Using mentoring to improve the foundation placement in psychiatry: review of literature and a practical example

In the past few years, mentoring in clinical settings has attracted the attention of medical educators, clinicians, managers, and policy makers. Most of the Royal Colleges of medical and surgical specialities have some form of mentoring schemes and various regional divisions of Health Education England support mentoring and coaching in the workplace. Despite the importance of this topic and the great need to provide more support to doctors in recent times, there is a paucity of literature on examples of mentoring schemes in clinical settings and practicalities of setting up such schemes in hospitals. This paper describes the implementation of a mentoring scheme in a large mental health trust in the UK to support junior doctors and the issues involved in creating such scheme. We hope that this article will be useful to clinicians who would like to start similar schemes in their workplace

Study protocol for statin web-based investigation of side effects (StatinWISE):a series of randomised controlled N-of-1 trials comparing atorvastatin and placebo in UK primary care

Introduction: Statins are effective at preventing cardiovascular disease, widely prescribed, and their use is growing. Uncertainty persists about whether they cause symptomatic muscle adverse effects, such as pain and weakness, in the absence of statin myopathy. Discrepancies between data from observational studies, which suggest statins are associated with excess muscle symptoms, and from randomised trials, which suggest no such excess, have caused confusion. N-of-1 trials offer the opportunity to establish whether muscle symptoms during statin use are caused by statins in particular individuals. Methods and analysis: This series of 200 randomised, double blinded N-of-1 trials in primary care will determine (i) the effect of statins on all muscle symptoms, and (ii) the effect of statins on muscle pain that is perceived to be statin related. Patients who are considering discontinuing statin use due to muscle symptoms, and those who have discontinued in the last three years due to such symptoms, will be recruited. Participants will be randomised to a sequence of six two-month treatment periods during which they will receive atorvastatin 20mg daily or matched placebo. On each of the last seven days of each treatment period, participants will rate their muscle symptoms on a Visual Analogue Scale (VAS). At the end of their trial, participants will be shown numerical and graphical summaries of their own symptom data during statin and placebo periods. The primary analysis on the aggregate data from all participants will be a linear mixed model for VAS muscle symptom score, comparing scores during treatment with statin and placebo. Ethics and dissemination: This trial received a favourable opinion from South Central - Hampshire A Research Ethics Committee. Results will be published in a peer-reviewed medical journal. Dissemination of results to patients will take place via the media, website (statinwise.lshtm.ac.uk) and patient organisations

Functional analysis of drug resistance-associated mutations in the Trypanosoma brucei Adenosine Transporter 1 (TbAT1) and the proposal of a structural model for the protein

The Trypanosoma brucei aminopurine transporter P2/TbAT1 has long been implicated in the transport of, and resistance to, the diamidine and melaminophenyl arsenical classes of drugs that form the backbone of the pharmacopoeia against African trypanosomiasis. Genetic alterations including deletions and single nucleotide polymorphisms (SNPs) have been observed in numerous strains and clinical isolates. Here, we systematically investigate each reported mutation and assess their effects on transporter function after expression in a tbat1 -/- T. brucei line. Out of a set of six reported SNPs from a reported ‘resistance allele’, none significantly impaired sensitivity to pentamidine, diminazene or melarsoprol, relative to the TbAT1-WT allele, although several combinations, and the deletion of the codon for residue F316, resulted in highly significant impairment. These combinations of SNPs, and ΔF316, also strongly impaired the uptake of [3H]-adenosine and [3H]-diminazene, identical to the tbat1-/- control. The TbAT1 protein model predicted that residues F19, D140 and F316 interact with the substrate of the transporter. Mutation of D140 to alanine resulted in an inactive transporter, whereas the mutation F19A produced a transporter with a slightly increased affinity for [3H]-diminazene, but reduced the uptake rate. The results presented here validate earlier hypotheses of drug binding motifs for TbAT1

The effect of statins on muscle symptoms in primary care:the StatinWISE series of 200 N-of-1 RCTs

Background: Uncertainty persists about whether or not statins cause symptomatic muscle adverse effects (e.g. pain, stiffness and weakness) in the absence of severe myositis.Objectives: To establish the effect of statins on all muscle symptoms, and the effect of statins on muscle symptoms that are perceived to be statin related.Design: A series of 200 double-blinded N-of-1 trials.Setting: Participants were recruited from 50 general practices in England and Wales.Participants: Patients who were considering discontinuing statin use and those who had discontinued statin use in the last 3 years because of perceived muscle symptoms.Interventions: Participants were randomised to a sequence of six 2-month treatment periods during which they received 20 mg of atorvastatin daily or a matched placebo.Main outcome measures: The primary outcome was self-reported muscle symptoms rated using a visual analogue scale on the last week of each treatment period. Secondary outcomes included the participant's belief about the cause of their muscle symptoms, the site of muscle symptoms, how the muscle symptoms affected the participant, any other symptoms they experienced, adherence to medication, the participant's decision about statin treatment following the trial, and whether or not they found their own trial result helpful.Results: A total of 151 out of 200 (75.5%) randomised participants provided one or more visual analogue scale measurements in a placebo period and one or more measurements in a statin period, and were included in the primary analysis. There was no evidence of a difference in muscle symptom scores between statin and placebo periods (mean difference statin minus placebo -0.11, 95% confidence interval -0.36 to 0.14; p = 0.398). Withdrawals, adherence and missing data were similar during the statin periods and the placebo periods.Conclusions: Among people who previously reported severe muscle symptoms while taking statins, this series of randomised N-of-1 trials found no overall effect of statins on muscle symptoms compared with the placebo. The slight difference in withdrawals due to muscle symptoms suggests that statins may contribute to symptoms in a small number of patients. The results are generalisable to patients who are considering discontinuing or have already discontinued statins because of muscle symptoms, and who are willing to re-challenge or participate in their own N-of-1 trial.Future work: We recommend that additional statins and doses are explored using N-of-1 trials. More broadly, N-of-1 trials present a useful tool for exploring transient symptoms with other medications.Limitations: This study used 20-mg doses of atorvastatin only. Furthermore, a dropout rate of 43% was observed, but this was accounted for in the power calculations.Trial registration: Current Controlled Trials ISRCTN30952488 and EudraCT 2016-000141-31.</p

Statin treatment and muscle symptoms:series of randomised, placebo controlled n-of-1 trials

OBJECTIVE: To establish the effect of statins on muscle symptoms in people who had previously reported muscle symptoms when taking statins. DESIGN: Series of randomised, placebo controlled n-of-1 trials. SETTING: Primary care across 50 sites in the United Kingdom, December 2016 to April 2018. PARTICIPANTS: 200 participants who had recently stopped or were considering stopping treatment with statins because of muscle symptoms. INTERVENTIONS: Participants were randomised to a sequence of six double blinded treatment periods (two months each) of atorvastatin 20 mg daily or placebo. MAIN OUTCOME MEASURES: At the end of each treatment period, participants rated their muscle symptoms on a visual analogue scale (0-10). The primary analysis compared symptom scores in the statin and placebo periods. RESULTS: 151 participants provided symptoms scores for at least one statin period and one placebo period and were included in the primary analysis. Overall, no difference in muscle symptom scores was found between the statin and placebo periods (mean difference statin minus placebo -0.11, 95% confidence interval -0.36 to 0.14; P=0.40)). Withdrawals because of intolerable muscle symptoms were 18 participants (9%) during a statin period and 13 (7%) during a placebo period. Two thirds of those completing the trial reported restarting long term treatment with statins. CONCLUSIONS: No overall effect of atorvastatin 20 mg on muscle symptoms compared with placebo was found in participants who had previously reported severe muscle symptoms when taking statins. Most people completing the trial intended to restart treatment with statins. N-of-1 trials can assess drug effects at the group level and guide individual treatment. TRIAL REGISTRATION: ISRCTN30952488, EUDRACT 2016-000141-31, NCT02781064

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The use of gas chromatography/pulsed HID to monitor formaldehyde - field and laboratory measurements

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Complex and contradictory: the doing of gender on regional development boards

In this paper we explore the complex, and in many ways contradictory, picture of how gender is enacted and reinforced within regional development boards/commissions in NSW and WA. While the number of women on these regional organisations has increased over the past decade, the overwhelming sense of these organisations is one of homogeneity. Members of the boards/commission are very alike in age and socio-economic circumstances, highlighting that body counting by sex doesn't adequately capture gender, which we take to be a socially constructed facet of identity. Recognising gender as a social construction (West and Zimmerman, 2002), where the doing of masculinity is privileged over femininity takes our analysis to a deeper level. In this context, as Ministerially appointed organisations, the individuals appointed can be seen to be privileged through the social structures. Their roles, while ambiguous, provide status to those involved and benefits through increased networking and knowledge. Their membership positions them within the (masculine) hegemony (Connell, 2005). For women to be appointed to these roles, they have had to perform much like their male counterparts, so they can 'pass' for the elite and their nominations be accepted by the Minister; that is, they are connected, have a high profile and they are able to understand and conform to the 'rules' of the boards/commissions (in terms of being able to make it to meetings, fit in socially with the group, like mindedness...)