Brain-derived neurotrophic factor in primary headaches

Brain derived neurotrophic factor (BDNF) is associated with pain modulation and central sensitization. Recently, a role of BDNF in migraine and cluster headache pathophysiology has been suspected due to its known interaction with calcitonin gene-related peptide. Bi-center prospective study was done enrolling four diagnostic groups: episodic migraine with and without aura, episodic cluster headache, frequent episodic tension-type headache, and healthy individuals. In migraineurs, venous blood samples were collected twice: outside and during migraine attacks prior to pain medication. In cluster headache patients serum samples were collected in and outside cluster bout. Analysis of BDNF was performed using enzyme-linked immunosorbent assay technique. Migraine patients revealed significantly higher BDNF serum levels during migraine attacks (n = 25) compared with headache-free intervals (n = 53, P < 0.01), patients with tension-type headache (n = 6, P < 0.05), and healthy controls (n = 22, P < 0.001). There was no significant difference between patients with migraine with aura compared with those without aura, neither during migraine attacks nor during headache-free periods. Cluster headache patients showed significantly higher BDNF concentrations inside (n = 42) and outside cluster bouts (n = 24) compared with healthy controls (P < 0.01, P < 0.05). BDNF is increased during migraine attacks, and in cluster headache, further supporting the involvement of BDNF in the pathophysiology of these primary headaches.     

Influence of early post-burn enteral nutrition on clinical outcomes of patients with extensive burns

Sepsis commonly occurs in severe post-burn patients, often resulting in death. We aimed to evaluate the influence of early enteral feeding on outcomes in patients with extensive burns, including infection incidence, healing and mortality. We retrospectively reviewed 60 patients with extensive burns, 35 who had received early enteral nutrition and 25 who had received parenteral nutrition. Average healing time, infection incidence and mortality were clinically observed. Hemoglobin and serum albumin were monitored weekly in both groups during treatment. Causative organisms were identified in patients with sepsis. Infection incidence was significantly less in the enteral nutrition group than the parenteral nutrition group (17.1% vs 44.0%; p = 0.023); and latency duration was longer in the enteral nutrition group than in the parenteral nutrition group (30.5 ± 4.7 days vs 14.5 ± 2.3 days; p<0.001). Duration of antibiotic therapy of the enteral nutrition group was significantly shorter than that of the parenteral nutrition group (12.5 ± 3.0 days vs 19.8 ± 3.6 days; p<0.001). Mean hemoglobin results (10.1 ± 1.3 g/L vs 8.3 ± 1.5 g/L; p<0.001) and serum albumin results (44.7 ± 5.7 g/L vs 36.2 ± 6.9 g/L; p<0.001) of enteral nutrition and parenteral nutrition groups, respectively, provided an overview of systemic nutrition and protein metabolism, suggesting higher systemic nutrition and protein synthesis in enteral nutrition group than in parenteral nutrition group. Risk of post-burn infection is reduced in burn patients who are supported by earliest possible enteral nutrition.     

Relationship between dietary folate intake and plasma monocyte chemoattractant protein-1 and interleukin-8 in heart failure patients

This study aimed to examine the association of dietary vitamin intakes with plasma pro-inflammatory cytokine levels in Korean heart failure patients. Stable outpatients with heart failure were recruited and finally 91 patients were included. Dietary intakes were estimated by a developed semi-quantitative food frequency questionnaire. The simultaneous measurement of 17 cytokines was performed along with analysis of plasma C-reactive protein. Plasma C-reactive protein levels significantly correlated with dietary intakes of vitamin C (r = −0.30, p<0.005), β-carotene (r = −0.23, p<0.05), and folate (r = −0.31, p<0.005). However, these associations were no longer significant after adjusting for traditional risk factors for heart failure. On the other hand, plasma levels of monocyte chemoattractant protein-1 significantly correlated with dietary folate intake (r = −0.31, p<0.001), and plasma interleukin-8 levels significantly correlated with dietary intakes of vitamin C (r = −0.38, p<0.001), β-carotene (r = –0.42, p<0.001), and folate (r = −0.38, p<0.001) after the adjustment. Dietary folate intake was found as a primary influencing factor on plasma levels of monocyte chemoattractant protein-1 (p<0.005, R² = 0.20) and interleukin-8 (p<0.001, R² = 0.32) through a stepwise multiple linear regression analysis. Dietary folate intake was significantly associated with plasma levels of monocyte chemoattractant protein-1 and interleukin-8 which indicates dietary folate may have a potentially beneficial role in the prevention and treatment of heart failure.     

Cardiac injury is associated with inflammation in geriatric COVID‐19 patients

BackgroundGeriatric patients with coronavirus disease (COVID‐19) are at high risk of developing cardiac injury. Identifying the factors that affect high‐sensitivity cardiac troponin I may indicate the cause of cardiac injury in elderly patients, and this could hopefully assist in protecting heart function in this patient population.MethodsOne hundred and eighty inpatients who were admitted for COVID‐19 were screened. Patients older than 60 years were included in this study, and the clinical characteristics and laboratory results of the cohort were analyzed. The correlation between cardiac injury and clinical/laboratory variables was statistically analyzed, and further logistic regression was performed to determine how these variables influence cardiac injury in geriatric patients.ResultsAge (p < 0.001) significantly correlated with cardiac injury, whereas sex (p = 0.372) and coexisting diseases did not. Rising procalcitonin (p = 0.001), interleukin‐2 receptor (p < 0.001), interleukin 6 (p = 0.001), interleukin 10 (p < 0.001), tumor necrosis factor α (p = 0.001), high‐sensitivity C‐reactive protein (p = 0.001), D‐dimer (p < 0.001), white blood cells (p < 0.001), neutrophils (p = 0.001), declining lymphocytes (p < 0.001), and natural killer cells (p = 0.005) were associated with cardiac injury and showed predictive ability in the multivariate logistic regression.ConclusionOur results suggest that age and inflammatory factors influence cardiac injury in elderly patients. Interfering with inflammation in this patient population may potentially confer cardiac protection.     

Relationship between the cAMP levels in leukocytes and the cytokine balance in patients surviving gram negative bacterial pneumonia

Lipopolysaccharide-stimulated leukocytes secrete proinflammatory cytokines including tumor necrosis factor-α and interleukin-12. Over-activation of host defense systems may result in severe tissue damage and requires regulation. Granulocyte colony-stimulating factor and interleukin-10 are candidate cytokines for inducing tolerance to lipopolysaccharide re-stimulation. We compared cytokines secreted by lipopolysaccharide-stimulated blood cells from patients who had survived gram negative bacterial pneumonia (Pseudomonas aeruginosa, Escherichia coli or Proteus mirabilis, n = 26) and age-matched healthy volunteers (n = 18). Interleukin-12p70 and tumor necrosis factor-α expression was significantly lower in patients (p = 0.0039 and p<0.001) compared to healthy controls, while granulocyte colony-stimulating factor production was markedly higher in patients (p<0.001). Levels of interleukin-10 were comparable. Granulocyte colony-stimulating factor expression was inversely correlated with interleukin-12p70 (R = −0.71, p<0.001) and tumor necrosis factor-α (R = −0.64, p<0.001) expression; interleukin-10 showed no significant correlation. In unstimulated leukocytes from patients, cAMP levels were significantly raised (p = 0.020) and were correlated inversely with interleukin-12p70 levels (R = −0.81, p<0.001) and directly with granulocyte colony-stimulating factor (R = 0.72, p = 0.0020), matrix metalloproteinase-9 (R = 0.67, p = 0.0067) and interleukin-10 (R = 0.54, p = 0.039) levels. Our results demonstrate that granulocyte colony-stimulating factor production by lipopolysaccharide-stimulated leukocytes is a useful indicator of tolerance induction in surviving pneumonia patients and that measuring cAMP in freshly isolated leukocytes may also be clinically significant.     

Beneficial effect of aged garlic extract on periodontitis: a randomized controlled double-blind clinical study

The purpose of this study is to assess the long-term efficacy of aged garlic extract to improve periodontitis. Two hundred and one participants were randomly stratified and assigned equally to the regimen group or the control group. At the start, 12 month, and 18 month subjects received dental examination and periodontal evaluation. Probing Pocket Depth and Gingival Recession were examined. For each efficacy parameter, the mean value of examination was calculated and assessed using paired-difference t tests. Statistical tests were two-sided using a 5% significance level. The mean value of pocket depth for the aged garlic extract group at 18 month was 1.06 ± 0.49 as compared to the baseline value of 1.89 ± 0.74 (p<0.001) and the corresponding value of 1.50 ± 0.46 for the placebo group (p<0.001), indicating the beneficial effect of aged garlic extract on periodontitis. According to a Multiple linear regression analysis the only three variables which reached statistical significance as predictors of PPD level were the baseline PPD scores (p<0.001), smoking (p = 0.020), and consumption of daily dose of aged garlic extract (p<0.001). These results demonstrated that aged garlic extract is an effective supplement for preventing or improving periodontal disease. The well demonstrated benefits of aged garlic extract for the oral disease may also be used as a means to improve general health because of the close relationship between periodontitis and some systemic diseases such as diabetes, hypertension, atherosclerosis, and others.     

Validation of criterion-based patient assignment and treatment effectiveness of a multidisciplinary modularized managed care program for headache

This prospective observational study evaluates the validity of an algorithm for assigning patients to a multidisciplinary modularized managed care headache treatment program. N = 545 chronic headache sufferers [migraine (53.8 %), migraine + tension type (30.1 %), tension type (8.3 %) or medication overuse headache (6.2 %), other primary headaches (1.5 %)] were assigned to one of four treatment modules differing with regard to the number and types of interventions entailed (e.g., medication, psychological intervention, physical therapy, etc.). A rather simple assignment algorithm based on headache frequency, medication use and psychiatric comorbidity was used. Patients in the different modules were compared with regard to the experienced burden of disease. 1-year follow-up outcome data are reported (N = 160). Headache frequency and analgesic consumption differed significantly among patients in the modules. Headache-related disability was highest in patients with high headache frequency with/without medication overuse or psychiatric comorbidity (modules 2/3) compared to patients with low headache frequency and medication (module 0). Physical functioning was lowest in patients with chronic headache regardless of additional problems (modules 1/2/3). Psychological functioning was lowest in patients with severe chronicity with/without additional problems (module 2/3) compared to headache suffers with no/moderate chronicity (module 0/1). Anxiety or depression was highest in patients with severe chronicity. In 1-year follow-up, headache frequency (minus 45.3 %), consumption of attack-aborting drugs (minus 71.4 %) and headache-related disability decreased (minus 35.9 %). Our results demonstrate the clinical effectiveness and the criterion validity of the treatment assignment algorithm based on headache frequency, medication use and psychiatric comorbidity.     

Relationship between the estimates of desaturase activities and cardiometabolic phenotypes in Koreans

In the present study, we evaluated the relationships of estimated desaturase activities with cardiometabolic risk factors including abdominal obesity, atherogenic lipoprotein phenotype and inflammation in Koreans. Ninety-three healthy volunteers participated in this cross-sectional study. LDL particle size was determined using gradient gel electrophoresis and inflammatory markers including C-reactive protein, soluble intercellular adhesion molecule-1, and adiponectin were measured. Stearoyl–coA desaturase, delta-6 desaturase and delta-5 desaturase were estimated as precursor to fatty acid ratios. The results showed that stearoyl–coA desaturase was correlated with body mass index (r = 0.235, p<0.05), triglyceride (r = 0.261, p<0.001), and HDL-cholesterol (r = −0.226, p<0.05). Stearoyl–coA desaturase was associated with only triglyceride (r = 0.283, p<0.01). Delta-6 desaturase was correlated with body mass index (r = 0.236, p<0.05), waist circumference (r = 0.218, p<0.05), triglyceride (r = 0.399, p<0.001), C-reactive protein (r = 0.333, p<0.001), soluble intercellular adhesion molecule-1 (r = 0.229, p<0.05), HDL-cholesterol (r = −0.325, p<0.01), LDL particle size (r = −0.297, p<0.01) and adiponectin (r = −0.233, p<0.05). In contrast, delta-5 desaturase was correlated with body mass index (r = −0.324, p<0.01), waist circumference (r = −0.276, p<0.01), triglyceride (r = −0.329, p<0.01), C-reactive protein (r = −0.215, p<0.05), HDL-cholesterol (r = 0.262, p<0.05) and LDL particle size (r = 0.278, p<0.01). Stepwise multiple regression analysis revealed that delta-6 desaturase (p<0.01) together with waist circumference (p<0.001) were found to be independent factors for determining plasma levels of C-reactive protein (R² = 0.230). Estimated desaturase activities are closely associated with the features of cardiometabolic risk in Koreans.     

Anti-CGRP monoclonal antibodies in chronic migraine with medication overuse: real-life effectiveness and predictors of response at 6 months

BackgroundIn daily practice, anti-CGRP monoclonal antibodies (MAbs) may be useful in chronic migraine (CM) with medication overuse (MO), but data is limited. We evaluated their effectiveness in a real-life clinical cohort.MethodsThis is a prospective study conducted in CM patients with and without medication overuse treated with monthly MAbs during 6 months (erenumab/galcanezumab). We collected headache characteristics, including acute medication intake, through an electronic diary. We compared patients (1) with and without MO at baseline, (2) with and without ongoing MO after treatment, defining MO resolution as < 10 or 15 days/month of acute medication intake, according to analgesic type, during the 6-month treatment.ResultsOf 139 CM patients completing 6-month treatment with anti-CGRP MAbs, 71.2% (99/139) had MO at baseline. After 6 months, patients with and without MO at baseline had significant and similar proportions of ≥50% reduction in migraine days/month (MO: 63.6% vs. non-MO: 57.5%, p = 0.500). 60.6% (60/99) no longer satisfied MO definition. Reduction in headache frequency compared to baseline occurred in both MO-ongoing and MO-resolution group, although those who stopped overusing had a greater improvement (headache days/month: − 13.4 ± 7.6 vs. -7.8 ± 7.2, p < 0.0001). No differences in MO resolution were observed according to the MAbs used. Baseline lower pain severity was associated with MO resolution (OR [95%]:0.236[0.054–0.975]; p = 0.049).ConclusionsIn real-life anti-CGRP MAbs are as effective in CM patients with MO as in patients without it and facilitate MO cessation. Reduction in headache frequency and acute medication days/month occurs regardless of whether patients stop overusing or not.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01328-1.     

Serum levels of N-acetyl-aspartate in migraine and tension-type headache

Serum levels of N-acetyl-aspartate (NAA) may be considered a useful marker of neuronal functioning. We aimed to measure serum NAA in cohorts of migraine and tension-type headache patients versus controls, performing correlations with main clinical features. A total of 147 migraine patients (including migraine without aura, with aura and chronic migraine), 65 tension-type headache (including chronic and frequent episodic tension-type headache) and 34 sex- and age-matched controls were selected. Serum was stored at −80 °C. Quantification of NAA was achieved by the standard addition approach and analysis was performed with liquid-chromatography–mass-spectrometry (LC/MS) technique. The NAA levels were significantly decreased in migraine group (0.065 ± 0.019 mol/L), compared with both tension-type headache patients (0.078 ± 0.016 mol/L) and controls (0.085 ± 0.013 mol/L). Control subjects were significantly different from migraine with and without aura and chronic migraine, who differed significantly from episodic and chronic tension-type headache. Migraine with aura patients showed lower NAA levels when compared to all the other headache subtypes, including migraine without aura and chronic migraine. In the migraine group, no significant correlation was found between NAA serum levels, and headache frequency, allodynia and interval from the last and the next attack. The low NAA in the serum may be a sign of neuronal dysfunction predisposing to migraine, probably based on reduced mitochondria function.     

Sociodemographic differences in medication use, health-care contacts and sickness absence among individuals with medication-overuse headache

The objective of this study was to analyse sociodemographic differences in medication use, health-care contacts and sickness absence among individuals with medication-overuse headache (MOH). A cross-sectional, population survey was conducted, in which 44,300 Swedes (≥15 years old) were interviewed over telephone. In total, 799 individuals had MOH. Of these, 47 % (n = 370) only used over-the-counter medications. During the last year, 46 % (n = 343) had made a headache-related visit to their physician and 14 % (n = 102) had visited a neurologist. Among individuals aged <30 years, the number of days/month with headache was greater than the number of days with medication use, whereas the opposite was true for those ≥30 years. Both the proportion using prophylactic medication and the proportion having consulted a neurologist were smaller among those who only had elementary school education than among those with higher education (p = 0.021 and p = 0.046). Those with a lower level of education also had a higher number of days/month with headache and with medication use than those with a higher educational level (p = 0.011 and p = 0.018). The MOH-sufferers have limited contacts with health-care and preventive measures thus need to include other actors as well. Particular efforts should be directed towards those with low educational levels, and more research on medication use in relation to age is required.     

The daily response for proton pump inhibitor treatment in Japanese reflux esophagitis and non-erosive reflux disease

We investigated comparison according to reflux esophagitis and non-erosive reflux disease about “daily” symptom improvement for proton pump inhibitor treatment. We enrolled 57 reflux esophagitis and 90 non-erosive reflux disease patients. They took rabeprazole 10 mg/day for 28 days and completed “daily” in the Frequency Scale for the Symptoms of GERD from baseline until day 14, and after 28 days of treatment. The efficacy endpoint was the improvement rates in Frequency Scale for the Symptoms of GERD, based on baseline. Frequency Scale for the Symptoms of GERD was decreased in reflux esophagitis and non-erosive reflux disease (p<0.001) and was significantly lower in reflux esophagitis than in non-erosive reflux disease from the first day of treatment (p<0.05). Symptomatic improvement rates were also significantly higher in reflux esophagitis (50.3 ± 44.9%) than in non-erosive reflux disease (31.7 ± 43.2%) from the first day of treatment (p<0.0001). The symptomatic improvement rates in reflux esophagitis were significant increased from the second day of treatment until after 28 days of treatment (p = 0.0006), however, these in non-erosive reflux disease were significant increased from third days until after 28 days of treatment (p = 0.0002). In non-erosive reflux disease, the improvement of dysmotility symptom was particularly gradual as well as of reflux symptom, too. As for results of prediction of proton pump inhibitor response (completed symptom resolution) form early symptom improvement within 1 week, it was able to predict proton pump inhibitor response from the symptom improvement rate on 3 days in reflux esophagitis and on day 7 in non-erosive reflux disease. In conclusion, the prediction of the proton pump inhibitor response in non-erosive reflux disease was slow in comparison with reflux esophagitis. The cause was gradual improvement of dysmotility symptom.     

Changes in Clinical Parameters in Patients with Tension-type Headache Following Massage Therapy: A Pilot Study

Complementary and alternative medicine approaches to treatment for tension-type headache are increasingly popular among patients, but evidence supporting its efficacy is limited. The objective of this study was to assess short term changes on primary and secondary headache pain measures in patients with tension-type headache (TTH) receiving a structured massage therapy program with a focus on myofascial trigger point therapy. Participants were enrolled in an open label trial using a baseline control with four 3-week phases: baseline, massage (two 3-week phases) and follow-up. Twice weekly, 45-minute massage sessions commenced following the baseline phase. A daily headache diary was maintained throughout the study in which participants recorded headache incidence, intensity, and duration. The Headache Disability Index was administered upon study entry and at 3-week intervals thereafter. 18 subjects were enrolled with 16 completing all headache diary, evaluation, and massage assignments. Study participants reported a median of 7.5 years with TTH. Headache frequency decreased from 4.7±0.7 episodes per week during baseline to 3.7±0.9 during treatment period 2 (P<0.001); reduction was also noted during the follow-up phase (3.2±1.0). Secondary measures of headache also decreased across the study phases with headache intensity decreasing by 30% (P<0.01) and headache duration from 4.0±1.3 to 2.8±0.5 hours (P<0.05). A corresponding improvement in Headache Disability Index was found with massage (P<0.001). This pilot study provides preliminary evidence for reduction in headache pain and disability with massage therapy that targets myofascial trigger points, suggesting the need for more rigorously controlled studies.     

Migraine and behavior in children: influence of maternal headache frequency

We took advantage of a large population study in order to measure child behavior, as captured by the Child Behavior Checklist (CBCL) as a function of headache status in the children and their mothers. Of the target sample, consents and analyzable data were obtained from 1,856 families (85.4 %). Headache diagnoses were defined according to the second edition of the International Classification of Headache Disorders, and behavioral and emotional symptoms were assessed by the validated Brazilian version of the CBCL. We calculated the relative risk of abnormalities in the CBCL domains as a function of headache status in the children, after adjusting by a series of main effect models. Children with migraine were more likely to present abnormal scores in several of the CBCL scales, relative to children without migraine, and maternal migraine status contributed little to the model. However, when the mother had daily headaches, both children with and without migraine had similar CBCL scores. In multivariate analyses, migraine status in the children predicted CBCL scores (p < 0.01). Headache status and headache frequency in the mother did not predict CBCL scores in children with migraine but predicted in children without migraine (p < 0.01). The burden of migraine to the family is complex. Children with migraine are more likely to have behavioral and emotional symptoms than children without migraine. Children without migraine may be affected, in turn, by frequent headaches experienced by their mothers.     

Impact of sex hormonal changes on tension-type headache and migraine: a cross-sectional population-based survey in 2,600 women

Sex hormones have some implications on headaches. The objective of the study was to investigate the effects of hormonal changes comparatively on tension-type headache (TTH) and migraine, in a population-based sample. A nationwide face-to-face prevalence study was conducted using a structured electronic questionnaire. 54.3 % of the migraineurs reported that the probability of experiencing headache during menstruation was high, whereas 3.9 % had headache only during menstruation. Forward logistic regression analysis revealed that menstruation was a significant trigger for migraine in comparison to TTH. On the other hand, nearly double the number of TTH sufferers reported “pure menstrual headache” compared to migraineurs (p = 0.02). Menstrual headaches caused significantly higher MIDAS grades. One-third of the definite migraineurs reported improvement during pregnancy and oral contraceptives significantly worsened migraine. Menopause had a slight improving effect on migraine compared to TTH. Sex hormonal changes have major impacts particularly on migraine; however, the effects of hormonal fluctuations on TTH should not be underestimated.

Electronic supplementary material

The online version of this article (doi:10.1007/s10194-012-0475-0) contains supplementary material, which is available to authorized users.     

Drug-dependence behaviour and outcome of medication-overuse headache after treatment

This study aimed at determining the causes of failure of the different proposed strategies to ensure improvement of medication-overuse headache (MOH) patients, since they have not been investigated so far, especially with regard to aspects related to cognitive and behavioural aspects of symptomatic drugs overused by them. One hundred and twenty in-patients, 82 females (68.3 %), median age 49 (42–56) years, affected by MOH were admitted to the study and treated with abrupt discontinuation of the medication overused, a 6-day in-patient detoxification regimen and an immediate start of personalized prophylactic treatment, then followed for 1 year. Leeds Dependence Questionnaire (LDQ), among all the clinical variables, was administered at baseline and at 1-year follow-up visit to assess substance dependence. Of the 120 patients enrolled, 68 (56.7 %) were successfully detoxified (Responder-group), while 52 (43.3 %) were not (Non-Responder-group). At baseline, the mean LDQ total score was slightly higher in the Non-Responder group than in the Responder group (12.08 ± 2.14 vs. 11.94 ± 1.98). Although this difference was not significant at baseline (p > 0.05), the LDQ total score was significantly different (p < 0.001) at the 1-year follow-up visit between the responder group (7.8 ± 2.3) and the Non-Responder group (12.1 ± 2.1). Moreover, the pattern of the responses of the patients in the responder group differed from that of the Non-Responder-group in the items relating to the compulsion to start, compulsion to continue, primacy of effect, constancy of state and cognitive set. The results showed that patients of the Non-Responder group showed a drug dependence pattern similar to that previously described in addicts. Conversely, in patients who positively responded to the procedure, drug-abuse behaviour seemed to be a consequence of chronic headache, reflecting the need for daily analgesic use to cope with everyday life.     

Primary headaches during the COVID-19 lockdown in Germany: analysis of data from 2325 patients using an electronic headache diary

BackgroundLockdown measures due to the COVID-19 pandemic have led to lifestyle changes, which in turn may have an impact on the course of headache disorders. We aimed to assess changes in primary headache characteristics and lifestyle factors during the COVID-19 lockdown in Germany using digital documentation in the mobile application (app) M-sense.Main bodyWe analyzed data of smartphone users, who entered daily data in the app in the 28-day period before lockdown (baseline) and in the first 28 days of lockdown (observation period). This analysis included the change of monthly headache days (MHD) in the observation period compared to baseline. We also assessed changes in monthly migraine days (MMD), the use of acute medication, and pain intensity. In addition, we looked into the changes in sleep duration, sleep quality, energy level, mood, stress, and activity level. Outcomes were compared using paired t-tests.The analysis included data from 2325 app users. They reported 7.01 ± SD 5.64 MHD during baseline and 6.89 ± 5.47 MHD during lockdown without significant changes (p > 0.999). MMD, headache and migraine intensity neither showed any significant changes. Days with acute medication use were reduced from 4.50 ± 3.88 in the baseline to 4.27 ± 3.81 in the observation period (p < 0.001). The app users reported reduced stress levels, longer sleep duration, reduced activity levels, along with a better mood, and an improved energy level during the first lockdown month (p ≤ 0.001).In an extension analysis of users who continued to use M-sense every day for 3 months after initiation of lockdown, we compared the baseline and the subsequent months using repeated-measures ANOVA. In these 539 users, headache frequency did not change significantly neither (6.11 ± 5.10 MHD before lockdown vs. 6.07 ± 5.17 MHD in the third lockdown month, p = 0.688 in the ANOVA). Migraine frequency, headache and migraine intensity, and acute medication use were also not different during the entire observation period.ConclusionDespite slight changes in factors that contribute to the generation of headache, COVID-19-related lockdown measures did not seem to be associated with primary headache frequency and intensity over the course of 3 months.     

Fremanezumab in the prevention of high-frequency episodic and chronic migraine: a 12-week,multicenter, real-life,cohort study (the FRIEND study)

BackgroundFremanezumab has demonstrated to be effective, safe, and tolerated in the prevention of episodic or chronic migraine (CM) in randomized, placebo-controlled trials (RCTs). Real-life studies are needed to explore drug effects in unselected patients in routine circumstances and to provide higher generalizability results. This study explores the effectiveness, safety, and tolerability of fremanezumab in a real-life population of individuals affected by high-frequency episodic (HFEM: 8–14 days/month) or CM.MethodsThis is a 12-week multicenter, prospective, cohort, real-life study. We considered all consecutive patients affected by HFEM or CM visited at 9 Italian headache centers from 28/07/2020 to 11/11/2020. Eligible patients were given subcutaneous fremanezumab at the doses of 225 mg monthly or 675 mg quarterly, according to their preference. Primary study endpoints were the change in monthly migraine days (MMDs) in HFEM and monthly headache days (MHDs) in CM patients at weeks 9–12 compared to baseline. Secondary endpoints encompassed variation in monthly analgesic intake (MAI), Numerical Rating Scale (NRS), HIT-6 and MIDAS scores, and ≥ 50%, ≥ 75% and 100% responder rates at the same time intervals.ResultsSixty-seventh number migraine patients had received ≥ 1 subcutaneous fremanezumab dose and were considered for safety analysis, while 53 patients completed 12 weeks of treatment and were included also in the effectiveness analysis. Fremanezumab was effective in both HFEM and CM, inducing at week 12 a significant reduction in MMDs (-4.6, p < 0.05), MHDs (-9.4, p < 0.001), MAI (-5.7, p < 0.05; -11.1, p < 0.001), NRS (-3.1, p < 0.001; -2.5, p < 0.001), and MIDAS scores (-58.3, p < 0.05; -43.7; p < 0.001). HIT-6 was significantly reduced only in HFEM patients (-18.1, p < 0.001). Remission from CM to episodic migraine and from MO to no-MO occurred in 75% and 67.7% of the patients. The ≥ 50%, ≥ 75% and 100% responder rates at week 12 were 76.5%, 29.4% and 9.9% in HFEM and 58.3%, 25% and 0% in CM. Younger age emerged as a positive response predictor (OR = 0.91; 95% CI 0.85–0.98, p = 0.013). Treatment-emergent adverse events were uncommon (5.7%) and mild. No patient discontinued fremanezumab for any reason.ConclusionsFremanezumab seems more effective in real-life than in RCTs. Younger age emerges as a potential response predictor.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-022-01396-x.     

Comorbidity profiles of chronic migraine sufferers in a national database in Taiwan

Chronic migraine (CM; ≥15 headache days per month, ≥3 months) is associated with a higher prevalence of comorbidities than episodic migraine (<15 headache days per month). However, it is unclear whether a similar pattern exists in Asian patients. To examine this, a retrospective matched cohort study was conducted using the Taiwan National Health Insurance Research Database. CM cases were defined as patients with at least one neurological outpatient visit with a primary or secondary ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) code of 346.11, diagnosed by neurologists at medical centers during 2007–2008. The study group was compared with patients suffering from other migraine subtypes and non-migraineurs in the general population. Both comparison groups were matched with CM sufferers at a 4:1 ratio by age, gender, urbanization level of the residence, income, and hospital setting. Relative risk (RR) was calculated using conditional logistic regression. Compared with patients with other migraines (n = 2,226), CM sufferers (n = 681) had a higher risk of hyperlipidemia (RR = 1.32; P = 0.041), asthma (RR = 1.77; P = 0.007), depression (RR = 1.88; P < 0.0001), bipolar disorder (RR = 1.81; P = 0.022) and anxiety disorders (RR = 1.48; P = <0.0001). Compared with the non-migraineurs (n = 3,790), CM sufferers (n = 948) had significantly increased risks of cardiovascular disease, sinusitis, asthma, gastrointestinal ulcers, vertigo and psychiatric disorders by 1.6–3.9-fold. In conclusion, CM is associated with significant comorbidities in Asian patients. Differences in the comorbidity profiles of CM compared with other migraines have highlighted that patients with CM differ not just in terms of headache frequency but also in other important aspects.     

Correlation between symptomatic improvement and quality of life in patients with reflux and dyspeptic symptoms

We investigated the correlation between symptomatic improvement and quality of life in Japanese gastroesophageal reflux disease patients with PPI. Eighty one patients with reflux and dyspeptic symptom were enrolled. The evaluation of the symptom was used he Frequency Scale for the Symptom of GERD in 3 categories: total score of 12 questions, score related to reflux symptoms, and score related to dyspeptic symptoms and the evaluation of the quality of life was use the 8-item Short Form Health Survey in 2 categories, the physical component summary score and mental component summary score. All patients administered rabeprazole 10 mg/day for 8 weeks. We investigated the correlation between symptomatic improvement with proton pump inhibitor and quality of life. Significant symptomatic improvement was seen in the total score of 12 questions (26.7 ± 8.8 → 17.5 ± 5.9, p<0.0001), score related to reflux symptoms (14.9 ± 5.4 → 9.6 ± 3.6, p<0.0001), and score related to dyspeptic symptoms (11.8 ± 4.3 → 8.0 ± 2.9, p<0.0001). Significant improvement in quality of life was seen in the physical component summary score (47.8 ± 6.6 → 50.0 ± 5.9, p = 0.0209) and mental component summary score (47.4 ± 8.5 → 50.4 ± 5.3, p = 0.0133) with proton pump inhibitor. With proton pump inhibitor, a significant positive correlation was seen between the improvement rates in total score of 12 questions, score related to dyspeptic symptoms and in mental component summary score at 8 weeks (total score of 12 questions: r = 0.275, p = 0.0265, score related to dyspeptic symptoms: r = 0.367, p = 0.0027). In conclusion, quality of life was associated with improvement in dyspeptic symptoms with proton pump inhibitor treatment.