The health-related quality of life in hyperhidrosis and co-morbidities

Quality of Life Research - Hyperhidrosis has been associated with a reduced health-related quality of life (HRQoL). The role of common confounding factors of this association such as stress and...     

Ovarian cancer early detection by circulating CA125 in the context of anti‐CA125 autoantibody levels: Results from the EPIC cohort

CA125 is the best ovarian cancer early detection marker to date; however, sensitivity is limited and complementary markers are required to improve discrimination between ovarian cancer cases and non‐cases. Anti‐CA125 autoantibodies are observed in circulation. Our objective was to evaluate whether these antibodies (1) can serve as early detection markers, providing evidence of an immune response to a developing tumor, and (2) modify the discriminatory capacity of CA125 by either masking CA125 levels (resulting in lower discrimination) or acting synergistically to improve discrimination between cases and non‐cases. We investigated these objectives using a nested case–control study within the European Prospective Investigation into Cancer and Nutrition cohort (EPIC) including 250 cases diagnosed within 4 years of blood collection and up to four matched controls. Circulating CA125 antigen and antibody levels were quantified using an electrochemiluminescence assay. Adjusted areas under the curve (aAUCs) by 2‐year lag‐time intervals were calculated using conditional logistic regression calibrated toward the absolute risk estimates from a pre‐existing epidemiological risk model as an offset‐variable. Anti‐CA125 levels alone did not discriminate cases from controls. For cases diagnosed <2 years after blood collection, discrimination by CA125 antigen was suggestively higher with higher anti‐CA125 levels (aAUC, highest antibody tertile: 0.84 [0.76–0.92]; lowest tertile: 0.76 [0.67–0.86]; p_het = 0.06). We provide the first evidence of potentially synergistic discrimination effects of CA125 and anti‐CA125 antibodies in ovarian early detection. If these findings are replicated, evaluating CA125 in the context of its antibody may improve ovarian cancer early detection.     

Assessing the causal association between 25‐hydroxyvitamin D and the risk of oral and oropharyngeal cancer using Mendelian randomization

Circulating 25‐hydroxyvitamin D (25OHD) is an appealing potential intervention for cancer risk and has been associated with oral and oropharyngeal cancer risk but evidence is inconsistent. The availability of genetic variants, uncorrelated with known confounders, but predictive of 25OHD and genetic data in a large oral and oropharyngeal cancer collaboration aids causal inference when assessing this association. A total of 5,133 oral and oropharyngeal cancer cases and 5,984 controls with genetic data were included in the study. Participants were based in Europe, North America and South America and were part of the Genetic Associations and Mechanisms in Oncology (GAME‐ON) Network. Five genetic variants reliably associated with circulating 25OHD were used to create a relative genetic measure of 25OHD. In the absence of measured 25OHD, two‐sample Mendelian randomization using individual level outcome data were used to estimate causal odds ratios (OR) for cancer case status per standard deviation increase in log25OHD. Analyses were replicated in an independent population‐based cohort (UK Biobank). In the GAME‐ON study, there was little evidence of a causal association between circulating 25OHD and oral cancer (OR = 0.86 [0.68;1.09], p = 0.22), oropharyngeal cancer (OR = 1.28 [0.72;2.26], p = 0.40) or when sites were combined (OR = 1.01 [0.74;1.40], p = 0.93). Replication in UK Biobank and pooled estimates produced similar results. Our study suggests that a clinically relevant protective effect of 25OHD on oral and oropharyngeal cancer risk is unlikely and supplementation of the general population with 25OHD is unlikely to be beneficial in preventing these cancers.     

Amyloid precursor-like protein 1 is differentially upregulated in neuroendocrine tumours of the gastrointestinal tract

We have examined the global gene expression profile of small intestinal carcinoids by microarray analysis. High expression of a number of genes was found including amyloid precursor-like protein 1 (APLP1). Quantitative real-time PCR and western blot analysis demonstrated higher expression of APLP1 in carcinoid metastases relative to primary tumours indicating a role of APLP1 in tumour dissemination. Tissue microarray analysis of gastroentero-pancreatic tumours demonstrated a high frequency of APLP1 expression and a low frequency of APLP2 expression in neuroendocrine (NE) tumours when compared with non-NE tumours at the same sites. Meta-analysis of gene expression data from a large number of tumours outside the gastrointestinal tract confirmed a correlation between APLP1 expression and NE phenotype where high expression of APLP1 was accompanied by downregulation of APLP2 in NE tumours. Cellular localization of APLP1, APLP2 and amyloid precursor protein (APP) in carcinoid cells (GOT1) by confocal microscopy demonstrated partial co-localization with synaptophysin. This suggests that the APP family of proteins is transported to the cell membrane by synaptic microvesicles and that they may influence tumour cell adhesion and invasiveness. We conclude that APLP1 is differentially upregulated in gastrointestinal NE tumours and that APLP1 may be important for the dissemination of small intestinal carcinoids. Identification of APLP1 in NE tumours offers a novel target for treatment and may also serve as a tumour-specific marker.     

Analysis of the rigid and deformable component of setup inaccuracies on portal images in head and neck radiotherapy

The issue of setup errors consisting of translation, rotation and deformation components in head and neck radiotherapy is addressed with a piecewise registration of small independent regions on a portal image to their reference position. These rectangular regions are termed featurelets as they contain relevant anatomical features. The resulting displacement vectors of each featurelet reflect both the center-of-mass (COM), i.e. the rigid, and the non-rigid component of the setup error. The displacement vectors of a series of daily portal images were subjected to a principal component analysis. In addition to the mean, systematic displacement of each featurelet, this analysis yields correlated patterns of anatomical deformations. Hence, the physiological movements of an individual patient can be obtained without a biomechanical model. It is shown that in the presence of setup errors that are due to rotations or deformations a correction by the COM displacement may deteriorate the error of parts of the anatomy further. The featurelet analysis can be used to refine setup correction protocols, tune spatially variable setup margins in treatment planning and optimize patient immobilization devices.     

Zolmitriptan nasal spray provides fast relief of migraine symptoms and is preferred by patients: a Swedish study of preference in clinical practice

Abstract The objectives were to compare patient preference for zolmitriptan nasal spray with their current acute therapies for migraine (by asking whether or not they wished to continue to use zolmitriptan nasal spray), to determine patients reasons for this choice and to evaluate efficacy of zolmitriptan nasal spray. Patients with an established diagnosis for migraine (IHC criteria) who were already receiving a migraine-specific treatment were enrolled in an open-label, clinical experience study in a clinical practice. Patients were invited to treat up to 6 migraine attacks with 5 mg of zolmitriptan nasal spray. Data from 232 patients were analysed. Most patients (89%) were already using a triptan as migraine treatment. The majority of patients (68.5%) wished to continue using zolmitriptan nasal spray; the most common reason being its fast onset of action. Almost half of the patients (47.8%) wishing to continue with zolmitriptan nasal spray reported few or no adverse events as a motivating reason. Of patients currently using sumatriptan nasal spray, tablet or injection, 90.9%, 74.2% and 70.6%, respectively, wanted to continue using zolmitriptan nasal spray. Most patients are satisfied with, and wish to continue using, zolmitriptan nasal spray.