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Stably acquired mutations in hematopoietic cells represent substrates of selection that may lead to clonal hematopoiesis (CH), a common state in cancer patients that is associated with a heightened risk of leukemia development. Owing to technical and sample size limitations, most CH studies have characterized gene mutations or mosaic chromosomal alterations (mCAs) individually. Here we leverage peripheral blood sequencing data from 32,442 cancer patients to jointly characterize gene mutations (n = 14,789) and mCAs (n = 383) in CH. Recurrent composite genotypes resembling known genetic interactions in leukemia genomes underlie 23% of all detected autosomal alterations, indicating that these selection mechanisms are operative early in clonal evolution. CH with composite genotypes defines a patient group at high risk of leukemia progression (3-year cumulative incidence 14.6%, CI: 7–22%). Multivariable analysis identifies mCA as an independent risk factor for leukemia development (HR = 14, 95% CI: 6–33, P, Patients with solid cancers have high rates of clonal haematopoiesis associated with increased risk of secondary leukemias. Here, by using peripheral blood sequencing data from patients with solid non-hematologic cancer, the authors profile the landscape of mosaic chromosomal alterations and gene mutations, defining patients at high risk of leukemia progression.

Background: Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome (ARDS) but it is unknown whether prone positioning improves outcomes in mechanically ventilated patients with moderate to severe ARDS due to COVID-19. Methods: A cohort study at a New York City hospital at the peak of the early pandemic in the United States, under crisis conditions. The aim was to determine the benefit of prone positioning in mechanically ventilated patients with ARDS due to COVID-19. The primary outcome was in-hospital death. Secondary outcomes included changes in physiologic parameters. Fine-Gray competing risks models with stabilized inverse probability treatment weighting (sIPTW) were used to determine the effect of prone positioning on outcomes. In addition, linear mixed effects models (LMM) were used to assess changes in physiology with prone positioning. Results: Out of 335 participants who were intubated and mechanically ventilated, 62 underwent prone positioning, 199 met prone positioning criteria and served as controls and 74 were excluded. The intervention and control groups were similar at baseline. In multivariate-adjusted competing risks models with sIPTW, prone positioning was significantly associated with reduced mortality (SHR 0.61, 95% CI 0.46-0.80, P < 0.005). Using LMM to evaluate the impact of positioning maneuvers on physiological parameters, the oxygenation-saturation index was significantly improved during days 1-3 ( P < 0.01) whereas oxygenation-saturation index (OSI), oxygenation-index (OI) and arterial oxygen partial pressure to fractional inspired oxygen (PaO2: FiO2) were significantly improved during days 4-7 (P < 0.05 for all). Conclusions: Prone positioning in patients with moderate to severe ARDS due to COVID-19 is associated with reduced mortality and improved physiologic parameters. One in-hospital death could be averted for every 8 patients treated. Replicating results and scaling the intervention are important, but prone positioning may represent an additional therapeutic option in patients with ARDS due to COVID-19.

Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease (CVD) and both are prevalent in men with testosterone deficiency. Long-term effects of testosterone therapy (TTh) on NAFLD are not well studied. This observational, prospective, cumulative registry study assesses long-term effects of testosterone undecanoate (TU) on hepatic physiology and function in 505 hypogonadal men (T levels ≤350 ng/dL). Three hundred and twenty one men received TU 1000 mg/12 weeks for up to 12 years following an initial 6-week interval (T-group), while 184 who opted against TTh served as controls (C-group). T-group patients exhibited decreased fatty liver index (FLI, calculated according to Mayo Clinic guidelines) (83.6 ± 12.08 to 66.91 ± 19.38), γ-GT (39.31 ± 11.62 to 28.95 ± 7.57 U/L), bilirubin (1.64 ± 4.13 to 1.21 ± 1.89 mg/dL) and triglycerides (252.35 ± 90.99 to 213 ± 65.91 mg/dL) over 12 years. Waist circumference and body mass index were also reduced in the T-group (107.17 ± 9.64 to 100.34 ± 9.03 cm and 31.51 ± 4.32 to 29.03 ± 3.77 kg/m2). There were 25 deaths (7.8%) in the T-group of which 11 (44%) were cardiovascular related. In contrast, 28 patients (15.2%) died in C-group, and all deaths (100%) were attributed to CVD. These data suggest that long-term TTh improves hepatic steatosis and liver function in hypogonadal men. Improvements in liver function may have contributed to reduced CVD-related mortality.

More than 5 million patients are admitted to US intensive care units (ICUs) each year. Many of these patients have risk factors for dysphagia. Dysphagia must be promptly addressed and appropriately treated to avoid the deleterious impacts of aspiration and malnutrition. Therefore, clinicians must be aware of ways to identify and treat dysphagia. This review will highlight the risk factors, mechanisms, and impact of dysphagia in the ICU as well as provide screening, diagnostic, and management options.

Prostate cancer affects a significant proportion of men worldwide. Evidence from genetic and clinical studies suggests that there may be a causal association between prostate cancer and the human papilloma virus (HPV). As HPV is a vaccine-preventable pathogen, the possibility of a role in prostate cancer causation may reinforce the importance of effective HPV vaccination campaigns. This is of particular relevance in light of the COVID-19 pandemic, which may have considerable effects on HPV vaccine uptake and distribution.

Background Globally the population of older adults is increasing. It is estimated that by 2050 the number of adults over the age of 60 will represent over 21% of the world’s population. Frailty is a clinical condition associated with ageing resulting in an increase in adverse outcomes. It is considered the greatest challenge facing an ageing population affecting an estimated 16% of community-dwelling populations worldwide. Aim The aim of this systematic review is to explore how wearable sensors have been used to assess frailty in older adults. Method Electronic databases Medline, Science Direct, Scopus, and CINAHL were systematically searched March 2020 and November 2020. A search constraint of articles published in English, between January 2010 and November 2020 was applied. Papers included were primary observational studies involving; older adults aged > 60 years, used a wearable sensor to provide quantitative measurements of physical activity (PA) or mobility and a measure of frailty. Studies were excluded if they used non-wearable sensors for outcome measurement or outlined an algorithm or application development exclusively. The methodological quality of the selected studies was assessed using the Appraisal Tool for Cross-sectional Studies (AXIS). Results Twenty-nine studies examining the use of wearable sensors to assess and discriminate between stages of frailty in older adults were included. Thirteen different body-worn sensors were used in eight different body-locations. Participants were community-dwelling older adults. Studies were performed in home, laboratory or hospital settings. Postural transitions, number of steps, percentage of time in PA and intensity of PA together were the most frequently measured parameters followed closely by gait speed. All but one study demonstrated an association between PA and level of frailty. All reports of gait speed indicate correlation with frailty. Conclusions Wearable sensors have been successfully used to evaluate frailty in older adults. Further research is needed to identify a feasible, user-friendly device and body-location that can be used to identify signs of pre-frailty in community-dwelling older adults. This would facilitate early identification and targeted intervention to reduce the burden of frailty in an ageing population.

To explore the differences in perceived patient safety culture in cancer nurses working in Estonia, Germany, the Netherlands, and the United Kingdom.An exploratory cross-sectional survey.In 2018, 393 cancer nurses completed the 12 dimensions of the Hospital Survey on Patient Safety Culture.The mean score for the overall patient safety grade was 61.3. The highest rated dimension was "teamwork within units" while "staffing" was the lowest in all four countries. Nurses in the Netherlands and in the United Kingdom, scored higher on "communication openness", the "frequency of events reported", and "non-punitive response to errors", than nurses from Estonia or Germany. We found statistically significant differences between the countries for the association between five of the 12 dimensions with the overall patient safety grade: overall perception of patient safety, communication openness, staffing, handoffs and transitions and non-punitive response to errors.Patient safety culture, as reported by cancer nurses, varies between European countries and contextual factors, such as recognition of the nursing role and education have an impact on it. Cancer nurses' role in promoting patient safety is a key concern and requires better recognition on a European and global level.Cancer Nursing Societies in any country can use these data as an indication on how to improve patient care in their country. Recognition of cancer nursing as a distinct specialty in nursing will help to improve patient safety.目的: 探讨在爱沙尼亚、德国、荷兰和英国工作的癌症护士对病人安全文化的认知差异。 设计: 探索性横向调查。 方法: 2018年,393名癌症护士完成了医院患者安全文化调查的12个维度。 结果: 总体患者安全等级的平均分数为61.3。评分最高的维度是“单位内的团队合作”,而“人员配备”在所有四个国家中都是最低的。荷兰和英国的护士在“沟通开放性”、“事件报告频率”和“对错误的非惩罚性反应”方面得分高于爱沙尼亚和德国的护士。我们发现,在12个维度中,有5个维度与患者总体安全等级之间存在统计学上的显著差异:患者总体安全感知、沟通开放性、人员配备、交接和过渡以及对错误的非惩罚性反应。 结论: 癌症护士所报告的患者安全文化在欧洲国家之间存在差异,而护理角色的认知和教育等环境因素也会对其产生影响。癌症护士在促进患者安全方面的作用是一个关键问题,需要在欧洲和全球层面上得到更好的认识。 影响: 任何国家的癌症护理协会都可以利用这些数据作为改善本国患者护理的指示。认识到癌症护理是护理的一个独特的专业将有助于提高患者安全性。.

In a larger study where the aim was to investigate choice and control in decision making, the role of partners was significant. Reported here are the experiences of those partners of young people with cancer.A qualitative, exploratory case study approach was used.In the larger study, 22 participants were recruited including five adolescents and young adults with cancer, two sets of parents/carers and three individual parents, five healthcare professionals linked to the adolescent or young adult with cancer and five friends or partners. Data were collected between February 2014 and February 2015 and included interviews, non-participant observation and documentary analysis.Three themes were identified relating to partner experience derived from partner and patient interview data: "practical support", "putting your partner first" and "acting as a confidante/ally".These findings reveal new knowledge of partner experience when adolescents and young adults have cancer. Richer in-depth understandings of partner experience are required to improve the care of adolescents and young adults with cancer and those around them.These findings will inform the development of guidance and further research which will enhance the knowledge of partner experience for those involved in cancer care in the adolescent and young adult age group.目的: 研究的主要目的是研究决策中的选择和控制,服务者在决策中起很大作用。研究主要内容是患癌青年服务者的经历。 设计: 研究使用定性,案例探索研究方法。 方法: 研究参与者共有22位,包括5位患癌青少年和青年、两对父母/照顾者和3 位离异父母、5位患癌青少年和青年分别的健康护理专家和5位朋友。数据收集始于2014年2月到2015年2月截止,收集数据包括采访、局外观察、纪录片分析。 结果: 从服务者和病人采访数据中得出三类主题的服务患癌青少年和青年经历:“实际服务”“以服务者为第一位”“作为知己或盟友” 结论: 研究发现服务患癌青少年和青年的新经历。要提高对患癌青少年和青年的服务,首先需要对这些服务患癌青少年和青年的经历有深刻的丰富的理解。 影响: 这一发现将会促进指导政策的发展和更深入的研究,进一步促进人们对服务患癌青少年和青年经历的理解。.

Understanding antibiotic use may help predict emergence of antimicrobial resistance. We evaluated antibiotic prescription trends in rural Burkina Faso, where little is known about antibiotic consumption. Antibiotic prescription data for 20 communities were extracted through record review in six primary health-care facilities serving the communities. The number of antibiotic prescriptions per child-year was calculated using population-based census data from the communities. A total of 1,444 antibiotic prescriptions were made from March to June 2017 among 3,401 children in the communities. The frequency of antibiotic prescription was 1.70 prescriptions per child-year (95% CI: 1.61–1.79). Penicillins were the most common (1.04 prescriptions per child-year, 95% CI: 1.01–1.06), followed by sulfonamides (0.69 prescriptions per child-year, 95% CI: 0.67–0.71) and macrolides (0.38 prescriptions per child-year, 95% CI: 0.37–0.40). Continued monitoring of antibiotic consumption in diverse settings will be important to understand the potential for emergence of antibiotic resistance.

Aims and objectivesTo explore the role that Donor Transplant Co‐ordinators have played and the future potential of Specialist Nurses for Organ Donation (SN‐ODs), within organ donation strategies in the UK and other countries.BackgroundOrgan donation and transplantation rates vary extensively around the world. However, there is a universal shortage of deceased donors, prompting different approaches to increase transplantation rates. Within the UK, the Clinical Lead for Organ Donation and Specialist Nurse in Organ Donation undertake a key role in the implementation of the Organ Donation Strategy. The Human Transplantation (Wales) Act 2015 is a recent development which facilities a deemed (presumed) consent approach to organ donation, the Specialist Nurse in Organ Donation undertakes a major role identifying the potential donor in this situation by confirming the deemed consent status of the donor and supporting bereaved relatives. UK governments in England and Scotland are currently seeking legislative changes to an opt‐out system of organ donation, in line with the Wales change.DesignThis discursive paper explores the role from Donor Transplant Co‐ordinator to Specialist Nurse in Organ Donation (SN‐OD) within organ donation policy in different settings, but with a specific focus on the UK. The paper clarifies the current and future potential of nurses working with bereaved families when requesting authorisation for donation.Implications for nursingThe current scope and future potential of Donor Transplant Co‐ordinator and Specialist Nurse in Organ Donation roles need better recognition. Little empirical data exist about the key role that these nurses play in the organ donation process, especially in relation to gaining authorisation to proceed to donation.ConclusionThere is a need to clarify the role of the Specialist Nurse in Organ Donation and their impact on improving rates of organ donation.

The 690,000 cases of cancer caused worldwide each year by HPV (human papillomavirus) are among the easiest of all cancers to prevent. However, the actions so far taken in terms of both policy and practice by health systems in many European states have neither matched the scale of the problem nor seized the opportunities for disease prevention potentially offered by vaccination and screening. Treatments for HPV-caused cancers are also inequitably provided across the region and widespread misinformation about HPV undermines efforts to improve public health. The European Cancer Organisation's HPV Action Network has made the case for action for the elimination of all the cancers caused by HPV through gender-neutral vaccination, effective cervical cancer screening, better quality treatments, and public and professional education across Europe. The World Health Organisation's new global strategy for the elimination of cervical cancer (launched in November 2020), together with Europe's Beating Cancer Plan (February 2021), together provide a major opportunity to tackle decisively all the cancers caused by HPV. The Beating Cancer Plan, which was significantly influenced by evidence provided by the HPV Action Network, commits to supporting EU member states' efforts to extend routine vaccination of girls and boys and to creating a new EU-supported Cancer Screening Scheme to help Member States ensure that 90% of the EU population who qualify for cervical cancer screening are offered it by 2025. The goal of HPV cancer elimination is now both possible and achievable. The challenge is to ensure implementation and delivery by EU member states and more widely across the European region.

The increased use of sensor technology has been crucial in releasing the potential for remote rehabilitation. However, it is vital that human factors, that have potential to affect real-world use, are fully considered before sensors are adopted into remote rehabilitation practice. The smart sensor devices for rehabilitation and connected health (SENDoc) project assesses the human factors associated with sensors for remote rehabilitation of elders in the Northern Periphery of Europe. This article conducts a literature review of human factors and puts forward an objective scoring system to evaluate the feasibility of balance assessment technology for adaption into remote rehabilitation settings. The main factors that must be considered are: Deployment constraints, usability, comfort and accuracy. This article shows that improving accuracy, reliability and validity is the main goal of research focusing on developing novel balance assessment technology. However, other aspects of usability related to human factors such as practicality, comfort and ease of use need further consideration by researchers to help advance the technology to a state where it can be applied in remote rehabilitation settings.

Background Hospitalized patients with COVID-19 demonstrate a higher risk of developing thromboembolism. Anticoagulation (AC) has been proposed for high-risk patients, even without confirmed thromboembolism. However, benefits and risks of AC are not well assessed due to insufficient clinical data. We performed a retrospective analysis of outcomes from AC in a large population of COVID-19 patients. Methods We retrospectively reviewed 1189 patients hospitalized for COVID-19 between March 5 and May 15, 2020, with primary outcomes of mortality, invasive mechanical ventilation, and major bleeding. Patients who received therapeutic AC for known indications were excluded. Propensity score matching of baseline characteristics and admission parameters was performed to minimize bias between cohorts. Results The analysis cohort included 973 patients. Forty-four patients who received therapeutic AC for confirmed thromboembolic events and atrial fibrillation were excluded. After propensity score matching, 133 patients received empiric therapeutic AC while 215 received low dose prophylactic AC. Overall, there was no difference in the rate of invasive mechanical ventilation (73.7% versus 65.6%, p = 0.133) or mortality (60.2% versus 60.9%, p = 0.885). However, among patients requiring invasive mechanical ventilation, empiric therapeutic AC was an independent predictor of lower mortality (hazard ratio [HR] 0.476, 95% confidence interval [CI] 0.345–0.657, p p p = 0.063). Additionally, no significant difference in mortality was found between patients receiving empiric therapeutic AC versus prophylactic AC in various subgroups with different D-dimer level cutoffs. Patients who received therapeutic AC showed a higher incidence of major bleeding (13.8% vs 3.9%, p p = 0.008), while those with a score of ≥3 had a higher risk of major bleeding (Odds ratio: 1.883, CI: 1.114–3.729, p = 0.016). Conclusion Empiric use of therapeutic AC conferred survival benefit to patients requiring invasive mechanical ventilation, but did not show benefit in non-critically ill patients hospitalized for COVID-19. Careful bleeding risk estimation should be pursued before considering escalation of AC intensity.

IntroductionThere is an increasing body of evidence to suggest that visibility of prostate cancer on magnetic resonance (MRI) may be related to likelihood of adverse pathological outcomes. Biochemical recurrence (BCR) after radical prostatectomy remains a significant clinical challenge and a means of predicting likelihood of this prior to surgery could inform treatment choice. It appears that MRI could be a potential candidate strategy for BCR prediction, and as such, there is a need to review extant literature on the prognostic capability of MRI. Here, we describe a protocol for a systematic review and meta-analysis of the utility of biparametric MRI (bpMRI) and multiparametric MRI (mpMRI) in predicting BCR following radical prostatectomy for prostate cancer treatment.Methods and analysisPubMed, MEDLINE, Embase and Cochrane databases will be searched and screening will be guided by the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. In order to meet the inclusion criteria, papers must be English-language articles involving patients who have had bpMRI or mpMRI for suspected prostate cancer and have undergone radical prostatectomy as definitive therapy. Patients must have had prostate-specific antigen monitoring before and after surgery. All relevant papers published from July 1977 to October 2020 will be eligible for inclusion. The Newcastle-Ottawa score will be used to determine the quality and bias of the studies. This protocol is written in-line with the PRISMA protocol 2015 checklist.Ethics and disseminationThere are no relevant ethical concerns. Dissemination of this protocol will be via peer-reviewed journals as well as national and international conferences.PROSPERO registration numberCRD42020206074.

Antibody detection of prior SARS-CoV-2 infection depends on severity, assay, and timing with implications for serosurveillance., Interpretation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurveillance studies is limited by poorly defined performance of antibody assays over time in individuals with different clinical presentations. We measured antibody responses in plasma samples from 128 individuals over 160 days using 14 assays. We found a consistent and strong effect of disease severity on antibody magnitude, driven by fever, cough, hospitalization, and oxygen requirement. Responses to spike protein versus nucleocapsid had consistently higher correlation with neutralization. Assays varied substantially in sensitivity during early convalescence and time to seroreversion. Variability was dramatic for individuals with mild infection, who had consistently lower antibody titers, with sensitivities at 6 months ranging from 33 to 98% for commercial assays. Thus, the ability to detect previous infection by SARS-CoV-2 is highly dependent on infection severity, timing, and the assay used. These findings have important implications for the design and interpretation of SARS-CoV-2 serosurveillance studies.

Introduction\ud A global shortage of radiologists is affecting the timely provision of imaging reports and thus healthcare delivery. This situation has been the main driving factor behind successful role extension by radiographers into areas that traditionally were within the scope of radiologists, including image interpretation and reporting. The shortage of radiologists is even worse in developing countries like Ghana. There is a need for policy to guide the introduction and implementation of role extension in Ghana.\ud Methods\ud A qualitative, single case study with multiple sites across the country was used. A sample of 16 participants, including 8 radiographers, 3 radiologists, 3 medical officers, a senior official each from the Ministry of Health and the Allied Health Professions Council, were interviewed about role extension.\ud Results\ud The findings indicate the need for a guiding policy of role extension to be spear headed by the Ministry of Health to gain the needed credibility. The findings suggest the policy should be made to meet the local needs of the country. It also established the policy should regulate education and training and the scope of practice.\ud Conclusion\ud The study established the need for policy to guide the introduction and practice of role extension in diagnostic radiography in Ghana. The study also established the need for a broad consultation of all key stakeholders based on an internationally accepted consensus building model.

Cribriform, from the Latin for 'sieve-like,' describes an aggressive prostate cancer pattern associated with poor prognosis, including biochemical recurrence after prostatectomy [1]. Following progressive integration of multiparametric magnetic resonance imaging (mpMRI) into risk stratification for suspected prostate cancer, there has been understandable concern that particular morphologies (including, intraductal, mucinous and cribriform) may have reduced visibility on mpMRI [2]. If undetected, mpMRI-invisible pathology may avoid biopsy interrogation, resulting in delayed presentation, management, and adverse clinical outcome. However, evidence surrounding mpMRI conspicuity of cribriform disease is contradictory, and given the clinical importance of this phenomenon, warrants discussion.

As cases of coronavirus disease 2019 (COVID-19) mount worldwide, attention is needed on potential long-term neurologic impacts for the majority of patients who experience mild to moderate illness managed as outpatients. To date, there has not been discussion of persistent neurocognitive deficits in patients with milder COVID-19. We present two cases of non-hospitalized patients recovering from COVID-19 with persistent neurocognitive symptoms. Commonly used cognitive screens were normal, while more detailed testing revealed working memory and executive functioning deficits. An observational cohort study of individuals recovering from COVID-19 (14 or more days following symptom onset) identified that among the first 100 individuals enrolled, 14 were non-hospitalized patients reporting persistent cognitive issues. These 14 participants had a median age of 39 years (interquartile range: 35–56), and cognitive symptoms were present for at least a median of 98 days (interquartile range: 71–120 following acute COVID-19 symptoms); no participants with follow-up evaluation reported symptom resolution. We discuss potential mechanisms to be explored in future studies, including direct viral effects, indirect consequences of immune activation, and immune dysregulation causing auto-antibody production.

Treatment with immune checkpoint inhibitors (ICI) has demonstrated clinical benefit for a wide range of cancer types. Because only a subset of patients experience clinical benefit, there is a strong need for biomarkers that are easily accessible across diverse practice settings. Here, in a retrospective cohort study of 1714 patients with 16 different cancer types treated with ICI, we show that higher neutrophil-to-lymphocyte ratio (NLR) is significantly associated with poorer overall and progression-free survival, and lower rates of response and clinical benefit, after ICI therapy across multiple cancer types. Combining NLR with tumor mutational burden (TMB), the probability of benefit from ICI is significantly higher (OR = 3.22; 95% CI, 2.26-4.58; P, There is an unmet clinical need for simple, accessible biomarkers to select patients who are more likely to respond to immune checkpoint therapy. Here the authors show that a lower neutrophil-to-lymphocyte ratio is associated with better overall and progressive-free survival, as well as higher rate of response, in a multi-cancer cohort of patients treated with immune checkpoint inhibitors.

The age‐standardised incidence of cervical cancer in Europe varies widely by country (between 3 and 25/100000 women‐years) in 2018. Human papillomavirus (HPV) vaccine coverage is low in countries with the highest incidence and screening performance is heterogeneous among European countries. A broad group of delegates of scientific professional societies and cancer organisations endorse the principles of the WHO call to eliminate cervical cancer as a public health problem, also in Europe. All European nations should, by 2030, reach at least 90% HPV vaccine coverage among girls by the age of 15 years and also boys, if cost‐effective; they should introduce organised population‐based HPV‐based screening and achieve 70% of screening coverage in the target age group, providing also HPV testing on self‐samples for nonscreened or underscreened women; and to manage 90% of screen‐positive women. To guide member states, a group of scientific professional societies and cancer organisations engage to assist in the rollout of a series of concerted evidence‐based actions. European health authorities are requested to mandate a group of experts to develop the third edition of European Guidelines for Quality Assurance of Cervical Cancer prevention based on integrated HPV vaccination and screening and to monitor the progress towards the elimination goal. The occurrence of the COVID‐19 pandemic, having interrupted prevention activities temporarily, should not deviate stakeholders from this ambition. In the immediate postepidemic phase, health professionals should focus on high‐risk women and adhere to cost‐effective policies including self‐sampling., What's new? Cervical cancer incidence, human papillomavirus (HPV) vaccination coverage, and screening performance vary widely across Europe. This report addresses for the first time the issue of how Europe should respond to the ambitious call from the World Health Organization to reduce the incidence of cervical cancer to less than 4/100,000/year. To meet this target, all European countries should put in place programs to reach 90% and 70% of HPV vaccination and screening coverage, respectively, and manage 90% of screen‐positive women by 2030. Despite the temporary interruptions of prevention activities caused by COVID‐19, the pandemic should not deviate stakeholders from this ambition.

Microwave imaging (MWI) can be used as an alternate imaging modality for monitoring bone health. Evaluation and characterization of MWI prototype is a precursor step before in vivo investigation of bone dielectric properties. This paper presents experimental evaluation of a novel two layered simplified cylindrical shaped 3D printed human calcaneus bone phantom along with corresponding MWI prototype designed to image the bone phantom. The shape of the calcaneus bone was approximated with a cylinder. The external and internal layers represent cortical bone and trabecular bone respectively. Each layer of the phantom was filled with respective liquid tissue mimicking mixture (TMM). A MWI prototype was designed having six microstrip antennas in order to hold calcaneus bone phantom. The bone phantom was placed in the imaging prototype and scattered signals were measured at each antenna. Moreover, the performance of the system was explored by examining microwave measurement sensitivity. Based on the measured scattered signals the map of dielectric properties will be constructed by employing MWI algorithm and will be communicated in our future work. This two layered 3D printed human calcaneus bone phantom and imaging prototype can be used as a valuable test platform for pre-clinical assessment of calcaneus bone imaging for monitoring osteoporosis. European Union's Horizon 2020 Programme/ERC Grant Agreement BioElecPro n. 637780. non-peer-reviewed

Background Our understanding of the different effects of targeted versus nontargeted violence on Ebola virus (EBOV) transmission in Democratic Republic of the Congo (DRC) is limited. Methods We used time-series data of case counts to compare individuals in Ebola-affected health zones in DRC, April 2018–August 2019. Exposure was number of violent events per health zone, categorized into Ebola-targeted or Ebola-untargeted, and into civilian-induced, (para)military/political, or protests. Outcome was estimated daily reproduction number (Rt) by health zone. We fit linear time-series regression to model the relationship. Results Average Rt was 1.06 (95% confidence interval [CI], 1.02–1.11). A mean of 2.92 violent events resulted in cumulative absolute increase in Rt of 0.10 (95% CI, .05–.15). More violent events increased EBOV transmission (P = .03). Considering violent events in the 95th percentile over a 21-day interval and its relative impact on Rt, Ebola-targeted events corresponded to Rt of 1.52 (95% CI, 1.30–1.74), while civilian-induced events corresponded to Rt of 1.43 (95% CI, 1.21–1.35). Untargeted events corresponded to Rt of 1.18 (95% CI, 1.02–1.35); among these, militia/political or ville morte events increased transmission. Conclusions Ebola-targeted violence, primarily driven by civilian-induced events, had the largest impact on EBOV transmission., A time-series study of the 2018–2020 Ebola virus disease outbreak in the Democratic Republic of the Congo found both Ebola-targeted and untargeted violence increased transmission, though targeted violence, primarily driven by civilian-involved events, had the largest impact.

Recent studies have found a significant dielectric contrast between healthy and osteoporotic human trabecular bones. This dielectric contrast can be exploited by microwave imaging for monitoring human bone health. The tissue mimicking phantoms play a vital role for preclinical testing of microwave imaging system. This paper presents anatomically realistic multi-layered 3D printed and carbon black based human calcaneus structure. The liquid and solid based tissue mimicking mixtures are also proposed to mimic the dielectric properties of skin, muscle, cortical bone, and trabecular bone. The liquid tissue mimicking mixtures are composed of Triton X-100, water, and salt, whereas the solid tissue mimicking mixtures are composed of carbon black, graphite, polyurethane, and isopropanol. The dielectric properties of the tissue mimicking mixtures were measured using an open-ended coaxial probe measurement technique across 0.5 8.5 GHz. The average percentage difference between the relative permittivity and conductivity of reference data and proposed liquid tissue mimicking mixtures was found to be 7.8% and 9.6% for skin, 0.38% and 14% for muscle, 9.6% and 5% for cortical bone, and 3.4% and 2.4 % for trabecular bone, respectively, across 0.5 8.5 GHz. For solid tissue mimicking mixtures, this difference was found to be 3.93% and 0.64% for skin, 6.13% and 9.21% for cortical bone, and 10.66% and 41.82% for trabecular bone, respectively for relative permittivity and conductivity. The proposed tissue mimicking mixtures along with 3D printed structures can be used as a valuable test platform for microwave bone imaging system development. peer-reviewed

Purpose Cancer nurses across Europe are being tasked with delivery of an increasing number of complex treatments and supportive care interventions as a result of ongoing advances in cancer research, and a rise in cancer incidence due to demographic changes. However, all health systems delivering cancer treatment innovations require access to an educated and motivated nursing workforce to meet demand. This study by the European Oncology Nursing Society examines comparative features of cancer nursing in Estonia, Germany, the Netherlands (NL) and the United Kingdom (UK). Methods Descriptive qualitative study using focus groups and individual interviews drawing on the views of cancer nurses, managers and stakeholders from four European countries (n = 97). Data collection was designed around national cancer nursing conferences held in Berlin (Germany), Ede (NL), Harrogate (UK) and Tallinn and Tartu between May 2017 and April 2018. Participants included a mix of nursing grades and specialisms. Findings According to the participants education and career structure for cancer nursing was most well-developed in the Netherlands and the United Kingdom. In Germany and Estonia developments were taking place at Masters level. None of the countries had recordable qualifications in cancer nursing. Variations existed in terms of advanced practice roles and salary. Workload pressures were common, and were rising, and wellbeing initiatives were not identified. Nurses reported gaining positive feedback from caring for patients. Discussion As demand for cancer treatment continues to grow there is a need to ensure an adequate supply of cancer nurses with the appropriate education and career structure to support patients. This study provides insights from four countries and suggests the need for better recognition as well as working conditions, education and career structures that advance the potential of the cancer nursing role in Europe., Highlights • What is already known about the topic? • Cancer remains a leading cause of death, despite advances in treatment and care. • Increasingly high nursing workloads are evident in Europe alongside workforce shortages. • Major changes taking place in the treatment of cancer require more individualised and targeted treatment approaches. • In some countries, cancer nurses adopt advanced roles that include prescribing and treatment co-ordination, as well as conducting clinical procedures as part of advanced roles. • What this paper adds. • Comparative qualitative insights concerning cancer nursing in Estonia, Germany, the Netherlands and the United Kingdom. • None of the countries formally recorded cancer nursing qualifications. • Despite common European Union Directives there are disparities in the availability of specialist cancer nursing education. • Working conditions (hours and pay) vary widely across EU countries. • Despite increasing workloads, a high degree of commitment and job satisfaction was reported by cancer nurses.

Cancer-associated venous thromboembolism (CAT) is a well-described complication of cancer and a leading cause of death in cancer patients. The purpose of this study was to assess potential associations of molecular signatures with CAT, including tumor-specific mutations and the presence of clonal hematopoiesis. We analyzed deep-coverage targeted DNA-sequencing data of >14,000 solid tumor samples using the MSK-IMPACT™ platform to identify somatic alterations associated with VTE. Endpoint was defined as the first instance of cancer-associated pulmonary embolism and/or proximal/distal lower extremity deep vein thrombosis. Cause-specific Cox proportional hazards regression was used, adjusting for pertinent clinical covariates. Of 11,695 evaluable individuals, 72% had metastatic disease at time of IMPACT. Tumor-specific mutations in KRAS (HR=1.34 [1.09-1.64]; adjusted p=0.08), STK11 (HR=2.12 [1.55-2.89]; adjusted pKEAP1 (HR=1.84 [1.21-2.79]; adjusted p=0.07), CTNNB1 (HR=1.73 [1.15-2.60]; adjusted p=0.09), CDKN2B (HR= 1.45 [1.13-1.85], adjusted p=0.07) and MET (HR=1.83 [1.15-2.92]; adjusted p=0.09) were associated with a significantly increased risk of CAT independent of tumor type. Mutations in SETD2 were associated with a decreased risk of CAT (HR=0.35 [0.16-0.79], adjusted p=0.09). The presence of clonal hematopoiesis was not associated with an increased VTE rate. This is the first large-scale analysis to elucidate tumor-specific genomic events associated with CAT. Somatic tumor mutations of STK11, KRAS, CTNNB1, KEAP1, CDKN2B and MET were associated with an increased risk of VTE in solid tumor patients. Further analysis is needed to validate these findings and identify additional molecular signatures unique to individual tumor types.Key PointsTumor mutations in STK11, KRAS, CTNNB1, KEAP1, CDKN2B, MET and SETD2 modulate the risk of cancer-associated thrombosis.The presence of clonal hematopoiesis does not affect the risk of cancer-associated thrombosis.

Objective\ud To explore factors that influence the introduction of role extension in radiography and to discuss its potential for improved healthcare in Ghana.\ud Key findings\ud Key findings of this review are the lack of literature on role extension in radiography in Ghana. The factors that have influenced the introduction of role extension in radiography globally include a shortage of radiologists, increased demand for radiology services, government policy and radiographer's desire for professional development.\ud Conclusions\ud Evidence indicates that radiographers can report radiographs as accurately as radiologists and appropriate education improves their performance. Radiographer-led reporting is the professional practise most likely to deliver local patient benefit. Developments in professional perceptions, training, education and regulation of reporting are required to establish confidence in radiography-led reporting.\ud Implications for practice\ud Radiographer reporting has the potential to improve patient outcomes, reduce waiting times, increase job satisfaction for radiographers and result in financial savings.

Acquired mutations are pervasive across normal tissues. However, understanding of the processes that drive transformation of certain clones to cancer is limited. Here we study this phenomenon in the context of clonal hematopoiesis (CH) and the development of therapy-related myeloid neoplasms (tMNs). We find that mutations are selected differentially based on exposures. Mutations in ASXL1 are enriched in current or former smokers, whereas cancer therapy with radiation, platinum and topoisomerase II inhibitors preferentially selects for mutations in DNA damage response genes (TP53, PPM1D, CHEK2). Sequential sampling provides definitive evidence that DNA damage response clones outcompete other clones when exposed to certain therapies. Among cases in which CH was previously detected, the CH mutation was present at tMN diagnosis. We identify the molecular characteristics of CH that increase risk of tMN. The increasing implementation of clinical sequencing at diagnosis provides an opportunity to identify patients at risk of tMN for prevention strategies. Environmental exposures shape patterns of selection for mutations in clonal hematopoiesis. Cancer therapies promote the growth of clones with mutations that are strongly enriched in treatment-related myeloid neoplasms.

BACKGROUND: The introduction of multiparametric magnetic resonance imaging (mpMRI) has improved the diagnosis of suspected prostate cancer, accurately risk-stratifying men before a biopsy. However, pre-biopsy mpMRI represents a significant deviation from the traditional approach of prostate specific antigen testing with subsequent systematic transrectal ultrasound-guided prostate biopsy and we have not yet explored the views of men who experience this new pathway. The purpose of the PACT study (PAtient views and aCceptance of mulTiparametric MRI) is to explore men’s perceptions of mpMRI. METHODS: PACT will be conducted at teaching hospitals in which mpMRI is central to the prostate cancer diagnostic pathway using a two-phase, mixed-methods, quantitative and qualitative approach. In phase I, men referred with suspected prostate cancer will complete detailed surveys to explore their views on the mpMRI-directed pathway compared to the traditional pathway and on what constitutes ‘significant’ prostate cancer. In phase II, these themes will be expanded upon with in-depth, semi-structured interviews. Qualitative data will be transcribed and thematically analysed, and quantitative questionnaire responses will be analysed statistically. DISCUSSION: PACT will provide the first detailed insight into patient perceptions on the use and acceptability of mpMRI. Furthermore, results from PACT will help contribute to the resolution of outstanding controversies that surround this technology.

Download PDFPDF\udUrology\udProtocol\udGenetic landscape of prostate cancer conspicuity on multiparametric MRI: a protocol for a systematic review and bioinformatic analysis\ud\ud Joseph M Norris1, Benjamin S Simpson1, Marina A Parry2, Clare Allen3, Rhys Ball4, Alex Freeman4, Daniel Kelly5, Alex Kirkham3, Veeru Kasivisvanathan1, Hayley C Whitaker1, Mark Emberton1\ud\udAuthor affiliations\udAbstract\ud\udIntroduction The introduction of multiparametric MRI (mpMRI) has enabled enhanced risk stratification for men at risk of prostate cancer, through accurate prebiopsy identification of clinically significant disease. However, approximately 10%–20% of significant prostate cancer may be missed on mpMRI. It appears that the genomic basis of lesion visibility or invisibility on mpMRI may have key implications for prognosis and treatment. Here, we describe a protocol for the first systematic review and novel bioinformatic analysis of the genomic basis of prostate cancer conspicuity on mpMRI.\ud\udMethods and analysis A systematic search of MEDLINE, PubMed, EMBASE and Cochrane databases will be conducted. Screening, data extraction, statistical analysis and reporting will be performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Included papers will be full text articles, written between January 1980 and December 2019, comparing molecular characteristics of mpMRI-visible lesions and mpMRI-invisible lesions at the DNA, DNA-methylation, RNA or protein level. Study bias and quality will be assessed using a modified Newcastle-Ottawa score. Additionally, we will conduct a novel bioinformatic analysis of supplementary material and publicly available data, to combine transcriptomic data and reveal common pathways highlighted across studies. To ensure methodological rigour, this protocol is written in accordance with the PRISMA Protocol 2015 checklist.\ud\udEthics and dissemination Ethical approval will not be required, as this is an academic review of published literature. Findings will be disseminated through publications in peer-reviewed journals, and presentations at national and international conferences.

Increased emphasis on the child’s voice and point of view in care and treatment has led to an expansion in the development of methods to access and identify their perspectives. Drawing on our experiences in a study of children with leukemia in hospital, this article explains the challenges and opportunities that arise in the use of five commonly used methods in a study of hospitalized children’s experiences with health care professionals, including the “Draw and Write” technique, a sticker activity, a paper–person exercise, informal interviews, and participant observation. Each of these methods was examined with regard to ease of use, data generation, and utility of data for accessing children’s perspectives and development of initial clinical guidance.

Background: Advances in research and technology coupled with an increased cancer incidence and prevalence have resulted in significant expansion of cancer nurse role, in order to meet the growing demands and expectations of people affected by cancer (PABC). Cancer nurses are also tasked with delivering an increasing number of complex interventions as a result of ongoing clinical trials in cancer research. However much of this innovation is undocumented, and we have little insight about the nature of novel interventions currently being designed or delivered by cancer nurses. Objectives: To identify and synthesise the available evidence from clinical trials on interventions delivered or facilitated by cancer nurses. Data sources and review methods: A systematic review of randomised controlled trials (RCT), quasi-RCTs and controlled before and after studies (CBA) of cancer nursing interventions aimed at improving the experience and outcomes of PABC. Ten electronic databases (CENTRAL, MEDLINE, AMED, CINAHL, EMBASE, Epistemonikos, CDSR, DARE, HTA, WHO ICTRP) were searched between 01 January 2000 and 31 May 2016. No language restrictions were applied. Bibliographies of selected studies and relevant Cochrane reviews were also hand-searched. Interventions delivered by cancer nurses were classified according to the OMAHA System. Heat maps were used to highlight the volume of evidence available for different cancer groups, intervention types and stage of cancer care continuum. Results: The search identified 22,450 records; we screened 16,169 abstracts and considered 925 full papers, of which 214 studies (247,550 participants) were included in the evidence synthesis. The majority of studies were conducted in Europe (n = 79) and USA (n = 74). Interventions were delivered across the cancer continuum from prevention and risk reduction to survivorship, with the majority of interventions delivered during the treatment phase (n = 137). Most studies (131/214) had a teaching, guidance or counselling component. Cancer nurse interventions were targeted at primarily breast, prostate or multiple cancers. No studies were conducted in brain, sarcoma or other rare cancer types. The majority of the studies (n = 153) were nurse-led and delivered by specialist cancer nurses (n = 74) or advanced cancer nurses (n = 29), although the quality of reporting was poor. Conclusions: To the best of our knowledge, this is the first review to synthesise evidence from intervention studies across the entire cancer spectrum. As such, this work provides new insights into the nature of the contribution that cancer nurses have made to evidence-based innovations, as well as highlighting areas in which cancer nursing trials can be developed in the future. This project is jointly funded by the European Oncology Nursing Society (EONS) and the European Cancer Organisation (ECCO).

We commend Alanee et al for their detailed description of prostate cancers not detected by multiparametric magnetic resonance imaging (mpMRI). 1 They analyzed radical prostatectomy findings for 33 men lacking mpMRI-conspicuous prostate cancer (defined as Prostate Imaging Reporting and Data System [PI-RADS] scores 1-2) on preoperative mpMRI. They found 27% (9/33) of men with negative mpMRI had Gleason Grade Group (GGG) 3-5 cancer at prostatectomy, including 9 with extraprostatic extension, and 1 with Gleason grade 5 + 5 disease. Ostensibly, these findings are at odds with contemporary evidence in which mpMRI-invisible disease harbors reassuring molecular and histopathological features (ie, overall GGG ≤2). 2 , 3 We believe that this discrepancy is attributable to certain methodological concerns, including quality of mpMRI acquisiton. 4

ObjectiveTo explore recipients’ perspectives on the range and origins of their emotional experiences during their ‘bad news’ consultations.MethodsParticipants were four bereaved families of children who had changed from active treatment to palliative care in paediatric oncology. Data was collected using emotional touchpoint storytelling. The names (descriptors) given to the emotional experiences were linguistically classified. Explanations of their perceived origins were examined using applied thematic analysis.Results 26 descriptors were given, relating to bodily sensations, affective states, evaluations and cognitive conditions. Three themes were identified in the origins of these experiences – ‘becoming aware’, ‘the changes’ and ‘being in this situation’. Parents described strong emotional displays during the consultation including physical collapse. These related to the internal process of ‘becoming aware’. Three descriptors were given as originating from the clinicians and their delivery of the news – ‘supported’, ‘included’, ‘trusting’. ConclusionsRecipients perceive their emotional experiences as mainly originating from the news itself, and perceived consequences of it, rather than its delivery. Strong emotional reactions during the interaction are not necessarily an indicator of ineffectual delivery.Practice ImplicationsFindings offer a thematic framing that may support and deepen practitioners’ understanding of recipients’ emotional reactions during bad news consultations.

To discuss the risks that heteronormative assumptions play in prostate cancer care and how these may be addressed.There is international evidence to support the case that LGBT patients with cancer are less likely to report poor health or self-disclose sexual orientation. Gender-specific cancers, such as prostate cancer, require particular interventions in terms of supportive care. These may include advice about side-effect management (such as incontinence or erectile dysfunction), treatment choices and social and emotional issues. In this paper, we discuss and analyse the heteronormative assumptions and culture that exist around this cancer. We argue that this situation may act as a barrier to effective supportive care for all Lesbian women, Gay, Transgender and Bisexual patients, in this case men who have sex with men. [Correction added on 21 September 2017, after first online publication: The first sentence of the Background section has been revised for clarity in this current version.] DESIGN: Theoretical exploration of heteronormativity considered against the clinical context of prostate cancer.Identification and inclusion of relevant international evidence combined with clinical discussion.This paper posits a number of questions around heteronormativity in relation to prostate cancer information provision, supportive care and male sexuality. While assumptions regarding sexual orientation should be avoided in clinical encounters, this may be difficult when heteronormative assumptions dominate. Existing research supports the assertion that patient experience, including the needs of LGBT patients, should be central to service developments.Assumptions about sexual orientation should be avoided and recorded accurately and sensitively, and relational models of care should be promoted at the start of cancer treatment in an appropriate manner. These may assist in reducing the risks of embarrassment or offence to nonheterosexual patients, or to professionals who may adopt heteronormative assumptions.Having an awareness of the risks of making heteronormative assumptions in clinical practice will be useful for all health professionals engaged in prostate cancer care. This awareness can prevent embarrassment or upset for patients and ensure a more equitable provision of service, including men with prostate cancer who do not identify as heterosexual.

Background\udDespite increasing international awareness of the impact of cancer on young adults, to date there has been limited in-depth research to understand their experiences following a diagnosis using a qualitative and longitudinal perspective.\udObjectives\udTo explore the impact of cancer on young adults’ evolving sense of self and identity over one year from the time of diagnosis. In addition, to contribute further to an understanding of innovative research methods used to examine this experience.\udDesign\udThis was a longitudinal narrative study using visual methods and a psychosocial lens. Narrative was used to re-present experiences over time.\udSetting and Sample\udRecruitment was from a Principal Treatment Centre for Teenagers and Young Adults with Cancer and a Cancer Centre for Adults in the United Kingdom. Total population sampling was used over a six-month period, recruiting 18 young adults aged between 16 and 30, one to three months from a diagnosis of bone cancer, lymphoma or leukaemia.\udMethods\udIn depth, free association narrative interviews at three-time points over a year were undertaken. Photographs were used to help with story-telling. Extensive reflexive field notes, debriefing and the use of a psychosocial research group, also formed data sources. Forty interviews were conducted with 18 participants: eight took part in three interviews, six in two interviews and four in one interview. Analysis focused on the holistic ‘case’ of the individual temporally. In-depth, visual images were analysed from discussion in the narrative text. Through memoing, coding and comparison, themes were developed across all cases and a conceptual framework developed.\udResults\udThe conceptual framework illustrates the renegotiation of self over time through narrative. This was ‘biographically’ during young adult development and across ‘cancer time’; through the core components of: the inner world, (psyche, emotion and coping); self as embodied; self as relating to others, and self as relating to place. Stories indicated that there was a constant inter- relationship over time between the renegotiation of identity and adaption of biography.\udConclusions\udThe focus in this paper is on ‘the temporality of cancer’ through the first year from diagnosis, and the juxtaposed process of managing biographical and developmental milestones. The importance of developing health care and research which enables narrative and the patient's voice has been highlighted. It emphasizes the need for professionals to ‘be with’ and ‘walk alongside’ through the intensity of a biographically and identity changing illness.\udTweetable abstract: A longitudinal narrative study exploring the impact of cancer on young adults’ evolving sense of self and identity over one year from the time of diagnosis.

To report the Card Games approach used to study men's talk about their risk for prostate cancer and as a method of data collection to analyse patterns of talk among distinct cultural groups.A constructivist grounded theory approach using focus groups to analyse men's social talk about prostate cancer.Data were collected using three focus groups with African-Caribbean, Somali, and White British men. The focus groups were conducted in a location of the men's choice with a focus group facilitator and observer. Four Card Games were given to the men to encourage social talk.The African-Caribbean men had the most democratic talk with the use of agreement and disagreement and the Somali men were the most inclusive of others and used the most humour. The White British men were competitive in their talk and the least inclusive of each other's views.The Card Games revealed differences in the pattern of talk, which provided insight into how men may use social talk to develop their understanding of prostate cancer risk. This is useful for healthcare professionals as it provides a grounding for structuring discussions with men about prostate cancer, while understanding of how risk-related knowledge may be reconstructed in social talk and interactions.The methodology discussed in this paper addressed the use of focus group to analyse talk of men from culturally diverse groups. The use of Card Games allowed the talk between the men to take centre stage and this allowed differences in the social talk of the men to become apparent. The use of this methodology could have an impact on approaches to researching cultural understandings of cancer risk, which may provide evidence on effective delivery of sociocultural relevant health education relating to cancer screening.目的: 报告使用纸牌游戏研究男性前列腺癌风险的话题,并作为一种数据收集方法,分析不同文化群体之间的谈话模式。 设计: 以构成主义实地理论方法,使用焦点小组分析男性前列腺癌的社会话题。 方法: 采用非洲加勒比黑人、索马里和英国白人男性三个焦点组收集数据。由一名焦点小组主持人和观察员在选定男性的地区进行焦点小组。为鼓励人们交谈,给他们四种游戏的纸牌。 结果: 非洲裔加勒比男性以同意和不同意的方式开展谈论,最为民主;索马里男性的谈话最包容和最幽默。英国白人男性的谈话中充满竞争意味,对彼此的观点最不包容。 结论: 纸牌游戏揭示了谈话模式的差异,为了解男性如何利用社交谈话来提高对前列腺癌风险的认识提供依据。这对医疗护理人员很有用,其为与男性展开前列腺癌的讨论提供了依据,同时了解如何在社交谈话和互动中重建风险相关知识。 影响: 本文讨论的方法是利用焦点小组分析来自不同文化群体的男性的谈话。使用纸牌游戏使得男人之间的谈话成为核心,并明显显示出这些人群之间的社交谈话差异。这一方法的使用可能会影响对研究癌症风险的文化理解方法,其可能为有效开展与癌症筛查社会文化相关的健康教育提供证据。.

Multiparametric magnetic resonance imaging (mpMRI) has enhanced risk stratification for men at risk of prostate cancer, through accurate pre‐biopsy detection of high‐risk disease [1]. However, it has become apparent that not all clinically significant prostate cancer is detected by mpMRI. Approximately 10‐20% of significant disease is invisible to mpMRI, depending on the threshold set for significance, and on the quality of mpMRI acquisition and interpretation. The threshold for significance has recently been challenged by the 29‐year follow‐up of the SPCG‐4 study, in which men with overall Gleason score 3 + 4 did not suffer prostate‐cancer‐related death [2], whilst those with overall Gleason score 4 + 3 did suffer prostate‐cancer related death (adjusted relative risk 5.73; 95% CI 1.59–20.67) potentially suggesting a new threshold for clinically significant disease. This finding is important, given that in PROMIS, no men with overall Gleason score 4 + 3 had negative pre‐biopsy mpMRI [1], indicating that actually mpMRI may identify all truly significant cancer (if SPCG‐4 is used to guide our threshold). Nonetheless, over the past two years, there has been increasing drive to better understand the nature of mpMRI‐inconspicuous disease, particularly at the molecular level.

As of June 16, 2019, an Ebola virus disease (EVD) outbreak has led to 2136 reported cases in the northeastern region of the Democratic Republic of the Congo (DRC). As this outbreak continues to threaten the lives and livelihoods of people already suffering from civil strife and armed conflict, relatively simple mathematical models and their short-term predictions have the potential to inform Ebola response efforts in real time. We applied recently developed non-parametrically estimated Hawkes point processes to model the expected cumulative case count using daily case counts from May 3, 2018, to June 16, 2019, initially reported by the Ministry of Health of DRC and later confirmed in World Health Organization situation reports. We generated probabilistic estimates of the ongoing EVD outbreak in DRC extending both before and after June 16, 2019, and evaluated their accuracy by comparing forecasted vs. actual outbreak sizes, out-of-sample log-likelihood scores and the error per day in the median forecast. The median estimated outbreak sizes for the prospective thee-, six-, and nine-week projections made using data up to June 16, 2019, were, respectively, 2317 (95% PI: 2222, 2464); 2440 (95% PI: 2250, 2790); and 2544 (95% PI: 2273, 3205). The nine-week projection experienced some degradation with a daily error in the median forecast of 6.73 cases, while the six- and three-week projections were more reliable, with corresponding errors of 4.96 and 4.85 cases per day, respectively. Our findings suggest the Hawkes point process may serve as an easily-applied statistical model to predict EVD outbreak trajectories in near real-time to better inform decision-making and resource allocation during Ebola response efforts. Keywords: Ebola virus disease, Hawkes point process, Mathematical modeling, Democratic Republic of Congo, Compartmental models

Background As of February 25, 2019, 875 cases of Ebola virus disease (EVD) were reported in North Kivu and Ituri Provinces, Democratic Republic of Congo. Since the beginning of October 2018, the outbreak has largely shifted into regions in which active armed conflict has occurred, and in which EVD cases and their contacts have been difficult for health workers to reach. We used available data on the current outbreak, with case-count time series from prior outbreaks, to project the short-term and long-term course of the outbreak. Methods For short- and long-term projections, we modeled Ebola virus transmission using a stochastic branching process that assumes gradually quenching transmission rates estimated from past EVD outbreaks, with outbreak trajectories conditioned on agreement with the course of the current outbreak, and with multiple levels of vaccination coverage. We used two regression models to estimate similar projection periods. Short- and long-term projections were estimated using negative binomial autoregression and Theil-Sen regression, respectively. We also used Gott’s rule to estimate a baseline minimum-information projection. We then constructed an ensemble of forecasts to be compared and recorded for future evaluation against final outcomes. From August 20, 2018 to February 25, 2019, short-term model projections were validated against known case counts. Results During validation of short-term projections, from one week to four weeks, we found models consistently scored higher on shorter-term forecasts. Based on case counts as of February 25, the stochastic model projected a median case count of 933 cases by February 18 (95% prediction interval: 872–1054) and 955 cases by March 4 (95% prediction interval: 874–1105), while the auto-regression model projects median case counts of 889 (95% prediction interval: 876–933) and 898 (95% prediction interval: 877–983) cases for those dates, respectively. Projected median final counts range from 953 to 1,749. Although the outbreak is already larger than all past Ebola outbreaks other than the 2013–2016 outbreak of over 26,000 cases, our models do not project that it is likely to grow to that scale. The stochastic model estimates that vaccination coverage in this outbreak is lower than reported in its trial setting in Sierra Leone. Conclusions Our projections are concentrated in a range up to about 300 cases beyond those already reported. While a catastrophic outbreak is not projected, it is not ruled out, and prevention and vigilance are warranted. Prospective validation of our models in real time allowed us to generate more accurate short-term forecasts, and this process may prove useful for future real-time short-term forecasting. We estimate that transmission rates are higher than would be seen under target levels of 62% coverage due to contact tracing and vaccination, and this model estimate may offer a surrogate indicator for the outbreak response challenges., Author summary As of February 25, 2019, 875 cases of Ebola virus disease (EVD) were reported in North Kivu and Ituri Provinces, Democratic Republic of Congo. Since the beginning of October 2018, the outbreak has largely shifted into regions in which active armed conflict has been reported, and in which EVD cases and their contacts have been difficult for health workers to reach. We used an ensemble of models to estimate EVD transmission rates and to forecast the short- and long-term course of the outbreak. Our models project that a final size of roughly up to 300 additional cases is most likely, and estimate that transmission rates are higher than would be seen under optimal levels of contact tracing and vaccination. While a catastrophic outbreak is not projected, is it not ruled out, and prevention and vigilance are warranted.

ObjectivesThe aim of this study was to explore the barriers to accessing cancer services faced by adults with pre-existing physical disabilities.DesignCross-sectional, exploratory qualitative study. Data were collected by semistructured interviews and analysed thematically.SettingParticipants were recruited through statutory and third sector organisations in England and Wales between October 2017 and October 2018.Participants18 people with a diagnosis of cancer and a pre-existing physical disability.ResultsThe findings illustrate that people with physical disabilities in England and Wales face a variety of barriers to accessing cancer services. The overall theme that emerged was that participants experienced a lack of attitudinal and institutional preparation both from healthcare professionals and healthcare facilities. This overall theme is illustrated through three subthemes: lack of acknowledgment of disability, unseeing disability and physical inaccessibility.ConclusionsAs the population ages and increasing numbers of people live with cancer and disability, it is important to develop knowledge to respond to the needs of this population. The mere existence of services does not guarantee their usability. Services need to be relevant, flexible, and accessible and offered in a respectful manner. It is important that healthcare professionals work towards inclusive healthcare provision, enabling the utilisation of services by all. Necessary steps to be taken include better communication between the various professionals and across the different teams involved in patients’ care, raising awareness of how physical disability can affect or interact with cancer-related treatment and creating more accessible physical environments.

Somatostatin receptor ligands (SRL) and GHR antagonists are used for persistent or recurrent acromegaly following noncurative surgery and as primary therapy for patients unsuitable for surgery. We tested in vitro action of a novel oral SRL compound ONO-5788 and its active metabolite (ONO-ST1-641) which signals via SST2. With IRB approval and informed consent, 12 human somatotroph adenomas, obtained at transsphenoidal resection were cultured. In the 1st cohort, 8 somatotroph adenomas were treated with ONO-ST1-641 (0, 100, 1000 nM) and octreotide (OCT, 100 nM) for 24 h, and media collected at 2, 6, and 24 h respectively to assess GH and PRL concentrations by ELISA. Cells harvested at 24 h were used to measure mRNA levels of SST2 and SST5, hormone genes and cell cycle genes CDKN1A, CDKN1B by qPCR. Three of 8 tumors (38%) responded to ONO-ST1-641 and OCT as early as 2 and 6 h. GH was significantly reduced by OCT (18% to 58% reduction, P

Evaluations of community-based antiretroviral therapy (ART) programmes have demonstrated positive outcomes, but little is known about the impact of tapering community-based ART. The objective of this study was to assess 24-month HIV retention outcomes of a community-based ART programme and its tapered visit frequency in Koidu City, Sierra Leone. This retrospective, quasi-experimental study compared outcomes of 52 HIV-infected persons initiated on community-based ART against 91 HIV-infected persons receiving the standard of care from November 2009 to February 2013. The community-based ART pilot programme was designed to strengthen the standard of care through a comprehensive, patient-centred case management strategy. The strategy included medical, educational, psychological, social, and economic support. Starting in October 2011, the frequency of home visits was tapered from twice daily every day per week to once daily three days per week. Outcomes were retention in care at 12 and 24 months and adherence to ART over a three-month time period. Participants who received community-based ART had significantly higher retention than those receiving standard of care. At 12 months, retention rates for community-based ART and standard of care were 61.5% and 31.9%, respectively (p < .01). At 24 months, retention rates for community based ART and standard of care were 73.1% and 44.0%, respectively (p < .01). Significant differences in levels of adherence were observed when comparing community-based ART against persons receiving standard of care (p < .05). No differences in adherence levels were observed between groups of people receiving various frequencies of home visits. Our pilotprogramme in Koidu City provides new evidence that community-based ART has the potential to improve retention and adherence outcomes for HIV-infected persons, regardless of the frequency of home visits. Overcoming the barriers to HIV care requires a comprehensive, patient-centred approach that may include clinic-based and community-based interventions.Keywords: HIV/AIDS; community-based ART programme; adherence; retention in care; Sierra Leone

Background While qualitative assessments of Ebola virus disease (EVD)-related stigma have been undertaken among survivors and the general public, quantitative tools and assessment targeting survivors have been lacking. Methods and findings Beginning in June 2015, EVD survivors from seven Liberian counties, where most of the country’s EVD cases occurred, were eligible to enroll in a longitudinal cohort. Seven stigma questions were adapted from the People Living with HIV Stigma Index and asked to EVD survivors over the age of 12 at initial visit (median 358 days post-EVD) and 18 months later. Primary outcome was a 7-item EVD-related stigma index. Explanatory variables included age, gender, educational level, pregnancy status, post-EVD hospitalization, referred to medical care and EVD source. Proportional odds logistic regression models and generalized linear mixed-effects models were used to assess stigma at initial visit and over time. The stigma questions were administered to 859 EVD survivors at initial visit and 741 (86%) survivors at follow-up. While 63% of survivors reported any stigma at initial visit, only 5% reported any stigma at follow-up. Over the 18-month period, there was a significant decrease in stigma among EVD survivors (Adjusted Odds Ratio [AOR], 0.02; 95% Confidence Interval [CI], 0.01–0.04). At initial visit, having primary, junior high or vocational education, and being referred to medical care was associated with higher odds of stigma (educational level: AOR, 1.82; 95%CI, 1.27–2.62; referred: AOR, 1.50; 95%CI, 1.16–1.94). Compared to ages of 20–29, those who had ages of 12–19 or 50+ experienced lower odds of stigma (12–19: AOR, 0.32; 95%CI, 0.21–0.48; 50+: AOR, 0.58 95%CI, 0.37–0.91). Conclusions Our data suggest that EVD-related stigma was much lower more than a year after active Ebola transmission ended in Liberia. Among survivors who screened negative for stigma, additional probing may be considered based on age, education, and referral to care., Author summary Survivors of Ebola virus disease (EVD) experienced stigma throughout the 2013–2016 West African outbreak, but post-outbreak experiences of EVD-related stigma have been limited to qualitative studies. We adapted a 7-item EVD-related stigma index from the HIV literature, which was administered to EVD survivors of the observational cohort, Ebola Natural History Study, in Liberia beginning in June 2015. While 63% of 859 EVD survivors reported any EVD-related stigma during the end of the outbreak in Liberia, only 5% of 741 survivors reported any stigma 18-months post-outbreak, suggesting that survivors experienced little to no EVD-related stigma in the absence of active Ebola virus transmission. Among survivors who screened negative for stigma, additional probing may be considered based on age, education, and referral to care.

As of May 27, 2018, 6 suspected, 13 probable and 35 confirmed cases of Ebola virus disease (EVD) had been reported in Équateur Province, Democratic Republic of Congo. We used reported case counts and time series from prior outbreaks to estimate the total outbreak size and duration with and without vaccine use. We modeled Ebola virus transmission using a stochastic branching process model that included reproduction numbers from past Ebola outbreaks and a particle filtering method to generate a probabilistic projection of the outbreak size and duration conditioned on its reported trajectory to date; modeled using high (62%), low (44%), and zero (0%) estimates of vaccination coverage (after deployment). Additionally, we used the time series for 18 prior Ebola outbreaks from 1976 to 2016 to parameterize the Thiel-Sen regression model predicting the outbreak size from the number of observed cases from April 4 to May 27. We used these techniques on probable and confirmed case counts with and without inclusion of suspected cases. Probabilistic projections were scored against the actual outbreak size of 54 EVD cases, using a log-likelihood score. With the stochastic model, using high, low, and zero estimates of vaccination coverage, the median outbreak sizes for probable and confirmed cases were 82 cases (95% prediction interval [PI]: 55, 156), 104 cases (95% PI: 58, 271), and 213 cases (95% PI: 64, 1450), respectively. With the Thiel-Sen regression model, the median outbreak size was estimated to be 65.0 probable and confirmed cases (95% PI: 48.8, 119.7). Among our three mathematical models, the stochastic model with suspected cases and high vaccine coverage predicted total outbreak sizes closest to the true outcome. Relatively simple mathematical models updated in real time may inform outbreak response teams with projections of total outbreak size and duration.

Aims\ud Low testosterone in men is associated with increased cardiovascular events and mortality. Testosterone has beneficial effects on several cardiovascular risk factors including cholesterol, endothelial dysfunction and inflammation as key mediators of atherosclerosis. Although evidence suggests testosterone is anti-atherogenic, its mechanism of action is unknown. The present study investigates whether testosterone exerts anti-atherogenic effects by stimulating cholesterol clearance from macrophages via activation of liver X receptor (LXRα), a nuclear master regulator of cellular cholesterol homeostasis, lipid regulation, and inflammation.\ud \ud Main methods\ud Using human monocyte THP-1 cells differentiated into macrophages, the effect of testosterone (1–10 nM) treatment (24–72 h) on the expression of LXRα and LXR- targets apolipoprotein E (APOE), ATP-binding cassette transporter A1 (ABCA1), sterol regulatory element-binding transcription factor 1 (SREBF1) and fatty acid synthase (FAS), was investigated via qPCR and western blotting, with or without androgen receptor blockade with flutamide or LXR antagonism with CPPSS-50. Cholesterol clearance was measured by monitoring fluorescent dehydroergosterol (DHE) cellular clearance and ABCA1 cellular translocation was observed via immunocytochemistry in testosterone treated macrophages.\ud \ud Key findings\ud Testosterone increased mRNA and protein expression of LXRα, APOE, ABCA1, SREBF1 and FAS. These effects were blocked by flutamide and independently by LXR antagonism with CPPSS-50. Furthermore testosterone stimulated cholesterol clearance from the macrophages and promoted the translocation of ABCA1 toward the cell membrane.\ud \ud Significance\ud Testosterone acts via androgen receptor-dependent pathways to stimulate LXRα and downstream targets to induce cholesterol clearance in human macrophages. This may, in part, explain the anti-atherogenic effects of testosterone frequently seen clinically.

Early detection of Rheumatoid Arthritis (RA) and other neurological conditions is vital for effective treatment. Existing methods of detecting RA rely on observation, questionnaires, and physical measurement, each with their own weaknesses. Pharmaceutical medications and procedures aim to reduce the debilitating effect, preventing the progression of the illness and bringing the condition into remission. There is still a great deal of ambiguity around patient diagnosis, as the difficulty of measurement has reduced the importance that joint stiffness plays as an RA identifier. The research areas of medical rehabilitation and clinical assessment indicate high impact applications for wearable sensing devices. As a result, the overall aim of this research is to review current sensor technologies that could be used to measure an individual’s RA severity. Other research teams within RA have previously developed objective measuring devices to assess the physical symptoms of hand steadiness through to joint stiffness. Unfamiliar physical effects of these sensory devices restricted their introduction into clinical practice. This paper provides an updated review among the sensor and glove types proposed in the literature to assist with the diagnosis and rehabilitation activities of RA. Consequently, the main goal of this paper is to review contact systems and to outline their potentialities and limitations. Considerable attention has been paid to gloved based devices as they have been extensively researched for medical practice in recent years. Such technologies are reviewed to determine whether they are suitable measuring tools.

Objectives: This paper uses clinical audit to determine the extent and dosimetric impact of additional imaging for patients undergoing ocular proton beam therapy who have no clips visible in the collimated beam. Methods: An audit was conducted on 399 patients treated at The National Centre for Eye Proton Therapy between 3 July 2017 and 14 June 2019. The mean total number of image pairs over the course of treatment for patients with and without clips visible in the collimated beam were compared. Results: Among 364 evaluable patients, 333 had clips visible in the collimated beam and 31 did not. There was a statistically significant increase of five image pairs required for patients with no clips visible compared with those with clips visible (mean 14.6 vs 9.6 image pairs, respectively; p = 2.74 × 10–6). This equated to an additional 1.5 mGy absorbed dose, representing an increase in secondary cancer induction risk from 0.0004 to 0.0007%. Conclusions: The small increase in concomitant dose and set-up time for patients with no clips visible in the collimated beam is not clinically significant. Advances in knowledge: This novel work highlights clinical audit from real on-treatment geometric verification data and frequencies, rather than protocols, for ocular proton beam therapy; something not present in the literature. The simple and straightforward methodology is easily and equally applicable to clinical audits (especially those under Ionising Radiation (Medical Exposure) Regulations) for photon techniques.

An epidemic of Ebola virus disease (EVD) beginning in 2013 has claimed an estimated 11 310 lives in West Africa. As the EVD epidemic subsides, it is important for all who participated in the emergency Ebola response to reflect on strengths and weaknesses of the response. Such reflections should take into account perspectives not usually included in peer-reviewed publications and after-action reports, including those from the public sector, nongovernmental organizations (NGOs), survivors of Ebola, and Ebola-affected households and communities. In this article, we first describe how the international NGO Partners In Health (PIH) partnered with the Government of Sierra Leone and Wellbody Alliance (a local NGO) to respond to the EVD epidemic in 4 of the country's most Ebola-affected districts. We then describe how, in the aftermath of the epidemic, PIH is partnering with the public sector to strengthen the health system and resume delivery of regular health services. PIH's experience in Sierra Leone is one of multiple partnerships with different stakeholders. It is also one of rapid deployment of expatriate clinicians and logistics personnel in health facilities largely deprived of health professionals, medical supplies, and physical infrastructure required to deliver health services effectively and safely. Lessons learned by PIH and its partners in Sierra Leone can contribute to the ongoing discussion within the international community on how to ensure emergency preparedness and build resilient health systems in settings without either.

Aims The aim of this study was to explore the role stressors experienced by executive nurse directors and strategies employed to maintain resilience. Background Recent financial pressures on and care quality scandals in the UK NHS impact on the work of executive nurse directors. The short length of tenure and the high number of vacancies for these posts point to the exacting demands of the role and raise questions about the support mechanisms available for the most senior nurses in NHS organizations. Design A grounded constructivist study. Methods Semi-structured telephone interviews conducted between February–July, 2014. Results Stressors were both chronic (workload, lack of corporate responsibility for quality, reductions in quality team staffing, tensions between financial solvency and care quality and personal vulnerability) and acute (dealing with complaints and major incidents). Resilience required the support of fellow executives, peers, family and mentors and could be enhanced by self-discipline, good preparation for the post and ongoing coaching. Conclusion Recent fiscal austerity and scandals relating to quality of care have increased pressure on executive nurse directors. Increasing size of organizations, limited resources devoted to quality combined with poorly defined limits of responsibility are all major stressors and executive nurse directors, both in the United Kingdom and internationally, need clear strategies to maintain resilience. Repetitive demands for data by oversight organizations may detract from more important quality assurance strategies.