CASNET2: evaluation of an electronic safety netting cancer toolkit for the primary care electronic health record: protocol for a pragmatic stepped-wedge RCT.

INTRODUCTION: Safety-netting in primary care is the best practice in cancer diagnosis, ensuring that patients are followed up until symptoms are explained or have resolved. Currently, clinicians use haphazard manual solutions. The ubiquitous use of electronic health records provides an opportunity to standardise safety-netting practices.A new electronic safety-netting toolkit has been introduced to provide systematic ways to track and follow up patients. We will evaluate the effectiveness of this toolkit, which is embedded in a major primary care clinical system in England:Egerton Medical Information System(EMIS)-Web. METHODS AND ANALYSIS: We will conduct a stepped-wedge cluster RCT in 60 general practices within the RCGP Research and Surveillance Centre (RSC) network. Groups of 10 practices will be randomised into the active phase at 2-monthly intervals over 12 months. All practices will be activated for at least 2 months. The primary outcome is the primary care interval measured as days between the first recorded symptom of cancer (within the year prior to diagnosis) and the subsequent referral to secondary care. Other outcomes include referrals rates and rates of direct access cancer investigation.Analysis of the clustered stepped-wedge design will model associations using a fixed effect for intervention condition of the cluster at each time step, a fixed effect for time and other covariates, and then include a random effect for practice and for patient to account for correlation between observations from the same centre and from the same participant. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the North West-Greater Manchester West National Health Service Research Ethics Committee (REC Reference 19/NW/0692). Results will be disseminated in peer-reviewed journals and conferences, and sent to participating practices. They will be published on the University of Oxford Nuffield Department of Primary Care and RCGP RSC websites. TRIAL REGISTRATION NUMBER: ISRCTN15913081; Pre-results.

Conurbation, Urban, and Rural Living as Determinants of Allergies and Infectious Diseases: Royal College of General Practitioners Research and Surveillance Centre Annual Report 2016-2017.

BACKGROUND: Living in a conurbation, urban, or rural environment is an important determinant of health. For example, conurbation and rural living is associated with increased respiratory and allergic conditions, whereas a farm or rural upbringing has been shown to be a protective factor against this. OBJECTIVE: The objective of the study was to assess differences in general practice presentations of allergic and infectious disease in those exposed to conurbation or urban living compared with rural environments. METHODS: The population was a nationally representative sample of 175 English general practices covering a population of over 1.6 million patients registered with sentinel network general practices. General practice presentation rates per 100,000 population were reported for allergic rhinitis, asthma, and infectious conditions grouped into upper and lower respiratory tract infections, urinary tract infection, and acute gastroenteritis by the UK Office for National Statistics urban-rural category. We used multivariate logistic regression adjusting for age, sex, ethnicity, deprivation, comorbidities, and smoking status, reporting odds ratios (ORs) with 95% CIs. RESULTS: For allergic rhinitis, the OR was 1.13 (95% CI 1.04-1.23; P=.003) for urban and 1.29 (95% CI 1.19-1.41; P<.001) for conurbation compared with rural dwellers. Conurbation living was associated with a lower OR for both asthma (OR 0.70, 95% CI 0.67-0.73; P<.001) and lower respiratory tract infections (OR 0.94, 95% CI 0.90-0.98; P=.005). Compared with rural dwellers, the OR for upper respiratory tract infection was greater in urban (OR 1.06, 95% CI 1.03-1.08; P<.001) but no different in conurbation dwellers (OR 1.00, 95% CI 0.97-1.03; P=.93). Acute gastroenteritis followed the same pattern: the OR was 1.13 (95% CI 1.01-1.25; P=.03) for urban dwellers and 1.04 (95% CI 0.93-1.17; P=.46) for conurbation dwellers. The OR for urinary tract infection was lower for urban dwellers (OR 0.94, 95% CI 0.89-0.99; P=.02) but higher in conurbation dwellers (OR 1.06, 95% CI 1.00-1.13; P=.04). CONCLUSIONS: Those living in conurbations or urban areas were more likely to consult a general practice for allergic rhinitis and upper respiratory tract infection. Both conurbation and rural living were associated with an increased risk of urinary tract infection. Living in rural areas was associated with an increased risk of asthma and lower respiratory tract infections. The data suggest that living environment may affect rates of consultations for certain conditions. Longitudinal analyses of these data would be useful in providing insights into important determinants.

Diaryl and heteroaryl sulfides: synthesis via sulfenyl chlorides and evaluation as selective anti-breast-cancer agents.

A mild protocol for the synthesis of diaryl and heteroaryl sulfides is described. In a one-pot procedure, thiols are converted to sulfenyl chlorides and reacted with arylzinc reagents. This method tolerates functional groups including aryl fluorides and chlorides, ketones, as well as N-heterocycles including pyrimidines, imidazoles, tetrazoles, and oxadiazoles. Two compounds synthesized by this method exhibited selective activity against the MCF-7 breast cancer cell line in the micromolar range.

Stereospecific nickel-catalyzed cross-coupling reactions of alkyl Grignard reagents and identification of selective anti-breast-cancer agents.

Alkyl Grignard reagents that contain ß-hydrogen atoms were used in a stereospecific nickel-catalyzed cross-coupling reaction to form C(sp(3))-C(sp(3)) bonds. Aryl Grignard reagents were also utilized to synthesize 1,1-diarylalkanes. Several compounds synthesized by this method exhibited selective inhibition of proliferation of MCF-7 breast cancer cells.

Traceless directing group for stereospecific nickel-catalyzed alkyl-alkyl cross-coupling reactions.

Stereospecific nickel-catalyzed cross-coupling reactions of benzylic 2-methoxyethyl ethers are reported for the preparation of enantioenriched 1,1-diarylethanes. The 2-methoxyethyl ether serves as a traceless directing group that accelerates cross-coupling. Chelation of magnesium ions is proposed to activate the benzylic C-O bond for oxidative addition.