PRimary care rEsponse to domestic violence and abuse in the COvid-19 panDEmic (PRECODE): protocol of a rapid mixed-methods study in the UK

BACKGROUND: The implementation of lockdowns in the UK during the COVID-19 pandemic resulted in a system switch to remote primary care consulting at the same time as the incidence of domestic violence and abuse (DVA) increased. Lockdown-specific barriers to disclosure of DVA reduced the opportunity for DVA detection and referral. The PRECODE (PRimary care rEsponse to domestic violence and abuse in the COvid-19 panDEmic) study will comprise quantitative analysis of the impact of the pandemic on referrals from IRIS (Identification and Referral to Improve Safety) trained general practices to DVA agencies in the UK and qualitative analysis of the experiences of clinicians responding to patients affected by DVA and adaptations they have made transitioning to remote DVA training and patient support. METHODS/DESIGN: Using a rapid mixed method design, PRECODE will explore and explain the dynamics of DVA referrals and support before and during the pandemic on a national scale using qualitative data and over four years of referrals time series data. We will undertake interrupted-time series and non-linear regression analysis, including sensitivity analyses, on time series of referrals to DVA services from routinely collected data to evaluate the impact of the pandemic and associated lockdowns on referrals to the IRIS Programme, and analyse key determinants associated with changes in referrals. We will also conduct an interview- and observation-based qualitative study to understand the variation, relevance and feasibility of primary care responses to DVA before and during the pandemic and its aftermath. The triangulation of quantitative and qualitative findings using rapid analysis and synthesis will enable the articulation of multiscale trends in primary care responses to DVA and complex mechanisms by which these responses have changed during the pandemic. DISCUSSION: Our findings will inform the implementation of remote primary care and DVA service responses as services re-configure. Understanding the adaptation of clinical and service responses to DVA during the pandemic is crucial for the development of evidence-based, effective remote support and referral beyond the pandemic. TRIAL REGISTRATION: PRECODE is an observational epidemiologic study, not an intervention evaluation or trial. We will not be reporting results of an intervention on human participants

Outcomes of preexisting diabetes mellitus in breast, colorectal, and prostate cancer.

This is the author accepted manuscript. The final version is available from Springer Verlag via the DOI in this record.PURPOSE: Preexisting diabetes is associated with increased morbidity and mortality in cancer. We examined the impact of incident cancer on the long-term outcomes of diabetes. METHODS: Using the United Kingdom Clinical Practice Research Datalink, we identified three cohorts of diabetes patients subsequently diagnosed with breast, colorectal, or prostate cancer, each matched to diabetic noncancer controls. Patients were required to have survived at least 1 year after cancer diagnosis (cases) or a matched index date (controls), and were followed up to 10 years for incident microvascular and macrovascular complications and mortality. Multivariate competing risks regression analyses were used to compare outcomes between cancer patients and controls. RESULTS: Overall, there were 3382 cancer patients and 11,135 controls with 59,431 person-years of follow-up. In adjusted analyses, there were no statistically significant (p ≤ 0.05) differences in diabetes complication rates between cancer patients and their controls in any of the three cancer cohorts. Combined, cancer patients were less likely (adjusted hazard ratio [HR] 0.88; 95% CI = 0.79-0.98) to develop retinopathy. Cancer patients were more likely to die of any cause (including cancer), but prostate cancer patients were less likely to die of causes associated with diabetes (HR 0.61; 95% CI = 0.43-0.88). CONCLUSIONS AND IMPLICATIONS: There is no evidence that incident cancer had an adverse impact on the long-term outcomes of preexisting diabetes. IMPLICATIONS FOR CANCER SURVIVORS: These findings are important for cancer survivors with preexisting diabetes because they suggest that substantial improvements in the relative survival of several of the most common types of cancer are not undermined by excess diabetes morbidity and mortality.This study was funded by the Population Research Committee, Cancer Research UK. Quality and Outcomes of Care for Chronic Conditions in Older Patients Diagnosed with Breast, Colorectal, or Prostate Cancer Compared to Non-Cancer Controls: An Observational Study Using the Clinical Practice Research Datalink (CPRD). Reference # 16609. 1 July 2013–29 February, 2016. In addition, Dr. Keating is supported by K24CA181510 from the US National Cancer Institute

Outcomes of preexisting diabetes mellitus in breast, colorectal, and prostate cancer.

This is the author accepted manuscript. The final version is available from Springer Verlag via the DOI in this record.PURPOSE: Preexisting diabetes is associated with increased morbidity and mortality in cancer. We examined the impact of incident cancer on the long-term outcomes of diabetes. METHODS: Using the United Kingdom Clinical Practice Research Datalink, we identified three cohorts of diabetes patients subsequently diagnosed with breast, colorectal, or prostate cancer, each matched to diabetic noncancer controls. Patients were required to have survived at least 1 year after cancer diagnosis (cases) or a matched index date (controls), and were followed up to 10 years for incident microvascular and macrovascular complications and mortality. Multivariate competing risks regression analyses were used to compare outcomes between cancer patients and controls. RESULTS: Overall, there were 3382 cancer patients and 11,135 controls with 59,431 person-years of follow-up. In adjusted analyses, there were no statistically significant (p ≤ 0.05) differences in diabetes complication rates between cancer patients and their controls in any of the three cancer cohorts. Combined, cancer patients were less likely (adjusted hazard ratio [HR] 0.88; 95% CI = 0.79-0.98) to develop retinopathy. Cancer patients were more likely to die of any cause (including cancer), but prostate cancer patients were less likely to die of causes associated with diabetes (HR 0.61; 95% CI = 0.43-0.88). CONCLUSIONS AND IMPLICATIONS: There is no evidence that incident cancer had an adverse impact on the long-term outcomes of preexisting diabetes. IMPLICATIONS FOR CANCER SURVIVORS: These findings are important for cancer survivors with preexisting diabetes because they suggest that substantial improvements in the relative survival of several of the most common types of cancer are not undermined by excess diabetes morbidity and mortality.This study was funded by the Population Research Committee, Cancer Research UK. Quality and Outcomes of Care for Chronic Conditions in Older Patients Diagnosed with Breast, Colorectal, or Prostate Cancer Compared to Non-Cancer Controls: An Observational Study Using the Clinical Practice Research Datalink (CPRD). Reference # 16609. 1 July 2013–29 February, 2016. In addition, Dr. Keating is supported by K24CA181510 from the US National Cancer Institute

Quality of diabetes care in breast, colorectal, and prostate cancer

This is the final version. Available on open access from Springer via the DOI in this recordPURPOSE: Overlooking other medical conditions during cancer treatment and follow-up could result in excess morbidity and mortality, thereby undermining gains associated with early detection and improved treatment of cancer. We compared the quality of care for diabetes patients subsequently diagnosed with breast, colorectal, or prostate cancer to matched, diabetic non-cancer controls. METHODS: Longitudinal cohort study using primary care records from the Clinical Practice Research Datalink, United Kingdom. Patients with pre-existing diabetes were followed for up to 5 years after cancer diagnosis, or after an assigned index date (non-cancer controls). Quality of diabetes care was estimated based on Quality and Outcomes Framework indicators. Mixed effects logistic regression analyses were used to compare the unadjusted and adjusted odds of meeting quality measures between cancer patients and controls, overall and stratified by type of cancer. RESULTS: 3382 cancer patients and 11,135 controls contributed 44,507 person-years of follow-up. In adjusted analyses, cancer patients were less likely to meet five of 14 quality measures, including: total cholesterol ≤ 5 mmol/L (odds ratio [OR] = 0.82; 95% confidence interval [CI], 0.75-0.90); glycosylated hemoglobin ≤ 59 mmol/mol (adjusted OR = 0.77; 95% CI, 0.70-0.85); and albumin creatinine ratio testing (adjusted OR = 0.83; 95% CI, 0.75-0.91). However, cancer patients were as likely as their matched controls to meet quality measures for other diabetes services, including retinal screening, foot examination, and dietary review. CONCLUSIONS: Although in the short-term, cancer patients were less likely to achieve target thresholds for cholesterol and HbA1c, they continued to receive high-quality diabetes primary care throughout 5 years post diagnosis. IMPLICATIONS FOR CANCER SURVIVORS: These findings are important for cancer survivors with pre-existing diabetes because they indicate that high-quality diabetes care is maintained throughout the continuum of cancer diagnosis, treatment, and follow-up.This study was funded by the Population Research Committee, Cancer Research UK. Quality and Outcomes of Care for Chronic Conditions in Older Patients Diagnosed with Breast, Colorectal, or Prostate Cancer Compared to Non-Cancer Controls: An Observational Study Using the Clinical Practice Research Datalink (CPRD). Reference # 16609. 1 July 2013–29 February, 2016. In addition, Dr. Keating is supported by K24CA181510 from the US National Cancer Institute

Gaming and gaming disorder: a mediation model gender, salience, age of gaming onset, and time spent gaming

Females in empirically based peer-reviewed studies of Internet gaming disorder (IGD) are underrepresented, despite evidence that there are only minor gender disparities present in online gaming. Moreover, few studies have specifically evaluated adult gender effects, within a formal diagnosis of IGD, and behavioral motivation, as defined by the reinforcing behavioral function. A mediation analysis evaluated the relationship between gender, behavioral motivation, and the diagnostic features in online gaming among adults to understand the impact of motivation on videogame playing. This study interviewed 304 adults (aged >18 years) in which 178 identified as female. Participants completed the Video Game Functional Assessment-Revised (VGFA-R) and the 20-item Internet Gaming Disorder Test (IGDT-20) through an online survey. Results showed that number of hours played per week, and subfactors of the VGFA-R differed between gender, indicating that the function and the maintaining of videogame play are essential in evaluating videogame addiction. These findings support and extend the literature's limited findings concerning gender and online gaming

Crowdsourcing for translational research: analysis of biomarker expression using cancer microarrays

Background: Academic pathology suffers from an acute and growing lack of workforce resource. This especially impacts on translational elements of clinical trials, which can require detailed analysis of thousands of tissue samples. We tested whether crowdsourcing – enlisting help from the public – is a sufficiently accurate method to score such samples. Methods: We developed a novel online interface to train and test lay participants on cancer detection and immunohistochemistry scoring in tissue microarrays. Lay participants initially performed cancer detection on lung cancer images stained for CD8, and we measured how extending a basic tutorial by annotated example images and feedback-based training affected cancer detection accuracy. We then applied this tutorial to additional cancer types and immunohistochemistry markers – bladder/ki67, lung/EGFR, and oesophageal/CD8 – to establish accuracy compared with experts. Using this optimised tutorial, we then tested lay participants’ accuracy on immunohistochemistry scoring of lung/EGFR and bladder/p53 samples. Results: We observed that for cancer detection, annotated example images and feedback-based training both improved accuracy compared with a basic tutorial only. Using this optimised tutorial, we demonstrate highly accurate (>0.90 area under curve) detection of cancer in samples stained with nuclear, cytoplasmic and membrane cell markers. We also observed high Spearman correlations between lay participants and experts for immunohistochemistry scoring (0.91 (0.78, 0.96) and 0.97 (0.91, 0.99) for lung/EGFR and bladder/p53 samples, respectively). Conclusions: These results establish crowdsourcing as a promising method to screen large data sets for biomarkers in cancer pathology research across a range of cancers and immunohistochemical stains

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

Effectiveness and cost-effectiveness of implementing HIV testing in primary care in East London: protocol for an interrupted time series analysis

Introduction HIV remains underdiagnosed. Guidelines recommend routine HIV testing in primary care, but evidence on implementing testing is lacking. In a previous study, the Rapid HIV Assessment 2 (RHIVA2) cluster randomised controlled trial, we showed that providing training and rapid point-of-care HIV testing at general practice registration (RHIVA2 intervention) in Hackney led to cost-effective, increased and earlier diagnosis of HIV. However, interventions effective in a trial context may be less so when implemented in routine practice. We describe the protocol for an MRC phase IV implementation programme, evaluating the impact of rolling out the RHIVA2 intervention in a post-trial setting. We will use a longitudinal study to examine if the post-trial implementation in Hackney practices is effective and cost-effective, and a cross-sectional study to compare Hackney with two adjacent boroughs providing usual primary care (Newham) and an enhanced service promoting HIV testing in primary care (Tower Hamlets). Methods and analysis Service evaluation using interrupted time series and cost-effectiveness analyses. We will include all general practices in three contiguous high HIV prevalence East London boroughs. All adults aged 16 and above registered with the practices will be included. The interventions to be examined are: a post-trial RHIVA2 implementation programme (including practice-based education and training, external quality assurance, incentive payments for rapid HIV testing and incorporation of rapid HIV testing in the sexual health Local Enhanced Service) in Hackney; the general practice sexual health Network Improved Service in Tower Hamlets and usual care in Newham. Coprimary outcomes are rates of HIV testing and new HIV diagnoses. Ethics and dissemination The chair of the Camden and Islington NHS Research Ethics Committee, London, has endorsed this programme as an evaluation of routine care. Study results will be published in peer-reviewed journals and reported to commissioners

A framework for automated enrichment of functionally significant inverted repeats in whole genomes

<p>Abstract</p> <p>Background</p> <p>RNA transcripts from genomic sequences showing dyad symmetry typically adopt hairpin-like, cloverleaf, or similar structures that act as recognition sites for proteins. Such structures often are the precursors of non-coding RNA (ncRNA) sequences like microRNA (miRNA) and small-interfering RNA (siRNA) that have recently garnered more functional significance than in the past. Genomic DNA contains hundreds of thousands of such inverted repeats (IRs) with varying degrees of symmetry. But by collecting statistically significant information from a known set of ncRNA, we can sort these IRs into those that are likely to be functional.</p> <p>Results</p> <p>A novel method was developed to scan genomic DNA for partially symmetric inverted repeats and the resulting set was further refined to match miRNA precursors (pre-miRNA) with respect to their density of symmetry, statistical probability of the symmetry, length of stems in the predicted hairpin secondary structure, and the GC content of the stems. This method was applied on the <it>Arabidopsis thaliana</it> genome and validated against the set of 190 known Arabidopsis pre-miRNA in the miRBase database. A preliminary scan for IRs identified 186 of the known pre-miRNA but with 714700 pre-miRNA candidates. This large number of IRs was further refined to 483908 candidates with 183 pre-miRNA identified and further still to 165371 candidates with 171 pre-miRNA identified (i.e. with 90% of the known pre-miRNA retained).</p> <p>Conclusions</p> <p>165371 candidates for potentially functional miRNA is still too large a set to warrant wet lab analyses, such as northern blotting, on all of them. Hence additional filters are needed to further refine the number of candidates while still retaining most of the known miRNA. These include detection of promoters and terminators, homology analyses, location of candidate relative to coding regions, and better secondary structure prediction algorithms. The software developed is designed to easily accommodate such additional filters with a minimal experience in Perl.</p