress itself and decreased leaf Mg levels under all the stresses. On the other hand, pathogen attack increased leaf accumulation of Si. This exploratory work presents the complexity of nutrient crosstalk under three stresses, and opens more questions about genetic networks that control plant physiological responses. Practically, we show a potential of Si application to improve P status and root health in oak seedlings, particularly in nurseries.

Sleep Symptoms and Disorders in Episodic Migraine: Assessment and Management.

PURPOSE OF REVIEW: We review research on sleep symptoms and disorders in patients with episodic migraine and propose a framework for evaluating sleep symptoms in this patient population. RECENT FINDINGS: Patients with episodic migraine consistently report poorer sleep on validated self-reports compared to those without migraine. In polysomnographic studies, children with migraine have objectively shorter sleep duration and lower percentage of REM sleep interictally. Prospective actigraphy studies in adults and children suggest that there are no significant changes in sleep duration, efficiency, or quality in the night before or after a migraine attack. The relationship between sleep and migraine is multifaceted. Patients with episodic migraine report poorer sleep and have higher risk of some sleep disorders, including insomnia, sleep-related bruxism, and restless legs syndrome. Sleep screening questions may be incorporated into headache evaluations. Care should be taken to avoid headache medications that may exacerbate sleep symptoms. Evidence-based treatments for insomnia may be initiated while patients await CBT-I. Further studies are needed to assess whether treatment of comorbid sleep disorders results in improvement in migraine-related burden in those with episodic migraine.

Significance of 1,25-Dihydroxyvitamin D3 on Overall Mortality in Peritoneal Dialysis Patients with COVID-19.

In previous publications, we pointed out the importance of mannosylation of fibrinogen for the development of cardiovascular complications and fucosylation as a predictor of peritoneal membrane dysfunction in patients on peritoneal dialysis (PD). After a follow-up period of 30 months from the onset of the COVID-19 pandemic, we evaluated the significance of 1,25-dihydroxyvitamin D3 (calcitriol) therapy, primary disease, biochemical and hematologic analyzes, and previously performed glycan analysis by lectin-based microarray as predictors of mortality in this patient group. After univariate Cox regression analysis, diabetes mellitus (DM) and calcitriol therapy were found to be potential predictors of mortality. Additional multivariate Cox regression analysis confirmed that only DM was a predictor of mortality. Nevertheless, the use of calcitriol in therapy significantly reduced mortality in this patient group, as shown by the Kaplan-Meier survival curve. The presence of DM as a concomitant disease proved to be a strong predictor of fatal outcome in PD patients infected with SARS-CoV-2. This is the first study to indicate the importance and beneficial effect of calcitriol therapy on survival in PD patients with COVID-19 infection. In addition, this study points to the possibility that adverse thrombogenic events observed in PD patients during the pandemic may be caused by aberrant fibrinogen glycosylation.

Weed Species from Tea Gardens as a Source of Novel Aluminum Hyperaccumulators.

Increased availability of toxic Al3+ is the main constraint limiting plant growth on acid soils. Plants adapted to acid soils, however, tolerate toxic Al3+, and some can accumulate Al in their aerial parts to a significant degree. Studies on Al-tolerant and Al-accumulating species have mainly focused on the vegetation of acid soils distributed as two global belts in the northern and southern hemispheres, while acid soils formed outside these regions have been largely neglected. The acid soils (pH 3.4-4.2) of the tea plantations in the south Caspian region of Northern Iran were surveyed over three seasons at two main locations. Aluminum and other mineral elements (including nutrients) were measured in 499 plant specimens representing 86 species from 43 families. Al accumulation exceeding the criterion for accumulator species (>1000 µg g-1 DW) was found in 36 species belonging to 23 families of herbaceous annual or perennial angiosperms, in addition to three bryophyte species. Besides Al, Fe accumulation (1026-5155 µg g-1 DW) was also observed in the accumulator species that exceeded the critical toxicity concentration, whereas no such accumulation was observed for Mn. The majority of analyzed accumulator plants (64%) were cosmopolitan or pluriregional species, with a considerable rate of Euro-Siberian elements (37%). Our findings, which may contribute to phylogenetic studies of Al accumulators, also suggest suitable accumulator and excluder species for the rehabilitation of acid-eroded soils and introduce new model species for investigating Al accumulation and exclusion mechanisms.

Increased Peritoneal Protein Loss and Diabetes: Is There a Link?

Increased peritoneal protein loss has been associated with the fast transport of small molecules, diabetes mellitus (DM), and a reduced survival in patients on peritoneal dialysis (PD), although some studies did not confirm the association with survival. In this single-center retrospective study, we investigated the relationship of baseline peritoneal albumin and protein loss with transport status, comorbidities including DM, and survival in 106 incident PD patients during the period of July 2005-June 2014. Five-year survival rate was determined using Cox-regression analysis. There were not significant differences in D/Pcr or peritoneal protein and albumin loss between diabetics and non-diabetics. In the group of 66 non-diabetics, high and high-average transporters for creatinine had higher values for both peritoneal protein (11.85 ± 6.77 vs. 7.85 ± 4.36 g/day; p = 0.002) and albumin (5.03 ± 2.32 vs. 3.72 ± 1.54 g/day; p = 0.016) loss as compared to slow transporters. However, in the group of 40 diabetics, this association was not observed. Upon multivariable regression analysis, the independent association of D/PCr with peritoneal albumin (ß = 0.313; p = 0.008) and protein (ß = 0.441; p = 0.001) loss was found only in non-diabetics in whom ultrafiltration also appeared as a significant predictor of peritoneal protein loss (ß = 0.330; p = 0.000). A high comorbidity grade, older age, and low serum albumin were associated with mortality, but both peritoneal protein and albumin loss as well as D/Pcr were not determinants of survival. Baseline peritoneal protein and albumin loss was not associated with DM and did not predict survival. The clinical significance of the absence of association between fast peritoneal transport status and peritoneal protein flux in diabetics should be evaluated in a prospective study comprising a greater number of diabetics with evaluation of overhydration as a main inducing variable of protein leak.

Colored stains: Microbial survey of cellulose-based and lignin rich papers.

Over the centuries, various types of paper have been produced, each characterized by a different ratio of natural macromolecules, mainly lignin and cellulose. Handmade paper has a higher content of cellulose with respect to the early machine-made paper, where lignin is the other important component. Microorganisms are able to colonize and deteriorate both types. They can release on their surfaces pigments and colorants which produced anesthetic stains. To better understand the microbiota colonizing these stains, 17 samples were analyzed, from both handmade and machine-made paper surfaces, as well as library and archive environments. Combination of microbiological and high-throughput sequencing (HTS) approaches were applied. The culture-dependent methodology comprised: isolation, DNA identification, hydrolytic and paper staining assays. The HTS was performed by MinION platform and for the mycobiome a more suitable bioinformatics analysis pipeline, MetONTIIME based on QIIME2 framework, was applied. The paper model staining assay permitted the direct recognition of colorizing isolates which in combination with sequencing data evidenced a complex microbial community able to stain the two types of paper. Staining abilities were confirmed by frequently isolated and detected fungi as well as newly discovered ones Roussoella euonymi and Achaetomium. We have also evidenced the staining ability of several bacteria.

Silicon Differently Affects Apoplastic Binding of Excess Boron in Wheat and Sunflower Leaves.

Monocots and dicots differ in their boron (B) requirement, but also in their capacity to accumulate silicon (Si). Although an ameliorative effect of Si on B toxicity has been reported in various crops, differences among monocots and dicots are not clear, in particular in light of their ability to retain B in the leaf apoplast. In hydroponic experiments under controlled conditions, we studied the role of Si in the compartmentation of B within the leaves of wheat (Triticum vulgare L.) as a model of a high-Si monocot and sunflower (Helianthus annuus L.) as a model of a low-Si dicot, with the focus on the leaf apoplast. The stable isotopes 10B and 11B were used to investigate the dynamics of cell wall B binding capacity. In both crops, the application of Si did not affect B concentration in the root, but significantly decreased the B concentration in the leaves. However, the application of Si differently influenced the binding capacity of the leaf apoplast for excess B in wheat and sunflower. In wheat, whose capacity to retain B in the leaf cell walls is lower than in sunflower, the continuous supply of Si is crucial for an enhancement of high B tolerance in the shoot. On the other hand, the supply of Si did not contribute significantly in the extension of the B binding sites in sunflower leaves.

Interrelationships of Sleep Quality, Obesity Severity, and Clinical Headache Features among Women with Comorbid Migraine and Obesity.

Obesity and migraine are often comorbid. Poor sleep quality is also common among individuals with migraine and may be influenced by comorbidities such as obesity. However, understanding of migraine's relationship with sleep and the potential exacerbating effect of obesity remains limited. This study evaluated the associations of migraine characteristics and clinical features with sleep quality among women with comorbid migraine and overweight/obesity and assessed the interplay between obesity severity and migraine characteristics/clinical features in relation to sleep quality. Women seeking treatment for migraine and obesity (n = 127; NCT01197196) completed a validated questionnaire assessing sleep quality (Pittsburgh Sleep Quality Index-PSQI). Migraine headache characteristics and clinical features were assessed using smartphone-based daily diaries. Weight was measured in-clinic, and several potential confounders were assessed using rigorous methods. Nearly 70% of participants endorsed poor sleep quality. Greater monthly migraine days and the presence of phonophobia related to poorer sleep quality, and specifically poorer sleep efficiency, controlling for confounders. Obesity severity was neither independently associated nor interacted with migraine characteristics/features to predict sleep quality. Poor sleep quality is common among women with comorbid migraine and overweight/obesity, although obesity severity does not appear to uniquely relate to or exacerbate the association between migraine and sleep in this population. Results can guide research on mechanisms of the migraine-sleep link and inform clinical care.

Effects of Eligibility Criteria on Patient Selection and Treatment Implications from 10 Multidomain Dementia Prevention Trials: A Population-Based Study.

INTRODUCTION: Dementia prevention trials have so far shown little benefit of multidomain interventions against cognitive decline. Recruitment strategies in these trials often centre around dementia risk or cardiovascular risk profile, but it is uncertain whether this leads to inclusion of individuals who may benefit most from the intervention. We determined the effects of eligibility criteria on the recruitment of potential trial participants in the general population. METHODS: In a systematic search until January 1, 2022, we identified all published and ongoing large (≥500 participants), phase-3 multidomain trials for the prevention of cognitive decline or dementia. We applied trial eligibility criteria to 5,381 participants of the population-based Rotterdam Study (mean age: 72 years, 58% women), to compare participant characteristics, predicted risk of cardiovascular disease, and dementia risk, between trial eligible and ineligible persons. RESULTS: We identified 10 trials, of which 5 had been published (DR's EXTRA, FINGER, preDIVA, MAPT, and HATICE) and 5 are ongoing (US-POINTER, MIND-CHINA, MYB, AgeWell.de, and J-Mint). Among all Rotterdam Study participants, eligibility across published trials ranged from 48% for MAPT to 87% for preDIVA, in line with original trial reports. Variability in eligibility was wider for ongoing trials, from 1% for US-POINTER to over 94% for MYB trial. Over 70% of trial eligible individuals are recommended preventive intervention in routine care based on their cardiovascular risk, similar for lipid-lowering (71%) and blood pressure-lowering treatment (73%). Ten-year risks of dementia were similar for eligible compared to ineligible individuals (12 vs. 11%). CONCLUSION: Multidomain dementia prevention trials fail to preferentially include those at the highest risk of dementia and mostly include individuals who qualify for interventions already on the basis of cardiovascular prevention guidelines. These findings call for better targeted enrolment of individuals for whom trial results can improve clinical decision-making.

A Study on Mortality Predictors in Hemodialysis Patients Infected with COVID-19: Impact of Vaccination Status.

The global outbreak of COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has prompted significant public health concerns. This study focuses on 442 chronic hemodialysis patients diagnosed with COVID-19, emphasizing the impact of vaccination status on clinical outcomes. The study investigates the correlation between vaccination status and laboratory findings, aiming to identify predictive factors for mortality. Results indicate that vaccination status plays a crucial role in outcomes. Full vaccination, evidenced by two or three doses, is associated with better outcomes, including reduced incidence of bilateral pneumonia and lower risks of complications such as hemorrhage and thrombosis. Laboratory analyses reveal significant differences between vaccinated and unvaccinated patients in parameters like C-reactive protein, ferritin, and white blood cell counts. Univariate and multivariate Cox proportional hazards regression analyses identify several factors influencing mortality, including comorbidities, pneumonia development, and various inflammatory markers. In conclusion among hemodialysis patients affected by COVID-19 infection, vaccination with at least three doses emerges as a protective factor against fatal outcomes. Independent predictors of mortality are CRP levels upon admission, maximum CRP values during the illness and cardiovascular comorbidities. Noteworthy lymphocytopenia during infection exhibits a notable level of specificity and sensitivity in predicting mortality.

Efficacy of lasmiditan for the acute treatment of perimenstrual migraine.

BACKGROUND: Perimenstrual migraine attacks in women with menstrual migraine is difficult to treat. This post-hoc analysis evaluated the efficacy of lasmiditan, a high affinity and selective 5-HT1F receptor agonist, for perimenstrual attacks. METHODS: Patients from two randomized, double-blind, placebo-controlled clinical trials (MONONOFU and CENTURION) were instructed to treat an attack with a single dose of study medication within four hours of pain onset. After dosing, the proportion of patients who achieved freedom from migraine-related head pain, most bothersome symptom, and disability was reported at baseline up to 48 hours after dose and pooled data were evaluated. RESULTS: A total of 303 patients (MONONOFU N = 78; CENTURION N = 225) treated perimenstrual migraine attacks with lasmiditan 50 mg (N = 24), 100 mg (N = 90), 200 mg (N = 110), and placebo (N = 79). More patients achieved migraine-related head pain freedom with lasmiditan 200 mg versus placebo at all time points assessed. At 2 hours, 33.6% of patients in the 200-mg group (p < 0.001), and 16.7% of patients in the 100-mg (p = 0.11) and 50-mg (p = 0.19) groups were pain free, compared with 7.6% in the placebo group. CONCLUSIONS: Lasmiditan treatment of perimenstrual migraine attacks was associated with freedom from migraine-related head pain at two hours, early onset of efficacy, and sustained efficacy.Clinical Trial registration: NCT03962738 and NCT03670810.

The longitudinal relation of inflammation to incidence of vasomotor symptoms.

OBJECTIVE: Vasomotor symptoms (VMS), the most frequently reported symptoms during the menopausal transition, have been associated with inflammation. Whether inflammation is a risk factor for or a consequence of VMS remains unclear. The objectives of these analyses were to determine if elevated proinflammatory marker levels were associated with increased incident VMS in women without VMS at baseline and whether these associations varied by menopause transition stage or race/ethnicity. METHODS: We used longitudinal data on incident VMS, high-sensitivity C-reactive protein (hs-CRP; n = 1,922) and interleukin-6 (IL-6; n = 203) from 13 follow-up visits in the Study of Women's Health Across the Nation, which included five racial/ethnic groups of midlife women. We performed multivariable discrete-time survival analyses to determine adjusted hazard ratios (aHRs) for the association of these proinflammatory markers with incident VMS in women without VMS at baseline. RESULTS: We found no significant associations of incident VMS with dichotomized hs-CRP (>3 vs ≤3 mg/L) at baseline, concurrent or prior visit (aHRs, 1.04-2.03) or IL-6 (>1.44 vs ≤1.44 pg/mL) at visit 1, concurrent or prior visit (aHRs, 0.67-1.62), or continuous hs-CRP or IL-6 values over 13 follow-up visits (with nonsignificant adjusted increased hazards ranging from 0% to 2%). CONCLUSIONS: Our results showed no significant association of the proinflammatory biomarkers, hs-CRP or IL-6, either concurrently or with subsequent incident VMS, indicating that inflammation was unlikely to be a risk factor for VMS. Thus, clinical treatments directed at reducing inflammation would be unlikely to reduce the occurrence of VMS.

The importance of an early onset of migraine prevention: an evidence-based, hypothesis-driven scoping literature review.

Recently approved migraine preventive therapies facilitate rapid control of migraine activity, potentially improving patients' lives and minimizing the societal burden of migraine. This review synthesizes available evidence on rates and timing of early onset of migraine prevention and identifies patient-level outcomes related to early onset prevention. This evidence-based scoping review identified all available clinical trial evidence regarding the early onset of prevention of migraine, under the hypothesis 'Patients with migraine (episodic or chronic) report additional benefits when receiving an approved migraine preventive treatment that demonstrates an early onset of prevention'. Early onset of prevention was defined as migraine preventive benefits within 30 days post-administration. PubMed, EMBASE, and CINAHL were searched for publications between 1988 and 2020. Overall, 16 publications described 18 studies. All studies were conducted in approved treatments [four anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies and one chemodenervation agent] in patients with episodic/chronic migraine; no publications were identified for traditional oral agents for early migraine prevention. Compared to placebo, erenumab (three studies) reduced weekly migraine days within 1 week; fremanezumab (six studies) increased reports of no headache of at least moderate severity on Day 1 and significantly reduced migraine frequency within 1 week; galcanezumab (three studies) significantly reduced the mean number of patients with migraine beginning Day 1 and each day of the first week; eptinezumab (four studies) significantly reduced migraine attack likelihood on Day 1 by > 50% versus baseline; and onabotulinumtoxinA (two studies) reduced headache and migraine days within 1 week. Four publications described function, disability, and quality of life improvements as early as Week 4; none reported cost-benefit. Anti-CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, and eptinezumab) and a chemodenervation agent (onabotulinumtoxinA) provide clinically relevant benefits during the first treatment week. Literature describing clinically relevant benefits regarding early onset of prevention in patients with migraine is limited.

Predictive models for determining treatment response to nonprescription acute medications in migraine: Results from the American Migraine Prevalence and Prevention Study.

OBJECTIVE: To identify predictors of acute treatment response for nonprescription (over-the-counter [OTC]) medications among people with migraine and develop improved models for predicting treatment response. BACKGROUND: Pain freedom and sustained pain relief are important priorities in the acute treatment of migraine. OTC medications are widely used for migraine; however, it is not clear which treatment works best for each patient without going through the trial and error process. METHODS: A prediction model development study was completed using the 2006 American Migraine Prevalence and Prevention Study survey, from participants who were aged ≥18, met criteria and headache day frequency for episodic migraine, did not take prescription medication for migraine, and used ≥1 of the following acute migraine medication classes: acetaminophen, aspirin, NSAIDs, or caffeine containing combination products (CCP). Two items from the Migraine Treatment Optimization Questionnaire were used to evaluate treatment response, adequate 2-h pain freedom (2hPF) and 24-h pain relief (24hPR), which were defined by a response to treatment ≥half the time at 2 h and 24 h post treatment, respectively. We identified predictors of adequate treatment response and developed models to predict probability of treatment response to each medication class. RESULTS: The sample included 3852 participants (3038 [79.0%] females) with an average age of 45.0 years (SD = 12.8). Only 1602/3852 (41.6%) and 1718/3852 (44.6%) of the participants reported adequate 2hPF and 24hPR, respectively. Adequate treatment-response was significantly predicted by lower average headache pain intensity, less cutaneous allodynia, and lower depressive symptom scores. Lower migraine symptom severity was predictive of adequate 2hPF and fewer monthly headache days was predictive of adequate 24hPR. Among participants reporting OTC monotherapy (n = 2168, 56.3%) individuals taking CCP were more likely to have adequate 2hPF (OR = 1.55, 95% CI 1.23-1.95) and 24hPR (OR = 1.79, 95% CI 1.18-1.88) in comparison with those taking acetaminophen. Predictive models were modestly predictive of responders to OTC medications (c-statistics = 0.65; 95% CI 0.62-0.68). CONCLUSION: These results show that response to acute migraine treatments is not optimized in the majority of people with migraine treating with OTC medications. Predictive models can improve our ability to choose the best therapeutic option for individuals with episodic migraine and increase the proportion of patients with optimized response to treatments.