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Background Global annual cancer incidence is forecast to rise to 27.5M by 2040, a 62% rise from 2018. For most cancers, prevention and early detection are the most effective ways of reducing mortality. This study maps trials in cancer screening, prevention and early diagnosis (SPED) to identify areas of unmet need and highlight research priorities. Methods A systematic mapping review was conducted to evaluate all clinical trials focused on cancer SPED, irrespective of tumour type. The National Cancer Research Institute (NCRI) portfolio, EMBASE, PubMed and Medline were searched for relevant papers published between 01/01/2007 and 01/04/2020. References were exported into Covidence software and double-screened. Data were extracted and mapped according to tumour site, geographical location, and intervention type. Results 117,701 abstracts were screened, 5157 full texts reviewed, and 2888 studies included. 1184 (52%) trials focussed on screening, 554 (24%) prevention, 442 (20%) early diagnosis and 85 (4%) a combination. Colorectal, breast and cervical cancer comprised 61% of all studies compared with 6.4% in lung and 1.8% in liver cancer. The latter two are responsible for 26.3% of global cancer deaths compared with 19.3% for the former three. Number of studies varied markedly according to geographical location; 88% were based in North America, Europe or Asia. Conclusions This study shows clear disparities in the volume of research conducted across different tumour types and according to geographical location. These findings will help drive future research effort so that resources can be directed towards major challenges in cancer SPED.

Funder: Wellcome Trust, OBJECTIVES: This study aimed to understand and explore patient and general practitioner (GP) experiences of 'traditional' and 'one-stop' prostate cancer diagnostic pathways in England. DESIGN: Qualitative study using semi-structured interviews, analysed using inductive thematic analysis SETTING: Patients were recruited from National Health Service (NHS) Trusts in London and in Devon; GPs were recruited via National Institute for Health Research (NIHR) Clinical Research Networks. Interviews were conducted in person or via telephone. PARTICIPANTS: Patients who had undergone a MRI scan of the prostate as part of their diagnostic work-up for possible prostate cancer, and GPs who had referred at least one patient for possible prostate cancer in the preceding 12 months. RESULTS: 22 patients (aged 47-80 years) and 10 GPs (6 female, aged 38-58 years) were interviewed. Patients described three key themes: cancer beliefs in relation to patient's attitudes towards prostate cancer;communication with their GP and specialist having a significant impact on experience of the pathway and pathway experience being influenced by appointment and test burden. GP interview themes included: the challenges of dealing with imperfect information in the current pathway; managing uncertainty in identifying patients with possible prostate cancer and sharing this uncertainty with them, and other social, cultural and personal contextual influences. CONCLUSIONS: Patients and GPs reported a range of experiences and views of the current prostate cancer diagnostic pathways in England. Patients valued 'one-stop' pathways integrating prostate MRI and diagnostic consultations with specialists over the more traditional approach of several hospital appointments. GPs remain uncertain how best to identify patients needing referral for urgent prostate cancer testing due to the lack of accurate triage and risk assessment strategies.

Lymphomas are a diverse and relatively common cancer type in the UK. Early diagnosis of lymphoma is vital for improving patient outcomes. The majority of patients diagnosed with lymphoma have a life expectancy of more than 5 years. Lymphoma treatments can have long-term health consequences, and patients with a history of lymphoma have a higher risk of subsequently developing other cancers. More robust evidence for the early diagnosis of lymphoma in primary care has been published in recent years, and the classification of lymphoma has recently been updated by the World Health Organisation. This article focuses on the diagnosis of lymphoma in adolescents and adults and the on-going care needs of patients who are being treated for lymphoma or have survived a diagnosis of lymphoma. Further information about lymphoma and other cancers in children can be found in the InnovAiT article by Dr Jennifer Kelly published in 2017.

Introduction Black men are twice as likely to be diagnosed with prostate cancer than White men. Raised prostate-specific antigen (PSA) levels can indicate an increased risk of prostate cancer, however it is not known whether PSA levels differ for men of different ethnic groups. Methods PubMed and Embase were searched to identify studies that reported levels of PSA for men of at least two ethnic groups without a prostate cancer diagnosis or symptoms suggestive of prostate cancer. An adaptation of the Newcastle-Ottawa scale was used to assess risk of bias and study quality. Findings were stratified into the following broad ethnic groups: White, Black, Asian, Hispanic, and Other. Data were analysed in a narrative synthesis due to the heterogeneity of reported PSA measures and methods in the included studies. Results A total of 654 197 males from 13 studies were included. By ethnicity, this included 536 201 White (82%), 38 287 Black (6%), 38 232 Asian (6%), 18 029 Pacific Island (3%), 13 614 Maori (2%), 8 885 Hispanic (1%), and 949 Other ( Conclusions Black men without prostate cancer have higher PSA levels than White or Hispanic men, which reflects the higher rates of prostate cancer diagnosis in Black men. Despite that, the diagnostic accuracy of PSA for prostate cancer for men of different ethnic groups is unknown, and current guidance for PSA test interpretation does not account for ethnicity. Future research needs to determine whether Black men are diagnosed with similar rates of clinically significant prostate cancer to White men, or whether raised PSA levels are contributing to overdiagnosis of prostate cancer in Black men.

BACKGROUND Maternal mortality in East Africa is high with a maternal mortality rate of 428 per 100,000 live births. Malawi, whilst comparing favourably to East Africa as a whole, continues to have a high maternal mortality rate (349 per 100,000 live births) despite it being reduced by 53% since 2000. To make further improvements in maternal healthcare, initiatives must be carefully targeted and evaluated to achieve maximum influence. The Malawian Government is committed to improving maternal health; however, to achieve this goal, the quality of care must be high. Furthermore, such a goal requires enough staff with appropriate training. There are not enough midwives in Malawi; therefore, focusing on staff working lives has the potential to improve care and retain staff within the system. OBJECTIVE This study aimed to identify ways in which working lives of maternity healthcare workers could be enhanced to improve clinical care. STUDY DESIGN We conducted a 1-year ethnographic study of 3 district-level hospitals in Malawi. Data were collected through observations and discussions with staff and analyzed iteratively. The ethnography focused on the interrelationships among staff as these relationships seemed most important to working lives. The field jottings were transcribed into electronic documents and analyzed using NVivo. The findings were discussed and developed with the research team, participants, and other researchers and healthcare workers in Malawi. To understand the data, we developed a conceptual model, “the social order of the hospital,” using Bourdieu's work on political sociology. The social order was composed of the social structure of the hospital (hierarchy), rules of the hospital (how staff in different staff groups behaved), and precedent (following the example of those before them). RESULTS We used the social order to consider the different core areas that emerged from the data: processes, clinical care, relationships, and context. The Malawian system is underresourced with staff unable to provide high-quality care because of the lack of infrastructure and equipment. However, some processes hinder them on national and local level, for example staff rotations and poorly managed processes for labeling drugs. The staff are aware of the clinical care they should provide; however, they sometimes do not provide such care because they are working with the predefined system and they do not want to disrupt it. Within all of this, there are hierarchical relationships and a desire to move to the next level of the system to ensure a better life with more benefits and less direct clinical work. These elements interact to keep care at its most basic as disruption to the “usual” way of doing things is challenging and creates more work. CONCLUSION To improve the working lives of the Malawian maternity staff, it is necessary to focus on improving the working culture, relationships, and environment. This may help the next generation of Malawian maternity staff to be happier at work and to better provide respectful, comprehensive, high-quality care to women.

BACKGROUND: Globally, many mothers and their babies die during pregnancy and childbirth. A key element of optimizing outcomes is high- quality antenatal care. The Government of Nepal has significantly improved antenatal care and health outcomes through high-level commitment and investment; however, only 69% of patients attend the 4 recommended antenatal appointments.OBJECTIVE: This study aimed to evaluate the quality and perceptions of antenatal care in Nepal to understand compliance with the Nepalese standards.STUDY DESIGN: This cross-sectional study was conducted at a tertiary referral and private hospital in Kathmandu and a secondary hos- pital in Makwanpur, Nepal. The study recruited 538 female inpatients on postnatal wards during the 2-week data collection period from May 2019 to June 2019. A review of case notes and verbal survey of women to understand the pregnancy information they received and their sat- isfaction with antenatal care were performed. We created a summary score of the completeness of antenatal care services received ranging from 0 to 50 (50 indicating complete conformity with standards) and investigated the determinants of attending 4 antenatal care visits and patient satisfaction.RESULTS: The median antenatal care attendance was 4 visits at the secondary and referral hospitals and 8 visits at the private hospital. However, 24% of the patients attended CONCLUSION: Few women achieved full compliance with the Nepali antenatal care standards; however, some services were delivered well. To improve, each antenatal contact needs to meet its clinical aims and be respectful. To achieve this communication and counseling training for staff, investment in health promotion and delivery of core services are needed. It is important that these interventions address key issues, such as attendance in the first trimester of pregnancy, improving privacy and optimizing communication around danger signs. However, they must be designed alongside staff and service users and their efficacy tested before widespread investment or implementation.

This is the author accepted manuscript. The final version is available from Wiley via the link in this record

BackgroundAppreciative Inquiry is a motivational, organisational change intervention, which can be used to improve the quality and safety of healthcare. It encourages organisations to focus on the positive and investigate the best of ‘what is’ before thinking of ‘what might be’, deciding ‘what should be’ and experiencing ‘what can be’. Its effects in healthcare are poorly understood. This review seeks to evaluate whether Appreciative Inquiry can improve healthcare.MethodsMajor electronic databases and grey literature were searched. Two authors identified reports of Appreciative Inquiry in clinical settings by screening study titles, abstracts and full texts. Data extraction, in duplicate, grouped outcomes into an adapted Kirkpatrick model: participant reaction, attitudes, knowledge/skills, behaviour change, organisational change and patient outcomes.ResultsWe included 33 studies. One randomised controlled trial, 9 controlled observational studies, 4 qualitative studies and 19 non-controlled observational reports. Study quality was generally poor, with most having significant risk of bias. Studies report that Appreciative Inquiry impacts outcomes at all Kirkpatrick levels. Participant reaction was positive in the 16 studies reporting it. Attitudes changed in the seventeen studies that reported them. Knowledge/skills changed in the 14 studies that reported it, although in one it was not universal. Behaviour change occurred in 12 of the 13 studies reporting it. Organisational change occurred in all 23 studies that reported it. Patient outcomes were reported in eight studies, six of which reported positive changes and two of which showed no change.ConclusionThere is minimal empirical evidence to support the effectiveness of Appreciative Inquiry in improving healthcare. However, the qualitative and observational evidence suggests that Appreciative Inquiry may have a positive impact on clinical care, leading to improved patient and organisational outcomes. It is, therefore, worthy of consideration when trying to deliver improvements in care. However, high-quality studies are needed to prove its effects.PROSPERO registration numberCRD42015014485.

INTRODUCTION: Stillbirth is associated with significant physical, psychosocial and economic consequences for parents, families, wider society and the healthcare system. There is emerging momentum to design and evaluate interventions for care after stillbirth and in subsequent pregnancies. However, there is insufficient evidence to inform clinical practice compounded by inconsistent outcome reporting in research studies. To address this paucity of evidence, we plan to develop a core outcome set for stillbirth care research, through an international consensus process with key stakeholders including parents, healthcare professionals and researchers. METHODS AND ANALYSIS: The development of this core outcome set will be divided into five distinct phases: (1) Identifying potential outcomes from a mixed-methods systematic review and analysis of interviews with parents who have experienced stillbirth; (2) Creating a comprehensive outcome long-list and piloting of a Delphi questionnaire using think-aloud interviews; (3) Choosing the most important outcomes by conducting an international two-round Delphi survey including high-income, middle-income and low-income countries; (4) Deciding the core outcome set by consensus meetings with key stakeholders and (5) Dissemination and promotion of the core outcome set. A parent and public involvement panel and international steering committee has been convened to coproduce every stage of the development of this core outcome set. ETHICS AND DISSEMINATION: Ethical approval for the qualitative interviews has been approved by Berkshire Ethics Committee REC Reference 12/SC/0495. Ethical approval for the think-aloud interviews, Delphi survey and consensus meetings has been awarded from the University of Bristol Faculty of Health Sciences Research Ethics Committee (Reference number: 116535). The dissemination strategy is being developed with the parent and public involvement panel and steering committee. Results will be published in peer-reviewed specialty journals, shared at national and international conferences and promoted through parent organisations and charities. PROSPERO REGISTRATION NUMBER: CRD42018087748., National Institute of Health Research

BackgroundThe number of blood tests done in primary care has been increasing over the past 20 years. Some estimates suggest that up to one-quarter of these tests may not have been needed. This could lead to a cascade effect of further investigations, appointments, or referrals, as well as anxiety for patients, increased workload, and costs to the health service. To better understand the impact and sequelae of blood tests on patients, it is necessary to know why blood tests are requested and what is done with the results.AimTo explore who orders blood tests and why, and how test results are actioned in primary care.Design & settingRetrospective audit of electronic health records in general practices across the UK.MethodThe Primary care Academic CollaboraTive (PACT), a UK-wide network of primary care health professionals, will be utilised to collect data from individual practices. PACT members will be asked to review the electronic health records of 50 patients who had recent blood tests in their practice, and manually extract anonymised data on who requested the test, the indication, the result, and subsequent actions. Data will also be collected from PACT members to assess the feasibility of the collaborative model.ConclusionPACT offers a unique opportunity to extract clinical data which cannot otherwise be obtained. Understanding the indications for tests will help identify priority areas for research to optimise testing and patient safety in primary care.

Objective: To assess the impact of the fourth Be Clear on Cancer (BCoC) ‘Blood in Pee’ (BiP) campaign (July to September 2018) on bladder and kidney cancer symptom awareness and outcomes in England. Methods: In this uncontrolled before and after study, symptom awareness and reported barriers to GP attendance were assessed using panel and one-to-one interviews. The Health Improvement Network (THIN), National Cancer Registration and Analysis Service (NCRAS) and NHS Cancer Waiting Times (CWT) data were analysed to assess the impact on GP attendances, urgent cancer referrals, cancer diagnoses and 1-year survival. Analyses used Poisson, negative binomial and Cox regression. Results: Symptom awareness and intention to consult a GP after one episode of haematuria increased following the campaign. GP attendance with haematuria (rate ratio (RR) 1.17, 95% confidence interval (CI): 1.07–1.28) and urgent cancer referrals (RR 1.18 95% CI: 1.08–1.28) increased following the campaign. Early-stage diagnoses increased for bladder cancer (difference in percentage 2.8%, 95% CI: −0.2%–5.8%), but not for kidney cancer (difference −0.6%, 95% CI: −3.2%–2.1%). Conclusions: The fourth BCoC BiP campaign appears to have been effective in increasing bladder cancer symptom awareness and GP attendances, although long-term impacts are unclear.

Additional file 2. PRISMA 2020 Checklist.

Additional file 1. Database search strategy.

Objective To develop a sepsis care bundle for the initial management of maternal sepsis in low resource settings. Design Modified Delphi process. Setting Participants from 34 countries. Population Healthcare practitioners working in low resource settings (n = 143; 34 countries), members of an expert panel (n = 11) and consultation with the World Health Organization Global Maternal and Neonatal Sepsis Initiative technical working group. Methods We reviewed the literature to identify all potential interventions and practices around the initial management of sepsis that could be bundled together. A modified Delphi process, using an online questionnaire and in‐person meetings, was then undertaken to gain consensus on bundle items. Participants ranked potential bundle items in terms of perceived importance and feasibility, considering their use in both hospitals and health centres. Findings from the healthcare practitioners were then triangulated with those of the experts. Main outcome measure Consensus on bundle items. Results Consensus was reached after three consultation rounds, with the same items deemed most important and feasible by both the healthcare practitioners and expert panel. Final bundle items selected were: (1) Fluids, (2) Antibiotics, (3) Source identification and control, (4) Transfer (to appropriate higher‐level care) and (5) Monitoring (of both mother and neonate as appropriate). The bundle was given the acronym ‘FAST‐M’. Conclusion A clinically relevant maternal sepsis bundle for low resource settings has been developed by international consensus. Tweetable abstract A maternal sepsis bundle for low resource settings has been developed by international consensus., Tweetable abstract A maternal sepsis bundle for low resource settings has been developed by international consensus.

BackgroundProstate Specific Antigen (PSA) is a commonly used test to detect prostate cancer. Attention has mostly focused on the use of PSA in screening asymptomatic patients, but the diagnostic accuracy of PSA for prostate cancer in patients with symptoms is less well understood.MethodsA systematic database search was conducted of Medline, EMBASE, Web of Science, and the Cochrane library. Studies reporting the diagnostic accuracy of PSA for prostate cancer in patients with symptoms were included. Two investigators independently assessed the titles and abstracts of all database search hits and full texts of potentially relevant studies against the inclusion criteria, and data extracted into a proforma. Study quality was assessed using the QUADAS-2 tool by two investigators independently. Summary estimates of diagnostic accuracy were calculated with meta-analysis using bivariate mixed effects regression.Results563 search hits were assessed by title and abstract after de-duplication, with 75 full text papers reviewed. 19 studies met the inclusion criteria, 18 of which were conducted in secondary care settings (one from a screening study cohort). All studies used histology obtained by Transrectal Ultrasound guided biopsy (TRUS) as a reference test, usually only for patients with elevated PSA or abnormal prostate examination. Pooled data from 14,489 patients found estimated sensitivity of PSA for prostate cancer was 0.93 (95% CI 0.88, 0.96) and specificity was 0.20 (95% CI 0.12, 0.33). The area under the receiving-operator characteristic curve was 0.72 (95% CI 0.68, 0.76). All studies were assessed as having a high risk of bias in at least one QUADAS-2 domain.ConclusionsCurrently available evidence suggests PSA is highly sensitive but poorly specific for prostate cancer detection. However, significant limitations in study design and reference test reduces the certainty of this estimate. There is very limited evidence for the performance of PSA in primary care, the healthcare setting where most PSA testing is performed.

Objectives To develop a consensus statement on current best practice of active surveillance (AS) in the UK, informed by patients and clinical experts. Subjects and Methods A consensus statement was drafted on the basis of three sources of data: systematic literature search of national and international guidelines; data arising from a Freedom of Information Act request to UK urology departments regarding their current practice of AS; and survey and interview responses from men with localized prostate cancer regarding their experiences and views of AS. The Prostate Cancer UK Expert Reference Group (ERG) on AS was then convened to discuss and refine the statement. Results Guidelines and protocols for AS varied significantly in terms of risk stratification, criteria for offering AS, and protocols for AS between and within countries. Patients and healthcare professionals identified clinical, emotional and process needs for AS to be effective. Men with prostate cancer wanted more information and psychological support at the time of discussing AS with the treating team and in the first 2 years of AS, and a named healthcare professional to discuss any questions or concerns they had. The ERG agreed 30 consensus statements regarding best practice for AS. Statements were grouped under headings: ‘Inclusion/Exclusion Criteria’; ‘AS follow-up protocol’ and ‘When to stop AS’. Conclusion Significant variation currently exists in the practice of AS in the UK and internationally. Men have clear views on the level of involvement in treatment decisions and support from their treating professionals when receiving AS. The Prostate Cancer UK AS ERG has developed a set of consensus statements for best practice in AS. Evidence for best practice in AS, and the use of multiparametric magnetic resonance imaging in AS, is still evolving, and further studies are needed to determine how to optimize AS outcomes

BackgroundMost cancers in sub-Saharan Africa (SSA) are diagnosed at advanced stages, with limited treatment options and poor outcomes. Part of this may be linked to various events occurring in patients’ journey to diagnosis. Using the model of pathways to treatment, we examined the evidence regarding the routes to cancer diagnosis in SSA.Design and settingsA systematic review of available literature was performed.MethodsThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Between 30 September and 30 November 2019, seven electronic databases were searched using terms relating to SSA countries, cancer and routes to diagnosis comprising the population, exposure and outcomes, respectively. Citation lists of included studies were manually searched to identify relevant studies. Furthermore, ProQuest Dissertations & Theses Global was searched to identify appropriate grey literature on the subject.Results18 of 5083 references identified met the inclusion criteria: eight focused on breast cancer; three focused on cervical cancer; two each focused on lymphoma, Kaposi’s sarcoma and childhood cancers; and one focused on colorectal cancer. With the exception of Kaposi’s sarcoma, definitive diagnoses were made in tertiary healthcare centres, including teaching and regional hospitals. The majority of participants initially consulted within primary care, although a considerable proportion first used complementary medicine before seeking conventional medical help. The quality of included studies was a major concern, but their findings provided important insight into the pathways to cancer diagnosis in the region.ConclusionThe proportion of patients who initially use complementary medicine in their cancer journey may explain a fraction of advanced-stage diagnosis and poor survival of cancer in SSA. However, further research would be necessary to fully understand the exact role (or activities) of primary care and alternative care providers in patient cancer journeys.

Additional file 2. Staff longitudinal survey questionnaire and constructs addressed within it.

Additional file 1: Round 1 online questionnaire.

Additional file 5. Qualitative summary from the Community Hospital.

Additional file 2: Round 2 online questionnaire.

Additional file 3. Qualitative summary from the Referral Hospital.

Additional file 1. Session outlines for the 11 session Appreciative Inquiry Intervention.

Additional file 4. Qualitiative summary from the District Hospital.

Maternal Near Miss cases have similarities with those dying from such complications and so present an important opportunity to improve practice. This study was conducted to assess the prevalence of Maternal Near Miss events and identify the delays experienced.This was a facility-based cross-sectional study conducted in three tertiary referral hospitals from three provinces of Nepal. All the women surviving a near miss event during six months data collection period were included in the study.There were 67 near miss cases, 7 maternal deaths, and 9158 live births in the study hospitals during the data collection period. This resulted in Maternal Near Miss ratio of 7.31/1000 live births and facility-based Maternal Mortality Ratio of 76/100,000 live births. Severe obstetric haemorrhage (54%) was the most frequent clinical cause of near miss, followed by hypertensive disorders (43%). At least one type of delay was experienced by 85% women. First delay occurred in 63% (42 of 67) cases, second delay occurred in 52% (33 of 62) cases and third delay occurred in 55% (37 of 67) cases.This study found out that all three delays were common among women experiencing maternal near miss event. Raising awareness regarding dangers signs, improving referral system and strengthening ability of health workers can help in reducing these delays.

Background Active surveillance (AS) is a management option for men diagnosed with lower risk prostate cancer. There is wide variation in all aspects of AS internationally, from patient selection to investigations and follow-up intervals, and a lack of clear evidence on the optimal approach to AS. This study aimed to provide guidance for clinicians from an international panel of prostate cancer experts. Methods A modified Delphi approach was undertaken, utilising two rounds of online questionnaires followed by a face-to-face workshop. Participants indicated their level of agreement with statements relating to patient selection for AS via online questionnaires on a 7-point Likert scale. Factors not achieving agreement were iteratively developed between the two rounds of questionnaires. Draft statements were presented at the face-to-face workshop for discussion and consensus building. Results 12 prostate cancer experts (9 Urologists, 2 academics, 1 radiation oncologist) participated in this study from a range of geographical regions (4 USA, 4 Europe, 4 Australia). Complete agreement on statements presented to the participants was 29.4% after Round One and 69.5% after Round Two. Following robust discussions at the face-to-face workshop, agreement was reached on the remaining statements. Conclusions The lack of consistency in the practice of AS for men with lower risk prostate cancer between and within countries was reflected in this modified Delphi study. There are, however, areas of common practice and agreement from which clinicians practicing in the current environment can use to inform their clinical practice to achieve the best outcomes for patients.

ObjectiveTo implement a modified obstetric early warning system (MOEWS) to promote identification and stabilization of unwell women.MethodsA before-and-after study of MOEWS implementation took place between April 2013 and January 2014 in a government referral hospital in Bulawayo, Zimbabwe. After piloting MOEWS, cesarean case files were retrospectively assessed to compare preoperative stabilization. A longitudinal “spot-check” study measured use of MOEWS and action taken on abnormal results. A quality indicator was introduced to assess ongoing implementation.ResultsAnalysis of women undergoing cesarean before (n=79) and after (n=85) MOEWS implementation showed that preoperative stabilization improved significantly post-intervention (odds ratio 2.78, 95% confidence interval 1.39–5.54). The longitudinal analysis of women at baseline (n=43) and after (n=85) MOEWS implementation also showed a significant improvement in action taken (1/24 [4%] vs 28/45 [62%]; P=0.001). The 6-month aggregated quality indicator revealed that 78 (62%) of 125 patients had a completed MOEWS chart, with appropriate stabilization of 65 (93%) of 70 women.ConclusionImplementation of MOEWS improved women's care through action being taken on abnormal observations. Before whole-scale adoption of MOEWS in low-resource settings, the study should be scaled up and repeated to ensure replicable findings.

Non-invasive prenatal testing is regularly used to screen for aneuploidies and Rhesus status of a fetus. Since 1997 when free fetal DNA (ffDNA) in the maternal circulation was first identified, it has been hypothesized that it may be possible to use non-invasive prenatal testing (NIPT) to identify high-risk pregnancies including pre-eclampsia, growth restriction and preterm birth. Since then there has been much interest in this area as a way to identify and understand disease processes. This review presents the current evidence for this approach. For pre-eclampsia the hypothesis is that ffDNA would increase but the evidence for this is heterogenous across studies and trimesters. There is however increasing agreement between studies that by the third trimester ffDNA is more likely to be raised in pre-eclamptic patients than controls. For preterm birth, again, the main hypothesis is that ffDNA should increase. The results are also heterogenous, with some studies finding increased ffDNA prior to preterm birth, and others finding no change. For fetal growth restriction, there are competing theories for reduced and increased ffDNA and some studies suggest that levels are raised and some reduced. There are complexities in interpreting all of this evidence as the studies' designs, patient populations, and especially in the context of growth restriction, the definitions are not clear. Furthermore, authors use different biochemical tests and different units to describe their results, making meta-analysis difficult. All of these issues and conflicting findings lead us to the conclusion that currently there is yet no definitive place in clinical practice for NIPT to support the diagnosis and management of high-risk pregnancies. However, it is vital that this research continues as it could open the door to better understanding of the disease process and novel approaches to management.

> Ted is a 65-year-old retired arts teacher. He was recently diagnosed with localised prostate cancer. He has been to see the urologist to discuss his prognosis and treatment options. Men and clinicians face difficult decisions with regards to treatments for prostate cancer. For our patients, they can be faced with a choice of radical treatments, which carry a high risk of incontinence and sexual dysfunction, or active surveillance, which can be perceived to go against the strong public cancer narrative of ‘find it early and treat it’. Although studies such as the PROTECT trial suggest minimal reductions in mortality from aggressive treatments when compared with active surveillance,1 prostate cancer still causes a significant number of cancer-related deaths. Predicting the long-term outcomes for men with a diagnosis of localised disease is difficult, although new methods for understanding a man’s risk and informing treatment decisions are being developed and refined. Clearly communicating the potential risks, benefits, and uncertainties with men is vital to help them navigate these difficult choices, which can be made easier with their GP by their side. > Ted hasn’t come to a decision about whether to undergo radical treatment for his prostate cancer or active surveillance. He makes an appointment to see you to run through his options. Most patients …

Objective To identify and characterize patient-centered outcomes (PCOs) relating to multiparametric MRI (mpMRI) and MRI-guided biopsy as diagnostic tests for possible prostate cancer. Methods Medline via OVID, EMBASE, PsycInfo, and the Cochrane Central register of Controlled Trials (CENTRAL) were searched for relevant articles. Hand searching of reference lists and snowballing techniques were performed. Studies of mpMRI and MRI-guided biopsy that measured any PCO were included. There were no restrictions placed on year of publication, language, or country for study inclusion. All database search hits were screened independently by two reviewers, and data were extracted using a standardized form. Results Overall, 2,762 database search hits were screened based on title and abstract. Of these, 222 full-text articles were assessed, and 10 studies met the inclusion criteria. There were 2,192 participants featured in the included studies, all of which were conducted in high-income countries. Nineteen different PCOs were measured, with a median of four PCOs per study (range 1-11). Urethral bleeding, pain, and urinary tract infection were the most common outcomes measured. In the four studies that compared mpMRI or MRI-guided biopsy to transrectal ultrasound biopsy, most adverse outcomes occurred less frequently in MRI-related tests. These four studies were assessed as having a low risk of bias. Discussion PCOs measured in studies of mpMRI or MRI-guided biopsy thus far have mostly been physical outcomes, with some evidence that MRI tests are associated with less frequent adverse outcomes compared with transrectal ultrasound biopsy. There was very little evidence for the effect of mpMRI and MRI-guided biopsy on emotional, cognitive, social, or behavioral outcomes.

Angina pectoris is chest pain due to insufficient coronary artery blood flow and/or increased myocardial oxygen demand. In 2012, angina affected 3.05% of men and 1.79% of women in the UK. Stable angina is a chronic disease that can progress to unstable angina or myocardial infarction. Lifestyle modification, medications, and cardiac intervention/cardiothoracic surgery all play a part in its management. Patients with angina are mostly managed in primary care, where the focus of care is on maintaining quality of life and preventing disease progression.

Currently, primary care based trainees and clinicians can apply for research fellowships, with funded time to spend on research, but these are highly competitive and available only to the lucky few. In hospital specialties, networks of trainees that take part in the same research projects, known as trainee collaboratives, are well established and provide an alternative opportunity for engaging in research.1–3 We have recently set up the ‘Primary care Academic CollaboraTive’ (PACT), a new UK-wide network of mostly non-academic trainees and clinicians who will collectively take part in research projects. In this editorial, we discuss the challenges and potential of this alternative research model. In many countries, primary care research is designed and driven forward by University academics; there are advantages of this. One example is that academics have specific training in how to conduct research, experience of what works and doesn’t work, expertise in particular fields, knowledge of the latest research internationally, and networks with other leading experts. A further advantage is that within universities, teams of topic and methodological experts (for example, with specific skills in qualitative methods, systematic reviews, trials, and epidemiology) work together to answer complex research questions. Furthermore, universities have strong links with patients, health services, and policy makers to ensure research …

Background:Nodal metastasis is an important prognostic factor in head and neck squamous cell carcinoma. This study aimed to determine the average nodal basin yield per level of neck dissection, and to investigate if age, gender, body mass index, tumour size, depth of tumour invasion and p16 status influence nodal yield.Method:A retrospective review of 185 patients with head and neck squamous cell carcinoma generated 240 neck dissection specimens.Results:The respective mean nodal yields for levels I, II, III, IV and V were 5.27, 9.43, 8.49, 7.43 and 9.02 in non-cutaneous squamous cell carcinoma patients, and 4.2, 7.57, 9.65, 4.33 and 12.29 in cutaneous squamous cell carcinoma patients. Multiple regression analysis revealed that p16-positive patients with mucosal squamous cell carcinoma yielded, on average, 2.4 more nodes than their p16-negative peers (p = 0.04, 95 per cent confidence interval = 0.116 to 4.693). This figure was 3.84 (p = 0.008, 95 per cent confidence interval = 1.070 to 6.605) for p16-positive patients with oral cavity squamous cell carcinoma.Conclusion:In mucosal squamous cell carcinoma, p16-positive status significantly influenced nodal yield, with the impact being more pronounced in oral cavity squamous cell carcinoma patients.

BACKGROUND: Preparing healthcare providers to manage relatively rare life-threatening emergency situations effectively is a challenge. Training sessions enable staff to rehearse for these events and are recommended by several reports and guidelines. In this review we have focused on interactive training, this includes any element where the training is not solely didactic but provides opportunity for discussions, rehearsals, or interaction with faculty or technology. It is important to understand the effective methods and essential elements for successful emergency training so that resources can be appropriately targeted to improve outcomes.OBJECTIVES: To assess the effects of interactive training of healthcare providers on the management of life-threatening emergencies in hospital on patient outcomes, clinical care practices, or organisational practices, and to identify essential components of effective interactive emergency training programmes.SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL and ERIC and two trials registers up to 11 March 2019. We searched references of included studies, conference proceedings, and contacted study authors.SELECTION CRITERIA: We included randomised trials and cluster-randomised trials comparing interactive training for emergency situations with standard/no training. We defined emergency situations as those in which immediate lifesaving action is required, for example cardiac arrests and major haemorrhage. We included all studies where healthcare workers involved in providing direct clinical care were participants. We excluded studies outside of a hospital setting or where the intervention was not targeted at practicing healthcare workers. We included trials irrespective of publication status, date, and language.DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane and Cochrane Effective Practice and Organisation of Care (EPOC) Group. Two review authors independently extracted data and assessed the risk of bias of each included trial. Due to the small number of studies and the heterogeneity in outcome measures, we were unable to perform the planned meta-analysis. We provide a structured synthesis for the following outcomes: survival to hospital discharge, morbidity rate, protocol or guideline adherence, patient outcomes, clinical practice outcomes, and organisation-of-care outcomes. We used the GRADE approach to rate the certainty of the evidence and the strength of recommendations for each outcome.MAIN RESULTS: We included 11 studies that reported on 2000 healthcare providers and over 300,000 patients; one study did not report the number of participants. Seven were cluster randomised trials and four were single centre studies. Four studies focused on obstetric training, three on obstetric and neonatal care, two on neonatal training, one on trauma and one on general resuscitations. The studies were spread across high-, middle- and low-income settings.Interactive training may make little or no difference in survival to hospital discharge for patients requiring resuscitation (1 study; 30 participants; 98 events; low-certainty evidence). We are uncertain if emergency training changes morbidity rate, as the certainty of the evidence is very low (3 studies; 1778 participants; 57,193 patients, when reported). We are uncertain if training alters healthcare providers' adherence to clinical protocols or guidelines, as the certainty of the evidence is very low (3 studies; 156 participants; 558 patients). We are uncertain if there were improvements in patient outcomes following interactive training for emergency situations, as we assessed the evidence as very low-certainty (5 studies, 951 participants; 314,055 patients). We are uncertain if training for emergency situations improves clinical practice outcomes as the certainty of the evidence is very low (4 studies; 1417 participants; 28,676 patients, when reported). Two studies reported organisation-of-care outcomes, we are uncertain if interactive emergency training has any effect on this outcome as the certainty of the evidence is very low (634 participants; 179,400 patient population).We examined prespecified subgroups and found no clear commonalities in effect of multidisciplinary training, location of training, duration of the course, or duration of follow-up. We also examined areas arising from the studies including focus of training, proportion of staff trained, leadership of intervention, and incentive/trigger to participate, and again identified no clear mediating factors. The sources of funding for the studies were governmental, local organisations, or philanthropic donors.AUTHORS' CONCLUSIONS: We are uncertain if there are any benefits of interactive training of healthcare providers on the management of life-threatening emergencies in hospital as the certainty of the evidence is very low. We were unable to identify any factors that may have allowed us to identify an essential element of these interactive training courses.We found a lack of consistent reporting, which contributed to the inability to meta-analyse across specialities. More trials are required to build the evidence base for the optimum way to prepare healthcare providers for rare life-threatening emergency events. These trials need to be conducted with attention to outcomes important to patients, healthcare providers, and policymakers. It is vitally important to develop high-quality studies adequately powered and with attention to minimising the risk of bias.

OBJECTIVES: To develop a consensus statement on current best practice of active surveillance (AS) in the UK, informed by patients and clinical experts. SUBJECTS AND METHODS: A consensus statement was drafted on the basis of three sources of data: systematic literature search of national and international guidelines; data arising from a Freedom of Information (FOI) Act request to UK urology departments regarding their current practice of AS; survey and interview responses from men with localised prostate cancer regarding their experiences and views of AS. The Prostate Cancer UK Expert Reference Group (ERG) on Active Surveillance was then convened to discuss and refine the statement. RESULTS: Guidelines and protocols for AS varied significantly in terms of risk stratification, criteria for offering AS, and protocols for AS between and within countries. Patients and healthcare professionals identified clinical, emotional and process needs for AS to be effective. Men with prostate cancer wanted more information and psychological support at the time of discussing AS with the treating team and in the first two years of AS, and a named healthcare professional to discuss any questions or concerns they had. The ERG agreed 30 consensus statements regarding best practice for AS. Statements were grouped under headings - 'Inclusion/Exclusion Criteria'; 'Active surveillance follow up protocol' and 'When to stop active surveillance'. CONCLUSION: Significant variation currently exists in the practice of AS in the UK and internationally. Men have clear views on the level of involvement in treatment decisions and support from their treating professionals when receiving AS. The Prostate Cancer UK AS ERG has developed a set of consensus statements for best practice in AS. Evidence for best practice in AS, and the use of multi-parametric magnetic resonance imaging (mpMRI) in AS, is still evolving, and further studies are needed to determine how to optimise AS outcomes. This article is protected by copyright. All rights reserved.

Indirect maternal deaths account for over a quarter of maternal deaths worldwide. Deaths from indirect causes include communicable and non-communicable diseases, as well as pre-existing and new conditions. Prevention of indirect maternal deaths has received less attention than direct causes of death, where interventions can be targeted around the time of delivery. Indirect deaths can be more complex to address as pregnancy brings unique health challenges due to the changing physiology of a pregnant woman. These physiological changes are summarised alongside the impact of some communicable (e.g. malaria) and non-communicable diseases (e.g. cardiovascular disease) on indirect deaths. The challenges in diagnosing, and therefore measuring, indirect deaths are discussed, as are challenges in deciding whether these deaths are incidental or exacerbated by pregnancy. A focus on improving both research and health policy is needed to address the challenges brought about by the increasing burden of indirect deaths.

This chapter discusses direct causes of maternal death, which account for nearly three quarters of maternal deaths worldwide. These deaths occur disproportionately in low-resource settings and are largely due to obstetric complications. It is therefore possible to significantly reduce these deaths. We discuss the five most important causes: postpartum haemorrhage, abortion-related deaths, hypertensive disorders, sepsis, and obstructed labour. The three delays in deciding, reaching, and receiving adequate care are then used to consider the broad areas to address to reduce direct maternal deaths. Possible strategies which could be implemented to reduce preventable direct maternal deaths such as implementing women’s groups and skills training are discussed. Finally, we highlight some of the challenges surrounding reducing direct deaths, including difficulties in measurement and increasing skilled attendance at birth. To overcome these challenges and prevent direct maternal deaths, comprehensive strategies addressing both community and health systems issues need to be employed.

Multidisciplinary training has improved maternity outcomes when the training has been well attended, regular, in house, used high-fidelity simulators, and integrated teamwork training. If these principles were used in other settings, better clinical care may result. This before-after study sought to establish whether a short multidisciplinary training intervention can improve recognition of the deteriorating patient using an aggregated physiological parameter scoring system (Early Warning Score [EWS]). Nursing, medical, and allied nursing staff participated in an hour-long training session, using real-life scenarios with simple tools and structured debriefing. After training, staff were more likely to calculate EWS scores correctly (68.02% vs 55.12%; risk ratio [RR] = 1.24, 95% confidence interval [CI] = 1.07-1.44), and observations were more likely to be performed at the correct frequency (78.57% vs 68.09%; RR = 1.20, 95% CI = 1.09-1.32). Multidisciplinary training, according to core principles, can lead to more accurate identification of deteriorating patients, with implications for subsequent care and outcome.

Background Maternal mortality is high in Loreto, Peru, but can be reduced by high quality antenatal care. Indicators for the quality of antenatal care received include the timing (with respect to gestational age) and number of antenatal appointments attended, the delivery of antenatal services and health information, and women’s perceptions about their care. This study investigated these indicators amongst women receiving antenatal care in predominantly the San Juan Bautista district of Iquitos, Loreto. This was to identify areas for improvement through comparison with antenatal guidelines published by the Ministry of Health, Peru, and the World Health Organization. Methods A total of 134 women were recruited at the Centro de Salud, San Juan—a primary care centre in Iquitos. Information about the delivery of antenatal services and the number of and gestational ages at appointments attended was collected from 121/134 women’s hand-held antenatal cards. The delivery of health information and women’s perceptions about their antenatal care were investigated through questionnaires (133/134 completed). Descriptive statistics, such as frequencies and valid percentages, were determined. Results Hand-held antenatal cards revealed that 52.9% of participants began their antenatal care in the first trimester. Compared to national guidelines, 42.1% attended appointments at recommended gestational ages and no women received all recommended antenatal services. Most women received information about identifying complications in pregnancy and health and lifestyle topics. Over 85% of women reported satisfaction with their antenatal care. Conclusions Timely antenatal attendance and delivery of services should be encouraged to meet national and global standards. Although all services were not delivered in a combined manner according to national guidelines, individual services were mostly delivered to a high standard and therefore a high proportion of women were satisfied with their antenatal care.

Background The estimated annual global burden of miscarriage is 33 million out of 210 million pregnancies. Many women undergoing miscarriage have surgery to remove pregnancy tissues, resulting in miscarriage surgery being one of the most common operations performed in hospitals in low-income countries. Infection is a serious consequence and can result in serious illness and death. In low-income settings, the infection rate following miscarriage surgery has been reported to be high. Good quality evidence on the use of prophylactic antibiotics for surgical miscarriage management is not available. Given that miscarriage surgery is common, and infective complications are frequent and serious, prophylactic antibiotics may offer a simple and affordable intervention to improve outcomes. Methods Eligible patients will be approached once the diagnosis of miscarriage has been made according to local practice. Once informed consent has been given, participants will be randomly allocated using a secure internet facility (1:1 ratio) to a single dose of oral doxycycline (400 mg) and metronidazole (400 mg) or placebo. Allocation will be concealed to both the patient and the healthcare providers. A total of 3400 women will be randomised, 1700 in each arm. The medication will be given approximately 2 hours before surgery, which will be provided according to local practice. The primary outcome is pelvic infection 2 weeks after surgery. Women will be invited to the hospital for a clinical assessment at 2 weeks. Secondary outcomes include overall antibiotic use, individual components of the primary outcome, death, hospital admission, unplanned consultations, blood transfusion, vomiting, diarrhoea, adverse events, anaphylaxis and allergy, duration of clinical symptoms, and days before return to usual activities. An economic evaluation will be performed to determine if prophylactic antibiotics are cost-effective. Discussion This trial will assess whether a single dose of doxycycline (400 mg) and metronidazole (400 mg) taken orally 2 hours before miscarriage surgery can reduce the incidence of pelvic infection in women up to 2 weeks after miscarriage surgery. Trial registration Registered with the ISRCTN (international standard randomised controlled trial number) registry: ISRCTN 97143849. (Registered on April 17, 2013). Electronic supplementary material The online version of this article (10.1186/s13063-018-2598-3) contains supplementary material, which is available to authorized users.

Introduction Prostate cancer is the most common cancer in men in the UK, with nearly 40 000 diagnosed in 2014; and it is the second most common cause of male cancer-related mortality. The clinical conundrum is that most men live with prostate cancer rather than die from it, while existing treatments have significant associated morbidity. Recent studies have shown very low mortality rates (1% after a median of 10-year follow-up) and no treatment-related reductions in mortality, in men with localised prostate cancer. This study will identify prognostic factors associated with prostate cancer progression to help differentiate aggressive from more indolent tumours in men with localised disease at diagnosis, and so inform the decision to adopt conservative (active surveillance) or radical (surgery or radiotherapy) management strategies. Methods and analysis The Clinical Practice Research Datalink (CPRD) contains 57 318 men who were diagnosed with prostate cancer between 1 January 1987 and 31 December 2016. These men will be linked to the Office for National Statistics (ONS) and the National Cancer Registration and Analysis Service registry databases for mortality, TNM stage, Gleason grade and treatment data. Men with a diagnosis date prior to 1 January 1987 and men with lymph node or distant metastases at diagnosis will be excluded. A priori determined prognostic factors potentially associated with prostate cancer mortality, the end point of cancer progression, will be measured at baseline, and the participants followed through to development of cancer progression, death or the end of the follow-up period (31 December 2016). Cox proportional hazards regression will be used to estimate crude and mutually adjusted HRs. Mortality risk will be predicted using flexible parametric survival models that can accurately fit the shape of the hazard function. Ethics and dissemination This study protocol has approval from the Independent Scientific Advisory Committee for the UK Medicines and Healthcare products Regulatory Agency Database Research (protocol 17_041). The findings will be presented in peer-reviewed journals and local CPRD researcher meetings.