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blished by BMJ.OBJECTIVES To measure the frequency of patients making avoidable emergency department (ED) attendances after contact with NHS 111 and to examine whether these attendances can be predicted reliably. DESIGN Analysis of 16 563 946 calls made to 111, where each call was linked with a record of whether the patient attended ED within 24 hours. SETTING All regions of England from March 2015 to October 2017. PARTICIPANTS AND DATA Our main regression model used a sample of 10 954 783 calls, each with detailed patient-level information. MAIN OUTCOME Whether patients made an unadvised, non-urgent type 1 ED ('avoidable') attendance within 24 hours of calling 111. RESULTS Of 16 563 946 calls to 111, 12 894 561 (77.8%) were not advised to go to ED (ie, they were advised to either attend primary care, attend another non-ED healthcare service or to self-care). Of the calls where the patient was not advised to go to the ED, 691 783 (5.4%) resulted in the patient making an avoidable ED attendance within 24 hours. Among other factors, calls were less likely to result in these attendances when they received clinical input (adjusted OR 0.52, 95% CI 0.51 to 0.53) but were more likely when the patient was female (OR 1.07, 95% CI 1.06 to 1.08) or aged 0-4 years (OR 1.34, 95% CI 1.33 to 1.35). CONCLUSIONS For every 20 calls where 111 did not advise people to attend the ED, 1 resulted in avoidable ED attendance within 24 hours. These avoidable attendances could be predicted, to a certain extent, based on call characteristics. ZK-62711 in vivo ZK-62711 in vivo It may be possible to use this information to help 111 call handlers identify which callers are at higher risk of these attendances. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.INTRODUCTION Arthroscopic partial meniscectomy (APM) after degenerative meniscus tears is one of the most frequently performed surgeries in orthopaedics. Although several randomised controlled trials (RCTs) have been published that showed no clear benefit compared with sham treatment or non-surgical treatment, the incidence of APM remains high. The common perception by most orthopaedic surgeons is that there are subgroups of patients that do need APM to improve, and they argue that each study sample of the existing trials is not representative for the day-to-day patients in the clinic. Therefore, the objective of this individual participant data meta-analysis (IPDMA) is to assess whether there are subgroups of patients with degenerative meniscus lesions who benefit from APM in comparison with non-surgical or sham treatment. ZK-62711 in vivo METHODS AND ANALYSIS An existing systematic review will be updated to identify all RCTs worldwide that evaluated APM compared with sham treatment or non-surgical treatment in patients with ethical concerns remain. This IPDMA will provide the evidence base to update and tailor diagnostic and treatment protocols as well as (international) guidelines for patients for whom orthopaedic surgeons consider APM. The results will be submitted for publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER CRD42017067240. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. link2 No commercial re-use. See rights and permissions. Published by BMJ.INTRODUCTION Young people aged 16 to 24 have the highest prevalence of genital chlamydia and gonorrhoea compared with other age groups and re-infection rates following treatment are high. Long-term adverse health effects include subfertility and ectopic pregnancy, particularly among those with repeated infections. We developed the safetxt intervention delivered by text message to reduce sexually transmitted infection (STI) by increasing partner notification, condom use and (STI) testing among young people in the UK. link3 METHODS AND ANALYSIS A single-blind randomised trial to reliably establish the effect of the safetxt intervention on chlamydia and gonorrhoea infection at 1 year. We will recruit 6250 people aged 16 to 24 years who have recently been diagnosed with chlamydia, gonorrhoea or non-specific urethritis from health services in the UK. Participants will be allocated to receive the safetxt intervention (text messages designed to promote safer sexual health behaviours) or to receive the control text messageployer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.INTRODUCTION A relevant subsample of patients with chronic low back pain (CLBP) have manifested augmented central pain processing, central sensitisation (CS). Patients with CLBP have limited functioning and participation. Theoretically, physical functioning in patients with CLBP can plausibly be linked to CS; however, evidence to explain such association is scarce. link2 Moreover, there is no gold standard for CS diagnosis. The objectives of the study are (1) to analyse the association between instruments assessing reference symptoms and signs attributed to CS; (2) to analyse whether reference symptoms and signs attributed to CS are associated with functioning measurement outcomes; and (3) to analyse whether changes (between baseline and discharge) in reference symptoms and signs attributed to CS are related to changes in each of the functioning measurement outcomes. METHODS AND ANALYSIS A cross-sectional and longitudinal observational study is performed with measurements taken at baseline and discharge of an inter stakeholders. TRIAL REGISTRATION NUMBER NTR7167/NL6980. link2 © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.OBJECTIVE To estimate the impact of using the Aptima messenger RNA (mRNA) high-risk human papilloma virus (HR-HPV) assay versus a DNA HR-HPV assay in a primary HPV cervical screening programme. DESIGN One hypothetical cohort followed for 3 years through HPV primary cervical screening. SETTING England. PARTICIPANTS A hypothetical cohort of women aged 25-65 years tested in the National Health Service (NHS) Cervical Screening Programme (CSP) for first call or routine recall testing. METHODS A decision tree parameterised with data from the CSP (2017/18) and the HORIZON study. Uncertainty analyses were conducted using data from the FOCAL and GAST studies, other DNA HPV tests in addition to one-way and probabilistic sensitivity and scenarios analyses, to test the robustness of results. INTERVENTIONS Aptima mRNA HR-HPV assay and a DNA HR-HPV assay (cobas 4800 HPV assay). MAIN OUTCOME MEASURES Primary total colposcopies and total costs for the cohort. Secondary total HPV and cytology tests, number lost to follow-up. RESULTS At baseline for a population of 2.25 million women, an estimated £15.4 million (95% credibility intervals (CI) £6.5 to 24.1 million) could be saved and 28 009 (95% CI 27 499 to 28 527) unnecessary colposcopies averted if Aptima mRNA assays are used instead of a DNA assay, with 90 605 fewer unnecessary HR-HPV and 253 477 cytology tests performed. These savings are due to a lower number of HPV positive samples in the mRNA arm. When data from other primary HPV screening trials were compared, results indicated that using the Aptima mRNA assay generated cost savings and reduced testing in every scenario. CONCLUSION Using the Aptima mRNA assay versus a DNA assay would almost certainly yield cost savings and reduce unnecessary testing and procedures, benefiting the NHS and women in the CSP. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE To qualitatively analyse different types of dissemination of information during monthly group calls between researchers, providers and clinical staff used to establish best practices for implementing an asthma shared decision-making (SDM) intervention. Evaluating dissemination of information can provide a better understanding of how best practices are shared, informing implementation approaches to improve the uptake of new evidence and overcome barriers. SETTING 10 primary care practices in North Carolina. PARTICIPANTS Providers and clinical staff participated in monthly group phone calls with researchers to share best practices during implementation of a SDM intervention for asthma patients. DESIGN The research team transcribed and coded statements using content analysis into three different knowledge types Knowledge Position, Knowledge Form and Knowledge Object. Knowledge Objects were further classified using directed content analysis where the research team interpreted the content objects throughccurred. These exploratory dissemination of information results provide additional mechanisms for evaluating implementation science. TRIAL REGISTRATION NUMBER NCT02047929; Post-results. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.NHS vanguards, under-pressure to perform, required better contracting and data management arrangements with evaluation teams, to ensure that integrated service outcomes could be reported effectively. This communication reflects the experience of evaluating an NHS vanguard and suggests how academic teams can improve capacity for complex programme evaluation of rapid improvements in integrated services. This should be based on a shared commitment to data collection and management. Also, robust knowledge exchange processes can enable systems change and sustainability. The identifying features of the particular site have been withheld. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Chromatin-associated architectural proteins are part of a fundamental support system for cellular DNA-dependent processes and can maintain/modulate the efficiency of DNA replication, transcription, and DNA repair. Interestingly, prognostic outcomes of many cancer types have been linked with the expression levels of several of these architectural proteins. The High Mobility Group Box (HMGB) architectural protein family has been well studied in this regard. link3 The differential expression levels of HMGB proteins and/or mRNAs and their implications in cancer etiology and prognosis present the potential of novel targets that can be explored to increase the efficacy of existing cancer therapies. HMGB1, the most studied member of the HMGB protein family, has pleiotropic roles in cells including an association with nucleotide excision repair, base excision repair, mismatch repair, and DNA double-strand break repair. Moreover, the HMGB proteins have been identified in regulating DNA damage responses and cell survival following treatment with DNA-damaging agents, and as such, may play roles in modulating the efficacy of chemotherapeutic drugs by modulating DNA repair pathways. Here, we discuss the functions of HMGB proteins in DNA damage processing, and their potential roles in cancer etiology, prognosis and therapeutics. Copyright ©2020, American Association for Cancer Research.Patient-Derived Xenografts (PDXs) are tumor-in-mouse models for cancer. PDX collections, such as the NCI PDXNet, are powerful resources for preclinical therapeutic testing. However, variations in experimental and analysis procedures have limited interpretability. To determine the robustness of PDX studies, the PDXNet tested temozolomide drug response for three pre-validated PDX models (sensitive, resistant, and intermediate) across four blinded PDX Development and Trial Centers (PDTCs) using independently selected SOPs. Each PDTC was able to correctly identify the sensitive, resistant, and intermediate models, and statistical evaluations were concordant across all groups. link3 We also developed and benchmarked optimized PDX informatics pipelines, and these yielded robust assessments across xenograft biological replicates. These studies show that PDX drug responses and sequence results are reproducible across diverse experimental protocols. In addition, we share the range of experimental procedures that maintained robustness, as well as standardized cloud-based workflows for PDX exome-seq and RNA-Seq analysis and for evaluating growth.
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