Estimating the economic burden of cardiovascular events in patients receiving lipid-modifying therapy in the UK.

OBJECTIVES: To characterise the costs to the UK National Health Service of cardiovascular (CV) events among individuals receiving lipid-modifying therapy. DESIGN: Retrospective cohort study using Clinical Practice Research Datalink records from 2006 to 2012 to identify individuals with their first and second CV-related hospitalisations (first event and second event cohorts). Within-person differences were used to estimate CV-related outcomes. SETTING: Patients in the UK who had their first CV event between January 2006 and March 2012. PARTICIPANTS: Patients ≥18 years who had a CV event and received at least 2 lipid-modifying therapy prescriptions within 180 days beforehand. PRIMARY AND SECONDARY OUTCOME MEASURES: Direct medical costs (2014 £) were estimated in 3 periods: baseline (pre-event), acute (6 months afterwards) and long-term (subsequent 30 months). Primary outcomes included incremental costs, resource usage and total costs per period. RESULTS: There were 24 093 patients in the first event cohort of whom 5274 were included in the second event cohort. The mean incremental acute CV event costs for the first event and second event cohorts were: coronary artery bypass graft/percutaneous transluminal coronary angioplasty (CABG/PTCA) £5635 and £5823, myocardial infarction £4275 and £4301, ischaemic stroke £3512 and £4572, heart failure £2444 and £3461, unstable angina £2179 and £2489 and transient ischaemic attack £1537 and £1814. The mean incremental long-term costs were: heart failure £848 and £2829, myocardial infarction £922 and £1385, ischaemic stroke £973 and £682, transient ischaemic attack £705 and £1692, unstable angina £328 and £677, and CABG/PTCA £-368 and £599. Hospitalisation accounted for 95% of acute and 61% of long-term incremental costs. Higher comorbidity was associated with higher long-term costs. CONCLUSIONS: Revascularisation and myocardial infarction were associated with the highest incremental costs following a CV event. On the basis of real-world data, the economic burden of CV events in the UK is substantial, particularly among those with greater comorbidity burden

The COVID-19 Psychological Distress Scale (CPDS-16): development and initial validation

The outbreak of COVID-19 has caused psychological distress among the Indian population. There are several scales that assess fear and distress related to COVID-19 among individuals. However, these scales are context-specific and lack multi-cultural environment applicability in countries such as India. Therefore, the present study developed a psychometric instrument to assess psychological responses to COVID-19 among the Indian population. A total of 420 participants (60.5% females, Mage=25.89 years) were recruited online using a convenience sampling technique. The 16-item COVID-19 Psychological Distress Scale (CPDS-16) was developed based on the extensive review of the existing scales on psychological constructs related to COVID-19 (yielding four scales with a total of 37 items) and independent review by two external experts. Internal consistency and reliability of the scale was established by using corrected item-total correlations, Cronbach's alpha, and McDonald's omega. Factor structure of the scale was determined by using exploratory factor analysis (EFA). Convergent validity of the scale was established by correlating CPDS-16 scores with the three subscales of the Depression, Anxiety, and Stress Scale (DASS-21). Corrected item-total correlations (range = 0.43 to 0.70), Cronbach's alpha (α = 0.90), and McDonald's omega (ω = 0.89) provided evidence for very good internal consistency and reliability of the scale. EFA of the CPDS-16 demonstrated a two-factor structure identified as 'individual level distress' (10 items) and 'community level distress' (6 items). Convergent validity of the scale was established using the DASS-21 with statistically significant and positive correlations between CPDS-16 and the three DASS-21 subscales (i.e., depression, anxiety, and stress). The CPDS-16 is a reliable and valid instrument in assessing psychological distress caused due to COVID-19 with robust psychometric properties. The scale can be administered rapidly and is useful in screening psychological distress caused due to COVID-19

Internet gaming disorder, loneliness, and insomnia among Indians during the COVID-19 pandemic

Introduction: The lockdown and stay at home orders implemented by the Indian government to inhibit the spread of COVID-19 disrupted the lifestyle of most individuals in the country. This appeared to result in behavioral changes such as increased internet usage, feelings of loneliness, and disturbance of sleeping patterns. Objectives: The objective of the present study was to examine IGD prevalence and its association with loneliness and insomnia among the Indian population during the COVID-19 pandemic. Based on the previous literature, it was hypothesized that IGD would be positively associated with both loneliness and severity of insomnia. Materials and Methods: Utilizing a cross-sectional design, a total of 372 participants (54% males, 42.4% females; 3.5% other; mean age 23.26 years [SD=9.07]) completed an anonymous self-report survey. The three key variables were assessed using the Internet Gaming Disorder Scale-Short Form (IGDS9-SF), the UCLA Loneliness Scale (Version 3), and the Insomnia Severity Index (ISI). Results: The prevalence of IGD among Indians during the COVID-19 pandemic was 0.8% in the total sample and 2.02% among gamers. Regression analysis indicated that IGD was associated with average hours spent online gaming per day (β=0.164; p=0.02), loneliness (β=0.177; p=0.01), and severity of insomnia (β=0.483; p<0.001). Conclusion: The study indicated average hours spent online gaming, loneliness, and severity of insomnia as predictors of IGD. Future research is required to develop a comprehensive understanding of internet gaming behaviors during unprecedented times such as COVID-19

Dependence on Dectin-1 Varies With Multiple Candida Species

This is the final version. Available from Frontiers Media via the DOI in this recordFour Candida spp. (albicans, glabrata, tropicalis, parapsilosis) cause >95% of invasive Candida infections. C. albicans elicits immune responses via pathogen recognition receptors including C-type lectin-like receptors (CLRs). The CLR, Dectin-1 is important for host immunity to C. albicans and C. glabrata, however, whether Dectin-1 is important for host defense against C. tropicalis or C. parapsilosis is unknown. Therefore, we compared the involvement of Dectin-1 in response to these four diverse Candida spp. We found that Dectin-1 mediates innate cytokine responses to these Candida spp. in a species- and cell-dependent manner. Dectin-1 KO mice succumbed to infection with highly virulent C. albicans while they mostly survived infection with less virulent Candida spp. However, Dectin-1 KO mice displayed increased fungal burden following infection with each Candida spp. Additionally, T cells from Dectin-1 KO mice displayed enhanced effector functions likely due to the inability of Dectin-1 KO mice to clear the infections. Together, these data indicate that Dectin-1 is important for host defense to multiple Candida spp., although the specific roles for Dectin-1 varies with different Candida spp.Wellcome TrustRoyal SocietyUK Dementia Research InstituteMRC Centre for Medical Mycolog

Mammography screening: views from women and primary care physicians in Crete

Background: Breast cancer is the most commonly diagnosed cancer among women and a leading cause of death from cancer in women in Europe. Although breast cancer incidence is on the rise worldwide, breast cancer mortality over the past 25 years has been stable or decreasing in some countries and a fall in breast cancer mortality rates in most European countries in the 1990s was reported by several studies, in contrast, in Greece have not reported these favourable trends. In Greece, the age-standardised incidence and mortality rate for breast cancer per 100.000 in 2006 was 81,8 and 21,7 and although it is lower than most other countries in Europe, the fall in breast cancer mortality that observed has not been as great as in other European countries. There is no national strategy for screening in this country. This study reports on the use of mammography among middleaged women in rural Crete and investigates barriers to mammography screening encountered by women and their primary care physicians. Methods: Design: Semi-structured individual interviews. Setting and participants: Thirty women between 45–65 years of age, with a mean age of 54,6 years, and standard deviation 6,8 from rural areas of Crete and 28 qualified primary care physicians, with a mean age of 44,7 years and standard deviation 7,0 serving this rural population. Main outcome measure: Qualitative thematic analysis. Results: Most women identified several reasons for not using mammography. These included poor knowledge of the benefits and indications for mammography screening, fear of pain during the procedure, fear of a serious diagnosis, embarrassment, stress while anticipating the results, cost and lack of physician recommendation. Physicians identified difficulties in scheduling an appointment as one reason women did not use mammography and both women and physicians identified distance from the screening site, transportation problems and the absence of symptoms as reasons for non-use. Conclusion: Women are inhibited from participating in mammography screening in rural Crete. The provision of more accessible screening services may improve this. However physician recommendation is important in overcoming women's inhibitions. Primary care physicians serving rural areas need to be aware of barriers preventing women from attending mammography screening and provide women with information and advice in a sensitive way so women can make informed decisions regarding breast caner screening

Management of lipid-lowering therapy in patients with cardiovascular events in the UK: a retrospective cohort study

Objectives To describe low-density lipoprotein (LDL) cholesterol management and lipid-lowering treatment patterns in patients with a cardiovascular (CV) event. Design Retrospective cohort study using Clinical Practice Research Datalink records linked with Hospital Episode Statistics data. Setting Routine clinical practice in the UK from 2006 to 2012. Participants Individuals ≥18 years were selected at their first CV-related hospitalisation (first event cohort) if they had received ≥2 lipid-lowering therapy prescriptions within 180 days beforehand. Patients were stratified into four mutually exclusive subgroups based on the presence or absence of vascular disease and of diabetes. Those with a second CV hospitalisation within 36 months were included in a separate cohort (second event cohort). Primary and secondary outcome measures LDL levels in the year prior to the CV event and 12 months later as well as measures of adherence to lipid-lowering therapy during the 12 months after the CV hospitalisation. Results There were 24 093 patients in the first event cohort, of whom 5274 were included in the second event cohort. Most received moderate intensity statins at baseline and 12 months. Among the four first event cohort subgroups at baseline, the proportions with an LDL of <1.8 mmol/L was similar between the two diabetic cohorts (36% to 38%) and were higher than those in the two non-diabetic cohorts (17% to 22%) and in the second event cohort (31%). An incremental 5% to 9% had an LDL below 1.8 mmol/L at 12 months, suggesting intensification of therapy. The proportion of adherent patients (medication possession ratio of≥0.8) was highest for statins, ranging from 68% to 72%. For ezetimibe, the range was 65% to 70%, and for fibrates, it was 48% to 62%. Conclusions Despite the existence of effective therapies for lowering cholesterol, patients do not reach achievable LDL targets

Essentials of Filoviral Load Quantification

Quantitative measurement of viral load is an important parameter in the management of filovirus disease outbreaks because viral load correlates with severity of disease, survival, and infectivity. During the ongoing Ebola virus disease outbreak in parts of Western Africa, most assays used in the detection of Ebola virus disease by more than 44 diagnostic laboratories yielded qualitative results. Regulatory hurdles involved in validating quantitative assays and the urgent need for a rapid Ebola virus disease diagnosis precluded development of validated quantitative assays during the outbreak. Because of sparse quantitative data obtained from these outbreaks, opportunities for study of correlations between patient outcome, changes in viral load during the course of an outbreak, disease course in asymptomatic individuals, and the potential for virus transmission between infected patients and contacts have been limited. We strongly urge the continued development of quantitative viral load assays to carefully evaluate these parameters in future outbreaks of filovirus disease

Targeted knock-down of miR21 primary transcripts using snoMEN vectors induces apoptosis in human cancer cell lines

We have previously reported an antisense technology, 'snoMEN vectors', for targeted knock-down of protein coding mRNAs using human snoRNAs manipulated to contain short regions of sequence complementarity with the mRNA target. Here we characterise the use of snoMEN vectors to target the knock-down of micro RNA primary transcripts. We document the specific knock-down of miR21 in HeLa cells using plasmid vectors expressing miR21-targeted snoMEN RNAs and show this induces apoptosis. Knock-down is dependent on the presence of complementary sequences in the snoMEN vector and the induction of apoptosis can be suppressed by over-expression of miR21. Furthermore, we have also developed lentiviral vectors for delivery of snoMEN RNAs and show this increases the efficiency of vector transduction in many human cell lines that are difficult to transfect with plasmid vectors. Transduction of lentiviral vectors expressing snoMEN targeted to pri-miR21 induces apoptosis in human lung adenocarcinoma cells, which express high levels of miR21, but not in human primary cells. We show that snoMEN-mediated suppression of miRNA expression is prevented by siRNA knock-down of Ago2, but not by knock-down of Ago1 or Upf1. snoMEN RNAs colocalise with Ago2 in cell nuclei and nucleoli and can be co-immunoprecipitated from nuclear extracts by antibodies specific for Ago2

Gemcitabine diphosphate choline is a major metabolite linked to the Kennedy pathway in pancreatic cancer models in vivo.

BACKGROUND: The modest benefits of gemcitabine (dFdC) therapy in patients with pancreatic ductal adenocarcinoma (PDAC) are well documented, with drug delivery and metabolic lability cited as important contributing factors. We have used a mouse model of PDAC: KRAS(G12D); p53(R172H); pdx-Cre (KPC) that recapitulates the human disease to study dFdC intra-tumoural metabolism. METHODS: LC-MS/MS and NMR were used to measure drug and physiological analytes. Cytotoxicity was assessed by the Sulphorhodamine B assay. RESULTS: In KPC tumour tissue, we identified a new, Kennedy pathway-linked dFdC metabolite (gemcitabine diphosphate choline (GdPC)) present at equimolar amounts to its precursor, the accepted active metabolite gemcitabine triphosphate (dFdCTP). Utilising additional subcutaneous PDAC tumour models, we demonstrated an inverse correlation between GdPC/dFdCTP ratios and cytidine triphosphate (CTP). In tumour homogenates in vitro, CTP inhibited GdPC formation from dFdCTP, indicating competition between CTP and dFdCTP for CTP:phosphocholine cytidylyltransferase (CCT). As the structure of GdPC precludes entry into cells, potential cytotoxicity was assessed by stimulating CCT activity using linoleate in KPC cells in vitro, leading to increased GdPC concentration and synergistic growth inhibition after dFdC addition. CONCLUSIONS: GdPC is an important element of the intra-tumoural dFdC metabolic pathway in vivo