Early indicators of primary brain tumours: a population-based study with 10 years' follow-up.

BACKGROUND AND PURPOSE: To improve diagnoses of primary brain tumours, knowledge about early indicators is needed. Nationwide Danish health registries were used to conduct a population-based case-control study including all persons diagnosed with a primary brain tumour between 2005 and 2014 in Denmark. METHODS: All 5135 adults diagnosed with a primary brain tumour in the Danish Cancer Registry were matched to 19 572 general population comparisons from the Danish Civil Registration System. Conditional logistic regression analyses were applied to estimate age- and multivariable-adjusted odds ratios (ORs) for the occurrence of a primary brain tumour up to 10 years after hospital diagnoses or prescription of medications related to nervous system diseases and mental and behavioural disorders. RESULTS: Increased odds for primary brain tumour after nervous system diseases and mental and behavioural disorders manifested up to 10 years before tumour diagnosis were found. Increased odds were seen especially for hospital contacts for inflammatory nervous system diseases [OR 11.3; 95% confidence interval (CI) 6.5-19.7], epilepsy (OR 9.0; 95% CI 7.6-10.7) and antiepileptic medications (OR 3.6; 95% CI 3.2-4.0), whilst antidementia medications provided a strong, protective association for primary brain tumours (OR 0.5; 95% CI 0.3-0.8). CONCLUSIONS: Sub-groups of patients diagnosed with or being prescribed certain medications targeting nervous system diseases and mental and behavioural disorders may be at increased risk of being diagnosed with a primary brain tumour. Further studies should disentangle the potential underlying common pathogenetic pathways. The results are important for the development of systematic clinical approaches to ensure early diagnosis of primary brain tumours.

Genetically determined high activity of IL-12 and IL-18 in ulcerative colitis and TLR5 in Crohns disease were associated with non-response to anti-TNF therapy.

Anti-tumour necrosis factor-α (TNF-α) is used for treatment of severe cases of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. A recent study indicated that genetically determined high activity of pro-inflammatory cytokines, including interleukin-1ß (IL-1ß), IL-6 and interferon gamma (IFN-γ), are associated with non-response to anti-TNF therapy. Using a candidate gene approach, 21 functional single-nucleotide polymorphisms (SNPs) in 14 genes in the Toll-like receptors, the inflammasome and the IFNG pathways were assessed in 482 and 256 prior anti-TNF naïve Danish patients with CD and UC, respectively. The results were analysed using logistic regression (adjusted for age and gender). Eight functional SNPs were associated with anti-TNF response either among patients with CD (TLR5 (rs5744174) and IFNGR2 (rs8126756)), UC (IL12B (rs3212217), IL18 (rs1946518), IFNGR1 (rs2234711), TBX21 (rs17250932) and JAK2 (rs12343867)) or in the combined cohort of patient with CD and UC (IBD) (NLRP3 (rs10754558), IL12B (rs3212217) and IFNGR1 (rs2234711)) (P<0.05). Only the association with heterozygous genotype of IL12B (rs3212217) (OR: 0.24, 95% CI: 0.11-0.53, P=0.008) among patients with UC withstood Bonferroni correction for multiple testing. In conclusion, Our results suggest that SNPs associated with genetically determined high activity of TLR5 among patients with CD and genetically determined high IL-12 and IL-18 levels among patients with UC were associated with non-response. Further studies will evaluate whether these genes may help stratifying patients according to the expected response to anti-TNF treatment.

Associations between functional polymorphisms in the NFκB signaling pathway and response to anti-TNF treatment in Danish patients with inflammatory bowel disease.

Antitumor necrosis factor-α (TNF-α) is used for treatment of severe cases of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. Genetic markers may predict individual response to anti-TNF therapy. Using a candidate gene approach, 39 mainly functional single nucleotide polymorphisms (SNPs) in 26 genes regulating inflammation were assessed in 738 prior anti-TNF-naive Danish patients with IBD. The results were analyzed using logistic regression (crude and adjusted for age, gender and smoking status). Nineteen functional polymorphisms that alter the NFκB-mediated inflammatory response (TLR2 (rs3804099, rs11938228, rs1816702, rs4696480), TLR4 (rs5030728, rs1554973), TLR9 (rs187084, rs352139), LY96 (MD-2) (rs11465996), CD14 (rs2569190), MAP3K14 (NIK) (rs7222094)), TNF-α signaling (TNFA (TNF-α) (rs361525), TNFRSF1A (TNFR1) (rs4149570), TNFAIP3(A20) (rs6927172)) and other cytokines regulated by NFκB (IL1B (rs4848306), IL1RN (rs4251961), IL6 (rs10499563), IL17A (rs2275913), IFNG (rs2430561)) were associated with response to anti-TNF therapy among patients with CD, UC or both CD and UC (P ⩽ 0.05). In conclusion, the results suggest that polymorphisms in genes involved in activating NFκB through the Toll-like receptor (TLR) pathways, genes regulating TNF-α signaling and cytokines regulated by NFκB are important predictors for the response to anti-TNF therapy among patients with IBD. Genetically strong TNF-mediated inflammatory response was associated with beneficial response. In addition, the cytokines IL-1ß, IL-6 and IFN-γ may be potential targets for treating patients with IBD who do not respond to anti-TNF therapy. These findings should be examined in independent cohorts before these results are applied in a clinical setting.

Interrelations between migraine and tension-type headache in the general population.

In a cross-sectional epidemiological survey of a general population, headache disorders were diagnosed according to a structured interview and a neurological examination using the criteria of the International Headache Society. The prevalences and sex distribution of the primary headache disorders were assessed, and characteristics of and interrelationships between different types of headache were analyzed. Severity and frequency of migraine attacks were not correlated, indicating that the migraine attack is an all-or-none phenomenon triggered with an individually variable threshold. Tension-type headache, in contrast, showed increasing severity with increasing frequency, indicating that it is a graded phenomenon. In the previous year, 6% had migraine without aura (previously called "common migraine") and 4% had migraine with aura (previously called "classic migraine"); 63% had episodic tension-type headache and 3% chronic tension-type headache. In women, migraine without aura was twice as prevalent as migraine with aura; in men, an opposite trend emerged. In migraine without aura, pain was more severe than in migraine with aura. Tension-type headache in migraineurs was not significantly more prevalent than in nonmigraineurs and, except for greater frequency and severity, it did not deviate nosographically from pure tension-type headache. Our results support the contention that migraine and tension-type headache are distinct entities, contradict the so-called continuum-severity model, and indicate that the terms combination headache, mixed headache, and interval headache should be avoided.

Symptomatic and nonsymptomatic headaches in a general population.

We assessed the lifetime prevalences of headache disorders in a cross-sectional epidemiologic survey of a representative 25- to 64-year-old general population. We classified the headaches on the basis of a clinical interview and a physical and neurologic examination using the operational diagnostic criteria of the International Headache Society. Lifetime prevalence of idiopathic stabbing headache was 2%, of external compression headache 4%, and of cold stimulus headache 15%. Benign cough headache, benign exertional headache, and headache associated with sexual activity each occurred in 1%. Lifetime prevalence of hangover headache was 72%, of fever headache 63%, and of headache associated with disorders of nose or sinuses 15%. Headaches associated with severe structural lesions were rare. External compression headache, fever headache, headache associated with metabolic disorders, and headache associated with disorders of nose or sinuses all showed significant female preponderance. The symptomatic headaches and headaches unassociated with structural lesions were more prevalent among migraineurs. In subjects with tension-type headache, only hangover headache was overrepresented. There was no association between the headache disorders and abnormal routine blood chemistry or arterial hypertension. In women with migraine, however, diastolic blood pressure was significantly higher than in women without migraine.

The impact of migraine: Epidemiology, risk factors, and co-morbidities.

In Western countries, recent community-based studies of migraine prevalence using standardized diagnostic criteria give 1-year prevalence estimates of around 10 to 12%. The prevalence of migraine is age- and gender-dependent. Age at onset of migraine is earlier in boys than in girls. Migraine is two to three times more common in women than in men, with peak prevalence occurring during mid-life in both sexes. Current evidence also indicates that migraine prevalence is higher in Caucasians than in Africans or Asians. In some migraineurs, attacks may be frequent or prolonged, leading to considerable pain and disability. There has been much debate over predisposing factors, which are not sufficient by themselves to cause an attack, as well as precipitants, which immediately precede the attack. However, convincing data are lacking for most of these. Significant associations have been reported between migraine and certain psychiatric disorders, epilepsy, and stroke in women under the age of 45. These findings demonstrate that migraine is common, has a substantial impact on sufferers, and may be associated with other disorders.

Migraine prevalence. A review of population-based studies.

Obtaining accurate and reliable information on the prevalence of migraine is essential to understanding the burden it places on society. Although the epidemiology of headache has been described in more than 50 population-based studies, only 24 of these have described the gender- and age-specific prevalence of migraine. Essentially five different case definitions have been used in these studies. Variation in the prevalence of migraine among studies is largely due to differences in case definition and in the age and gender distribution of study populations. Among four recent studies that used the diagnostic criteria of the International Headache Society (IHS), a coherent picture emerges. The prevalence of migraine is approximately 6% among men and 15 to 17% among women. Prevalence varies by age, increasing to about age 40 years and declining thereafter in both men and women. The gender ratio also appears to vary by age, increasing from menarche to about age 42 years and declining thereafter. Although the use of the IHS criteria has resulted in a more coherent picture across population-based studies, efforts must be made to assess the reliability and validity of these criteria in population-based samples.

Epidemiology of headache in a general population--a prevalence study.

We present the first prevalence study of specific headache entities using the operational diagnostic criteria of the International Headache Society. One thousand 25-64 year old men and women, who lived in the western part of Copenhagen County were randomly drawn from the Danish National Central Person Registry. All subjects were invited to a general health examination focusing on headache and including: a self-administered questionnaire concerning sociodemographic variables, a structured headache interview and a general physical and neurological examination. The participation rate was 76%. Information about 79% of the non-participants showed a slightly differing headache prevalence which was not quantitatively important. The following results in participants are therefore representative of the total sample. The lifetime prevalences of headache (including anybody with any form of headache), migraine, and tension-type headache were 93, 8 and 69% in men; and 99, 25 and 88% in women. The point prevalence of headache was 11% in men and 22% in women. Prevalence of migraine in the previous year was 6% in men and 15% in women and the corresponding prevalences of tension-type headache were 63 and 86%. Differences according to sex were significant with a male: female ratio of 1:3 in migraine, and 4:5 in tension-type headache. The prevalence of tension-type headache decreased with increasing age, whereas migraine showed no correlation to age within the studied age interval. Headache disorders are extremely prevalent and represent a major health problem, which merits increased attention.

Migraine and tension-type headache in a general population: psychosocial factors.

In a cross-sectional study of headache disorders in a representative general population, the prevalence of migraine and tension-type headache was assessed in relation to various psychosocial factors. The random sample comprised 1000 25-64 year old men and women of whom 740 attended the investigation. The headache disorders were classified on the basis of a clinical interview, a physical and a neurological examination using the operational diagnostic criteria of the International Headache Society. None of the sociodemographic variables: marital status, cohabitation, educational level, occupational category or employment status were significantly associated with migraine or tension-type headache. In the univariate analyses tension-type headache was significantly associated with a high Neuroticism score on the Eysenck Personality Questionnaire whereas migraine was not. Variables on work conditions and psychosocial factors significantly associated with the headache disorders in univariate analyses were subjected to multivariate analysis. Migraine was significantly associated with exposure to chemicals and fumes at work in women and poor self-appraisal of health in men. In the univariate analyses tension-type headache was significantly related to a series of psychosocial variables. In the multivariate analyses it remained associated with a current feeling of fatigue in both sexes, time-pressure at work in women and exposure to fumes in men.

Prevalence and sex-ratio of the subtypes of migraine.

BACKGROUND: The aim of this study was to provide the prevalence and sex-ratio of subtypes of migraine diagnosed by neurological interview according to the criteria of the International Headache Society. METHODS: In all, 3000 males and 1000 females aged 40 years were randomly selected from the Danish population. They received a mailed questionnaire regarding migraine. The questionnaire response rate was 87%. People with self-reported migraine and a random sample of those reporting no migraine were invited to a headache interview, and a physical and a neurological examination. Those not reacting to the invitation were interviewed by telephone. Participation at the interview was 87%. Kappa was 0.77 validating self-reported migraine in the questionnaire against the diagnosis of the clinical interview. RESULTS: Lifetime prevalences of migraine without aura, migraine with aura, migraine aura without headache, and migrainous disorder were 8%, 4%, 1% and 1% in males and 16%, 7%, 3% and 2% in females. Overall lifetime prevalence of any type of migraine was 18%; 12% in males and 24% in females. This is lower than the sum of the prevalences since migraine diagnoses are not mutually exclusive. The male:female ratios of migraine without aura, migraine with aura, migraine aura without headache, and migrainous disorder were approximately 1:2. CONCLUSIONS: Migraine is more prevalent than previously thought. There was a significant preponderance in females of all the subtypes of migraine except migrainous disorder.

Impact of headache on sickness absence and utilisation of medical services: a Danish population study.

STUDY OBJECTIVE: The aim was to study the extent and type of health service utilisation, medication habits, and sickness absence due to the primary headaches. DESIGN: This was a cross sectional epidemiological survey of headache disorders in a general population. Headache was diagnosed according to a structured interview and a neurological examination using the criteria of the International Headache Society. SETTING: A random sample of 25-64 year-old individuals was drawn from the Danish National Central Person Registry. All subjects were living in the Copenhagen County. PARTICIPANTS: 740 subjects participated (76% of the sample); 119 had migraine and 578 had tension type headache. MAIN RESULTS: Among subjects with migraine 56% had, at some time, consulted their general practitioner because of the migraine. The corresponding percentage among subjects with tension type headache was 16. One or more specialists had been consulted by 16% of migraine sufferers and by 4% of subjects with tension type headache. The consultation rates of chiropractors and physiotherapists were 5-8%. Hospital admissions and supplementary laboratory investigations due to headache were rare (< 3%). Half of the migraine sufferers and 83% of subjects with tension type headache in the previous year had managed with at least one type of drug in the current year. Acetylsalicylic acid preparations and paracetamol were the most commonly used analgesics. Prophylaxis of migraine was used by 7%. In the preceding year 43% of employed migraine sufferers and 12% of employed subjects with tension type headache had missed one or more days of work because of headache. Most common was 1-7 days off work. The total loss of workdays per year due to migraine in the general population was estimated at 270 days per 1000 persons. For tension type headache the corresponding figure was 820. Women were more likely to consult a practitioner than men, whereas no significant sex difference emerged as regards absenteeism from work. CONCLUSIONS: The impact of the headache disorders on work performance in the general population is substantial, and the disorders merit increased attention.

Epidemiology of migraine.

The introduction of operational diagnostic criteria for the primary headaches in 1988 has provided new opportunities for comprehensive epidemiologic headache research. In recent years, several studies on the epidemiology of migraine have emerged. This review deals with methodologic considerations and provides a snapshot of the main findings in these studies. The importance of epidemiologic studies in clarifying the natural history of migraine is elucidated.

Classification of primary headaches.

In 1988, the International Headache Society (IHS) classification committee published operational diagnostic criteria for the primary headaches and a broad range of other headache disorders. These criteria have been translated into more than ten languages, providing uniform terminology for clinical practice, multinational clinical trials, and biologic and epidemiologic research. The criteria have also been evaluated in a number of field studies intended to address their generalizability, exhaustiveness, reliability, and validity. In the present publication the IHS criteria for migraine and tension-type headache are presented.

Prevalence of oromandibular dysfunction in a general population.

The prevalence of oromandibular dysfunction was studied in 735 subjects from a random sample population of 1,000 subjects aged 25 to 64 years. A diagnosis of oromandibular dysfunction was based on criteria established by the International Headache Society, as a subgroup to tension-type headache. Tenderness in pericranial or jaw muscles was not included. The most common symptoms were clenching (22%) and grinding of teeth (15%). The most common sign was irregular jaw movements on opening and closing (29%). The ratio of men to women for most symptoms and signs ranged from 2:3 to 1:3. This study serves as a base in evaluating the importance of oromandibular dysfunction as a causative factor for tension-type headache.

[Prevalence and sex distribution of different forms of migraine]. / Praevalens og kønsfordeling af de forskellige former for migraene.

The aim of this study was to provide prevalence and sex-ratio of subtypes of migraine diagnosed by neurological interview according to the criteria of the International Headache Society. In all, 3000 males and 1000 females aged 40 years were randomly selected from the Danish population. They received a mailed questionnaire regarding migraine. The questionnaire response rate was 87%. People with self-reported migraine and a random sample of those reporting no migraine were invited to a headache interview, and a physical and a neurological examination. Those not reacting to the invitation were interviewed by telephone. Participation in the interview was 87%. Kappa was 0.77 validating self-reported migraine in the questionnaire against the diagnosis of the clinical interview. Lifetime prevalences of migraine without aura, migraine with aura, migraine aura without headache, and migrainous disorder were 8%, 4%, 1% and 1% in males and 16%, 7%, 3% and 2% in females. Overall lifetime prevalence of any type of migraine was 18%, 12% in males and 24% in females. This is lower than the sum of the prevalences since migraine diagnoses are not mutually exclusive. The male:female ratios of migraine without aura, migraine with aura, migraine aura without headache, and migrainous disorder were approximately 1:2.

Secular changes in health care utilization and work absence for migraine and tension-type headache: a population based study.

OBJECTIVE: To assess changes in consultation rates, medication use and work absences due to migraine and tension-type headache (TTH) in Denmark over a 12-year period. METHODS: Surveys of the general population in 1989 and 2001. Medical doctors conducted all headache diagnostic interviews based on ICDH-I and II. The participation rate was 76% (740) in 1989 and 74% (711) in 2001. Headache status was categorized as pure migraine, pure frequent TTH (frequent episodic or chronic TTH), coexisting migraine and frequent TTH, and healthy subjects (no primary headache or only infrequent TTH). RESULTS: Headache-related consultation rates (OR = 1.6 (1.1-2.2)), especially specialist consultations (OR = 3.6 (2.3-5.6)), increased for all headache groups. Use of prescription medication because of headache increased moderately (OR = 2.1 (1.1-3.9)) while the use of prophylactic medication was stable (OR = 1.1 (0.3-4.0)). Both headache-related (OR = 1.1 (0.7-1.7)) and overall (OR = 0.9 (0.7-1.2)) absence rates were largely unchanged. Headache-related absence rates were higher for subjects with both headache types (OR = 7.5 (4.3-13.1)) or with pure migraine (OR = 3.6 (2.0-6.6)) than for subjects with frequent TTH alone. Triptans users had higher migraine headache frequency and tended to have higher absence rates than non-users. Overall absence rates were higher for subjects with both headache types (OR = 2.3 (1.3-4.0)) or with frequent TTH (OR = 1.9 (1.4-2.7)) than for healthy subjects. Pure migraine was not associated with higher overall absence rates (OR = 1.0 (0.6-1.6)). CONCLUSION: Despite an increase in headache consultation rates and in use of prescription medication and triptans, no improvement in work absence rates was observed. Consultations, medication use, and absence rates were highest for individuals with both migraine and frequent TTH.