A prospective audit examining non-attendance at a surgical outpatients clinic in Mater Dei Hospital, Malta, and methods to reduce this problem

Non-attendance at hospital outpatient clinics is a longstanding issue that has potentially serious clinical implications, and contributes a significant financial burden to health care services. The aims of this study were to identify the rate of non-attendance at a surgical outpatients clinic in Mater Dei Hospital, Malta, ascertain the reasons for non-attendance, and to identify patients’ opinions on the implementation of a text-messaging reminder system as a means of reducing the non- attendance rate. Four outpatient clinics were observed over one month and the total number of appointments documented. Non-attenders were contacted via telephone call and asked to explain their non-attendance and whether a text-messaging reminder system may have increased their likelihood of attendance. Of the 266 appointments (217 females, 49 males, mean age 56 + 16 years), 80 patients failed to turn up, representing a 30% non-attendance rate. The main reasons for non-attendance were forgetfulness (53%), and unawareness of the appointment (26%). 90% of non-attenders stated that a text-messaging reminder might have prevented them missing their appointment, with 97% suggesting that such as system would be an acceptable method of trying to reduce this problem. Thus application of a text- messaging reminder system represents a potential solution for reducing the high rate of missed outpatient appointments, which is both cost effective and well accepted by patients.peer-reviewe

Polypharmacy and Antidepressant Acceptability in Comorbid Depression and Type 2 Diabetes

BACKGROUND: Polypharmacy may increase the risk of drug interactions, side-effects and poor adherence. However, the impact of polypharmacy on antidepressant acceptability in individuals with type 2 diabetes (T2DM) is unknown. AIM: In adults with T2DM, to investigate the association between the number of prescribed medications and: i) early antidepressant discontinuation (<32 weeks); ii) switching antidepressant agents. DESIGN: Cohort study using UK primary care data from the years 2000-2018. METHODS: We used cox regression with penalised B-splines to describe the association between the number of concurrently prescribed medications at the time of starting antidepressant treatment, and each of our outcomes. RESULTS: We identified 73,808 individuals with comorbid depression and T2DM starting antidepressant treatment for the first time. The median number of concurrent medications prescribed was 7. Within 32 weeks, 44.26% of participants discontinued antidepressant treatment altogether, and 11.75% of participants switched antidepressant agents. We found an inverse relationship between the number of concurrent medications and discontinuing antidepressant treatment altogether. The median number of 7 concurrent medications was associated with a 65.06% decrease early antidepressant discontinuation HR 0.45, 95% CIs 0.37-0.55). We found no evidence of an association, in our main analysis, between the number of concurrent medications and switching antidepressant agents. CONCLUSIONS: Early discontinuation of antidepressants is common in adults with T2DM. However, individuals with higher levels of concurrent polypharmacy may be more adherent to treatment. These are likely to represent individuals with worse physical/mental health. Individuals with lower levels of concurrent polypharmacy may benefit from adherence support

Effects of UVB-induced oxidative stress on protein expression and specific protein oxidation in normal human epithelial keratinocytes: a proteomic approach

<p>Abstract</p> <p>Background</p> <p>The UVB component of solar ultraviolet irradiation is one of the major risk factors for the development of skin cancer in humans. UVB exposure elicits an increased generation of reactive oxygen species (ROS), which are responsible for oxidative damage to proteins, DNA, RNA and lipids. In order to examine the biological impact of UVB irradiation on skin cells, we used a parallel proteomics approach to analyze the protein expression profile and to identify oxidatively modified proteins in normal human epithelial keratinocytes.</p> <p>Results</p> <p>The expression levels of fifteen proteins - involved in maintaining the cytoskeleton integrity, removal of damaged proteins and heat shock response - were differentially regulated in UVB-exposed cells, indicating that an appropriate response is developed in order to counteract/neutralize the toxic effects of UVB-raised ROS. On the other side, the redox proteomics approach revealed that seven proteins - involved in cellular adhesion, cell-cell interaction and protein folding - were selectively oxidized.</p> <p>Conclusions</p> <p>Despite a wide and well orchestrated cellular response, a relevant oxidation of specific proteins concomitantly occurs in UVB-irradiated human epithelial Keratinocytes. These modified (i.e. likely dysfunctional) proteins might result in cell homeostasis impairment and therefore eventually promote cellular degeneration, senescence or carcinogenesis.</p

Renal neuroendocrine control of desiccation and cold tolerance by Drosophila suzukii

Background: Neuropeptides are central to the regulation of physiological, and behavioural processes in insects, directly impacting cold and desiccation survival. However, little is known about the control mechanisms governing these responses in D. suzukii. The close phylogenetic relationship of D. suzukii with D. melanogaster allows, through genomic and functional studies, an insight into the mechanisms directing stress tolerance in D. suzukii. Results: Capa, Leucokinin, DH44 and DH31 neuropeptides demonstrate a high level of conservation between D. suzukii and D. melanogaster with respect to peptide sequences, neuronal expression, receptor localisation, and diuretic function in the Malpighian tubules. Despite D. suzukii’s ability to populate cold environments, they proved sensitive to both cold and desiccation. Furthermore, in D. suzukii, Capa acts as a desiccation-and cold stress-responsive gene, while DH44 gene expression is increased only after desiccation exposure, and the LK gene after nonlethal cold stress recovery. Conclusion: This study provides a comparative investigation into stress tolerance mediation by neuroendocrine signalling in two Drosophila species, providing evidence that similar signalling pathways control fluid secretion in the Malpighian tubules. Identifying processes governing specific environmental stresses affecting D. suzukii could lead to the development of targeted integrated management strategies to control insect pest populations

Linking genomics and ecology to investigate the complex evolution of an invasive Drosophila pest

Drosophilid fruit flies have provided science with striking cases of behavioural adaptation and genetic innovation. A recent example is the invasive pest Drosophila suzukii, which, unlike most other Drosophila, lays eggs and feeds on undamaged, ripening fruits. This poses a serious threat for fruit cultivation, but also offers an interesting model to study evolution of behavioural innovation. We developed genome and transcriptome resources for D. suzukii. Coupling analyses of these data with field observations, we propose a hypothesis of the origin of its peculiar ecology. Using nuclear and mitochondrial phylogenetic analyses, we confirm its Asian origin, and reveal a surprising sister relationship between the eugracilis and the melanogaster subgroups. While the D. suzukii genome is comparable in size and repeat content to other Drosophila species, it has the lowest nucleotide substitution rate among the species analysed in this study. This finding is compatible with the overwintering diapause of D. suzukii, which results in a reduced number of generations per year compared to its sister species. Genome-scale relaxed clock analyses support a late Miocene origin of D. suzukii, concomitant with paleogeological and climatic conditions that suggest an adaptation to temperate montane forests, a hypothesis confirmed by field trapping. We propose a causal link between the ecological adaptations of D. suzukii in its native habitat and its invasive success in Europe and North America

Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores

Background: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers. Methods: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk. Results: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions. Conclusions: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.Peer reviewe

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Abstract The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared to information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known non-pathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification. This article is protected by copyright. All rights reserved.Peer reviewe