Coffee consumption and migraine: a population-based study.

Although coffee is one of the most consumed caffeinated beverages worldwide, the role of coffee consumption in migraine is controversial. This study examined the relationship between coffee consumption and clinical characteristics in participants with migraine compared to those with non-migraine headache. This cross-sectional study used data from a nationwide survey on headache and sleep. Coffee consumption was classified as no-to-low (< 1 cup/day), moderate (1-2 cups/day), or high (≥ 3 cups/day). Of the 3030 survey participants, 170 (5.6%) and 1,768 (58.3%) were identified as having migraine and non-migraine headache, respectively. Coffee consumption tended to increase in the order of non-headache, non-migraine headache, and migraine (linear-by-linear association, p = 0.011). Although psychiatric comorbidities (depression for migraine and anxiety for non-migraine headache) and stress significantly differed according to coffee consumption, most headache characteristics and accompanying symptoms did not differ among the three groups for participants with migraine and non-migraine headache. Response to acute headache treatment-adjusted for age, sex, depression, anxiety, stress, preventive medication use, and current smoking-was not significantly different by coffee consumption in participants with migraine and non-migraine headache. In conclusion, most headache-related characteristics and acute treatment response did not significantly differ by coffee consumption in migraine and non-migraine headache.

Classification of pediatric headache cases referred to a neurology department.

BACKGROUND: Headaches are very common in children. The patients often have mild symptoms, but on occasion may have severe, secondary headaches. The present study aimed to clarify the details of children with headaches seen at the outpatient clinic of a pediatric neurological department. METHODS: The present, retrospective observational study was conducted at a tertiary pediatric hospital in Japan and enrolled children referred to the neurology department outpatient clinic for headache between April 2018 and March 2021. RESULTS: In total, 113 cases of headache were examined; of these, 99 (87.6%) were primary headaches, one case (0.9%) was a secondary headache, and 13 (11.5%) were unclassified or unspecified. There were 46 cases (40.7%) of tension-type headache (TTH), both confirmed and suspected, 30 cases (26.5%) of migraine, and 23 cases (20.4%) of a combination of the TTH and migraine. One case of secondary headache was attributed to an infection. Arachnoid cysts were found in seven patients (7.8%). Acute drug treatments were administered to 93 patients (82.3%), with acetaminophen being the most common drug, followed by ibuprofen. Prophylactic drug treatments were administered to 39 patients (34.5%), with goreisan (a Chinese herbal medicine containing Alisma orientale, Poria cocos, Polyporus umbellatus, Atractylodes lancea, and Cinnamomum cassia) being the most common (41%). CONCLUSIONS: Few cases of secondary headache and none of emergency headache were diagnosed. The prevalence of arachnoid cysts was higher than in the general pediatric population, suggesting that arachnoid cysts might be associated with headache.

Review on Headache Related to Dietary Supplements.

PURPOSE OF REVIEW: The lifetime prevalence of headaches is 96%. Approximately 11% of the adult population worldwide has a migraine headache. Migraine is a complex disorder that is more than a simple headache. So far, many underlying mechanisms, i.e. inflammatory, vascular, neurogenic have been hypothesized. In recent years evidences proposed that an energy deficit due to changes in mitochondrial function contributes to migraine pathophysiology as an upstream disorder. Recent insights suggested that the coexistence of sensory-stimuli surplus and energy-reserve shortage activate the trigeminovascular system. Some nutrients are considered as essential elements in mitochondrial bioenergetics and some others are known as natural immuno-modulatory components. Also, evidence showed their beneficial effect in headache prophylaxis and treatment. In present study, we aimed to review the available data in this field. RECENT FINDINGS: Vitamin B group, magnesium, and Coenzyme Q10 (CoQ10) are well-known for their function in mitochondrial energy metabolism. On the other hand, studies support their beneficial role in controlling migraine headache symptoms. For instance, daily intake of 400-milligram riboflavin for 3 months resulted in more than 50% reduction in migraine attacks in more than half of the consumers. According to recent evidence, vitamin D and Omega-3 which are considered as famous immune-modulatory compounds are also reported to be effective in migraine prophylaxis. For example, every 22% reduction in migraine headache occurrence was reported for every 5 ng/ml rise in serum vitamin D. Supplementation with vitamin B group, CoQ10, magnesium, vitamin D and Omega-3 could be considered as an effective, less costly strategy in headache/migraine prophylaxis.

Predictors of Headache/Migraine and the Use of Complementary Medicine in U.S. Children: A Population-Based Analysis of 2017 National Health Interview Survey Data.

Background: This study set out to determine the prevalence and possible risk factors of headache and/or migraine in U.S. children, as well as the prevalence of complementary medicine use in this population. Methods: This is a secondary analysis of data from the 2017 U.S. National Health Interview Survey. Sociodemographic and clinical characteristics were compared between individuals with and without headaches. A backward stepwise procedure with a logistic regression statistic was used to test for potential predictors. Results: Six percent of children reported headaches and/or migraine within the past 12 months. Headaches were predicted by older age, female sex, non-Hispanic white ethnicity, and living in the southern United States. Inability to afford balanced meals and feeling sad or depressed in the past 6 months were also associated with higher odds of headache. A total of 19.2% of children with headaches reported using mind-body medicine, compared with 12.2% of children without headaches. Most frequently used therapy was yoga (57.2%), followed by spiritual meditation (31.1%) and mindfulness meditation (24.0%). The prevalence of visits to a complementary medicine practitioner or healer was 12.5%. Most frequently seen practitioners were chiropractors (62.1%), followed by naturopaths (21.2%), homeopaths (14.1%), and traditional healers (2.5%). Conclusions: The common use of complementary medicine among children suffering from headaches is worth noting. Understanding the motivation for using complementary medicine, as well as the choice of different forms of such therapy, may shed further light on the health-seeking behavior of this population.

The prevalence of complementary and alternative medicine use among Turkish patients with primary headache

Background/aim: The use of complementary and alternative medicine (CAM) is common in patients with primary headache. However, no study has been reported in which standardized modalities were questioned in a Turkish population. The aim of the present study was to investigate the frequency of CAM use and factors related to it in these patients. Materials and methods: Patients with a diagnosis of primary headache were included in this cross-sectional observational study. Demographic and disease specific characteristics were recorded. The use and effect of 15 CAM modalities were evaluated in accordance with the Traditional and Complementary Medicine Regulations. The patients were categorized into two groups according to their use of CAM procedures. Logistic regression analysis was further performed to assess the association between CAM use and related factors. Results: One hundred twenty patients [101 (84.2%) female, mean age 38.20 ± 12.24 years] were included. Use of CAM was reported in 33.3% of the patients. The most frequently used CAM modalities were phytotherapy (37.5%), cupping (27.5%), and chiropractic adjustment (17.5%). Compared with nonusers, CAM users showed a longer duration of disease (respectively mean 5.68 ± 4.96 years and 10.97 ± 8.57 years, p = 0.000). There were no differences with respect to age, sex, education, presence of systemic disease, headache subtypes, number of headache days in a month, or headache severity. Patients who underwent cupping reported that they benefited more than those who tried phytotherapy and multiple CAM methods (respectively 45.5%, 33.3%, 16.6%, p = 0.039). Subsequently, the logistic regression analysis showed a significant association between only disease duration and CAM use [respectively p value, OR (95% CI), and confidence intervals = 0.002 (1.143 (1.050­1.243)]. Conclusion: Our results suggest that Turkish patients with primary headache, especially those with long disease duration, use CAM modalities. Larger population-based studies are required to clarify the safety and efficacy of these methods.

Effects of Caffeinated and Decaffeinated Coffee on Hemodialysis-Related Headache (CoffeeHD): A Randomized Multicenter Clinical Trial.

OBJECTIVES: Historically, headache was reported in up to 76% of hemodialysis patients. Some authors suggested that headache resulted from caffeine withdrawal. This study aims to compare the incidence of headache and hypotension between patients drinking regular or decaffeinated coffee during dialysis. METHODS: One-hundred fifty-six patients were enrolled in this randomized, double-blind, placebo-controlled, multicenter study. Patients with atrial fibrillation were excluded. Group A was given 80 mL of regular coffee and group B 80 mL of decaffeinated coffee (placebo) in the middle of the session for 12 consecutive sessions. Ultrafiltration rate was fixed to a maximum of 13 mL/kg/hour. The primary outcome was the incidence of headache during dialysis. RESULTS: A total of 139 patients completed the trial (6.4% vs. 15.4% of withdrawal in Groups A and B, respectively). The number of sessions with headache was not significantly different between Group A and B (33.3% vs. 37.1% respectively, P = .522), nor the number of sessions with hypotension (27% vs. 26% respectively, P = .539). In a subgroup analysis, headache tended to be more frequent in Group B (P = .06) in 2 categories of patients: those with the highest potassium dialysate (K = 2) and the non-hypertensive patients. CONCLUSIONS: Headache occurred in 35% of patients during their chronic hemodialysis sessions. Caffeine intake did not prevent headache occurrence in these patients.

Use of medicinal plants for headache, and their potential implication in medication-overuse headache: Evidence from a population-based study in Nepal.

BACKGROUND: In Nepal, traditional treatment using medicinal plants is popular. Whereas medication-overuse headache is, by definition, caused by excessive use of acute headache medication, we hypothesized that medicinal plants, being pharmacologically active, were as likely a cause. METHODS: We used data from a cross-sectional, nationwide population-based study, which enquired into headache and use of medicinal plants and allopathic medications. We searched the literature for pharmacodynamic actions of the medicinal plants. RESULTS: Of 2100 participants, 1794 (85.4%) reported headache in the preceding year; 161 (7.7%) reported headache on ≥15 days/month, of whom 28 (17.4%) had used medicinal plants and 117 (72.7%) allopathic medication(s). Of 46 with probable medication-overuse headache, 87.0% (40/46) were using allopathic medication(s) and 13.0% (6/46) medicinal plants, a ratio of 6.7:1, higher than the overall ratio among those with headache of 4.9:1 (912/185). Of 60 plant species identified, 49 were pharmacodynamically active on the central nervous system, with various effects of likely relevance in medication-overuse headache causation. CONCLUSIONS: MPs are potentially a cause of medication-overuse headache, and not to be seen as innocent in this regard. Numbers presumptively affected in Nepal are low but not negligible. This pioneering project provides a starting point for further research to provide needed guidance on use of medicinal plants for headache.

Headache Characteristics and Psychological Factors Associated with Functional Impairment in Individuals with Persistent Posttraumatic Headache.

OBJECTIVE: Persistent posttraumatic headache (PPTH), one of the most common symptoms following mild traumatic brain injury, is often associated with substantial functional disability. The objective of this study was to assess the contribution of demographics, headache characteristics, and psychological symptoms to disability associated with PPTH. METHODS: Participants completed the State-Trait Anxiety Inventory (STAI), the Beck Depression Inventory (BDI), the Pain Catastrophizing Scale (PCS), and the Migraine Disability Assessment (MIDAS) questionnaire. Two linear regression models were formulated to interrogate the relationships between 1) demographics and headache characteristics with the MIDAS questionnaire and 2) demographics, headache characteristics, and psychological symptoms with the MIDAS questionnaire. A two-way stepwise regression using the Akaike information criterion was performed to find a parsimonious model describing the relationships between demographics, headache characteristics, and psychological measures with the MIDAS questionnaire. RESULTS: Participants included 58 patients with PPTH and 39 healthy controls (HCs). The median MIDAS score among those with PPTH was 48.0 (first quartile [1Q] = 20.0, third quartile [3Q] = 92.0), indicative of severe disability. Compared with the HCs, those with PPTH had higher scores on the BDI, STAI, and PCS. Older age predicted lower MIDAS scores (age: B=-0.11, P<0.01), whereas higher headache frequency, greater headache intensity, and higher trait anxiety scores predicted higher MIDAS scores in individuals with PPTH (headache frequency: B=0.07, P<0.001; headache intensity: B=0.51, P=0.04; trait anxiety score: B=1.11, P=0.01). CONCLUSIONS: Individuals with PPTH had substantial psychological symptoms and headache-related disability. Disability was partially explained by age, headache frequency and intensity, and trait anxiety. Holistic management of patients with PPTH to address headaches and psychological symptoms might reduce headache-associated disability.

Breakfast consumption is inversely associated with primary headaches in university students: The MEPHASOUS study.

OBJECTIVE: This study was conducted to examine the association between breakfast consumption pattern and primary headaches in a large population of university students. METHODS: This cross-sectional study was done on the MEPHASOUS dataset that contained the information of 83,677 university students, aged ≥18 years, from 28 provinces of Iran. Dietary intakes and breakfast consumption pattern were assessed using a validated self-administered dietary habits questionnaire. Primary headaches were determined according to the International Classification of Headache Disorders-3 (ICHD-3) criteria. Binary logistic regression in different adjusted models was used to assess the association between breakfast consumption and primary headaches. RESULTS: The mean age of participants was 21.50 ± 4.01. Primary headaches were prevalent among 9% of university students. A significant inverse association was seen between breakfast consumption and odds of primary headaches [odds ratio (OR): 0.57, 95 % confidence interval (CI): 0.51-0.62]. This association remained significant even after taking potential confounders into account; such that students who consumed breakfast frequently had 26 % lower odds of primary headaches compared with those who consumed it <1 day/week (OR: 0.74, 95 % CI: 0.65-0.85). Moreover, such a significant inverse association was observed in female students (OR: 0.54, 95 % CI: 0.49-0.61) as well as those with BMI < 25 kg/m2 (OR: 0.68, 95 % CI: 0.58-0.79). However, it became non-significant in male students and those with overweight or obesity. CONCLUSION: We found that frequent breakfast consumption is associated with a decreased odds of primary headaches in female students and those with BMI < 25 kg/m2. Further prospective studies are needed to confirm our findings.

The Role of Vitamin D in Primary Headache-from Potential Mechanism to Treatment.

Some studies have suggested a link between vitamin D and headache; however, the underlying physiological mechanisms are unclear. We aimed to summarize the available evidence on the relationship between vitamin D and the various subtypes of primary headaches, including migraines and tension-type headaches. All articles concerning the association between primary headache and vitamin D published up to October 2019 were retrieved by searching clinical databases, including: EMBASE, MEDLINE, PubMed, Google scholar, and the Cochrane library. All types of studies (i.e., observational, cross-sectional, case-control, and clinical trials) were included. We identified 22 studies investigating serum vitamin D levels in association with headaches. Eight studies also evaluated the effect of vitamin D supplementation on the various headache parameters. Among them, 18 studies showed a link between serum vitamin D levels and headaches, with the strongest connection reported between serum vitamin D levels and migraine. Overall, there is not enough evidence to recommend vitamin D supplementation to all headache patients, but the current literature indicates that it may be beneficial in some patients suffering headaches, mainly migraineurs, to reduce the frequency of headaches, especially in those with vitamin D deficiency.

Dairy consumption in relation to primary headaches among a large population of university students: The MEPHASOUS study.

AIM: To investigate the association between dairy consumption and primary headaches among a large population of university students. METHODS: Totally, 83,622 university students aged 18 years or older were included in the current cross-sectional study. Dietary intakes were assessed using a validated self-administered dietary habits questionnaire. Primary headaches were determined according to the International Classification of Headache Disorders-3 (ICHD-3) criteria. RESULTS: Totally, 9 % of participants suffered from primary headaches. A significant inverse association was observed between dairy consumption and odds of primary headaches (OR: 0.67, 95 % CI: 0.60-0.74). Such inverse association remained significant when potential confounders including demographic variables, physical activity, dietary factors, and BMI were taken into account; such that individuals in the highest category of dairy consumption were 19 % less likely to have primary headaches compared with those in the lowest category (OR: 0.81, 95 % CI: 0.72-0.92). Such an inverse association was also observed in women (OR: 0.79, 95 % CI: 0.68-0.93), but not in men. Stratified analysis based on body mass index revealed a significant inverse association between dairy consumption and primary headaches either in normal-weight individuals or those with overweight or obesity. CONCLUSION: We found that dairy consumption was inversely associated with primary headaches among university students.

Prevalence and burden of headache in children and adolescents in Austria - a nationwide study in a representative sample of pupils aged 10-18 years.

BACKGROUND: Headache disorders are highly prevalent worldwide, but not so well investigated in children and adolescents as in adults: few studies have included representative nationwide samples. No data exist for Austria until now. In a representative sample of children and adolescents in Austria, we estimated the prevalence and attributable burden of headache disorders, including the new diagnostic category of "undifferentiated headache" (UdH) defined as mild headache lasting less than 1 hour. METHODS: Within the context of a broader national mental health survey, children and adolescents aged 10-18 years were recruited from purposively selected schools. Mediated self-completed questionnaires included sociodemographic enquiry (gender, age, socioeconomic status, family constellation, residence [urban or rural] and migration background). Prevalence and attributable burden of all headache, UdH, migraine (definite plus probable), tension-type headache (TTH: definite plus probable) and headache on ≥15 days/month (H15+) were assessed using the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire for children and adolescents. Health-related quality of life (HrQoL) was assessed using the KIDSCREEN questionnaire. RESULTS: Of 7643 selected pupils, 3386 (44.3%) completed the questionnaires. The 1-year prevalence of headache was 75.7%, increasing with age and higher in girls (82.1%) than in boys (67.7%; p < 0.001). UdH, migraine, TTH and H15+ were reported by 26.1%, 24.2%, 21.6% and 3.0% of participants. Attributable burden was high, with 42% of those with headache experiencing restrictions in daily activities. Medication use (50% overall) was highest in H15+ (67%) and still considerable in UdH (29%). HrQoL was reduced for all headache types except UdH. Participants in single parent or patchwork families had a higher probability of migraine (respectively, OR 1.5, p < 0.001; OR 1.5, p < 0.01). Participants with a migration background had a lower probability of TTH (OR 0.7, p < 0.01). CONCLUSIONS: Headache disorders are both very common and highly burdensome in children and adolescents in Austria. This study contributes to the global atlas of headache disorders in these age groups, and corroborates and adds knowledge of the new yet common and important diagnostic category of UdH. The findings call for action in national and international health policies, and for further epidemiological research.

[Headache, abdominal and back pain in children and adolescents in Germany : Results from KiGGS Wave 2 and trends]. / Kopf­, Bauch- und Rückenschmerzen bei Kindern und Jugendlichen in Deutschland : Ergebnisse aus KiGGS Welle 2 und Trends.

BACKGROUND: Pain not only causes suffering in children and adolescents, but also leads to school absenteeism, medication intake, medical treatment, and an increased risk of recurrent pain in adulthood. OBJECTIVES: Based on data from the nationwide German Health Interview and Examination Survey for Children and Adolescents (KiGGS Wave 2, 2014-2017), the 3­month prevalence of recurrent headache, abdominal and back pain in girls and boys is reported, and is compared with the prevalence from the KiGGS baseline survey (2003-2006). The consequences of recurrent headache were also explored. MATERIALS AND METHODS: Data from >11,000 participants (KiGGS Wave 2) and from >12,000 (KiGGS baseline) participants aged between 3 and 17 years were analyzed. For 3­ to 10-year-olds, parents/guardians answered the questions, while 11- to 17-year-olds provided information themselves. RESULTS: In 3­ to 10-year-olds, recurrent abdominal pain was most prevalent, affecting one third of girls and one quarter of boys. Headache was the most frequent type of pain in 11- to 17-year-olds, affecting almost every second girl and about every third boy. The 3­month prevalence of recurrent headache, abdominal and back pain has increased in girls and boys, especially in the age groups 7 to 10 years and 11 to 13 years. Among recurrent headache sufferers, adolescents take medication almost twice as often as children. CONCLUSIONS: Headache, abdominal, and back pain are still and with increasing prevalence very common symptoms in children and adolescents in Germany. Their prevention requires a holistic view of children's health in the psychosocial living environment, and healthcare context.

Associations Between Daytime Sleepiness, Psychological Symptoms, Headache, and Abdominal Pain in Schoolchildren.

Daytime sleepiness and different symptoms are common problems affecting health and well-being of schoolchildren. This population-based cohort study included 568 children who were followed from ages 10 to 15 years. Daytime sleepiness, headache, abdominal pain, and psychological symptoms (depression, irritability or bad temper, nervousness, anxiety, and dejection) were assessed by self-administered questionnaires. The prevalence of frequent daytime sleepiness was 13% at the ages of 10 and 12 years and increased significantly up to 24% at the age of 15 (p < .0001). Daytime sleepiness as well as psychological symptoms were positively associated with headache and abdominal pain from ages 10 to 15 years. Headache in girls at the ages of 10 predicted the occurrence of headache at the age of 15. School nurses and other professionals need to understand the importance of a holistic evaluation of sleep and different symptoms in children. There is also a need for interventions targeting several co-occurring symptoms.

Utilization of complementary and alternative medicine and conventional medicine for headache or migraine during pregnancy: A cross-sectional survey of 1,835 pregnant women.

OBJECTIVES: Little is known about women's use of health services affected by headache or migraine during pregnancy. This paper directly addresses the research gap reporting on the healthcare utilization among Australian pregnant women experiencing headache or migraine. DESIGN AND SETTING: In this retrospective observational study, data on 1,835 Australian pregnant women were obtained from the nationally-representative Australian Longitudinal Study on Women's Health. Information on quality of life and health seeking behaviors regarding conventional medicine and complementary and alternative medicine providers was identified among these participants. Factors associated with healthcare use were analyzed using regression analyses. RESULTS: A total of 16% of the pregnant women surveyed experienced headache or migraine, and over 20% sought help from more than two types of healthcare practitioners for their headache or migraine. General practitioners (37.8%) were the most commonly consulted providers of pregnant women for their headache or migraine. Women with headache or migraine during pregnancy had worse health-related quality of life than those without. Education level and private health insurance status of pregnant women are the predictors of the use of healthcare practitioners for their management of headache or migraine (both p < 0.05). CONCLUSIONS: Headache or migraine during pregnancy significantly impacts upon pregnant women's quality of life. The use of multiple healthcare practitioners, including conventional medicine and complementary and alternative medicine practitioners, highlights the need for further research investigating health services utilization of pregnant women with headache or migraine in different severity and frequency to help inform effective and safe treatment.

Long-chain omega-3 fatty acids and headache in the U.S. population.

The objective of this study was to assess whether dietary intake of long-chain omega-3 polyunsaturated fatty acids (PUFAs) is associated with lower prevalence of headache in the U.S. POPULATION: This cross-sectional study used data for a nationally representative sample of 12,317 men and women aged ≥ 20 years participating in the National Health and Nutrition Examination Surveys of 1999-2004. Interviewers recorded self-report of severe headache or migraine in the past three months. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were quantified from 24-hour dietary recall using the U.S. Department of Agriculture National Nutrient Database. Serum concentration of C-reactive protein, a marker of inflammation and potential mediator of PUFA's analgesic properties, was quantified by latex-enhanced nephelometry. Multivariable generalized linear models estimated prevalence ratios (PR) with 95% confidence limits (CL) for severe headache or migraine adjusting for NHANES cycle, sociodemographic characteristics, body mass index and total energy intake. The unadjusted prevalence of severe headache or migraine was 22.0% (females 28.2%, males 15.5%). In multivariable analysis, greater intake of omega-3 PUFAs was associated with lower prevalence of severe headache or migraine: PR 0.94 (95% CL: 0.88, 0.99, p = 0.035) per log unit increase in EPA, and PR 0.94 (95% CL: 0.90, 0.99, p = 0.023) per log unit increase in DHA. The strength of association was greater for non-Mexican Hispanics than for other racial/ethnic groups but was not attenuated after adjustment for C-reactive protein. In conclusion, higher dietary intakes of EPA and DHA were associated with lower prevalence of headache supporting the hypothesis that omega-3 PUFAs may prevent or reduce headache.

Drugs for treating severe hypertension in pregnancy: a network meta-analysis and trial sequential analysis of randomized clinical trials.

AIMS: Several antihypertensive drugs are used in the treatment of severe hypertension in pregnancy. The present study is a network meta-analysis comparing the efficacy and safety of these drugs. METHODS: Electronic databases were searched for randomized clinical trials comparing drugs used in the treatment of severe hypertension in pregnancy. The number of women achieving the target blood pressure (BP) was the primary outcome. Doses required and time taken for achieving the target BP, failure rate, and incidences of maternal tachycardia, palpitation, hypotension, headache, and neonatal death and stillbirth were the secondary outcomes. Mixed treatment comparison pooled estimates were generated using a random-effects model. Odds ratios for the categorical and mean difference for the numerical outcomes were the effect estimates. RESULTS: Fifty-one studies were included in the systematic review and 46 in the meta-analysis. No significant differences in the number of patients achieving target BP was observed between any of the drugs. Diazoxide [-15 (-20.6, -9.4)], nicardipine [-11.8 (-22.3, -1.2)], nifedipine/celastrol [-19.3 (-27.4, -11.1)], nifedipine/vitamin D [-17.1 (-25.7, -9.7)], nifedipine/resveratrol [-13.9 (-22.6, -5.2)] and glyceryl trinitrate [-33.8 (-36.7, -31)] were observed to achieve the target BP (in minutes) more rapidly than hydralazine. Nifedipine required fewer doses than hydralazine for achieving the target BP. Glyceryl trinitrate and labetalol were associated with fewer incidences of tachycardia and palpitation respectively than hydralazine. Trial sequential analysis concluded adequate evidence for hydralazine and nifedipine compared with labetalol. Moderate quality of evidence was observed for direct comparison estimate between labetalol and hydralazine but was either low or very low for other comparisons. CONCLUSION: The present evidence suggests similar efficacy between nifedipine, hydralazine and labetalol in the treatment of severe hypertension in pregnancy. Subtle differences may exist in their safety profile. The evidence is inadequate for other drugs.

Headache in mitochondrial disorders.

Headache is a prominent feature in mitochondrial disorders (MIDs) but no comprehensive overview is currently available. This review aims at summarising and discussing findings concerning type, frequency, pathogenesis, and treatment of headache in MIDs. The most frequent headache types in MIDs are migraine and migraine-like headache (MLH). MLH is classified as secondary headache. More rarely, tension-type headache, trigemino-autonomic headache, or different secondary headaches can be found. Migraine or MLH may manifest with or without aura. MLH is frequently associated with an ongoing or previous stroke-like episode (SLE) or a seizure but may also occur independently of other neurological features. MLH may be associated with prolonged aura or visual phenomena after headache. Except for MLH, treatment of headache in MIDs is not at variance from other causes of headache. Beyond the broadly accepted subtype-related headache treatment, diet, cofactors, vitamins, and antioxidants may provide a supplementary benefit. Midazolam, l-arginine, or l-citrulline may be beneficial for MLH. The pathogenesis of headache in MIDs largely remains unsolved. However, since migraine and MLH respond both to triptanes, a shared pathomechanism is likely. In conclusion, migraine and MLH are the prominent headache types in MIDs. MLH may or may not be associated with current or previous SLEs. MLH is pathophysiologically different from migraine and requires treatment at variance from that of migraine with aura.

Prospective daily diary study reporting of any and all symptoms in healthy adults in Pakistan: prevalence and response.

OBJECTIVES: Prevalence of symptoms in everyday life and how people respond to these symptoms is little studied outside Western culture and developed countries. We sought to use modified diary methods to explore the prevalence of and responses to symptoms in Pakistan. DESIGN: Prospective daily survey of symptoms and response. SETTING: 8 cities across four provinces in Pakistan. PARTICIPANTS: Stratified intercept in each city to recruit 153 participants of which 151 completed. PRIMARY AND SECONDARY OUTCOME MEASURES: Each day for 30 days, participants were prompted by text message (short message service (SMS)) to complete a symptom diary. On days where symptoms were experienced, participants also reported how they responded. Prevalence was adjusted to population age and gender distributions. RESULTS: 92% of participants experienced symptoms (adjusted prevalence 94%, 95% CI 91% to 97%), with musculoskeletal pain (83%, adj. 84%, 95% CI 84% to 90%) and respiratory symptoms (75%, adj. 77%, 95% CI 71% to 84%) the most prevalent types of symptoms. Self-medication and use of home remedies and traditional medicines were the most common responses. Seeking professional help or using conventional medicine were less common, and self-medication responses included the use of antibiotics without prescription. The range of home remedies and traditional medicines was very diverse. CONCLUSIONS: While symptom experience in Pakistan was similar to Western countries, home remedies were much more frequently used to respond to symptoms. Understanding how people respond and manage their experience of symptoms outside formal healthcare is important for designing effective policy and interventions, and this needs to be understood within the broader context including the cultural and economic setting, the health system and other structural determinants of health.

Long-term safety of glycopyrrolate/eFlow® CS in moderate-to-very-severe COPD: Results from the Glycopyrrolate for Obstructive Lung Disease via Electronic Nebulizer (GOLDEN) 5 randomized study.

BACKGROUND: The use of long-acting bronchodilators is an essential component of the management of chronic obstructive pulmonary disease (COPD). The GOLDEN 5 Phase III, randomized, active-controlled, open-label study was conducted to evaluate the long-term safety and tolerability of a nebulized glycopyrrolate formulation (SUN-101) delivered via the investigational eFlow® Closed System (eFlow® CS) nebulizer in subjects with moderate-to-very-severe COPD. METHODS: Subjects were randomized in a 4:3 ratio to nebulized glycopyrrolate 50 µg twice daily (BID) or tiotropium 18 µg once daily (OD) and treated for 48 weeks. Subjects represented the general COPD population with real-world characteristics including severe disease, presence of comorbidities, and receiving background COPD therapy. Primary endpoints were the incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, and discontinuations due to TEAEs. Secondary endpoints included the number of subjects with major adverse cardiovascular events (MACE); change from baseline in trough forced expiratory volume in 1 s (FEV1), and assessment of patient-reported outcomes. RESULTS: 1086 subjects received at least one dose of study drug. The overall incidence of TEAEs was comparable for subjects treated with glycopyrrolate (69.4%) or tiotropium (67.0%). Serious TEAEs occurred at similar rates in both treatment groups (glycopyrrolate, 12.3%; tiotropium, 10.5%). The most frequent TEAEs were COPD exacerbation/worsening and cough. Discontinuation due to TEAEs was higher in the glycopyrrolate group (10.0%) than the tiotropium group (2.8%) and related, in part, to the open-label study design, prior use of long-acting muscarinic antagonists and aerosol-airway interactions. Fewer subjects in the glycopyrrolate group experienced MACE (glycopyrrolate, n = 3 [0.5%]; tiotropium, n = 8 [1.7%]). Nebulized glycopyrrolate treatment resulted in improvements in trough FEV1 that were maintained over 48 weeks. Patient-reported health outcomes showed improvements, supporting the increases in trough FEV1. CONCLUSIONS: Treatment with nebulized glycopyrrolate was well tolerated over 48 weeks with the most common adverse events being COPD worsening and cough. The overall and cardiac safety and tolerability profile and improvements in pulmonary function and patient-reported health outcomes support the use of nebulized glycopyrrolate as a maintenance treatment for moderate-to-very-severe COPD. CLINICAL TRIAL REGISTRATION NUMBER: NCT02276222.