National Cancer Diagnosis Audits for England 2018 versus 2014: a comparative analysis

BACKGROUND: Timely diagnosis of cancer in patients who present with symptoms in primary care is a quality-improvement priority. AIM: To examine possible changes to aspects of the diagnostic process, and its timeliness, before and after publication of the National Institute for Health and Care Excellence's (2015) guidance on the referral of suspected cancer in primary care. DESIGN AND SETTING: Comparison of findings from population-based clinical audits of cancer diagnosis in general practices in England for patients diagnosed in 2018 or 2014. METHOD: GPs in 1878 (2018) and 439 (2014) practices collected primary care information on the diagnostic pathway of cancer patients. Key measures including patient characteristics, place of presentation, number of pre-referral consultations, use of primary care investigations, and referral type were compared between the two audits by descriptive analysis and regression models. RESULTS: Among 64 489 (2018) and 17 042 (2014) records of a new cancer diagnosis, the percentage of patients with same-day referral (denoted by a primary care interval of 0 days) was higher in 2018 (42.7% versus 37.7%) than in 2014, with similar improvements in median diagnostic interval (36 days versus 40 days). Compared with 2014, in 2018: fewer patients had ≥3 pre-referral consultations (18.8% versus 26.2%); use of primary care investigations increased (47.9% versus 45.4%); urgent cancer referrals increased (54.8% versus 51.8%); emergency referrals decreased (13.4% versus 16.5%); and recorded use of safety netting decreased (40.0% versus 44.4%). CONCLUSION: In the 5-year period, including the year when national guidelines were updated (that is, 2015), there were substantial improvements to the diagnostic process of patients who present to general practice in England with symptoms of a subsequently diagnosed cancer

Impact of geography on Scottish cancer diagnoses in primary care:Results from a national cancer diagnosis audit

Funding The National Cancer Diagnosis Audit (NCDA) in Scotland received enabling support from Cancer Research UK and the Scottish Government. Acknowledgements This audit used data provided by patients and collected by NHS as part of their care and support. The authors would like to thank all GPs and health professionals who participated in the NCDA in Scotland, the members of the NCDA Steering Group, as well as contributing staff at Cancer Research UK; Information Services Division (NHS Scotland); Scottish Government; the Royal College of General Practitioners; and Macmillan Cancer Support. National Cancer Diagnosis Audit (2014) Steering Group: Sue Ballard (patient †), Patricia Barnett, David H Brewster, Cathy Burton, Anthony Cunliffe, Jane Fenton-May, Anna Gavin, Sara Hiom (chair), Peter Hutchison, Dyfed Huws, Maggie Kemmner, Rosie Loftus, Georgios Lyratzopoulos, Emma McNair, John Marsh (patient), Jodie Moffat, Sean McPhail, Peter Murchie, Andy Murphy, Sophia Nicola, Imran Rafi, Jem Rashbass, Richard Roope, Greg Rubin, Brian Shand, Ruth Swann, Janet Warlow, David Weller, and Jana Witt.Peer reviewedPostprin

Connecting Researchers to Data Repositories in the Earth, Space, and Environmental Sciences

The Repository Finder tool was developed to help researchers in the domain of Earth, space, and environmental sciences to identify appropriate repositories where they can deposit their research data and to promote practices that implement the FAIR Principles, encouraging progress toward sharing data that are findable, accessible, interoperable, and reusable. Requirements for the design of the tool were gathered through a series of workshops and working groups as a part of the Enabling FAIR Data initiative led by the American Geophysical Union that included the development of a decision tree that researchers may follow in selecting a data repository, interviews with domain repository managers, and usability testing. The tool is hosted on the web by DataCite and enables a researcher to query all data repositories by keyword or to view a list of domain repositories that accept data for deposit, support open access, and provide persistent identifiers. Metadata records from the re3data.org registry of research data repositories and the returned results highlight repositories that have achieved trustworthy digital repository certification through a formal procedure such as the CoreTrust Seal

Alimentação saudável na infância: representações sociais de famílias e crianças em idade escolar

O estudo investigou as representações sociais sobre alimentação saudável de famílias e crianças em idade escolar. Foi um estudo de casos múltiplos, com entrevistas semiestruturadas e desenhos. Participaram oito famílias de classe socioeconômica média e baixa, cinco com condições de segurança e três de insegurança alimentar. A análise revelou que a alimentação do campo, na infância dos pais, foi uma época difícil, porém, considerada mais saudável. Embora as famílias expressassem concepções normatizadas de alimentação saudável, várias forças, proximais e distais, tencionavam suas práticas atuais em outra direção. O acesso fácil a alimentos pouco saudáveis e as restrições financeiras, se somavam a vida corrida das famílias e a significados prazerosos associados as “porcarias/besteiras” como modo de sair da rotina. Os achados apontam que as representações sobre alimentação saudável abarcam diferentes contextos de sociabilidade da criança e são atravessados pelo contexto histórico e cultural das famílias, desafiando noções baseadas no conhecimento formal

Co-creation of a student-implemented allied health service in a First Nations remote community of East Arnhem Land, Australia

Objectives: To co-create a culturally responsive student-implemented allied health service in a First Nations remote community and to determine the feasibility and acceptability of the service. Design: Co-creation involved a pragmatic iterative process, based on participatory action research approaches. Feasibility and acceptability were determined using a mixed-method pre/postdesign. Setting: The service was in Nhulunbuy, Yirrkala and surrounding remote First Nations communities of East Arnhem Land, Northern Territory, Australia. Participants: Co-creation of the service was facilitated by the Northern Australia Research Network, guided by Indigenous Allied Health Australia leadership, with East Arnhem local community organisations and community members. Co-creation of the day-to-day service model involved local cultural consultants, service users and their families, staff of community organisations, students, supervisors, placement coordinators and a site administrator. Findings: A reciprocal learning service model was co-created in which culturally responsive practice was embedded. The service was feasible and acceptable: it was delivered as intended; resources were adequate; the service management system was workable; and the service was acceptable. Health outcome measures, however, were not appropriate to demonstrate impact, particularly through the lens of the people of East Arnhem. Recommendations for the service included: continuing the reciprocal learning service model in the long term; expanding to include all age groups; and connecting with visiting and community-based services. Conclusion: The co-created service was feasible and acceptable. To demonstrate the impact of the service, measures of health service impact that are important to First Nations people living in remote communities of northern Australia are required

Simplicial Gravity Coupled to Scalar Matter

A model for quantized gravity coupled to matter in the form of a single scalar field is investigated in four dimensions. For the metric degrees of freedom we employ Regge's simplicial discretization, with the scalar fields defined at the vertices of the four-simplices. We examine how the continuous phase transition found earlier, separating the smooth from the rough phase of quantized gravity, is influenced by the presence of scalar matter. A determination of the critical exponents seems to indicate that the effects of matter are rather small, unless the number of scalar flavors is large. Close to the critical point where the average curvature approaches zero, the coupling of matter to gravity is found to be weak. The nature of the phase diagram and the values for the critical exponents suggest that gravitational interactions increase with distance. \vspace{24pt} \vfillComment: (34 pages + 8 figures

Diagnosing cancer in primary care: results from the National Cancer Diagnosis Audit.

BACKGROUND: Continual improvements in diagnostic processes are needed to minimise the proportion of patients with cancer who experience diagnostic delays. Clinical audit is a means of achieving this. AIM: To characterise key aspects of the diagnostic process for cancer and to generate baseline measures for future re-audit. DESIGN AND SETTING: Clinical audit of cancer diagnosis in general practices in England. METHOD: Information on patient and tumour characteristics held in the English National Cancer Registry was supplemented by information from GPs in participating practices. Data items included diagnostic timepoints, patient characteristics, and clinical management. RESULTS: Data were collected on 17 042 patients with a new diagnosis of cancer during 2014 from 439 practices. Participating practices were similar to non-participating ones, particularly regarding population age, urban/rural location, and practice-based patient experience measures. The median diagnostic interval for all patients was 40 days (interquartile range [IQR] 15-86 days). Most patients were referred promptly (median primary care interval 5 days [IQR 0-27 days]). Where GPs deemed diagnostic delays to have occurred (22% of cases), patient, clinician, or system factors were responsible in 26%, 28%, and 34% of instances, respectively. Safety netting was recorded for 44% of patients. At least one primary care-led investigation was carried out for 45% of patients. Most patients (76%) had at least one existing comorbid condition; 21% had three or more. CONCLUSION: The findings identify avenues for quality improvement activity and provide a baseline for future audit of the impact of 2015 National Institute for Health and Care Excellence guidance on management and referral of suspected cancer

Phase I/II intra-patient dose escalation study of vorinostat in children with relapsed solid tumor, lymphoma, or leukemia

Background: Until today, adult and pediatric clinical trials investigating single-agent or combinatorial HDAC inhibitors including vorinostat in solid tumors have largely failed to demonstrate efficacy. These results may in part be explained by data from preclinical models showing significant activity only at higher concentrations compared to those achieved with current dosing regimens. In the current pediatric trial, we applied an intra-patient dose escalation design. The purpose of this trial was to determine a safe dose recommendation (SDR) of single-agent vorinostat for intra-patient dose escalation, pharmacokinetic analyses (PK), and activity evaluation in children (3-18 years) with relapsed or therapy-refractory malignancies. Results: A phase I intra-patient dose (de)escalation was performed until individual maximum tolerated dose (MTD). The starting dose was 180 mg/m(2)/day with weekly dose escalations of 50 mg/m(2) until DLT/maximum dose. After MTD determination, patients seamlessly continued in phase II with disease assessments every 3 months. PK and plasma cytokine profiles were determined. Fifty of 52 patients received treatment. n = 27/50 (54%) completed the intra-patient (de)escalation and entered phase II. An SDR of 130 mg/m(2)/day was determined (maximum, 580 mg/m(2)/day). n = 46/50 (92%) patients experienced treatment-related AEs which were mostly reversible and included thrombocytopenia, fatigue, nausea, diarrhea, anemia, and vomiting. n = 6/50 (12%) had treatment-related SAEs. No treatment-related deaths occurred. Higher dose levels resulted in higher C-max. Five patients achieved prolonged disease control (> 12 months) and showed a higher C-max (> 270 ng/mL) and MTDs. Best overall response (combining PR and SD, no CR observed) rate in phase II was 6/27 (22%) with a median PFS and OS of 5.3 and 22.4 months. Low levels of baseline cytokine expression were significantly correlated with favorable outcome. Conclusion: An SDR of 130 mg/m(2)/day for individual dose escalation was determined. Higher drug exposure was associated with responses and long-term disease stabilization with manageable toxicity. Patients with low expression of plasma cytokine levels at baseline were able to tolerate higher doses of vorinostat and benefited from treatment. Baseline cytokine profile is a promising potential predictive biomarker

Local and systemic therapy of recurrent medulloblastomas in children and adolescents: results of the P-HIT-REZ 2005 study

SIMPLE SUMMARY: A medulloblastoma recurrence is usually associated with an unfavorable prognosis. The German P-HIT-REZ 2005 Study gathered data from patients with relapsed medulloblastomas treated in different, non-randomized therapy arms dependent on preconditions of the patients (previous treatment, comorbidities, relapse pattern), the decision of treating physicians, and the patients’/parents’ choice. A total of 93 evaluable patients with refractory or relapsed medulloblastoma were enrolled. The main aim of this study was to analyze the impact of patient and disease characteristics as well as local and systemic therapies on post-relapse progression-free (PFS) and overall survival (OS). In multivariate analysis, a short time until the first recurrence (<18 months) was the strongest predictor for a worse PFS and OS, which was mainly associated with molecular subgroup 3. Metastatic disease, at relapse, only had a significant impact on OS. Re-biopsy, at relapse, is highly recommended to investigate the histopathological and molecular genetic tumor characteristics and to exclude a secondary malignancy. ABSTRACT: Recurrent medulloblastomas are associated with survival rates <10%. Adequate multimodal therapy is being discussed as having a major impact on survival. In this study, 93 patients with recurrent medulloblastoma treated in the German P-HIT-REZ 2005 Study were analyzed for survival (PFS, OS) dependent on patient, disease, and treatment characteristics. The median age at the first recurrence was 10.1 years (IQR: 6.9–16.1). Median PFS and OS, at first recurrence, were 7.9 months (CI: 5.7–10.0) and 18.5 months (CI: 13.6–23.5), respectively. Early relapses/progressions (<18 months, n = 30/93) found mainly in molecular subgroup 3 were associated with markedly worse median PFS (HR: 2.34) and OS (HR: 3.26) in regression analyses. A significant survival advantage was found for the use of volume-reducing surgery as well as radiotherapy. Intravenous chemotherapy with carboplatin and etoposide (ivCHT, n = 28/93) showed improved PFS and OS data and the best objective response rate (ORR) was 66.7% compared to oral temozolomide (oCHT, n = 47/93) which was 34.8%. Intraventricular (n = 43) as well as high-dose chemotherapy (n = 17) at first relapse was not related to a significant survival benefit. Although the results are limited due to a non-randomized study design, they may serve as a basis for future treatment decisions in order to improve the patients’ survival