Induction of labour for predicted macrosomia: study protocol for the 'Big Baby' randomised controlled trial.

INTRODUCTION: Large-for-gestational age (LGA) fetuses have an increased risk of shoulder dystocia. This can lead to adverse neonatal outcomes and death. Early induction of labour in women with a fetus suspected to be macrosomic may mitigate the risk of shoulder dystocia. The Big Baby Trial aims to find if induction of labour at 38+0-38+4 weeks' gestation, in pregnancies with suspected LGA fetuses, reduces the incidence of shoulder dystocia. METHODS AND ANALYSIS: The Big Baby Trial is a multicentre, prospective, individually randomised controlled trial of induction of labour at 38+0 to 38+4 weeks' gestation vs standard care as per each hospital trust (median gestation of delivery 39+4) among women whose fetuses have an estimated fetal weight >90th customised centile according to ultrasound scan at 35+0 to 38+0 weeks' gestation. There is a parallel cohort study for women who decline randomisation because they opt for induction, expectant management or caesarean section. Up to 4000 women will be recruited and randomised to induction of labour or to standard care. The primary outcome is the incidence of shoulder dystocia; assessed by an independent expert group, blind to treatment allocation, from delivery records. Secondary outcomes include birth trauma, fractures, haemorrhage, caesarean section rate and length of inpatient stay. The main trial is ongoing, following an internal pilot study. A qualitative reporting, health economic evaluation and parallel process evaluation are included. ETHICS AND DISSEMINATION: The study received a favourable opinion from the South West-Cornwall and Plymouth Health Research Authority on 23/03/2018 (IRAS project ID 229163). Study results will be reported in the National Institute for Health Research journal library and published in an open access peer-reviewed journal. We will plan dissemination events for key stakeholders. TRIAL REGISTRATION NUMBER: ISRCTN18229892.

Subacromial balloon spacer for irreparable rotator cuff tears of the shoulder (START:REACTS): a group-sequential, double-blind, multicentre randomised controlled trial.

BACKGROUND: New surgical procedures can expose patients to harm and should be carefully evaluated before widespread use. The InSpace balloon (Stryker, USA) is an innovative surgical device used to treat people with rotator cuff tears that cannot be repaired. We aimed to determine the effectiveness of the InSpace balloon for people with irreparable rotator cuff tears. METHODS: We conducted a double-blind, group-sequential, adaptive randomised controlled trial in 24 hospitals in the UK, comparing arthroscopic debridement of the subacromial space with biceps tenotomy (debridement only group) with the same procedure but including insertion of the InSpace balloon (debridement with device group). Participants had an irreparable rotator cuff tear, which had not resolved with conservative treatment, and they had symptoms warranting surgery. Eligibility was confirmed intraoperatively before randomly assigning (1:1) participants to a treatment group using a remote computer system. Participants and assessors were masked to group assignment. Masking was achieved by using identical incisions for both procedures, blinding the operation note, and a consistent rehabilitation programme was offered regardless of group allocation. The primary outcome was the Oxford Shoulder Score at 12 months. Pre-trial simulations using data from early and late timepoints informed stopping boundaries for two interim analyses. The primary analysis was on a modified intention-to-treat basis, adjusted for the planned interim analysis. The trial was registered with ISRCTN, ISRCTN17825590. FINDINGS: Between June 1, 2018, and July 30, 2020, we assessed 385 people for eligibility, of which 317 were eligible. 249 (79%) people consented for inclusion in the study. 117 participants were randomly allocated to a treatment group, 61 participants to the debridement only group and 56 to the debridement with device group. A predefined stopping boundary was met at the first interim analysis and recruitment stopped with 117 participants randomised. 43% of participants were female, 57% were male. We obtained primary outcome data for 114 (97%) participants. The mean Oxford Shoulder Score at 12 months was 34·3 (SD 11·1) in the debridement only group and 30·3 (10·9) in the debridement with device group (mean difference adjusted for adaptive design -4·2 [95% CI -8·2 to -0·26];p=0·037) favouring control. There was no difference in adverse events between the two groups. INTERPRETATION: In an efficient, adaptive trial design, our results favoured the debridement only group. We do not recommend the InSpace balloon for the treatment of irreparable rotator cuff tears. FUNDING: Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health and Care Research partnership.

Use of cast immobilisation versus removable brace in adults with an ankle fracture: multicentre randomised controlled trial.

OBJECTIVES: To assess function, quality of life, resource use, and complications in adults treated with plaster cast immobilisation versus a removable brace for ankle fracture. DESIGN: Multicentre randomised controlled trial. SETTING: 20 trauma units in the UK National Health Service. PARTICIPANTS: 669 adults aged 18 years and older with an acute ankle fracture suitable for cast immobilisation: 334 were randomised to a plaster cast and 335 to a removable brace. INTERVENTIONS: A below the knee cast was applied and ankle range of movement exercises started on cast removal. The removable brace was fitted, and ankle range of movement exercises were started immediately. MAIN OUTCOME MEASURES: Primary outcome was the Olerud Molander ankle score at 16 weeks, analysed by intention to treat. Secondary outcomes were Manchester-Oxford foot questionnaire, disability rating index, quality of life, and complications at 6, 10, and 16 weeks. RESULTS: The mean age of participants was 46 years (SD 17 years) and 381 (57%) were women. 502 (75%) participants completed the study. No statistically significant difference was found in the Olerud Molander ankle score between the cast and removable brace groups at 16 weeks (favours brace: 1.8, 95% confidence interval -2.0 to 5.6). No clinically significant differences were found in the Olerud Molander ankle scores at other time points, in the secondary unadjusted, imputed, or per protocol analyses. CONCLUSIONS: Traditional plaster casting was not found to be superior to functional bracing in adults with an ankle fracture. No statistically difference was found in the Olerud Molander ankle score between the trial arms at 16 weeks. TRIAL REGISTRATION: ISRCTN registry ISRCTN15537280.

Effect of Platelet-Rich Plasma Injection vs Sham Injection on Tendon Dysfunction in Patients With Chronic Midportion Achilles Tendinopathy: A Randomized Clinical Trial.

Importance: Platelet-rich plasma injections are used as a treatment for chronic midportion Achilles tendinopathy, but evidence for this treatment is limited. Objective: In adults with midportion Achilles tendinopathy, to assess the effects of a single platelet-rich plasma injection, compared with sham injection, on the outcome of the Victorian Institute of Sport Assessment-Achilles (VISA-A) score (a single composite measure of Achilles tendinopathy severity). Design, Setting, and Participants: A participant-blinded, multicenter randomized clinical trial that included 240 people from 24 sites assigned to either a platelet-rich plasma injection or a sham injection between April 2016 and February 2020. Final follow-up was July 2020. Participants were older than 18 years with midportion Achilles tendon pain for more than 3 months as confirmed by ultrasound, magnetic resonance imaging, or both. Interventions: A single intratendinous platelet-rich plasma injection (n = 121) or a single sham injection (insertion of a subcutaneous dry needle not entering the tendon) (n = 119). Main Outcomes and Measures: The primary outcome was the VISA-A score, measured 6 months after treatment allocation. The VISA-A score contains 8 questions that cover 3 domains of pain, function, and activity, analyzed as a composite score (range, 0 [worst symptoms] to 100 [no symptoms]; minimal clinically important difference in score, 12 points). The primary analysis was adjusted for laterality, age, sex, and baseline VISA-A score. Results: Among 240 patients assigned to a platelet-rich plasma or sham injection (mean age, 52 years; 138 [58%] women), 221 (92%) completed the trial. At 6-month follow-up, mean VISA-A score values in the plasma-rich plasma group vs the sham injection group were 54.4 vs 53.4 (adjusted mean difference, -2.7 [95% CI, -8.8 to 3.3]). The most common adverse events compared between patients in the platelet-rich plasma group vs the sham group were injection site discomfort (97 vs 73 patients), swelling (56 vs 52 patients) and bruising (48 vs 49 patients). Conclusions and Relevance: Among patients with chronic midportion Achilles tendinopathy, treatment with a single injection of intratendinous platelet-rich plasma, compared with insertion of a subcutaneous dry needle, did not reduce Achilles tendon dysfunction at 6 months. These findings do not support the use of this treatment for chronic midportion Achilles tendinopathy. Trial Registration: isrctn.org Identifier: ISRCTN13254422.

Protocol for a randomised controlled trial of Subacromial spacer for Tears Affecting Rotator cuff Tendons: a Randomised, Efficient, Adaptive Clinical Trial in Surgery (START:REACTS).

INTRODUCTION: Shoulder pain due to irreparable rotator cuff tears can cause substantial disability, but treatment options are limited. A balloon spacer is a relatively simple addition to a standard arthroscopic debridement procedure, but it is costly and there is no current randomised trial evidence to support its use. This trial will evaluate the clinical and cost-effectiveness of a subacromial balloon spacer for individuals undergoing arthroscopic debridement for irreparable rotator cuff tears.New surgical procedures can provide substantial benefit to patients. Good quality randomised controlled trials (RCTs) are needed, but trials in surgery are typically long and expensive, exposing patients to risk and the healthcare system to substantial costs. One way to improve the efficiency of trials is with an adaptive sample size. Such methods are well established in drug trials but have rarely, if ever, been used in surgical trials. METHODS AND ANALYSIS: Subacromial spacer for Tears Affecting Rotator cuff Tendons: a Randomised, Efficient, Adaptive Clinical Trial in Surgery (START:REACTS) is a participant and assessor blinded, adaptive, multicentre RCT comparing arthroscopic debridement with the InSpace balloon (Stryker, USA) to arthroscopic debridement alone for people with a symptomatic irreparable rotator cuff tear. It uses a group sequential adaptive design where interim analyses are performed using all of the 3, 6 and 12-month data that are available at each time point. A maximum of 221 participants will be randomised (1:1 ratio), this will provide 90% power (at the 5% level) for a 6 point difference in the primary outcome; the Oxford Shoulder Score at 12 months. A substudy will use deltoid-active MRI scans in 56 participants to assess the function of the balloon. Analysis will be on an intention-to-treat basis and reported according to principles established in the Consolidated Standards of Reporting Trials statement. ETHICS AND DISSEMINATION: NRES number 18/WM/0025. The results will be disseminated via peer-reviewed publications, presentations at conferences, lay summaries and social media. TRIAL REGISTRATION NUMBER: ISRCTN17825590.

Platelet rich plasma versus placebo for the management of Achilles tendinopathy: protocol for the UK study of Achilles tendinopathy management (ATM) multi-centre randomised trial.

INTRODUCTION: In the UK, 150 000 people every year experience mid-substance Achilles tendinopathy. Typically patients are offered a range of treatment options such as exercise, electrotherapy, injections and surgery. With large variations in current practice, there is a pressing need to establish which treatments are effective and which are not. This is the protocol for a multi-centre randomised trial of platelet rich plasma (PRP) versus placebo injection for patients with Achilles tendinopathy. METHODS AND ANALYSIS: Adult patients with mid-substance Achilles tendinopathy for longer than 3 months will be screened. Randomisation will be on a 1:1 basis, stratified by centre and bilateral presentation. Participants will be allocated to either a single PRP injection or placebo injection. A minimum of 240 patients will be recruited into the study; this number will provide 90% power to detect a difference of 12 points in Victorian Institute of Sport Assessment-Achilles score at 6 months. Quality of life, pain and complications data will be collected at baseline, 2-week, 3-month and 6-month post-randomisation. The differences between treatment groups will be assessed on an intention-to-treat basis. ETHICS, REGISTRATION AND DISSEMINATION: This trial was funded by Versus Arthritis and commenced on 1 September 2015 (Versus Arthritis 20831). National Research Ethic Committee approved this study on 30 October 2015 (15/WM/0359). It was registered on the International Standard Randomised Controlled Trial Number (ISRCTN) registry with reference number ISRCTN 13254422 on 28 October 2015. The first site opened to recruitment on 27 April 2016 and the trial was in active recruitment at the point of submitting the protocol paper. The results of this trial will be submitted to a peer-reviewed journal and will inform clinical practice with regard to the treatment of Achilles tendinopathy.

Acute Rehabilitation following Traumatic anterior shoulder dISlocAtioN (ARTISAN): protocol for a multicentre randomised controlled trial.

INTRODUCTION: First-time traumatic anterior shoulder dislocation (TASD) is predominantly managed non-operatively. People sustaining TASD have ongoing pain, disability and future risk of redislocation. There are no published randomised controlled trials (RCTs) comparing different non-operative rehabilitation strategies to ascertain the optimum clinically effective approach after TASD. METHODS AND ANALYSIS: In this multicentre adaptive RCT, with internal pilot, adults with a radiologically confirmed first time TASD treated non-surgically will be screened at a minimum of 30 sites. People with neurovascular complications, bilateral dislocations or are unable to attend physiotherapy will be excluded.Randomisation will be on a 1:1 treatment allocation, stratified by age, hand dominance and site. Participants will receive a single session of advice; or a single session of advice plus offer of further physiotherapy (maximum 4 months). The primary analysis will be the difference in Oxford Shoulder Instability Score at 6 months. A sample size of a minimum of 478 participants will allow us to show a four point difference with 90% power.An embedded qualitative study will explore the participants' experiences of the trial interventions. ETHICS, REGISTRATION AND DISSEMINATION: Funded by NIHR HTA (16/167/56), 1 June 2018; National Research Ethic Committee approved (18/WA/0236), 26 July 2018. First site opened 5 November 2018 and final results will be updated on trial registries and submitted to a peer-reviewed journal and will inform rehabilitation strategies after a TASD. Study Within A Trial (SWAT) funded by MRC (MR/R013748/1), 1 May 2019; registered on the MRC-HTMR All-Ireland Hub (reference number SWAT 121). TRIAL REGISTRATION NUMBER: ISRCTN63184243. (Trial stage: Pre-results).

Effects of soil- and climate data aggregation on simulated potato yield and irrigation water requirement.

Input data aggregation affects crop model estimates at the regional level. Previous studies have focused on the impact of aggregating climate data used to compute crop yields. However, little is known about the combined data aggregation effect of climate (DAEc) and soil (DAEs) on irrigation water requirement (IWR) in cool-temperate and spatially heterogeneous environments. The aims of this study were to quantify DAEc and DAEs of model input data and their combined impacts for simulated irrigated and rainfed yield and IWR. The Agricultural Production Systems sIMulator Next Generation model was applied for the period 1998-2017 across areas suitable for potato (Solanum tuberosum L.) in Tasmania, Australia, using data at 5, 15, 25 and 40 km resolution. Spatial variances of inputs and outputs were evaluated by the relative absolute difference (rAD¯) between the aggregated grids and the 5 km grids. Climate data aggregation resulted in a rAD¯ of 0.7-12.1%, with high values especially for areas with pronounced differences in elevation. The rAD¯ of soil data was higher (5.6-26.3%) than rAD¯ of climate data and was mainly affected by aggregation of organic carbon and maximum plant available water capacity (i.e. the difference between field capacity and wilting point in the effective root zone). For yield estimates, the difference among resolutions (5 km vs. 40 km) was more pronounced for rainfed (rAD¯ = 14.5%) than irrigated conditions (rAD¯ = 3.0%). The rAD¯ of IWR was 15.7% when using input data at 40 km resolution. Therefore, reliable simulations of rainfed yield require a higher spatial resolution than simulation of irrigated yields. This needs to be considered when conducting regional modelling studies across Tasmania. This study also highlights the need to separately quantify the impact of input data aggregation on model outputs to inform about data aggregation errors and identify those variables that explain these errors.

Ankle injury rehabilitation (AIR): a feasibility randomised controlled trial comparing functional bracing to plaster cast in the treatment of adult ankle fractures.

BACKGROUND: Approximately 9% of a trauma surgeon's workload in the UK is managing ankle fractures. Following an ankle fracture immobilisation with a plaster cast or removable orthotic is usual. The aim of this research was to assess the feasibility of a large multi-centre randomised controlled trial (RCT) to evaluate the difference between plaster cast and a removable orthotic for the management of adults with an ankle fracture. METHODS: A feasibility randomised controlled trial was undertaken in a UK trauma hospital in adults with an ankle fracture for which the treating clinician would consider plaster cast a reasonable management option. Exclusions included open or pathological fracture, unable to adhere to trial procedures, had other lower limb injury or required close contact casting. Participants were randomised using an independent telephone service to receive either plaster cast or removable orthotic. The primary outcome was to determine the recruitment and follow-up rates at 6 weeks, 3 and 6 months to assess the feasibility of a full RCT. RESULTS: Eighty five eligible patients presented during the 10-month recruitment period, 50 consented. Two patients were randomised who did not fulfil the eligibility criteria (protocol deviations), and 1 patient from each group crossed over. Follow-up at each time point was 92% at 6 weeks; 74% at 3 months and 83% at 6 months. CONCLUSIONS: Recruitment and follow-up data demonstrated feasibility of conducting a larger-scale randomised controlled trial. The distributional properties of the patient-reported outcome measures will be used to determine future sample sizes. TRIAL REGISTRATIONS: This study is registered with the ISRCTN (ISRCTN17809322), assigned 5 November 2015 and approved by the NRES Committee (The Black Country, 15/WM/0340), protocol version 2.0 (17 November 2015). It is co-sponsored by the University Hospitals Coventry and Warwickshire NHS Trust and University of Warwick and funded by the NIHR Research for Patient Benefit (PB-PG-0614-34,009). The trial sponsors have no direct involvement in any aspects of study design, conduct or decision to submit the report for publication.

Cast versus functional brace in the rehabilitation of patients treated for an ankle fracture: protocol for the UK study of ankle injury rehabilitation (AIR) multicentre randomised trial.

INTRODUCTION: Each year in the UK over 120 000 people fracture their ankle. It is not known what the best rehabilitation strategy is for these people. Traditionally standard care has involved immobilisation in a plaster cast but an alternative is a functional brace, which can be removed to allow early movement. This paper details the protocol for a multicentre randomised trial of plaster cast immobilisation versus functional bracing for patients with an ankle fracture. METHODS AND ANALYSIS: We will recruit adults with a fractured ankle, for which the treating clinician would consider plaster cast to be a reasonable management option. Randomisation will be on a 1:1 basis, stratified by centre, operative or non-operative management and age. Participants will be allocated to either plaster cast or a functional brace, both treatments are widely used. To have 90% power to detect a difference of 10 points on the primary outcome (Olerud and Molander Ankle Score) at the primary outcome time point (16 weeks), we need to randomise a minimum of 478 people. Quality of life and resource use will be collected at 6, 10, 16, 24 weeks and 12, 18, 24 months. The differences between treatment groups will be assessed on an intention-to-treat basis. The economic evaluation will adhere to the recommendations of the National Institute for Health and Care Excellence reference case. ETHICS, REGISTRATION AND DISSEMINATION: National Research Ethic Committee approved this study on 4 July 2017 (17/WM/0239). The first site opened to recruitment 9 October 2017. The results of this trial will be submitted to a peer-reviewed journal and will inform clinical practice. TRIAL REGISTRATION NUMBER: ISRCTN15537280; Pre-results.

Simultaneous detection and quantitation of organic impurities in methamphetamine by ultra-high-performance liquid chromatography-tandem mass spectrometry, a complementary technique for methamphetamine profiling.

The analysis of organic impurities plays an important role in the impurity profiling of methamphetamine, which in turn provides valuable information about methamphetamine manufacturing, in particular its synthetic route, chemicals, and precursors used. Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) is ideally suited for this purpose due to its excellent sensitivity, selectivity, and wide linear range in multiple reaction monitoring (MRM) mode. In this study, a dilute-and-shoot UHPLC-MS/MS method was developed for the simultaneous identification and quantitation of 23 organic manufacturing impurities in illicit methamphetamine. The developed method was validated in terms of stability, limit of detection (LOD), lower limit of quantification (LLOQ), accuracy, and precision. More than 100 illicitly prepared methamphetamine samples were analyzed. Due to its ability to detect ephedrine/pseudoephedrine and its high sensitivity for critical target markers (eg, chloro-pseudoephedrine, N-cyclohexylamphetamine, and compounds B and P), more impurities and precursor/pre-precursors were identified and quantified versus the current procedure by gas chromatography-mass spectrometry (GC-MS). Consequently, more samples could be classified by their synthetic routes. However, the UHPLC-MS/MS method has difficulty in detecting neutral and untargeted emerging manufacturing impurities and can therefore only serve as a complement to the current method. Despite this deficiency, the quantitative information acquired by the presented UHPLC-MS/MS methodology increased the sample discrimination power, thereby enhancing the capacity of methamphetamine profiling program (MPP) to conduct sample-sample comparisons.

Safety and feasibility evaluation of tourniquets for total knee replacement (SAFE-TKR): study protocol.

INTRODUCTION: This study is designed to determine whether a full randomised controlled trial (RCT) examining the clinical effectiveness and safety of total knee replacement surgery with or without a tourniquet is warranted and feasible. METHOD AND ANALYSIS: Single centre, patient-blinded and assessor-blinded RCT. A computer-generated randomisation service will allocate 50 participants into one of two trial treatments, surgery with or without a tourniquet. The primary objective is to estimate recruitment, crossovers and follow-up of patients. All patients will have an MRI scan of their brain preoperatively and day 1 or 2 postoperatively to identify ischaemic cerebral emboli (primary clinical outcome). Oxford Cognitive Screen, Montreal Cognitive Assessment and Mini-Mental State Examination will be evaluated as outcome tools for measuring cognitive impairment at days 1, 2 and 7 postoperatively. Thigh pain, blood transfusion requirements, venous thromboembolism, revision surgery, surgical complications, mortality and Oxford knee and five-level EuroQol-5D scores will be collected over 12 months. Integrated qualitative research study: 30 trial patients and 20 knee surgeons will take part in semistructured interviews. Interviews will capture views regarding the pilot trial and explore barriers and potential solutions to a full trial. Multicentre cohort study: UK National Joint Registry data will be linked to Hospital Episode Statistics to estimate the relationship between tourniquet use and venous thromboembolic event, length of hospital stay, risk of revision surgery and death. The study will conclude with a multidisciplinary workshop to reach a consensus on whether a full trial is warranted and feasible. ETHICS AND DISSEMINATION: National Research Ethics Committee (West Midlands-Edgbaston) approved this study on 27 January 2016 (15/WM/0455). The study is sponsored by University of Warwick and University Hospitals Coventry and Warwickshire. The results will be disseminated via high-impact peer-reviewed publication. TRIAL REGISTRATION NUMBER: ISRCTN20873088; Pre-results.

A protocol for a feasibility randomised controlled trial to assess the difference between functional bracing and plaster cast for the treatment of ankle fractures.

BACKGROUND: UK Hospital Episode Statistics 2013-2014 recorded 57,286 fractures of the lower limb including the ankle. This figure is expected to continue to increase due to a greater population of older adults. Following an ankle fracture, patients usually have their ankle immobilised with a plaster cast. This provides maximum support for the healing ankle but is associated with stiffness and muscle wasting. A Cochrane Review has concluded that functional bracing may reduce muscle wasting and speed recovery of ankle movement. The aim of this study is to determine the feasibility of conducting a full randomised controlled trial in adults with an ankle fracture followed by functional bracing and exercises versus standard plaster cast care. METHODS: This is a single-centre feasibility randomised controlled trial. All patients with a fractured ankle are potentially eligible. The trial will employ 1:1 random allocation, stratified by age and non-operative/operative management. Baseline demographic and pre-injury functional data, the Manchester-Oxford Foot and Ankle Questionnaire (MOXFQ) and Olerud and Molander Ankle Score (OMAS) will be collected alongside the EuroQol EQ-5D-5 L health-related quality of life questionnaire. A research associate will perform a clinical assessment and obtain X-rays in 6 weeks and 6 months post randomisation to record complications. Functional outcome and health-related quality of life will be collected in 6 weeks, 3 and 6 months post randomisation. DISCUSSION: This feasibility trial will provide authoritative high-quality evidence to inform the design of a definitive trial in this important area. TRIAL REGISTRATION SPONSORSHIP AND FUNDING: This study is registered with the ISRCTN (ISRCTN17809322), assigned 5 November 2015 and approved by the NRES Committee (The Black Country, 15/WM/0340), protocol version 2.0 (17 November 2015). It is co-sponsored by the University Hospitals Coventry and Warwickshire NHS Trust and University of Warwick and funded by the NIHR Research for Patient Benefit (PB-PG-0614-34009). The trial sponsors have no direct involvement in any aspects of study design, conduct or decision to submit the report for publication.

Isolation and characterization of a newly identified impurity in methamphetamine synthesized via reductive amination of 1-phenyl-2-propanone (P2P) made from phenylacetic acid/lead (II) acetate.

A trace processing impurity found in certain methamphetamine exhibits was isolated and identified as trans-N-methyl-4-methyl-5-phenyl-4-penten-2-amine hydrochloride (1). It was determined that this impurity was produced via reductive amination of trans-4-methyl-5-phenyl-4-penten-2-one (4), which was one of a cluster of related ketones generated during the synthesis of 1-phenyl-2-propanone (P2P) from phenylacetic acid and lead (II) acetate. This two-step sequence resulted in methamphetamine containing elevated levels of 1. In contrast, methamphetamine produced from P2P made by other methods produced insignificant (ultra-trace or undetectable) amounts of 1. These results confirm that 1 is a synthetic marker compound for the phenylacetic acid and lead (II) acetate method. Analytical data for 1 and 4, and a postulated mechanism for the production of 4, are presented. Copyright © 2015 John Wiley & Sons, Ltd.

UK DRAFFT - a randomised controlled trial of percutaneous fixation with kirschner wires versus volar locking-plate fixation in the treatment of adult patients with a dorsally displaced fracture of the distal radius.

BACKGROUND: Fractures of the distal radius are extremely common injuries in adults. However, the optimal management remains controversial. In general, fractures of the distal radius are treated non-operatively if the bone fragments can be held in anatomical alignment by a plaster cast or orthotic. However, if this is not possible, then operative fixation is required. There are several operative options but the two most common in the UK, are Kirschner-wire fixation (K-wires) and volar plate fixation using fixed-angle screws (locking-plates). The primary aim of this trial is to determine if there is a difference in the Patient-Reported Wrist Evaluation one year following K-wire fixation versus locking-plate fixation for adult patients with a dorsally-displaced fracture of the distal radius. METHODS/DESIGN: All adult patients with an acute, dorsally-displaced fracture of the distal radius, requiring operative fixation are potentially eligible to take part in this study. A total of 390 consenting patients will be randomly allocated to either K-wire fixation or locking-plate fixation. The surgery will be performed in trauma units across the UK using the preferred technique of the treating surgeon. Data regarding wrist function, quality of life, complications and costs will be collected at six weeks and three, six and twelve months following the injury. The primary outcome measure will be wrist function with a parallel economic analysis. DISCUSSION: This pragmatic, multi-centre trial is due to deliver results in December 2013. TRIAL REGISTRATION: Current Controlled Trials ISRCTN31379280 UKCRN portfolio ID 8956.

Why do physicians order unnecessary preoperative tests? A qualitative study.

BACKGROUND: Routine preoperative testing is ineffective and costly. We explored reasons for the continued use of unnecessary preoperative tests and approaches to limit such testing. METHODS: We interviewed 23 physicians and nurse administrators involved in preoperative decision-making in our local health care environment. We conducted interviews using a semi-structured format and analyzed the data using a template organizing style. RESULTS: Some interviewees feel routine preoperative tests are beneficial, others are ambivalent about preoperative tests in their practice, and many believe there is considerable unnecessary testing. As interviewees discussed factors that lead to the ordering of unnecessary preoperative tests, five major themes emerged: practice tradition, belief that other physicians want the tests done, medicolegal worries, concerns about surgical delays or cancellation, and lack of awareness of evidence and guidelines. Interviewees suggested that a consensus guideline, improved education, and increased collaboration between specialities could decrease unnecessary testing. CONCLUSIONS: Our qualitative findings demonstrate barriers to limiting unnecessary preoperative testing but also suggest interventions that could improve the preoperative testing process. Minimizing unnecessary preoperative tests could decrease cost, maximize quality, and improve the patient experience.

Facile syntheses of thiophene-substituted 1,4-diazabutadiene (alpha-diimine) ligands and their conversion to phosphenium triiodide salts.

Four novel N-aryl-2-thienyl substituted 1,4-diazabutadiene (alpha-diimine) ligands 5-8 have been prepared by cyanide ion-catalyzed intermolecular coupling of the appropriate aromatic aldimines. A ligand featuring a phenyl spacer moiety between a thiophene carbon atom and each imino nitrogen atom (12) has been prepared by a similar synthetic route. Ligands 5-8 and 12 were characterized on the basis of 1H and 13C NMR, IR and MS-CI spectroscopy. Upon treatment with PI3 in CH2Cl2 solution, ligands 5-8 undergo redox reactions to furnish the triiodide salts of the corresponding phosphenium cations 13-16 which were characterized by 1H, 13C and 31P NMR, and MS-CI spectroscopy. The phosphenium triiodide salt 15, and ligands 5-7 and 12 were also structurally authenticated.