Prevalence, Characteristics, and Patterns of Health Care Use for Chronic Headache in Two Areas of Italy. Results of A Questionnaire Interview in General Practice

We set out to define the prevalence, clinical features and severity of chronic headache among the affiliates of two groups of general practitioners (GPs) and to illustrate the diagnostic and therapeutic modalities employed. A semistructured questionnaire was completed for 2291 children and adults, seen at office or home consultations over a 6-month period by 44 GPs in two areas of Northern Italy (Varese and Sondrio) and Southern Italy (San Giovanni Rotondo), to assess the presence and the clinical features of chronic headache, the severity of the disease (i.e. the degree of interference with work and daily living activities), the diagnostic work-up, and the main treatment modalities. GPs attempted the classification of headache according to the International Headache Society (IHS) criteria. The sample comprised 910 men and 1381 women aged 2-92 years; 39% of cases reported chronic headache (Varese/Sondrio 40%; San Giovanni Rotondo 38%; men 28%; women 47%). Headache was mostly present for >10 years, with one to three attacks/month lasting 4-24 h. Headache was mild in 18% of cases, moderate in 29%, severe in 24%, and very severe in 29%. Diagnostic assessment and treatment varied in the study areas. Diagnostic work-up, hospital admissions, referral to headache centres, and treatment modalities tended to be correlated with headache severity. The GPs could not classify headache using the IHS categories in 27% of cases (Varese/Sondrio 11%; San Giovanni Rotondo 78%). An inverse correlation was found between case classification and use of subsidiary diagnostic and therapeutic aids. Chronic headache is common among individuals seen in general practice. The patterns of health care use tend to be correlated to its severity. A better knowledge of the IHS criteria may be directly related to lower management costs

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons