Environmental and psychological risk factors for migraine chronification in China: A multicenter prospective cohort study.

48.: The effect of brief biofeedback intervention on headache disability and analgesic use in episodic or chronic migraine and chronic tension type headache

The objective of this study was to compare the societal direct and indirect costs of chronic and episodic migraine in the United States. Episodic and chronic migraine are distinguished by the frequency of headache-days. Chronic migraine has a greater overall impact on quality of life than does episodic migraine. Individuals with chronic migraine also use more healthcare resources (resulting in higher direct costs) and experience greater decreases in productivity (resulting in higher indirect costs) than those with episodic migraine as shown in the American Migraine Prevalence and Prevention (AMPP) Study. The International Burden of Migraine Study utilized a web-based questionnaire to elicit data on several topics related to the burden of migraine illness, including health resource utilization and productivity losses. Potential survey participants were identified by Synovate Healthcare (Chicago, IL, USA) from a pool of registered panelists from various countries. The panelists were screened online to determine eligibility and to identify individuals with migraine (episodic or chronic), based on reported symptoms. Participants from the United States were divided into episodic and chronic migraine groups, based on reported headache-day per month frequency. Direct and indirect costs were estimated by applying estimated unit costs to reported headache-related productivity losses and resource use. Costs were compared between participants with episodic and chronic migraine. Mean [standard deviation] total annual cost of headache among people with chronic migraine ($8243 [$10,646]) was over three times that of episodic migraine ($2649 [$4634], P < .001). Participants with chronic migraine had significantly greater direct medical costs ($4943 [$6382]) and indirect (lost productivity) costs ($3300 [$6907]) than did participants with episodic migraine (direct, $1705 [$3591]; indirect, $943 [$2084]) (P < .001 for each). Unlike previous findings, direct medical costs constituted the majority of total headache-related costs for both chronic migraine (60.0%, $4943 of $8243) and episodic migraine (64.3%, $1705 of $2649) participants. A large portion of direct medical costs are attributable to pharmaceutical utilization among both chronic migraine (80%, $3925 of 4943) and episodic migraine (70%, $1196 of $1705) participants. The results of this study build on previous results of the AMPP Study, demonstrating that headache-related direct, indirect, and total costs are significantly greater among individuals with chronic migraine than with episodic migraine in the United States.

In chronic migraine, botulinum toxin type A may reduce the number of migraine days per month by 2 days compared with placebo treatment. Non-serious adverse events were probably experienced by 60/100 participants in the treated group compared with 47/100 in the placebo group. For people with episodic migraine, we remain uncertain whether or not this treatment is effective because the quality of this limited evidence is very low. Better reporting of outcome measures in published trials would provide a more complete evidence base on which to draw conclusions.

BackgroundThe clinical benefit of galcanezumab, demonstrated in randomized clinical trials (RCTs), remains to be quantified in real life. This study aimed at evaluating the effectiveness, safety and tolerability of galcanezumab in the prevention of high-frequency episodic migraine (HFEM) and chronic migraine (CM) in a real-life setting.MethodsThis multicenter prospective observational cohort study was conducted between November 2019 and January 2021 at 13 Italian headache centers. Consecutive adult HFEM and CM patients clinically eligible were enrolled and treated with galcanezumab subcutaneous injection 120 mg monthly with the first loading dose of 240 mg. The primary endpoint was the change in monthly migraine days (MMDs) in HFEM and monthly headache days (MHDs) in CM patients after 6 months of therapy (V6). Secondary endpoints were the Numerical Rating Scale (NRS), monthly painkiller intake (MPI), HIT-6 and MIDAS scores changes, ≥50% responder rates (RR), the conversion rate from CM to episodic migraine (EM) and Medication Overuse (MO) discontinuation.ResultsOne hundred sixty-three patients (80.5% female, 47.1 ± 11.7 years, 79.8% CM) were included. At V6, MMDs reduced by 8 days in HFEM and MHDs by 13 days in CM patients (both p < .001). NRS, MPI, HIT-6 and MIDAS scores significantly decreased (p < .001). Ten patients (6.1%) dropped out for inefficacy and classified as non-responders. Patients with ≥50%RRs, i.e. responders, were 76.5% in the HFEM and 63.5% in the CM group at V6. Among CM patients, the V6 responders presented a lower body mass index (p = .018) and had failed a lower number of preventive treatments (p = .013) than non-responders. At V6, 77.2% of CM patients converted to EM, and 82.0% ceased MO. Adverse events, none serious, were reported in up to 10.3% of patients during evaluation times.ConclusionsGalcanezumab in real life was safe, well tolerated and seemed more effective than in RCTs. Normal weight and a low number of failed preventives were positively associated with galcanezumab effectiveness in CM patients.Trial registrationClinicalTrials.govNCT04803513.

Migraine is a prevalent disabling neurological disorder associated with a wide range of medical and psychiatric comorbidities. Population- and clinic-based studies suggest that psychiatric comorbidities, particularly mood and anxiety disorders, are more common among persons with chronic migraine than among those with episodic migraine. Additional studies suggest that psychiatric comorbidities may be a risk factor for migraine chronification (i.e., progression from episodic to chronic migraine). It is important to identify and appropriately treat comorbid psychiatric conditions in persons with migraine, as these conditions may contribute to increased migraine-related disability and impact, diminished health-related quality of life, and poor treatment outcomes. Here, we review the current literature on the rates of several psychiatric comorbidities, including depression, anxiety, and post-traumatic stress disorder, among persons with migraine in clinic- and population-based studies. We also review the link between physical, emotional, and substance abuse, psychiatric disorders, and migraine. Finally, we review the data on psychiatric risk factors for migraine chronification and explore theories and evidence underlying the comorbidity between migraine and these psychiatric disorders.

The prevalence of drug-induced headache (DIHA) in the population is about 7%, and the relapse rate of DIHA after successful treatment is about 40% within 5 years.Objective: to analyze the risk factors for recurrence of DIHA and to develop a prognostic model for the probability of relapse after treatment.Material and methods. The characteristics of 117 patients with DIHA were analyzed on the basis of clinical data and questionnaire data using headache scales (MMAS-8, MIDAS, HALT, HIT-6, mTOQ-5), psycho-emotional profiles (PCS, Spielberger-Hanin Anxiety Scale, PHQ-9, BIS-11, TAS-26, SAGE test, LDQ) that were performed at the time of admission to the clinic and 9 months after the start of therapy. All patients enrolled in the study received a complex treatment that included an educational conversation, “detoxification” and symptomatic therapy during the withdrawal period along with a preventive treatment for chronic migraine (CM).Results. It was shown that there is still a low level of diagnosing of CM and DIHA. By creating a prediction model for the likelihood of recurrence of DIHA, we were able to identify the most important factors for an unfavorable course and recurrence of excessive analgesics use: frequency of analgesic use per day (OR 15.8; 95% C113.1—23.4), degree of alexithymia (score on TAS-26 scale: OR 11.3; 95% CI 6.3—18.1), frequency of combined analgesic use per month (OR 7.1; 95% CI 4.3—11.7), degree of pain catastrophizing on the PCS scale (OR 4.7; 95% CI 1.2—7.3), duration of symptomatic drug abuse (OR 3.2; 95% CI2.1—5.7).Conclusion. A high level of concomitant psychoemotional disorders, especially alexithymia and impulsive behaviour, is a significant risk factor for relapse and should be considered in the treatment of comorbid pathologies. It can be assumed that monoclonal antibodies against calcitonin gene-related peptides, botulinum therapy or combined treatment may be the treatment of choice in cases of ineffective prevention and detoxification attempts in the past as well as in cases of prolonged analgesic abuse.

Frecuencia e impacto del trastorno por estrés postraumático y los eventos vitales traumáticos en pacientes con migraña

Objectives This study aimed to investigate the frequency of analgesic administration within 48 h after endoscopic submucosal dissection (ESD) or its derivative techniques across different segments of the digestive tract, as well as the timing of the initial analgesic administration. Materials and Methods This retrospective observational study was built upon previous research. The primary outcomes assessed were the time to initial analgesic administration postoperatively and the frequency of analgesic use within 48 h after ESD surgery. Additionally, factors influencing painkiller administration in ESD patients were analyzed. Results Of the 2162 patients included in the study, 570 (26.36%) required postoperative analgesic medications. Most patients required their initial analgesic within 8 h following ESD, with the highest demand observed within 2 h. Multivariate Cox regression analysis indicated that intraoperative administration of ketorolac reduced the likelihood of analgesic administration within 2 h postoperatively (hazard ratio [HR] = 0.35, 95% confidence interval [CI]: 0.15–0.79, p = 0.012). The time to first analgesic administration did not differ significantly among patients with varying surgical sites (H = 2.043, p = 0.843) or surgical methods (H = 8.647, p = 0.071). Similarly, no significant difference was observed in the frequency of analgesic use within 48 h across different surgical sites (H = 3.817, p = 0.576). However, patients who underwent endoscopic submucosal excavation (ESE) surgery exhibited a lower frequency of analgesic use compared to those who underwent endoscopic full-thickness resection (EFR) surgery (p = 0.038). Conclusions A subset of patients undergoing ESD exhibited a need for analgesics within the initial 48-hour postoperative period. Clinicians should carefully assess patients’ pain needs and implement appropriate pain relief measures to improve postoperative outcomes. Trial registration Chinese Clinical Trial Registry; ChiCTR2300072854

BackgroundMigraine is common among females of reproductive age (estimated prevalence:17–24%) and may be associated with reproductive health through underlying central nervous system excitability, autoimmune conditions, and autonomic dysfunction. We evaluated the extent to which pre-pregnancy migraine diagnosis and medication use are associated with risk of spontaneous abortion (SAB).MethodsWe analyzed data from a preconception study of pregnancy planners (2013–2021). Eligible participants self-identified as female, were aged 21–45 years, resided in the USA or Canada, and conceived during follow-up (n = 7890). Participants completed baseline and bimonthly follow-up questionnaires for up to 12 months or until a reported pregnancy, whichever occurred first. Pregnant participants then completed questionnaires during early (~ 8–9 weeks) and late (~ 32 weeks) gestation. We defined migraineurs as participants who reported a migraine diagnosis or use of a medication to treat migraine. Preconception questionnaires elicited migraine medication use during the past 4 weeks, and SAB on follow-up and pregnancy questionnaires. We used Cox regression models with gestational weeks as the time scale to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations among preconception migraine, migraine medication use, and SAB, controlling for potential demographic, medical, and lifestyle confounders.ResultsNineteen percent of study pregnancies ended in SAB. History of migraine before conception was not appreciably associated with SAB risk (HR = 1.03, 95% CI: 0.91–1.06). Use of any migraine medication was associated with a modest increase in SAB risk overall (HR = 1.14, 95% CI: 0.96–1.36). We observed the greatest increase in risk among those taking migraine medications daily (HR = 1.38, 95% CI: 0.81–2.35) and those taking prescription migraine prophylaxis (HR = 1.43, 95% CI: 0.72–2.84) or combination analgesic and caffeine medications (HR = 1.42, 95% CI: 0.99–2.04).ConclusionsMigraine medication use patterns suggesting greater underlying migraine severity were associated with increased risk of SAB. This research adds to the limited information available on the reproductive effects of migraine.

Nonnarcotic analgesics are the most commonly used drugs in the United States. To our knowledge, the association between the use of these analgesics, particularly acetaminophen, and the risk of hypertension among men has not been extensively studied. The association between analgesic use and risk of incident hypertension was analyzed in a prospective cohort analysis of 16 031 male health professionals without a history of hypertension at baseline. Detailed information about the frequency of use of acetaminophen, nonsteroidal anti-inflammatory drugs, and aspirin was gathered at baseline and updated 2 years later. The relative risk of incident hypertension during 4 years of follow-up was analyzed using multivariable proportional hazards regression. We identified 1968 incident cases of hypertension. After adjusting for multiple potential confounders, men who used acetaminophen 6 to 7 days per week compared with nonusers had a relative risk for incident hypertension of 1.34 (95% confidence interval, 1.00-1.79; P=.01 for trend). This same comparison resulted in relative risks of 1.38 (95% confidence interval, 1.09-1.75; P=.002 for trend) for nonsteroidal anti-inflammatory drugs and 1.26 (95% confidence interval, 1.14-1.40; P<.001 for trend) for aspirin. We observed similar results when the number of pills per week was analyzed rather than frequency of use in days per week. The frequency of nonnarcotic analgesic use is independently associated with a moderate increase in the risk of incident hypertension. Given the widespread use of these medications and the high prevalence of hypertension, these results may have important public health implications.

Cephalic allodynia (CA) can be observed in 50-70% of patients with chronic migraine (CM). The aim of this trial was to assess the efficacy of botulinum toxin type A (Botx-A) in the treatment of CA associated with CM. In this placebo-controlled trial, patients were randomized either into Botx-A or 0.9% saline injections and efficacy measures were assessed every 4 weeks for 3 months. Efficacy endpoints were number of migraine episodes associated with CA, changes from baseline in visual analogical scale scores for pain (VAS) and frequency of common analgesics use for migraine. A total of 38 subjects were randomized to saline (n=18) or Botx-A (n=20). There were no significant differences in baseline between active intervention or placebo groups regarding mean age, number of headache episodes [mean 12.1 (9.22) and 17.00 (9.69) respectively; P=0.12], pain severity as measured by the VAS or frequency of analgesic use for headache episodes. Efficacy analysis showed that Botx-A injections led to an important decrease from baseline in the mean migraine episodes associated with CA after 12 weeks (5.20 versus 11.17; P=0.01). Also, VAS scores and frequency of analgesics use for headache were significantly reduced in the Botx-A group. This study suggests that Botx-A injections are superior to saline in the treatment of CA associated with CM, with mild self limited side effects.

ObjectiveTo test the hypothesis that statistically defined subgroups of migraine (based on constellations of comorbidities and concomitant conditions; henceforth comorbidities), previously identified using Chronic Migraine Epidemiology and Outcomes (CaMEO) Study data, differ in prognosis, as measured by rates of progression from episodic migraine (EM) to chronic migraine (CM).MethodsThe onset of CM was assessed up to 4 times over 12 months in individuals with EM and ≥1 comorbidity at baseline, based on constellations of comorbidities (comorbidity classes). The “fewest comorbidities” class served as reference. Individuals completing ≥1 follow-up survey from the web-based CaMEO Study were included. Covariates included sociodemographic variables and headache characteristics. Sex, income, cutaneous allodynia, and medication overuse were modeled as binary variables; age, body mass index, headache-related disability (Migraine Disability Assessment [MIDAS]), and Migraine Symptom Severity Scale as continuous variables. CM onset was assessed using discrete time analysis.ResultsIn the final sociodemographic model, all comorbidity classes had significantly elevated hazard ratios (HRs) for risk of progression to CM from EM, relative to fewest comorbidities. HRs for CM onset ranged from 5.34 (95% confidence interval [CI] 3.89–7.33; p ≤ 0.001) for most comorbidities to 1.53 (95% CI 1.17–2.01; p < 0.05) for the respiratory class. After adjusting for headache covariates independently, each comorbidity class significantly predicted CM onset, although HRs were attenuated.ConclusionsSubgroups of migraine identified by comorbidity classes at cross-section predicted progression from EM (with ≥1 comorbidity at baseline) to CM. The relationship of comorbidity group to CM onset remained after adjusting for indicators of migraine severity, such as MIDAS.Clinicaltrials.gov identifierNCT01648530.

BackgroundThe use of ondansetron (OND) has proven to be beneficial in the prognosis of critically ill patients. However, whether early OND use has a benefit in acute respiratory distress syndrome (ARDS) patients on mechanical ventilation (MV) is unknown. This study aimed to investigate the association of the early use of OND with the risk of 30-day mortality in ARDS patients who received MV support.MethodsThis cohort study retrospectively extracted patients with ARDS from the Medical Information Mart for Intensive Care (MIMIC)-IV database from 2008 to 2019. All potential covariates were incorporated in the univariate and multivariable Cox proportional hazard models with a two-way stepwise regression analysis. Univariate and multivariable Cox proportional hazard models were used to evaluate the association of early OND use with 30-day mortality before or after the propensity score matching (PSM), with hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analysis was performed stratified by age, gender, ARDS grades, ventilator-associated pneumonia (VAP), acute kidney injury (AKI), ventilation time, and vasopressor.ResultsOf the total 6,457 ARDS patients, 1,125 died within 30 days. After PSM, patients who received early OND use had lower odds of 30-day mortality compared with those who did not (HR =0.77, 95% CI: 0.63–0.94). The low dose of early OND use was associated with a decreased risk of 30-day mortality (HR =0.67, 95% CI: 0.54–0.83). Early OND use was related to lower odds of 30-day mortality of ARDS patients aged ≥65 years (HR =0.54, 95% CI: 0.43–0.67), with females (HR =0.77, 95% CI: 0.61–0.97) or males (HR =0.58, 95% CI: 0.47–0.72), with ARDS grades of mild (HR =0.57, 95% CI: 0.44–0.74), moderate (HR =0.76, 95% CI: 0.60–0.97) or severe (HR =0.69, 95% CI: 0.49–0.98), without VAP (HR =0.64, 95% CI: 0.55–0.76), with AKI (HR =0.62, 95% CI: 0.52–0.74), with short (<43.87 h, HR =0.65, 95% CI: 0.50–0.83) or long (≥43.87 h, HR =0.71, 95% CI: 0.58–0.87) ventilation time, and those who received vasopressor (HR =0.67, 95% CI: 0.56–0.80) or not (HR =0.65, 95% CI: 0.46–0.90).ConclusionsEarly OND use and daily low-dose OND use before MV support were associated with a decreased risk of 30-day mortality, which may be beneficial for the rational use of OND in ARDS patients.

BackgroundAnalgesics are the most common form of managing low back pain (LBP). No previous study has examined which domains and intensities of physical activity are most beneficial in reducing the frequency of analgesic use for LBP and its related activity limitation.MethodsThis cohort study forms part of the AUstralian Twin low BACK pain study, investigating the impact of physical activity on LBP. Information on demographics, LBP and health‐related factors, including physical activity, were collected at baseline. Data on the total counts of analgesic use and activity limitation for LBP were collected weekly for one‐year. Negative binomial regression models were conducted separately for each type of physical activity. Results were presented as incidence rate ratios (IRRs) and 95% confidence intervals (CIs).ResultsFrom an initial sample of 366 participants, 86 participants reported counts of analgesic use and 140 recorded counts of activity limitation across the follow‐up period. The negative binomial regression models for analgesic use counts indicated that engagement in moderate‐vigorous physical activity was protective for use of analgesics (IRR 0.97, 95% CI 0.96–0.99), while physical workload was associated with greater use (IRR 1.02, 95% CI 1.01–1.05). No other significant relationships were observed for the other measures of physical activity. For activity limitation counts, engagement in leisure activity was associated with less counts of activity limitation (IRR 0.94, 95% CI 0.81–0.99), while greater amounts of sedentary time was associated with higher counts (IRR 1.04, 95% CI 1.01–1.09). No other significant relationships were observed for the other measures of physical activity.ConclusionsOur findings highlight the potential importance of supporting engagement in moderate–vigorous and leisure physical activity as well as minimizing sedentary time and physical workload to reduce the risk of activity limitation and the need for analgesic use in people with LBP.SignificanceWe examined which domains and intensities of physical activity are most beneficial in reducing the frequency of analgesic use for low back pain and its related activity limitation. Engaging in moderate–vigorous and leisure physical activity as well as minimizing sedentary time and physical workload has the potential to reduce the risk of activity limitation and the need for analgesic use in people with low back pain.

To explore gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx) levels in the right thalamus of patients with episodic migraine (EM) and chronic migraine (CM) and their effects on the chronification of migraine. Migraine affects approximately 1 billion people worldwide, with 2.5%-3% of people with EM progressing to CM each year. Magnetic resonance spectroscopy studies have revealed altered GABA and Glx levels in the thalamus of patients with migraine without aura, but these neurometabolic concentrations are underexplored in the thalamus of patients with CM. In this cross-sectional study, patients with EM and CM were recruited. Mescher-Garwood point resolved spectroscopy sequence was used to acquire neurotransmitter concentrations in the right thalamus of patients with EM and CM and matched healthy controls (HCs). A total of 26 patients (EM, n= 11; CM, n= 15) and 16 age- and sex-matched HCs were included in the analysis. There were significantly lower GABA+/Water levels in the right thalamus of the CM group (mean ± standard deviation: 2.27 ± 0.4 [institutional units]) than that of the HC group (2.74 ± 0.4) (p= 0.026; mean difference [MD]=-0.5 [i.u.]), and lower Glx/Cr levels in the EM group (mean ± SD: 0.11 ± < 0.1) than in the HCs (0.13 ± < 0.1) and CM group (0.13 ± < 0.1) (p= 0.023, MD < -0.1, and p= 0.034, MD < -0.1, respectively). The GABA+/Glx ratio was lower in the CM group (mean ± SD: 0.38 ± 0.1) compared to the EM group (0.47 ± 0.1) (p= 0.024; MD=-0.1). The area under the curve for GABA+/Water levels in differentiating patients with CM from HCs was 0.83 (95% confidence interval 0.68, 0.98; p= 0.004). Correlation analyses within the migraine group revealed no significant correlation between metabolite concentration levels and headache characteristics after Bonferroni correction. Reduced GABA+/Water levels and imbalance of excitation/inhibition in the right thalamus may contribute to migraine chronification.