No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Safety and usability factors in development of a novel, automated treatment device for acute migraine
Abstract
A recent discovery revealed a therapeutic effect of external ear insufflation in the treatment of acute migraine headache. This finding led to the development of a treatment method and device for its delivery to human subjects. The challenges associated with developing an automated device, designed for unsupervised public use, included mitigation of risks associated with potential bodily harm as well as promoting the optimal user experience in terms of comfort and ease of use. The primary risk associated with this form of treatment device is the potential for compromise of the tympanic membrane due to accidental over-pressure at the external ear canal. User comfort in migraineurs poses challenges primarily driven by the fact that many report their primary headache pain is frequently associated with heightened sensitivity to sensory stimuli, such as light (photophobia), sound (phonophobia) and touch (allodynia). We took a number of measures to mitigate safety risks, promote consistency of the therapeutic effect, and improve user comfort. When the proprietary, automated, variable pulse insufflator device was used in a clinical setting with 30 subjects, all of whom were reporting for treatment while suffering from acute migraine, it brought about a 67% complete pain resolution rate at the 2-hour, post-treatment end-point. Users reported a consistently favorable and very comfortable experience with the device and treatment method. Overall, results appeared to demonstrate a promising, novel treatment option for acute migraine with appealing safety profile as an alternative or adjunct to drug treatment.
Pancreatic cancer presents a unique challenge for the development of effective oncotherapies. The tumor microenvironment (TME) of this type of tumor typically contains a dense desmoplastic barrier composed of aberrant extracellular matrix proteins, as well as an acidic hypoxic and necrotic core. Additionally, the immune system surrounding this type of tumor has often been suppressed by the TME. Hence, choosing the correct model of the tumor microenvironment within which to test a potential anti-cancer therapy is a critical experimental design decision. While the typical solid tumor contains a complex microenvironment including both phenotypic and genotypic heterogeneity, the methods used to model this disease state often do not reflect this complexity. This simplistic approach may have contributed to stagnant five-year survival rates experienced over the past four decades. Oncolytic bacteria, a class of bacteria with the innate ability to seek and destroy solid tumors has been revived from historical anecdotes in an attempt to overcome these challenges. Regardless of the promise of oncolytic bacteria, accurate assessment of their potential requires choosing the proper tumor model. This study explores the impact of cancer cell lines co-cultures with Wild-Type C. novyi to establish the efficacy of this oncolytic bacteria in a monolayer culture.
Atypical brainstem modulation of pain might contribute to changes in sensory processing typical of migraine. The study objective was to investigate whether migraine is associated with brainstem structural alterations that correlate with this altered pain processing.
MRI T1-weighted images of 55 migraine patients and 58 healthy controls were used to: (1) create deformable mesh models of the brainstem that allow for shape analyses; (2) calculate volumes of the midbrain, pons, medulla and the superior cerebellar peduncles; (3) interrogate correlations between regional brainstem volumes, cutaneous heat pain thresholds, and allodynia symptoms.
Migraineurs had smaller midbrain volumes (healthy controls = 61.28 mm³, SD = 5.89; migraineurs = 58.80 mm³, SD = 6.64; p = 0.038), and significant (p < 0.05) inward deformations in the ventral midbrain and pons, and outward deformations in the lateral medulla and dorsolateral pons relative to healthy controls. Migraineurs had a negative correlation between ASC-12 allodynia symptom severity with midbrain volume (r = − 0.32; p = 0.019) and a positive correlation between cutaneous heat pain thresholds with medulla (r = 0.337; p = 0.012) and cerebellar peduncle volumes (r = 0.435; p = 0.001).
Migraineurs with greater symptoms of allodynia have smaller midbrain volumes and migraineurs with lower heat pain thresholds have smaller medulla and cerebellar peduncles. The brainstem likely plays a role in altered sensory processing in migraine and brainstem structure might reflect severity of allodynia and hypersensitivity to pain in migraine.
Migraine is the most common disabling brain disorder. Chronic migraine, a condition characterized by the experience of migrainous headache on at least 15 days per month, is highly disabling. Patients with chronic migraine present to primary care, are often referred for management to secondary care, and make up a large proportion of patients in specialist headache clinics. Many patients with chronic migraine also have medication overuse, defined as using a compound analgesic, opioid, triptan or ergot derivative on at least 10 days per month. All doctors will encounter patients with chronic headaches. A basic working knowledge of the common primary headaches, and a rational manner of approaching the patient with these conditions, allows a specific diagnosis of chronic migraine to be made quickly and safely, and by making this diagnosis one opens up a substantial number of acute and preventive treatment options. This article discusses the current state of management of chronic migraine.
The aim of this article is to investigate the vascular safety profile of triptans through an analysis of the United States Food and Drug Administration Adverse Event Reporting System (FDA_AERS) database with a special focus on serious and unexpected adverse events.
A CASE/NON-CASE analysis was performed on the reports entered in the FDA_AERS from 2004 to 2010: CASES were reports with at least one event included in the MedDRA system organ classes 'Cardiac disorder' or 'Vascular disorders', whereas NON-CASES were all the remaining reports. Co-reported cardiovascular drugs were used as a proxy of cardiovascular risk and the adjusted reporting odds ratio (adj.ROR) with 95% confidence intervals (95% CI) was calculated. Disproportionality signals were defined as adj.ROR value >1. Adverse events were considered unexpected if not mentioned on the relevant label.
Among 2,131,688 reports, 7808 concerned triptans. CASES were 2593 among triptans and 665,940 for all other drugs. Unexpected disproportionality signals were found in the following high-level terms of the MedDRA hierarchy: 'Cerebrovascular and spinal necrosis and vascular insufficiency' (103 triptan cases), 'Aneurysms and dissections non-site specific' (15), 'Pregnancy-associated hypertension' (10), 'Reproductive system necrosis and vascular insufficiency' (3).
Our analysis revealed three main groups of unexpected associations between triptans and serious vascular events: ischaemic cerebrovascular events, aneurysms and artery dissections, and pregnancy-related vascular events. A case-by-case assessment is needed to confirm or disprove their plausibility and large-scale analytical studies should be planned for risk rate estimation. In the meantime, clinicians should pay special attention to migraine diagnosis and vascular risk assessment before prescribing a triptan, also promptly reporting any unexpected event to pharmacovigilance systems.
Background: Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs).
Methods: Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis.
Findings: Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350 000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient -0·37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa.
Conclusions: Rates of YLDs per 100 000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world.
Funding: Bill & Melinda Gates Foundation.
To describe the prevalence, sociodemographic profile, and the burden of migraine in the United States in 1999 and to compare results with the original American Migraine Study, a 1989 population-based study employing identical methods.
A validated, self-administered questionnaire was mailed to a sample of 20 000 households in the United States. Each household member with severe headache was asked to respond to questions about symptoms, frequency, and severity of headaches and about headache-related disability. Diagnostic criteria for migraine were based on those of the International Headache Society. This report is restricted to individuals 12 years and older.
Of the 43 527 age-eligible individuals, 29 727 responded to the questionnaire for a 68.3% response rate. The prevalence of migraine was 18.2% among females and 6.5% among males. Approximately 23% of households contained at least one member suffering from migraine. Migraine prevalence was higher in whites than in blacks and was inversely related to household income. Prevalence increased from aged 12 years to about aged 40 years and declined thereafter in both sexes. Fifty-three percent of respondents reported that their severe headaches caused substantial impairment in activities or required bed rest. Approximately 31% missed at least 1 day of work or school in the previous 3 months because of migraine; 51% reported that work or school productivity was reduced by at least 50%.
Two methodologically identical national surveys in the United States conducted 10 years apart show that the prevalence and distribution of migraine have remained stable over the last decade. Migraine-associated disability remains substantial and pervasive. The number of migraineurs has increased from 23.6 million in 1989 to 27.9 million in 1999 commensurate with the growth of the population. Migraine is an important target for public health interventions because it is highly prevalent and disabling.
To evaluate the disability profile and patterns of treatment and health care use for chronic migraine (CM) in the general population, in contrast to episodic migraine.
We identified 24,000 headache sufferers, drawn from more than 165,000 individuals representative of the US population. This sample has been followed up with annual surveys using validated questionnaires for the diagnosis of episodic migraine and CM. As a part of the survey, subjects were asked to report the specific medications currently used for their most severe headaches, as well as level of satisfaction with treatment.
Our sample consisted of 520 individuals with CM and 9,424 with episodic migraine. Over a 3-month period, more than half of the individuals with CM missed at least 5 days of household work, compared with 24.3% of those with episodic migraine (p < 0.001). Reduced productivity in household work for at least 5 days over 3 months was reported by 58.1% and 18.2% (p < 0.001); at least 5 days of missed family activities was reported by 36.9% and 9.5% (p < 0.001). The majority of the CM sufferers (87.6%) had previously sought care to discuss their headaches with a health professional. Migraine-specific acute treatments were used by 31.6% of respondents with CM and 24.8% with episodic migraine. Around 48% of the individuals with CM were satisfied with their acute therapies. Just 33.3% of those with CM were currently using preventive medications.
Chronic migraine (CM) is more disabling than episodic migraine in the population. Although most individuals with CM sought medical care for this disorder, the majority did not receive specific acute or preventive medications.
Eardrum (tympanic membrane) rupture in humans and animals in relation to various blast pressure-time patterns was reviewed. There were few systematic studies on eardrum rupture as a consequence of blast overpressure. Most reports did not describe the area of the eardrum destroyed. The peak overpressures required to produce a 50% incidence of eardrum rupture (P50) were summarized. Most of the animal data pertained to dogs. The highest P50 for dogs, 296 kPa, was associated with smooth-rising overpressure. For complex wave patterns occurring inside open shelters subjected to nuclear blasts, the P50 was 205 kPa. For fast-rising blasts in a shock tube it was 78 kPa, and 105 kPa for statically applied pressures. The duration of the overpressure was not a factor unless it was very short. The influence of the orientation of the head to the oncoming blast was demonstrated. An ear facing the blast may receive reflected overpressures several times that for one side-on to the blast. An ear on the downstream side of the head was exposed to about the same overpressure as the side-on ear. A P50 for humans of 100 kPa and a threshold of 35 kPa has been used widely in blast criteria. A recent study suggests a threshold (P1) of about 20 kPa, and gives the overpressures required to produce minor, moderate, and major eardrum ruptures. These data were presented in the form of curves showing the overpressures as a function of duration required to inflict a P1 and a P50 of eardrum rupture of the three levels of severity.
Common pain conditions appear to have an adverse effect on work, but no comprehensive estimates exist on the amount of productive time lost in the US workforce due to pain.
To measure lost productive time (absence and reduced performance due to common pain conditions) during a 2-week period.
Cross-sectional study using survey data from the American Productivity Audit (a telephone survey that uses the Work and Health Interview) of working adults between August 1, 2001, and July 30, 2002.
Random sample of 28 902 working adults in the United States.
Lost productive time due to common pain conditions (arthritis, back, headache, and other musculoskeletal) expressed in hours per worker per week and calculated in US dollars.
Thirteen percent of the total workforce experienced a loss in productive time during a 2-week period due to a common pain condition. Headache was the most common (5.4%) pain condition resulting in lost productive time. It was followed by back pain (3.2%), arthritis pain (2.0%), and other musculoskeletal pain (2.0%). Workers who experienced lost productive time from a pain condition lost a mean (SE) of 4.6 (0.09) h/wk. Workers who had a headache had a mean (SE) loss in productive time of 3.5 (0.1) h/wk. Workers who reported arthritis or back pain had mean (SE) lost productive times of 5.2 (0.25) h/wk. Other common pain conditions resulted in a mean (SE) loss in productive time of 5.5 (0.22) h/wk. Lost productive time from common pain conditions among active workers costs an estimated 61.2 billion dollars per year. The majority (76.6%) of the lost productive time was explained by reduced performance while at work and not work absence.
Pain is an inordinately common and disabling condition in the US workforce. Most of the pain-related lost productive time occurs while employees are at work and is in the form of reduced performance.
A recent health economic survey in Europe has suggested that migraine is the costliest among the neurological disorders. According to many studies, migraine and other disorders lead to widespread suffering, reduction of quality of life, and marked impairment of participation, both in work and social activities. The present literature survey was made in order to summarize what is known on the subject, as a preparation for a EU-supported study to assess the impact in several EU countries with similar methodology and the same research instrument. Previous studies have yielded relatively reliable data only for migraine, whereas the impact of tension-type headache is virtually unknown or only very incompletely known for most dimensions of headache impact. Some data do suggest, however, that this headache may be as important from a health economic and a public health perspective as migraine. In future studies it is important to get population-based data from various countries relevant for estimation of indirect (mostly absenteeism from work and reduced working efficiency when having headache) and direct costs (related to medication, consultations, investigations and hospitalisations). Also, the impact on ability to get education and participate in the workforce is very relevant, as is the impact on love life and family planning. The quality of life of headache patients should be measured by validated instruments. To get a complete picture, one should also ask about the effect on the life of partners and children, and on the possible impact even when headache-free (e.g. fear of the next attack).
Visual disturbances in migraineurs, such as visual aura, are typically episodic, that is, associated with the headache attack, and overlaid by head pain and other symptoms that impact the patient. In some patients, however, visual symptoms are dominant due to frequency (migraine aura status), duration (persistent migraine aura and other persistent positive visual phenomena), or complexity (visual snow syndrome). These syndromes are more rare and challenging to classify in clinical practice resulting in a lack of systematic studies on pathophysiology and treatment. We aim at describing clinical features and pathophysiological concepts of typical migraine aura with a focus on cortical spreading depression and differentiation from non-typical migraine aura. Additionally, we discuss nomenclature and the specifics of migraine aura status, persistent migraine aura, persistent positive visual phenomena, visual snow, and other migrainous visual disturbances. The term migraine with prolonged aura might be a useful bridge between typical aura and persistent aura. Further studies would be necessary to assess whether a return of the classification category eventually helps diagnosing or treating patients more effectively. A practical approach is presented to help the treating physician to assign the correct diagnosis and to choose a medication for treatment that has been successful in case reports of these rare but disabling conditions.
Background:
Although triptans are widely used in the acute management of migraine, there is uncertainty around the comparative efficacy of triptans among each other and vs non-triptan migraine treatments. We conducted systematic reviews and network meta-analyses to compare the relative efficacy of triptans (alone or in combination with other drugs) for acute treatment of migraines compared with other triptan agents, non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid (ASA), acetaminophen, ergots, opioids, or anti-emetics.
Methods:
The Cochrane Library, MEDLINE, and EMBASE were searched for randomized controlled trials that compared triptans (alone or in combination with other drugs) with placebo-controlled or active migraine treatments. Study selection, data extraction, and quality assessment were completed independently by multiple reviewers. Outcome data were combined and analyzed using a Bayesian network meta-analysis. For each outcome, odds ratios, relative risks, and absolute probability of response were calculated.
Results:
A total of 133 randomized controlled trials met the inclusion criteria. Standard dose triptans relieved headaches within 2 hours in 42 to 76% of patients, and 2-hour sustained freedom from pain was achieved for 18 to 50% of patients. Standard dose triptans provided sustained headache relief at 24 hours in 29 to 50% of patients, and sustained freedom from pain in 18 to 33% of patients. Use of rescue medications ranged from 20 to 34%. For 2-hour headache relief, standard dose triptan achieved better outcomes (42 to 76% response) than ergots (38%); equal or better outcomes than NSAIDs, ASA, and acetaminophen (46 to 52%); and equal or slightly worse outcomes than combination therapy (62 to 80%). Among individual triptans, sumatriptan subcutaneous injection, rizatriptan ODT, zolmitriptan ODT, and eletriptan tablets were associated with the most favorable outcomes.
Interpretation/conclusions:
Triptans are effective for migraine relief. Standard dose triptans are associated with better outcomes than ergots, and most triptans are associated with equal or better outcomes compared with NSAIDs, ASA, and acetaminophen. Use of triptans in combination with ASA or acetaminophen, or using alternative modes of administration such as injectables, may be associated with slightly better outcomes than standard dose triptan tablets.
Background
Public drug coverage for triptan medications varies across jurisdictions in Canada, which may lead to differences in usage patterns and patient risk for medication overuse headache.Methods
We conducted a population-based, cross-sectional analysis of publicly funded triptan use in seven provinces across Canada from January 1, 2012 to December 31, 2012. All patients who had filled at least one prescription for a triptan during the study period were included. We defined quantity limits of 6, 12, and 18 triptan units per month to assess the prevalence of high volumes of triptan use, which may place patients at risk for medication overuse headaches, and compared this prevalence between provinces with different funding restrictions.ResultsWe identified 14,085 publicly funded users of triptans in 2012 in the seven provinces studied, 82.5% of whom were aged less than 65 years (N = 11,631). The prevalence of triptan use ranged substantially by province, from 0.04% in Ontario to a maximum of 1.0% in Manitoba (P < .001). Furthermore, the percentage of patients in each province using more than 6, 12, or 18 units per month differed significantly between provinces (P < .001). In particular, the percentage of patients treated with more than 6 units per month ranged from as low as 2.1% in Saskatchewan to 43.8% in Ontario.Conclusions
Differing public drug reimbursement criteria for triptans may be one contributing factor that has led to our observation of considerable variation in both prevalence of triptan prescribing and potential overuse of these medications. We offer that monthly quantity limits may be considered as a tool to decrease risks for medication overuse headache.
Background and objectives:
The US National Center for Health Statistics, which is part of the Centers for Disease Control, conducts ongoing public health surveillance activities. The US Armed Forces also maintains a comprehensive database of medical information. We aimed to identify the most current prevalence estimates of migraine and severe headache in the United States adult civilian and active duty service populations from these national government surveys, to assess stability of prevalence estimates over time, and to identify additional information pertinent to the burden and treatment of migraine and other severe headache conditions.
Methods:
We searched for the most current publicly available summary statistics from the National Ambulatory Medical Care Survey, the National Hospital Ambulatory Medical Care Survey, and the National Health Interview Survey (NHIS). Summary data from the Defense Medical Surveillance System were also obtained, and PubMed was also searched for publications reporting summary statistics based on these studies. Data were abstracted, double-checked for accuracy, and summarized over time periods and as a function of demographic variables.
Results:
14.2% of US adults 18 or older reported having migraine or severe headache in the previous 3 months in the 2012 NHIS. The overall age-adjusted 3-month prevalence of migraine in females was 19.1% and in males 9.0%, but varied substantially depending on age. The prevalence of migraine was highest in females 18-44, where the 3-month prevalence of migraine or severe headache was 23.5%. The 3-month prevalence of migraine or severe headache has remained relatively stable over the period of2005-2012, with an average prevalence of 20.2% in females, 9.4% in males, and 14.9% overall [corrected]. During this time, the average female to male sex ratio for migraine or severe headache was 2.17. The unadjusted 1-year prevalence of migraine in active duty US military service members varied from 1% to 1.9% between 1998 and 2010, ranging from 0.7% to 1.2% in males and 3.5% to 6% in females. The 1-year prevalence of "other headache" in this military population ranged from a low of 1.9% in 2003 to a high of 3% in 2010. Headache or pain in the head was the fourth leading cause of visits to the emergency department (ED) in 2009-2010, accounting for 3.1% of all ED visits. Across all ambulatory care settings, migraine accounted for 0.5% of all visits and other headache presentations for 0.4% of all ambulatory care visits. 52.8% of all visits for migraine occurred in primary care settings, 23.2% in specialty outpatient settings, and 16.7% in EDs. In 2010, opioids were administered at 35% of ED visits for headache, while triptans were administered in only 1.5% of visits.
Conclusions:
This report summarizes the most recent government statistics on the prevalence and burden of migraine and severe headache in the US civilian and active duty military populations. The prevalence of migraine headaches is high, affecting roughly 1 out of every 7 Americans annually, and has remained relatively stable over the last 8 years. Migraine and headache are leading causes of outpatient and ED visits and remain an important public health problem, particularly among women during their reproductive years.
Background
Though nausea is a cardinal feature of migraine, its influence on migraine progression has not been evaluated. This article aims to evaluate persistent frequent headache-related nausea (PFN) in persons with episodic migraine (EM) as a predictor of new onset chronic migraine (CM).Methods
This prospective cohort study uses data from the 2007 and 2008 American Migraine Prevalence and Prevention study surveys to identify subgroups with episodic International Classification of Headache Disorders, 2nd edition defined migraine and either PFN or no or low frequency nausea (NLFN). PFN was defined by the presence of nausea ≥ half the time in both 2007 and 2008. NLFN was defined by nausea that was present < half the time, rarely or never in both years. Persons were considered CM in 2009 if they met symptom criteria for migraine with headaches ≥15 days per month over the preceding 3 months. Univariate differences in demographics for PFN and NLFN were evaluated with chi-square. Binary logistic regressions were performed hierarchically to assess progression to CM in 2009 as a function of nausea status in 2007 and 2008. The initial model included sociodemographic variables only. Subsequent models added the following variables in a hierarchical manner: migraine symptom severity composite score (to control for the impact of other headache features), headache-related disability, depression, opioid use, and an interaction term for nausea status and opioid use. Odds ratios (OR) and 95% confidence intervals (CI) contrasted PFN and NLFN on the rate of progression to CM in 2009.ResultsThere were 3182 respondents with headache symptom and frequency data available for all 3 years of the analysis. PFN was found in 43.7% (1389) of respondents, and 3.4% (47) progressed to CM. NLFN was seen in 27.6% (877) of the EM group, and 1.5% progressed to CM. In comparison with the NLFN group, PFN was more common in females (P < .001) and Caucasians (P < .06). PFN was associated with a doubling of the risk of progression to CM after adjusting for sociodemographic variables (OR 2.09, 95% CI 1.11-3.91, P = .022). Adding the symptom composite score and headache-related disability covariates to the model attenuated the association slightly (OR 2.00, 95% CI 1.03-3.87, P = .04). With the addition of depression, the association fell just below statistical significance but progression risk with PFN remained at nearly two-fold that of the NLFN group (OR 1.90, 95% CI 0.98-3.71, P = .059). When opioid use and the nausea by opioid use interaction are added to the final model, the significant effect and the doubling of CM progression risk for those with PFN was retained (OR 2.24, 95% CI 1.07-4.70, P = .033).Conclusions
Persistent frequent nausea is common (43.7%) among persons with episodic migraine. After controlling for sociodemographics, migraine symptom severity, headache-related disability, depression, and opioid medication use, migraineurs with frequent nausea that persisted for 2 years of study were twice as likely to progress to CM compared to those with no or low frequency nausea. The study is limited by self-reports of symptom and headache frequency data and the use of modified diagnostic criteria. Additional prospective research is needed to confirm study findings. Persistent frequent nausea could be a marker for the risk of progression to CM or it could be in the causal pathway.
Purpose of review:
Migraine attacks consist of head pain and hypersensitivities to somatosensory, visual, auditory, and olfactory stimuli. Investigating how the migraine brain simultaneously processes and responds to multiple incoming stimuli may yield insights into migraine pathophysiology and migraine symptoms.
Recent findings:
The presence and intensity of hypersensitivity to one stimulus type are positively associated with the presence and intensity of hypersensitivities to other stimuli and to headache intensity. Furthermore, exposure to visual, auditory, and olfactory stimuli can trigger migraine attacks. These relationships suggest a role for multisensory integration in migraine.
Summary:
Multisensory integration of somatosensory, visual, auditory, and olfactory stimuli by the migraine brain may be an important concept for understanding migraine.
Background:
This is an updated version of the original Cochrane review published in Issue 4, 2010 (Kirthi 2010). Migraine is a common, disabling condition and a burden for the individual, health services and society. Many sufferers choose not to, or are unable to, seek professional help and rely on over-the-counter analgesics. Co-therapy with an antiemetic should help to reduce nausea and vomiting commonly associated with migraine headaches.
Objectives:
To determine the efficacy and tolerability of aspirin, alone or in combination with an antiemetic, compared to placebo and other active interventions in the treatment of acute migraine headaches in adults.
Search methods:
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Relief Database, ClinicalTrials.gov, and reference lists for studies through 10 March 2010 for the original review and to 31 January 2013 for the update.
Selection criteria:
We included randomised, double-blind, placebo-controlled or active-controlled studies, or both, using aspirin to treat a migraine headache episode, with at least 10 participants per treatment arm.
Data collection and analysis:
Two review authors independently assessed trial quality and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk and numbers needed to treat (NNT) or harm (NNH) compared to placebo or other active treatment.
Main results:
No new studies were found for this update. Thirteen studies (4222 participants) compared aspirin 900 mg or 1000 mg, alone or in combination with metoclopramide 10 mg, with placebo or other active comparators, mainly sumatriptan 50 mg or 100 mg. For all efficacy outcomes, all active treatments were superior to placebo, with NNTs of 8.1, 4.9 and 6.6 for 2-hour pain-free, 2-hour headache relief, and 24-hour headache relief with aspirin alone versus placebo, and 8.8, 3.3 and 6.2 with aspirin plus metoclopramide versus placebo. Sumatriptan 50 mg did not differ from aspirin alone for 2-hour pain-free and headache relief, while sumatriptan 100 mg was better than the combination of aspirin plus metoclopramide for 2-hour pain-free, but not headache relief; there were no data for 24-hour headache relief.Adverse events were mostly mild and transient, occurring slightly more often with aspirin than placebo.Additional metoclopramide significantly reduced nausea (P < 0.00006) and vomiting (P = 0.002) compared with aspirin alone.
Authors' conclusions:
We found no new studies since the last version of this review. Aspirin 1000 mg is an effective treatment for acute migraine headaches, similar to sumatriptan 50 mg or 100 mg. Addition of metoclopramide 10 mg improves relief of nausea and vomiting. Adverse events were mainly mild and transient, and were slightly more common with aspirin than placebo, but less common than with sumatriptan 100 mg.
The aim of this review was to summarize population-based studies reporting prevalence and/or incidence of chronic migraine (CM) and to explore variation across studies. A systematic literature search was conducted. Relevant data were abstracted and estimates were subdivided based on the criteria used in each study. Sixteen publications representing 12 studies were accepted. None presented data on CM incidence. The prevalence of CM was 0-5.1%, with estimates typically in the range of 1.4-2.2%. Seven studies used Silberstein-Lipton criteria (or equivalent), with prevalence ranging from 0.9% to 5.1%. Three estimates used migraine that occurred ≥15 days per month, with prevalence ranging from 0 to 0.7%. Prevalence varied by World Health Organization region and gender. This review identified population-based studies of CM prevalence, although heterogeneity across studies and lack of data from certain regions leaves an incomplete picture. Future studies on CM would benefit from an International Classification of Headache Disorders consensus diagnosis that is clinically appropriate and operational in epidemiological studies.
Though noise induced hearing loss is no longer the most frequent occupational disease in the Federal Republic of Germany, the environmental pollution by the product "noise" in our technical and industrialized world has not been reduced. On the contrary, the situation is worsened by the rising influence of leisure noise. To avoid occupational hearing loss, the "Noise Injury Prevention Code" issued by the insurers would demand wearing personal ear protection, e.g. ear plugs, if ambient noise levels are above 85 dB(A). But there are working places in which such equipment would have precisely the adverse effect, because one of the reasons for possible damage to hearing is radio communication. In military aircraft cockpits for example noise exposure measurements showed ambient noise levels above 90 dB(A) during regular flight service nearly all the time. To be able to understand radio traffic in spite of the noisy environment, the headphone volume must be raised above the noise of the engines. The use of ear plugs can only be of limited value. Whereas pilots with normal hearing show only little impairment of speech intelligibility, those with noise-induced hearing losses show substantial impairment that varies in proportion to their hearing loss. Communication abilities may be drastically reduced which may compromise the reliability of radio traffic. To avoid compromising air security one has to demand a noise protection system which allows to reduce ambient noise levels without disturbing speech intelligibility in the inevitable radio communication. Nowadays active noise cancelling (ANC) systems by electronic compensation in different ways provide effective protection against noise induced hearing loss.(ABSTRACT TRUNCATED AT 250 WORDS)
Headache disorders constitute a public-health problem of enormous proportions, with an impact on both the individual sufferer and society. Epidemiological knowledge is required to quantitate the significance of these disorders. The effects on individuals can be assessed by examining prevalence, distribution, attack frequency and duration, and headache-related disability. The socio-economic burden includes both direct costs associated with health care utilization and costs associated with missed work due to sickness absence or reduced efficiency. The individual and socio-economic burden of headaches is substantial. Headache disorders deserve more attention, especially concerning strategies leading to adequate primary prevention, diagnosis and treatment.
Tympanometry [Relevant Paper
American Speech-Language-Hearing Association ("ASHA"). "Tympanometry [Relevant Paper]". Available from
www.asha.org/policy/RP1988-00027/, 1988.