Evaluating the UK's first national prescribing assessment for GPs in training using an online survey.

Background: GP trainees may not have experienced a systematic and comprehensive education in safe prescribing. Therefore, a self-assessment prescribing review was developed.

Aim: To determine whether the assessment was feasible, had face validity, and did not disadvantage particular groups of participants.

Comparison of the effectiveness of exclusively facilitated clinical teaching as an alternative to traditional practice-based primary care placements.

Introduction: COVID-19 presented major challenges to undergraduate GP placement capacity and there was an increased reliance on clinical training using facilitated simulation. The authors present a novel comparison of the effectiveness and cost-effectiveness of delivering a one-week primary care course using entirely GP-facilitated clinical teaching outside the GP setting against traditional practice-based GP clinical education.

Methods: A one-week GP placement was redeveloped from a traditional teaching model (TT-M) to an exclusively facilitated teaching model (FT-M) delivered outside the GP practice setting, using principles of blended learning, flipped classroom methods, e-learning and simulation.

A first-order approximation of floodplain soil organic carbon stocks in a river network: The South Platte River, Colorado, USA as a case study.

The lack of watershed-scale estimates of floodplain carbon stocks limits recognition of the important role of floodplains and river corridor restoration in efforts to enhance carbon sequestration. We use the South Platte River watershed of Colorado, USA as a case study to illustrate spatial patterns of, and controls on, floodplain carbon stocks at the watershed scale. This case study illustrates the disproportionate importance of floodplains for soil carbon stocks relative to adjacent uplands and provides an example of how spatially explicit data can be used to prioritize floodplain restoration with regard to carbon sequestration.

A river ran through it: Floodplains as America's newest relict landform.

Artificial levees are a major human modification of river corridors, but we still do not have a clear understanding of how artificial levees affect floodplain extent at regional and larger scales. We estimated changes in river-floodplain connectivity due to artificial levees in the contiguous United States (CONUS) using a combination of artificial levee databases, delineations of floodplain areas, and deletion of artificial levees from topography. Our results indicate that artificial levees do not only decrease floodplain extent but also alter locations of floodplain connectivity.

Levees don't protect, they disconnect: A critical review of how artificial levees impact floodplain functions.

Despite the recognition of floodplain importance in the scientific community, floodplains are not afforded the same legal protection as river channels. In the United States alone, flood-related economic losses were much higher in the second half of the 20th century than the first half despite the expenditure of billions of dollars on flood defenses. Partially to blame are the low appraisal and understanding of human impacts to floodplain functions.

The frequency and nature of prescribing problems by GPs-in-training (REVISiT): a retrospective review.

Background: Prescribing errors can cause significant morbidity and occur in about 5% of prescriptions in English general practices.

Aim: To describe the frequency and nature of prescribing problems in a cohort of GPs-in-training to determine whether they need additional prescribing support.

Design & Setting: A primary care pharmacist undertook a retrospective review of prescriptions issued between 9 October 2014 and 11 March 2015 by 10 GPs in their final year of training from 10 practices in England.

Developing good practice by understanding how UK medical schools address low level concerns: a survey study.

In the literature, a distinction is made between low-level concerns and what is regarded as fitness to practise concerns. The General Medical Council expects all UK medical schools to have a transparent process in place about how concerns about its medical students are identified monitored and responded to. However, internationally, there is currently no well-established consensus on what is good practice in managing low-level concerns.

The evaluation of an e-learning prescribing course for general practice.

Prescribed medication may lead to significant morbidity or mortality as a result of these medications causing adverse events, or because of a prescribing error. E-learning is a common tool used in supporting training in prescribing. This paper describes the development of an e-learning course and the subsequent evaluation undertaken by the users with the aim of obtaining an effective e-learning course for prescribing.

A qualitative evaluation of a prescribing e-learning package for general practice.

Background: The GMC PRACtiCe study identified a 1 in 20 error rate in prescriptions issued in general practice and identified a need for further training in prescribing. As a result, an e-Learning prescribing package was designed and launched to healthcare professionals through the Royal College of General Practitioners in January 2014.

Aim: This part of the study explored the longer-term impact on prescribing knowledge, attitudes and behaviours of practitioners completing the eLearning prescribing package.

An improved cell-permeable fluorogenic substrate as the basis for a highly sensitive test for NAD(P)H quinone oxidoreductase 1 (NQO1) in living cells.

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a flavoenzyme upregulated in response to oxidative stress and in some cancers. Its upregulation by compounds has been used as an indicator of their potential anti-cancer properties. In this study we have designed, produced and tested a fluorogenic coumarin conjugate which selectively releases highly fluorescent 4-methylumbelliferone (4-MU) in the presence of NQO1.

Studies relating to the synthesis, enzymatic reduction and cytotoxicity of a series of nitroaromatic prodrugs.

A series of N-nitroarylated-3-chloromethyl-1,2,3,4-tetrahydroisoquinoline derivatives, several of which also possessed a trifluoromethyl substituent, were prepared and assessed as potential nitroaromatic prodrugs. The enzymatic reduction of these compounds and their cytotoxicities were studied. The compounds were cytotoxic, but this is probably not related to their enzymatic reduction.

A BEME systematic review of UK undergraduate medical education in the general practice setting: BEME Guide No. 32.

Background: General practice is increasingly used as a learning environment in undergraduate medical education in the UK.

Aim: The aim of this project was to identify, summarise and synthesise research about undergraduate medical education in general practice in the UK.

Methods: We systematically identified studies of undergraduate medical education within a general practice setting in the UK from 1990 onwards.

Spores of Clostridium engineered for clinical efficacy and safety cause regression and cure of tumors in vivo.

Spores of some species of the strictly anaerobic bacteria Clostridium naturally target and partially lyse the hypoxic cores of tumors, which tend to be refractory to conventional therapies. The anti-tumor effect can be augmented by engineering strains to convert a non-toxic prodrug into a cytotoxic drug specifically at the tumor site by expressing a prodrug-converting enzyme (PCE). Safe doses of the favored prodrug CB1954 lead to peak concentrations of 6.

The synthesis of 2-nitroaryl-1,2,3,4-tetrahydroisoquinolines, nitro-substituted 5,6-dihydrobenzimidazo[2,1-a]isoquinoline N-oxides and related heterocycles as potential bioreducible substrates for the enzymes NAD(P)H: quinone oxidoreductase 1 and E. coli nitroreductase.

A series of 2-nitroaryl-1,2,3,4-tetrahydroisoquinolines 10 and nitro-substituted 5,6-dihydrobenzimidazo[2,1-a]isoquinoline N-oxides 11 have been synthesised and evaluated as potential bioreducible substrates for the enzymes NAD(P)H: quinone oxidoreductase 1 (NQO1) and Escherichia coli nitroreductase (NR). Also prepared and evaluated were 2-(3,5-dinitropyridin-2-yl)-1,2,3,4-tetrahydroisoquinoline 12 and 5,6-dihydro-10-nitropyrido[3″,2″:4',5']imidazo[2',1'-a]isoquinoline 12-oxide 13. Both compounds 10b and 13 were reduced faster by human NQO1 than by CB-1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide].

Synthesis and structure-activity relationships of nitrobenzyl phosphoramide mustards as nitroreductase-activated prodrugs.

A series of nitrobenzyl phosphoramide mustards and their analogs was designed and synthesized to explore their structure-activity relationships as substrates of nitroreductases from Escherichia coli and trypanosomes and as potential antiproliferative and antiparasitic agents. The position of the nitro group on the phenyl ring was important with the 4-nitrobenzyl phosphoramide mustard (1) offering the best combination of enzyme activity and antiproliferative effect against both mammalian and trypanosomatid cells. A preference was observed for halogen substitutions ortho to benzyl phosphoramide mustard but distinct differences were found in their SAR of substituted 4-nitrobenzyl phosphoramide mustards in E.

Quinone oxidoreductase-2-mediated prodrug cancer therapy.

DNA-damaging agents are widely used in cancer treatment despite their lack of tumor specificity. Human NQO2 (quinone oxidoreductase-2) is an atypical oxidoreductase because no endogenous electron donor has been identified to date. The enzyme converts CB1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide], in the presence of the synthetic nicotinamide cofactor analog EP0152R, to a cytotoxic bifunctional alkylating agent.

Testing double mutants of the enzyme nitroreductase for enhanced cell sensitisation to prodrugs: effects of combining beneficial single mutations.

Prodrug activation gene therapy for cancer involves expressing prodrug-activating enzymes in tumour cells, so they can be selectively killed by systemically administered prodrug. For example, Escherichia colinfsB nitroreductase (E.C.

Nitroreductase from Bacillus licheniformis: a stable enzyme for prodrug activation.

5-aziridinyl-2,4-dinitrobenzamide (CB1954) has potential applications in enzyme/prodrug targeted anti-cancer therapies since it can be activated by nitroreductases to form a cytotoxic, bifunctional hydroxylamine derivative. A nitroreductase that can activate CB1954 has been previously isolated from Escherichia coli, but its usefulness is limited by its poor stability and low catalytic efficiency for CB1954. We now report the identification and characterization of a nitroreductase enzyme from the thermophilic bacterium Bacillus licheniformis.

Functionalised cyclopentadienyl zirconium compounds as potential anticancer drugs.

New neutral and ionic functionalised zirconocene dichloride compounds have been isolated and characterised. The ionic zirconocene exhibits excellent cytotoxicity against a range of human tumour cell lines, which represents the first active anticancer zirconocene dichloride compound.

Functionalised cyclopentadienyl titanium compounds as potential anticancer drugs.

A number of new ionic titanocene compounds have been isolated and characterised, which exhibit excellent cytotoxicity against different human tumour cell lines including a defined cisplatin resistant cell line. A range of biological assays have been carried out to determine levels of cytotoxicity and levels of DNA interstrand crosslinking.

NAD(P)H:quinone oxidoreductase 1 and nrh:quinone oxidoreductase 2 activity and expression in bladder and ovarian cancer and lower NRH:quinone oxidoreductase 2 activity associated with an NQO2 exon 3 single-nucleotide polymorphism.

Purpose: NRH:quinone oxidoreductase 2 (NQO2) is a homologue of NAD(P)H:quinone oxidoreductase 1 (NQO1). Despite 54% homology with human NQO1, NQO2 has little endogenous enzymatic activity. However, NQO2 has potential as a therapeutic target because the addition of the nonbiogenic electron donor dihydronicotinamide riboside (NRH) selectively potentiates the bioactivation of the alkylating agent tretazicar (CB 1954).