The methodology of population surveys of headache prevalence,burden and cost: Principles and recommendations from the Global Campaign against Headache

The global burden of headache is very large, but knowledge of it is far from complete and needs still to be gathered. Published population-based studies have used variable methodology, which has influenced findings and made comparisons difficult. Among the initiatives of the Global Campaign against Headache to improve and standardize methods in use for cross-sectional studies, the most important is the production of consensus-based methodological guidelines. This report describes the development of detailed principles and recommendations. For this purpose we brought together an expert consensus group to include experience and competence in headache epidemiology and/or epidemiology in general and drawn from all six WHO world regions. The recommendations presented are for anyone, of whatever background, with interests in designing, performing, understanding or assessing studies that measure or describe the burden of headache in populations. While aimed principally at researchers whose main interests are in the field of headache, they should also be useful, at least in parts, to those who are expert in public health or epidemiology and wish to extend their interest into the field of headache disorders. Most of all, these recommendations seek to encourage collaborations between specialists in headache disorders and epidemiologists. The focus is on migraine, tension-type headache and medication-overuse headache, but they are not intended to be exclusive to these. The burdens arising from secondary headaches are, in the majority of cases, more correctly attributed to the underlying disorders. Nevertheless, the principles outlined here are relevant for epidemiological studies on secondary headaches, provided that adequate definitions can be not only given but also applied in questionnaires or other survey instruments.     

The price of pain in chronic rhinosinusitis

Background

Chronic rhinosinusitis (CRS) is associated with productivity losses exceeding US$13 billion annually. Although pain is well known to significantly affect patient productivity in other diseases, its economic impact on CRS‐related lost productivity has not been examined. The objective of this study was to determine whether CRS‐related facial pain correlates with lost productivity in patients with CRS.

Methods

Seventy patients with CRS were enrolled in a cross‐sectional investigation. Patients with a history of systemic inflammatory disease, ciliary dysfunction, chronic pain syndromes, migraines, and fibromyalgia were excluded. Pain was measured using the Brief Pain Inventory Short Form (BPI‐SF) and the Short‐Form McGill Pain Questionnaire (SF‐MPQ). Presenteeism, absenteeism and lost work, and household and overall productivity were assessed. Regression analysis was performed to assess potential confounders, including depression.

Results

Pain as measured with BPI‐SF and SF‐MPQ total scores correlated with all domains of productivity losses. Overall, lost productivity was significantly correlated with pain (R range, 0.354‐0.485; p < 0.001). Presenteeism (reduced work efficiency) had the highest correlation with all of the overall pain scores (R range, ?0.366 to ?0.515; p < 0.001). Lost household productivity time was the least affected by pain (R range, 0.267‐0.389; p < 0.05). These correlations remained statistically significant after regression analysis, which accounted for depression (p < 0.05).

Conclusion

A significant correlation exists between CRS‐related facial pain and productivity losses in patients with CRS that is independent of depression. Facial pain has the strongest correlation with presenteeism, which is the main driver of productivity losses and indirect costs associated with CRS.

     

Incorporation of N-acetylneuraminic acid into Haemophilus somnus lipooligosaccharide (LOS): enhancement of resistance to serum and reduction of LOS antibody binding

Haemophilus somnus isolates from cases of thrombotic meningoencephalitis, pneumonia, and other disease sites are capable of undergoing a high rate of phase variation in the oligosaccharide component of their lipooligosaccharides (LOS). In contrast, the LOS of commensal strains isolated from the normal reproductive tract phase vary little or not at all. In addition, the LOS of H. somnus shares conserved epitopes with LOS from Neisseria gonorrhoeae, Haemophilus influenzae, and other species that can incorporate sialic acid into their LOS. We now report that growth of disease isolates of H. somnus with CMP-N-acetylneuraminic acid (CMP-NeuAc) or NeuAc added to the medium resulted in incorporation of NeuAc into the LOS. However, NeuAc was not incorporated into the LOS of commensal isolates and one disease isolate following growth in medium containing CMP-NeuAc or NeuAc. Sialylated LOS was detected by an increase in the molecular size or an increase in the amount of the largest-molecular-size LOS electrophoretic bands, which disappeared following treatment with neuraminidase. Sialylated LOS could also be detected by reactivity with Limax flavus agglutinin lectin, which is specific for sialylated species, by dot blot assay; this reactivity was also reversed by neuraminidase treatment. H. somnus strain 2336 LOS was found to contain some sialic acid when grown in medium lacking CMP-NeuAc or NeuAc, although supplementation enhanced NeuAc incorporation. In contrast strain 738, an LOS phase variant of strain 2336, was less extensively sialylated when the growth medium was supplemented with CMP-NeuAc or NeuAc, as determined by electrophoretic profiles and electrospray mass spectrometry. The sialyltransferase of H. somnus strain 738 was confirmed to preferentially sialylate the Gal(beta)-(1-3)-GlcNAc component of the lacto-N-tetraose structure by capillary electrophoresis assay. Enhanced sialylation of the strain 2336 LOS inhibited the binding of monoclonal antibodies to LOS by enzyme immunoassay and Western blotting. Furthermore, sialylation of the LOS enhanced the resistance of H. somnus to the bactericidal action of antiserum to LOS. Sialylation and increased resistance to killing by normal serum also occurred in a deletion mutant that was deficient in the terminal Gal-GlcNAc disaccharide. LOS sialylation may therefore be an important virulence mechanism to protect H. somnus against the host immune system.     

Rib defects in patterns of multiple malformations: a retrospective review and phenotypic analysis of 47 cases

Rib anomalies may occur in isolation, as well as in association with abnormalities of vertebral segmentation and multi-system malformations. Specific entities include the VACTERL and MURCS associations, spondylocostal dysostosis, and spondylothoracic dysostosis. The relative significance of rib anomalies in other lesser known syndromes and associations remains unclear. To document the diagnoses and related defects in patients with rib anomalies as part of broader pattern of anomalies, we retrospectively identified 47 cases from a hospital population, and evaluated specific costal findings and associated birth defects. In our study, fusion was the most common pattern of rib anomaly (72%), followed by bifid (28%) and hypoplastic ribs (26%). Unrecognized patterns of multiple congenital anomalies (MCA) and VACTERL association were the commonest specific diagnoses with a frequency of 30 and 28%, respectively. An associated vertebral defect was found in 72% of the patients. Of those with no vertebral anomaly, the combinations of "rib and cardiac defects alone" and "rib and renal defects alone" were seen in one-third of the patients (4/13). Both the occurrence and type of rib anomaly were helpful in defining certain syndromes and enhanced the likelihood of identifying related malformations.     

Pattern and predictors of weight gain during pregnancy among HIV-1-infected women from Tanzania

Progression of HIV disease is often accompanied by weight loss and wasting. Gestational weight gain is a strong determinant of maternal and neonatal outcomes; however, the pattern and predictors of weight gain during pregnancy among HIV-positive women are unknown. We obtained monthly anthropometric measurements in a cohort of 957 pregnant women from Tanzania who were HIV infected. We estimated the weekly rate of weight gain at various points during the second and third trimesters of pregnancy and computed rate differences between levels of sociodemographic, nutritional, immunologic, and parasitic variables at the first prenatal visit. The change in mid-upper arm circumference (MUAC) from baseline to delivery was also examined. The rate of weight gain decreased progressively during pregnancy. There was an average decline of 1 cm in MUAC between weeks 12 and 38. Lower level of education and helminthic infections at first visit were associated with decreased adjusted rates of weight gain during the third trimester. High baseline MUAC, not contributing to household income, lower serum retinol and selenium concentrations, advanced clinical stage of HIV disease, and malaria infection were related to decreased rates of weight gain during the second trimester. Low baseline CD4 T-cell counts were related to a poorer pattern of weight gain throughout pregnancy. Prevention and treatment of parasitic infections and improvement of nutritional status are likely to enhance the pattern of gestational weight gain among HIV-infected women.     

Cognitive-behavioral treatment of late-life generalized anxiety disorder

This study addressed the efficacy of cognitive-behavioral therapy (CBT), relative to minimal contact control (MCC), in a sample of 85 older adults (age 60 years and over) with generalized anxiety disorder (GAD). All participants completed measures of primary outcome (worry and anxiety), coexistent symptoms (depressive symptoms and specific fears), and quality of life. Results of both completer and intent-to-treat analyses revealed significant improvement in worry, anxiety, depression, and quality of life following CBT relative to MCC. Forty-five percent of patients in CBT were classified as responders, relative to 8% in MCC. Most gains for patients in CBT were maintained or enhanced over 1-year follow-up. However, posttreatment scores for patients in CBT failed to indicate return to normative functioning.     

A mutation update on the LDS‐associated genes TGFB2/3 and SMAD2/3

The Loeys–Dietz syndrome (LDS) is a connective tissue disorder affecting the cardiovascular, skeletal, and ocular system. Most typically, LDS patients present with aortic aneurysms and arterial tortuosity, hypertelorism, and bifid/broad uvula or cleft palate. Initially, mutations in transforming growth factor‐β (TGF‐β) receptors (TGFBR1 and TGFBR2) were described to cause LDS, hereby leading to impaired TGF‐β signaling. More recently, TGF‐β ligands, TGFB2 and TGFB3, as well as intracellular downstream effectors of the TGF‐β pathway, SMAD2 and SMAD3, were shown to be involved in LDS. This emphasizes the role of disturbed TGF‐β signaling in LDS pathogenesis. Since most literature so far has focused on TGFBR1/2, we provide a comprehensive review on the known and some novel TGFB2/3 and SMAD2/3 mutations. For TGFB2 and SMAD3, the clinical manifestations, both of the patients previously described in the literature and our newly reported patients, are summarized in detail. This clearly indicates that LDS concerns a disorder with a broad phenotypical spectrum that is still emerging as more patients will be identified. All mutations described here are present in the corresponding Leiden Open Variant Database.     

A Novel Catechol-O-Methyltransferase Variant Associated with Human Disc Degeneration

Background: Disc degeneration and its associated low back pain are a major health care concern causing disability with a prominent role in this country''s medical, social and economic structure. Low back pain is devastating and influences the quality of life for millions. Low back pain lifetime prevalence approximates 80% with an estimated direct cost burden of $86 billion per year. Back pain patients incur higher costs, greater health care utilization, and greater work loss than patients without back pain.Methods: Research was performed following approval of our Institutional Review Board. DNA was isolated, processed and amplified using routine techniques. Amplified DNA was hybridized to Affymetrix Genome-Wide Human SNP Arrays. Quality control and genotyping analysis were performed using Affymetrix Genotyping Console. The Birdseed v2 algorithm was used for genotyping analysis. 2589 SNPs were selected a priori to enter statistical analysis using lotistic regression in SAS.Results: Our objective was to search for novel single nucleotide polymorphisms (SNPs) associated with disc degeneration. Four SNPs were found to have a significant relationship to disc degeneration; three are novel. Rs165656, a new SNP found to be associated with disc degeneration, was in catechol-O-methyltransferase (COMT), a gene with well-recognized pain involvement, especially in female subjects (p=0.01). Analysis confirmed the previously association between COMT SNP rs4633 and disc degeneration. We also report two novel disc degeneration-related SNPs (rs2095019 and rs470859) located in intergenic regions upstream to thrombospondin 2.Conclusions: Findings contribute to the challenging field of disc degeneration and pain, and are important in light of the high clinical relevance of low back pain and the need for improved understanding of its fundamental basis.