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Objective To assess the rates and predictors of traversing steps essential to good medical care for chronic migraine, including: (1) medical consultation, (2) accurate diagnosis, and (3) minimal pharmacologic treatment. Candidate predictors included socioeconomic, demographic, and headache‐specific variables. Background Previous research has established that barriers to effective management for episodic migraine include the absence of health insurance, lack of appropriate medical consultation, failure to receive an accurate diagnosis, and not being offered a regimen with acute and preventive treatments. Methods/Design The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study, a longitudinal web‐based panel study of migraine, included a cross‐sectional module focused on patterns of and barriers to medical care. Participants eligible for this analysis met the study criteria for chronic migraine, had evidence of headache‐related disability, and provided data on health insurance status. The main outcomes in the current analysis included the proportion of respondents who sought consultation for headache with a designated healthcare professional, self‐reported receiving a diagnosis of chronic or transformed migraine, and received minimal pharmacologic treatment for headache with a focus on prescribed acute and preventive treatments. Results In the CaMEO Study, 80,783 respondents provided study data, 16,789 (20.8% of respondents) met criteria for migraine, and 1476 (8.8% of those with migraine) met chronic migraine criteria. In total, 1254 participants (85.0% of those with chronic migraine) met inclusion criteria for this analysis. Of those, 512 respondents (40.8%) reported currently consulting with a healthcare professional for headache. Odds of consulting increased with increasing age (OR 1.02; 95% CI 1.01–1.03), body mass index (BMI) (OR 1.01; 95% CI 1.00–1.03), migraine‐related disability (OR 1.02; 95% CI 1.00–1.04), and migraine severity (OR 1.16; 95% CI 1.11–1.22) and presence of health insurance (OR 4.61; 95% CI 3.05–6.96). Among those consulting a healthcare professional, 126 (24.6%) received an accurate diagnosis and 56 of those with a correct diagnosis (44.4%) received both acute and preventive pharmacologic treatments; odds of a CM diagnosis were higher for women (OR 1.93; 95% CI 1.03–3.61), those with greater migraine severity (OR 1.25; 95% CI 1.14–1.37), and those currently consulting a specialist (OR 2.38; 95% CI 1.54–3.69). No predictors of receiving appropriate treatment were identified among those currently consulting. Among our sample of people with chronic migraine, only 56 (4.5%) individuals successfully traversed the series of 3 barriers to successful chronic migraine care (ie, consulted a healthcare professional for migraine, received an accurate diagnosis, and were prescribed minimal acute and preventive pharmacologic treatments). Conclusion Our findings suggest that <5% of persons with chronic migraine traversed 3 barriers to receiving care for headache (consultation, diagnosis, and treatment), representing a large unmet need for improving care in this population. Predictors of consulting a healthcare professional included age, having health insurance, greater migraine‐related disability, and greater migraine symptom severity. Among those consulting, predictors of an appropriate diagnosis included consulting a specialist, female sex, and greater migraine severity. Public health efforts are needed to improve outcomes for patients with chronic migraine by a range of interventions and educational efforts aimed at improving consultation rates, diagnostic accuracy, and adherence to minimal pharmacologic treatment.

Nodular fasciitis (NF) is a clonal self‐limited neoplastic proliferation characterized by rearrangements of the USP6 locus in most examples. To our knowledge well‐documented malignant behavior has never been previously observed in NF. In this report we present an unusual case of NF with classical histologic features that showed a protracted clinical course characterized by multiple recurrences and eventual metastatic behavior over a period of 10 years. Molecular analyses revealed the presence and amplification of the novel PPPR6‐USP6 gene fusion, which resulted in USP6 mRNA transcriptional upregulation. These findings further support the oncogenic role of the USP6 protease in mesenchymal neoplasia and expand the biologic potential of NF. © 2016 Wiley Periodicals, Inc.

Abstract Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. Cancer Res; 76(17); 5103–14. ©2016 AACR.

ObjectiveWhite matter hyperintensities (WMHs) are areas of increased signal on T2‐weighted magnetic resonance imaging (MRI) scans that most commonly reflect small vessel cerebrovascular disease. Increased WMH volume is associated with risk and progression of Alzheimer's disease (AD). These observations are typically interpreted as evidence that vascular abnormalities play an additive, independent role contributing to symptom presentation, but not core features of AD. We examined the severity and distribution of WMH in presymptomatic PSEN1, PSEN2, and APP mutation carriers to determine the extent to which WMH manifest in individuals genetically determined to develop AD.MethodsThe study comprised participants (n = 299; age = 39.03 ± 10.13) from the Dominantly Inherited Alzheimer Network, including 184 (61.5%) with a mutation that results in AD and 115 (38.5%) first‐degree relatives who were noncarrier controls. We calculated the estimated years from expected symptom onset (EYO) by subtracting the affected parent's symptom onset age from the participant's age. Baseline MRI data were analyzed for total and regional WMH. Mixed‐effects piece‐wise linear regression was used to examine WMH differences between carriers and noncarriers with respect to EYO.ResultsMutation carriers had greater total WMH volumes, which appeared to increase approximately 6 years before expected symptom onset. Effects were most prominent for the parietal and occipital lobe, which showed divergent effects as early as 22 years before estimated onset.InterpretationAutosomal‐dominant AD is associated with increased WMH well before expected symptom onset. The findings suggest the possibility that WMHs are a core feature of AD, a potential therapeutic target, and a factor that should be integrated into pathogenic models of the disease. Ann Neurol 2016;79:929–939

Abstract Background and Aims Depression and anxiety are often comorbid with alcoholism and contribute to craving and relapse. We aimed to estimate the prevalence of life‐time diagnoses of major depressive disorder (MDD), substance‐induced depression (SID), anxiety disorder (AnxD) and substance‐induced anxiety (SIA), the effects of these comorbidities on the propensity to drink in negative emotional states (negative craving), and test whether these effects differ by sex. Design Secondary analyses of baseline data collected in a single‐arm study of pharmacogenetic predictors of acamprosate response. Setting Academic medical center and affiliated community‐based treatment programs in the American upper mid‐west. Participants A total of 287 males and 156 females aged 18–80 years, meeting DSM‐IV criteria for alcohol dependence. Measurements The primary outcome measure was ‘propensity to drink in negative emotional situations’ (determined by the Inventory of Drug Taking Situations) and the key predictors/covariates were sex and psychiatric comorbidities, including MDD, SID, AnxD and SIA (determined by Psychiatric Research Interview of Substance and Mood Disorders). Findings The prevalence of the MDD, SID and AnxD was higher in females compared with males (33.1 versus 18.4%, 44.8 versus 26.4% and 42.2 versus 27.4%, respectively; P < 0.01, each), while SIA was rare (3.3%) and did not differ by sex. Increased propensity to drink in negative emotional situations was associated with comorbid MDD (β = 6.6, P = 0.013) and AnxD (β = 4.8, P = 0.042) as well as a SID × sex interaction effect ( P = 0.003), indicating that the association of SID with propensity to drink in negative emotional situations differs by sex and is stronger in males (β = 7.9, P = 0.009) compared with females (β = −6.6, P = 0.091). Conclusions There appears to be a higher prevalence of comorbid depression and anxiety disorders as well as propensity to drink in negative emotional situations in female compared with male alcoholics. Substance‐induced depression appears to have a sex‐specific effect on the increased risk for drinking in negative emotional situations in males.

BACKGROUND: Autoimmune hepatitis has diverse clinical phenotypes and outcomes that challenge current diagnostic criteria and management algorithms.OBJECTIVES: To highlight the major difficulties in diagnosis and management, describe the efforts to ease them and encourage further progress in problem solving.METHODS: The MEDLINE database was reviewed for published experiences from 1984 to 2013.RESULTS: Acute or acute severe (fulminant) hepatitis, asymptomatic mild disease, and histological findings of centrilobular necrosis or bile duct injury can confound diagnosis and treatment. Continuation of conventional therapy until normal liver test results and liver tissue reduces the frequency of relapse, but does not prevent its occurrence. Problematic patients can be identified using mathematical models, clinical phenotype, serological markers and the speed of improvement after treatment; however, their recognition and treatment are inconsistent. Mycophenolate mofetil can rescue patients with azathioprine intolerance but is less effective for refractory disease. Budesonide in combination with azathioprine can be used frontline, but is effective primarily in noncirrhotic, uncomplicated disease. Molecular and cellular interventions are feasible but largely unevaluated.DISCUSSION: Resolution of the current challenges requires revision of diagnostic criteria, characterization of biological markers that reflect pathogenic pathways, development of dynamic indexes based on changes in disease behaviour, and introduction of new pharmacological, molecular and cellular interventions that have undergone rigorous evaluation.CONCLUSION: These challenges reflect important remediable deficiencies in current management.