Aims
To evaluate the crossover design in migraine preventive treatment trials by assessing dropout rate, and potential period and carryover effect in four placebo-controlled randomized controlled ...trials (RCTs).
Methods
In order to increase statistical power, the study combined data from four different RCTs performed from 1998 to 2015 at St. Olavs Hospital, Norway. Among 264 randomized patients, 120 received placebo treatment before and 144 after active treatment.
Results
Only 26 (10%) dropped out during the follow-up period of 30–48 weeks, the majority (
n
= 19) in the first 12 weeks. No period effect was found, since the treatment sequence did not influence the responder rate after placebo treatment, being respectively for migraine 30.5% vs. 27.4% (
p
= 0.59) and for headache 25.0% vs. 24.8% (
p
= 0.97, Chi-square test) when placebo occurred early or late. Furthermore, no carryover effect was identified, since the treatment sequence did not influence the treatment effect (difference between placebo and active treatment). There was no significant difference between those who received active treatment first and those who received placebo first with respect to change in number of days per 4 week of headache (− 0.9 vs. -1.3,
p
= 0.46) and migraine (− 1.2 vs. -0.9,
p
= 0.35, Student’s t-test).
Conclusions
Summary data from four crossover trials evaluating preventive treatment in adult migraine showed that few dropped out after the first period. No period or carryover effect was found. RCT studies with crossover design can be recommended as an efficient and cost-saving way to evaluate potential new preventive medicines for migraine in adults.
Developmental dysplasia of the hip (DDH) is a congenital condition affecting 2–3% of all infants. DDH increases the risk of osteoarthritis, is the cause of 30 % of all total hip arthroplasties ...(THAs) in adults <40 years of age and can result in loss of life quality. Our aim was to explore the genetic background of DDH in order to improve diagnosis, management and longterm outcome.
We used the large, ongoing, longitudinal Trøndelag Health Study (HUNT) database. Case definition was based on ICD-9/-10 diagnoses of DDH, or osteoarthritis secondary to DDH. Analyses were performed using SAIGE software, with covariates including sex, batch, birth year and principal components. We included only single nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) ≥ 0.01, R2≥ 0.8 and Hardy-Weinberg equilibrium (HWE) P-value ≥ 0.0001. Significance level was set at p < 5 × 10−8. Meta-analysis using data from DDH and primary osteoarthritis genome-wide association studies (GWASs) was done using METAL software. The study was approved by the regional ethical committee.
Analysis included 69,500 individuals, of which 408 cases, and 8,531,386 SNPs. Two SNPs near COL11A1 were significantly associated with DDH; rs713162 (β = −0.43, SE = 0.07, p = 8.4 × 10−9) and rs6577334 (β = −0.43, SE = 0.08, p = 8.9 × 10−9). COL11A1 has previously been associated with acetabular dysplasia and osteoarthritis. Meta-analysis supported previous GWAS findings of both DDH and primary osteoarthritis.
This large, genome-wide case-control study indicates an association between COL11A1 and DDH and is an important contribution to investigating the etiology of DDH, with further research needed.
Bias with regard to participation in epidemiological studies can have a large impact on the generalizability of results. Our aim was to investigate the direction and magnitude of potential bias by ...comparing health-related factors among participants and non-participants in a MRI-study based on HUNT, a large Norwegian health survey.
Of 14,033 individuals aged 50-65, who had participated in all three large public health surveys within the Norwegian county of Nord-Trøndelag (HUNT 1, 2 and 3), 1,560 who lived within 45 minutes of travel from the city of Levanger were invited to a MRI study (MRI-HUNT). The sample of participants in MRI-HUNT (n = 1,006) were compared with those who were invited but did not participate (n = 554) and with those who were eligible but not invited (n = 12,473), using univariate analyses and logistic regression analyses adjusting for age and education level.
Self-reported health did not differ between the three groups, but participants had a higher education level and were somewhat younger than the two other groups. In the adjusted multivariate analyses, obesity was consistently less prevalent among participants. Significant differences in blood pressure and cholesterol were also found.
This is the first large population-based study comparing participants and non-participants in an MRI study with regard to general health. The groups were not widely different, but participants had a higher level of education, and were less likely to be obese and have hypertension, and were slightly younger than non-participants. The observed differences between participants and non-invited individuals are probably partly explained by the inclusion criterion that participants had to live within 45 minutes of transport to where the MRI examination took place. One will expect that the participants have somewhat less brain morphological changes related to cardiovascular risk factors than the general population. Such consequences underline the crucial importance of evaluation of non-participants in MRI studies.
Cross-sectional study. Between 1995 and 1997, all inhabitants aged 20 years and older in the Nord-Trøndelag county in Norway were invited to fill in 2 different questionnaires at different times ...concerning musculoskeletal complaints.
To estimate the incidence of musculoskeletal complaints lasting at least 15 days during the past month at 9 different anatomic sites in relation to age and gender.
Incidence data of musculoskeletal complaints are scarce.
Individuals who reported no musculoskeletal complaints lasting for at least 3 months during the past year were defined as a population at risk and were subjects for the incidence estimates.
Of 49,720 individuals (response rate 53.5%), the overall age-adjusted incidence of musculoskeletal complaints was 7.9% (95% confidence interval 7.5% to 8.2%) (women: 7.1%, men: 8.7%). The highest incidence rate was found for the lower back (women: 2.3%, men: 2.8%). The incidence of spinal complaints declined after age 60 years, whereas the incidence of complaints in lower limbs and distal upper limbs tended to be stable or increase in the older age groups.
In this, to our knowledge, first large-scale population-based study evaluating the incidence of musculoskeletal complaints, nearly 1 in 12 individuals reported musculoskeletal complaints lasting at least 15 days during the past month.
The Catechol-O-methyltransferase (COMT) gene contains a functional polymorphism, Val158Met, that has been found to influence human pain perception. In one study fibromyalgia was less likely among ...those with Val/Val genotype.
In the 1995-97 Nord-Trøndelag Health Study (HUNT), the association between Val/Met polymorphism at the COMT gene and chronic musculoskeletal complaints (MSCs) was evaluated in a random sample of 3017 individuals.
The distribution of the COMT Val158Met genotypes and alleles were similar between controls and the twelve different chronic MSCs groups. Even when the Met/Met and Val/Met genotypes were pooled, the distribution of the Val/Val genotype and other genotypes were similar between controls and the chronic MSCs groups.
In this population-based study, no significant association was found between Val/Met polymorphism at the COMT gene and chronic MSCs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To evaluate the life-time prevalence of self reported whiplash injury and the relationship to chronic musculoskeletal complaints (MSCs) and headache in a large unselected adult population.
Between ...1995 and 1997, all inhabitants 20 years and older in Nord-Trondelag county in Norway were invited to a comprehensive health survey. Out of 92,936 eligible for participation, a total of 59,104 individuals (63.6%) answered the question about whiplash injury (whiplash). Among these, 46,895 (79.3%) responded to the questions of musculoskeletal complaints and headache.
The total life-time prevalence of self reported whiplash injury was 2.9%, for women 2.7% and for men 3.0%. There was a significant association between self reported whiplash injury and headache (OR = 2.1; 95% CI 1.8-2.4), and chronic MSCs (OR = 3.3; 95% CI 2.8-3.8), evident for all ten anatomical sites investigated. The association was most pronounced for those with a combination of headache and chronic MSC for both men (OR = 4.8; 95% CI 3.6-6.2) and women (OR = 5.2; 95% CI 3.7-7.1).
Subjects with self reported whiplash injury had significantly more headache and musculoskeletal complaints than those without, and may in part be due to selective reporting. The causal mechanism remains unclear and cannot be addressed in the present study design.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
This systematic review focuses on chronic migraine patients with medication overuse headache using, respectively, topiramate, botulinum toxin type A, and human monoclonal antibodies ...targeting calcitonin gene-related peptide or its receptor.
Methods
A systematic search was conducted in the databases CENTRAL, MEDLINE, Embase and Web of Science until May 2022. We included randomized controlled trials reporting the outcomes of change in monthly headache/migraine days, ≥50% response rates and change in medication overuse status. Studies were excluded if response rates were not reported. Risk of bias assessment was performed using the Cochrane RoB2 tool. The quality of evidence for outcomes across included studies was evaluated according to the five factors outlined in Cochrane GRADE approach.
Findings
The initial search resulted in 1599 records. Following screening, 10 studies met our inclusion criteria, while seven studies with sufficient data were included in the meta-analysis. Studies assessing Botulinum toxin type A included 1139 patients and showed a mean reduction in headache frequency by 1.92 days per month compared to placebo (−1.92; 95% CI −2.68 to −1.16). Studies assessing human monoclonal antibodies included 1982 patients, and showed significant positive effect compared to placebo for all measured outcomes. The overall odds ratio for the ≥50% response rate was 2.90 (95% CI, 2.23 to 3.78). No significant difference was observed in the frequency of adverse effect for both Botulinum toxin type A and low dose of human monoclonal antibodies compared to placebo. There is currently insufficient evidence to determine the impact of topiramate in chronic migraine patients with medication overuse headache.
Interpretation
Botulinum toxin type A and human monoclonal antibodies targeting calcitonin gene-related peptide receptor were beneficial in reducing monthly migraine days and ≥50% response rate, but uncertainties remained for Botulinum toxin type A regarding response rate. The effect size for human monoclonal antibodies was greater with relatively lower drop-out rate. High-quality randomized trials are required to evaluate the effect of topiramate in chronic migraine patients with medication overuse headache.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Data from some population-based studies have indicated an increased risk of atrial fibrillation (AF) among patients with migraine, particularly among individuals with migraine with aura. ...The present study aimed to assess the association between primary headache disorders and AF.
Methods
In a population-based 9-year follow-up design, we evaluated the questionnaire-based headache diagnosis, migraine and tension-type headache (TTH) included, collected in the Trøndelag Health Study (HUNT3) conducted in 2006–2008, and the subsequent risk of AF in the period until December 2015. The population at risk consisted of 39,340 individuals ≥20 years without AF at HUNT3 baseline who answered headache questionnaire during HUNT3. The prospective association was evaluated by multivariable Cox proportional hazard models with 95% confidence intervals (CIs).
Results
Among the 39,340 participants, 1524 (3.8%) developed AF during the 9-year follow up, whereof 91% of these were ≥55 years. In the multivariable analyses, adjusting for known confounders, we did not find any association between migraine or TTH and risk of AF. The adjusted hazard ratios (HRs) were respectively 0.84 (95% CI = 0.64–1.11) for migraine, 1.16 (95% CI = 0.86–1.27) for TTH and 1.04 (95% CI = 0.86–1.27) for unclassified headache. However, in sensitivity analyses of individuals aged ≥55 years, a lower risk of AF was found for migraine (HR = 0.53; 95% CI = 0.39–0.73).
Conclusions
In this large population-based study, no increased risk of AF was found among individuals with migraine or TTH at baseline. Indeed, among individuals aged ≥55 years, migraine was associated with a lower risk for AF.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 ...controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.
The relationship between diabetes mellitus (DM) and chronic musculoskeletal complaints (MSCs) is unclear. The aim of this study was to investigate the association between DM, non-fasting glucose and ...chronic MSCs defined as pain and/or stiffness >or= 3 months during the past year in the general adult population.
The results were based on cross-sectional data from 64,785 men and women (aged >or= 20 years) who participated in the Nord-Trøndelag Health Survey, which included 1,940 individuals with known DM. Associations were assessed using multiple logistic regression, estimating prevalence odds ratio (OR) with 95% confidence intervals (CIs).
High non-fasting glucose was associated with a lower prevalence of chronic MSCs compared to a low glucose level. DM was associated with higher prevalence of chronic MSCs, in particular chronic widespread MSCs. In the multivariate analysis, adjusting for glucose level, BMI, age, gender and physical activity, chronic widespread MSCs was 1.6 times more likely (OR = 1.6, 95% CI 1.2-2.2) among individuals < 60 years of age with DM than among those without DM. The association between chronic widespread MSCs and DM was most evident among the group of individuals aged < 60 years with either type 2 DM or unclassified DM (OR = 1.8, 95% CI 1.3-2.5).
In this cross-sectional study a high non-fasting glucose was associated with lower prevalence of chronic MSCs. Among individuals with known DM chronic widespread MSCs were more likely.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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