Evaluation of a COVID-19 fundamental nursing care guideline versus usual care: The COVID-NURSE cluster randomized controlled trial.

AIM: To evaluate the impact of usual care plus a fundamental nursing care guideline compared to usual care only for patients in hospital with COVID-19 on patient experience, care quality, functional ability, treatment outcomes, nurses' moral distress, patient health-related quality of life and cost-effectiveness. DESIGN: Parallel two-arm, cluster-level randomized controlled trial. METHODS: Between 18th January and 20th December 2021, we recruited (i) adults aged 18 years and over with COVID-19, excluding those invasively ventilated, admitted for at least three days or nights in UK Hospital Trusts; (ii) nurses caring for them. We randomly assigned hospitals to use a fundamental nursing care guideline and usual care or usual care only. Our patient-reported co-primary outcomes were the Relational Aspects of Care Questionnaire and four scales from the Quality from the Patient Perspective Questionnaire. We undertook intention-to-treat analyses. RESULTS: We randomized 15 clusters and recruited 581 patient and 418 nurse participants. Primary outcome data were available for 570-572 (98.1%-98.5%) patient participants in 14 clusters. We found no evidence of between-group differences on any patient, nurse or economic outcomes. We found between-group differences over time, in favour of the intervention, for three of our five co-primary outcomes, and a significant interaction on one primary patient outcome for ethnicity (white British vs. other) and allocated group in favour of the intervention for the 'other' ethnicity subgroup. CONCLUSION: We did not detect an overall difference in patient experience for a fundamental nursing care guideline compared to usual care. We have indications the guideline may have aided sustaining good practice over time and had a more positive impact on non-white British patients' experience of care. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: We cannot recommend the wholescale implementation of our guideline into routine nursing practice. Further intervention development, feasibility, pilot and evaluation studies are required. IMPACT: Fundamental nursing care drives patient experience but is severely impacted in pandemics. Our guideline was not superior to usual care, albeit it may sustain good practice and have a positive impact on non-white British patients' experience of care. REPORTING METHOD: CONSORT and CONSERVE. PATIENT OR PUBLIC CONTRIBUTION: Patients with experience of hospitalization with COVID-19 were involved in guideline development and writing, trial management and interpretation of findings.

Hypoaminoacidemia underpins glucagon-mediated energy expenditure and weight loss.

Glucagon analogs show promise as components of next-generation, multi-target, anti-obesity therapeutics. The biology of chronic glucagon treatment, in particular, its ability to induce energy expenditure and weight loss, remains poorly understood. Using a long-acting glucagon analog, G108, we demonstrate that glucagon-mediated body weight loss is intrinsically linked to the hypoaminoacidemia associated with its known amino acid catabolic action. Mechanistic studies reveal an energy-consuming response to low plasma amino acids in G108-treated mice, prevented by dietary amino acid supplementation and mimicked by a rationally designed low amino acid diet. Therefore, low plasma amino acids are a pre-requisite for G108-mediated energy expenditure and weight loss. However, preventing hypoaminoacidemia with additional dietary protein does not affect the ability of G108 to improve glycemia or hepatic steatosis in obese mice. These studies provide a mechanism for glucagon-mediated weight loss and confirm the hepatic glucagon receptor as an attractive molecular target for metabolic disease therapeutics.

Contributors to negative biopsychosocial health or performance outcomes in rugby players (CoNBO): a systematic review and Delphi study protocol.

The importance of contributors that can result in negative player outcomes in sport and the feasibility and barriers to modifying these to optimise player health and well-being have yet to be established. Within rugby codes (rugby league, rugby union and rugby sevens), within male and female cohorts across playing levels (full-time senior, part-time senior, age grade), this project aims to develop a consensus on contributors to negative biopsychosocial outcomes in rugby players (known as the CoNBO study) and establish stakeholder perceived importance of the identified contributors and barriers to their management. This project will consist of three parts; part 1: a systematic review, part 2: a three-round expert Delphi study and part 3: stakeholder rating of feasibility and barriers to management. Within part 1, systematic searches of electronic databases (PubMed, Scopus, MEDLINE, SPORTDiscus, CINAHL) will be performed. The systematic review protocol is registered with PROSPERO. Studies will be searched to identify physical, psychological and/or social factors resulting in negative player outcomes in rugby. Part 2 will consist of a three-round expert Delphi consensus study to establish additional physical, psychological and/or social factors that result in negative player outcomes in rugby and their importance. In part 3, stakeholders (eg, coaches, chief executive officers and players) will provide perceptions of the feasibility and barriers to modifying the identified factors within their setting. On completion, several manuscripts will be submitted for publication in peer-reviewed journals. The findings of this project have worldwide relevance for stakeholders in the rugby codes. PROSPERO registration number CRD42022346751.

A Survey of the Criteria Used for the Selection of Alternative Comparator Products by Participating Regulators and Organizations of the International Pharmaceutical Regulators Programme.

The safety and efficacy of a generic product are partly based on demonstrating bioequivalence to the innovator product; however, when the innovator product is no longer available as a comparator product, a survey conducted within the Bioequivalence Working Group for Generics (BEWGG) of the International Pharmaceutical Regulators Programme (IPRP) indicated that the criteria for selecting an alternative comparator product varies. For most members of the BEWGG, an existing marketed generic that was approved based on a comparison with the locally registered innovator product can be used, contingent on criteria that ranges from allowing any generic to be used, to allowing only specific criteria-defined generics to be used. Notwithstanding the acceptability of a generic as an alternative comparator, it is not always the preferred comparator for several jurisdictions. Some jurisdictions require the use of a locally sourced alternative innovator comparator (e.g., the same medicinal ingredient manufactured by a different company) or a foreign innovator comparator. Unlike the other members of the BEWGG, the European Union (EU) has no such options available, rather mechanisms are in place to allow manufacturers to develop a new comparator. The criteria described herein regarding the use of an alternative comparator product can also be applied to scenarios where a specific strength of a series of strengths or an innovative fixed dose combination are discontinued. The results of the survey demonstrate that while criteria for selecting alternative comparator products are not harmonized among the BEWGG participants, the common concern for all jurisdictions is to select a comparator product that meets the safety and efficacy standards of the original innovator product.

Isolated & Combined Wearable Technology Underestimate the Total Energy Expenditure of Professional Young Rugby League Players; A Doubly Labelled Water Validation Study.

ABSTRACT: Costello, N, Deighton, K, Cummins, C, Whitehead, S, Preston, T, and Jones, B. Isolated & combined wearable technology underestimate the total energy expenditure of professional young rugby league players; a doubly labelled water validation study. J Strength Cond Res 36(12): 3398-3403, 2022-Accurately determining total energy expenditure (TEE) enables the precise manipulation of energy balance within professional collision-based sports. Therefore, this study investigated the ability of isolated or combined wearable technology to determine the TEE of professional young rugby league players across a typical preseason and in-season period. Total energy expenditure was measured via doubly labelled water, the criterion method, across a fourteen-day preseason ( n = 6) and 7-day in-season ( n = 7) period. Practical measures of TEE included SenseWear Pro3 Armbands in isolation and combined with metabolic power derived from microtechnology units. SenseWear Pro3 Armbands significantly under-reported preseason (5.00 [2.52] MJ·d -1 ; p = 0.002) and in-season (2.86 [1.15] MJ·d -1 ; p < 0.001) TEE, demonstrating a large and extremely large standardized mean bias, and a very large and large typical error, respectively. Combining metabolic power with SenseWear Pro3 Armbands almost certainly improved preseason (0.95 [0.15] MJ·d -1 ; Effect size = 0.32 ± 0.04; p < 0.001) and in-season (1.01 [0.15] MJ·d -1 ; ES = 0.88 ± 1.05; p < 0.001) assessment. However, SenseWear Pro3 Armbands combined with metabolic power continued to significantly under-report preseason (4.04 [2.38] MJ·d -1 ; p = 0.004) and in-season (2.18 [0.96] MJ·d -1 ; p = 0.002) expenditure, demonstrating a large and very large standardized mean bias, and a very large and large typical error, respectively. These findings demonstrate the limitations of utilizing isolated or combined wearable technology to accurately determine the TEE of professional collision-based sport athletes across different stages of the season.

Coaches' Assessment of Players Physical Performance: Subjective and Objective Measures are needed when Profiling Players.

This mixed methods study aimed to assess the agreement between coaches ranking of youth rugby league players compared against objective physical performance data and gather coaches' subjective descriptions of their players performance. Five hundred and eight male rugby league players (U16 n = 255, U18 n = 253) completed a fitness testing battery of anthropometric and physical performance measures. Subsequently, 22 rugby (n = 11) and strength and conditioning (S&C) coaches (n = 11) ranked each player's physical qualities using a 4-point Likert scale (1 - top 25%; 2-25-50%; 3-50-75%; and 4 - bottom 25%) and described their performance. U16 S&C coaches displayed fair agreement when assessing players body mass (39.3%, κ = 0.20). U18 rugby coaches demonstrated fair agreement for strength and size (42.5%, κ = 0.23) and body mass (48.7%, κ = 0.31) whilst both U18 rugby and S&C coaches showed fair agreement levels for endurance (39.8%, κ = 0.25, 44.3%, κ = 0.29), respectively. Three higher-order themes were identified from coaches' descriptions of players including physical, rugby and attitude characteristics when evaluating performance. Overall, coaches cannot accurately assess players physical performance against fitness testing data. Though, findings suggest coaches adopt a multidimensional approach when evaluating players performance. Practitioners within talent development systems should utilise both objective and subjective assessments when making decisions regarding players performance.HighlightsRugby and S&C coaches cannot accurately assess all aspects of players physical performance.The greatest assessment agreement was for body mass, strength and size, and endurance, while the poorest were for strength, acceleration, and maximum speed.Rugby and S&C coaches considered rugby, physical and attitude attributes when evaluating players.Findings highlight the complex nature of physical profiling. Subjective and objective measures are required to provide an accurate description of players physical performance.

Requirements for Additional Strength Biowaivers for Modified Release Solid Oral Dosage Forms in International Pharmaceutical Regulators Programme Participating Regulators and Organisations: Differences and Commonalities.

This article describes an overview of waivers of in vivo bioequivalence studies for additional strengths in the context of the registration of modified release generic products and is a follow-up to the recent publication for the immediate release solid oral dosage forms. The current paper is based on a survey among the participating members of the Bioequivalence Working Group for Generics (BEWGG) of the International Pharmaceutical Regulators Program (IPRP) regarding this topic. Most jurisdictions consider the extrapolation of bioequivalence results obtained with one (most sensitive) strength of a product series as less straightforward for modified release products than for immediate release products. There is consensus that modified release products should demonstrate bioequivalence not only in the fasted state but also in the fed state, but differences exist regarding the necessity of additional multiple dose studies. Fundamental differences between jurisdictions are revealed regarding requirements on the quantitative composition of different strengths and the differentiation of single and multiple unit dosage forms. Differences in terms of in vitro dissolution requirements are obvious, though these are mostly related to possible additional comparative investigations rather than regarding the need for product-specific methods. As with the requirements for immediate release products, harmonization of the various regulations for modified release products is highly desirable to conduct the appropriate studies from a scientific point of view, thus ensuring therapeutic equivalence.

A Survey of the Regulatory Requirements for the Waiver of In Vivo Bioequivalence Studies of Generic Products in Certain Dosage Forms by Participating Regulators and Organisations of the International Pharmaceutical Regulators Programme.

The requirements to waive in vivo bioequivalence studies for immediate release solid oral dosage forms based on the Biopharmaceutics Classifications System (BCS) are well known, and biowaivers[1] for other types of oral dosage forms based on pre-defined criteria may also be acceptable. Similarly, biowaivers for dosage forms such as injectable products may also be allowed if certain criteria are met. The current paper summarises the biowaiver requirements for oral solutions and suspensions, soft gelatin capsules and injectable products (intravenous injections, subcutaneous and intramuscular injections, emulsions for injection and micellar solutions for injection) among the participants of the Bioequivalence Working Group for Generics (BEWGG) of the International Pharmaceutical Regulators Programme (IPRP). A review of the requirements indicated that there was a trend towards convergence when the dosage form became less complex; however, the most common approach used by each of the jurisdictions was a case-by-case approach given that most jurisdictions do not have well defined guidelines to support all possible scenarios. Even in the simplest case of intravenous solutions, the acceptability of qualitative changes in excipients differ between the IPRP members.  Notwithstanding the differences, the dissemination of the information is a first step towards regulatory convergence regarding biowaivers for certain dosage forms and should be useful for pharmaceutical companies currently developing generic medicinal products for IPRP jurisdictions.

Overview of the testing and assessment of effects of microbial pesticides on bees: strengths, challenges and perspectives.

Currently, there is a growing interest in developing biopesticides and increasing their share in the plant protection market as sustainable tools in integrated pest management (IPM). Therefore, it is important that regulatory requirements are consistent and thorough in consideration of biopesticides' unique properties. While microbial pesticides generally have a lower risk profile, they present special challenges in non-target organism testing and risk assessment since, in contrast to chemical pesticides, their modes of action include infectivity and pathogenicity rather than toxicity alone. For this reason, non-target organism testing guidelines designed for conventional chemical pesticides are not necessarily directly applicable to microbial pesticides. Many stakeholders have recognised the need for improvements in the guidance available for testing microbial pesticides with honey bees, particularly given the increasing interest in development and registration of microbial pesticides and concerns over risks to pollinators. This paper provides an overview of the challenges with testing and assessment of the effects of microbial pesticides on honey bees (Apis mellifera), which have served as a surrogate for both Apis and non-Apis bees, and provides a foundation toward developing improved testing methods.

Adding web-based behavioural support to exercise referral schemes for inactive adults with chronic health conditions: the e-coachER RCT.

BACKGROUND: There is modest evidence that exercise referral schemes increase physical activity in inactive individuals with chronic health conditions. There is a need to identify additional ways to improve the effects of exercise referral schemes on long-term physical activity. OBJECTIVES: To determine if adding the e-coachER intervention to exercise referral schemes is more clinically effective and cost-effective in increasing physical activity after 1 year than usual exercise referral schemes. DESIGN: A pragmatic, multicentre, two-arm randomised controlled trial, with a mixed-methods process evaluation and health economic analysis. Participants were allocated in a 1 : 1 ratio to either exercise referral schemes plus e-coachER (intervention) or exercise referral schemes alone (control). SETTING: Patients were referred to exercise referral schemes in Plymouth, Birmingham and Glasgow. PARTICIPANTS: There were 450 participants aged 16-74 years, with a body mass index of 30-40 kg/m2, with hypertension, prediabetes, type 2 diabetes, lower limb osteoarthritis or a current/recent history of treatment for depression, who were also inactive, contactable via e-mail and internet users. INTERVENTION: e-coachER was designed to augment exercise referral schemes. Participants received a pedometer and fridge magnet with physical activity recording sheets, and a user guide to access the web-based support in the form of seven 'steps to health'. e-coachER aimed to build the use of behavioural skills (e.g. self-monitoring) while strengthening favourable beliefs in the importance of physical activity, competence, autonomy in physical activity choices and relatedness. All participants were referred to a standard exercise referral scheme. PRIMARY OUTCOME MEASURE: Minutes of moderate and vigorous physical activity in ≥ 10-minute bouts measured by an accelerometer over 1 week at 12 months, worn ≥ 16 hours per day for ≥ 4 days including ≥ 1 weekend day. SECONDARY OUTCOMES: Other accelerometer-derived physical activity measures, self-reported physical activity, exercise referral scheme attendance and EuroQol-5 Dimensions, five-level version, and Hospital Anxiety and Depression Scale scores were collected at 4 and 12 months post randomisation. RESULTS: Participants had a mean body mass index of 32.6 (standard deviation) 4.4 kg/m2, were referred primarily for weight loss and were mostly confident self-rated information technology users. Primary outcome analysis involving those with usable data showed a weak indicative effect in favour of the intervention group (n = 108) compared with the control group (n = 124); 11.8 weekly minutes of moderate and vigorous physical activity (95% confidence interval -2.1 to 26.0 minutes; p = 0.10). Sixty-four per cent of intervention participants logged on at least once; they gave generally positive feedback on the web-based support. The intervention had no effect on other physical activity outcomes, exercise referral scheme attendance (78% in the control group vs. 75% in the intervention group) or EuroQol-5 Dimensions, five-level version, or Hospital Anxiety and Depression Scale scores, but did enhance a number of process outcomes (i.e. confidence, importance and competence) compared with the control group at 4 months, but not at 12 months. At 12 months, the intervention group incurred an additional mean cost of £439 (95% confidence interval -£182 to £1060) compared with the control group, but generated more quality-adjusted life-years (mean 0.026, 95% confidence interval 0.013 to 0.040), with an incremental cost-effectiveness ratio of an additional £16,885 per quality-adjusted life-year. LIMITATIONS: A significant proportion (46%) of participants were not included in the primary analysis because of study withdrawal and insufficient device wear-time, so the results must be interpreted with caution. The regression model fit for the primary outcome was poor because of the considerable proportion of participants [142/243 (58%)] who recorded no instances of ≥ 10-minute bouts of moderate and vigorous physical activity at 12 months post randomisation. FUTURE WORK: The design and rigorous evaluation of cost-effective and scalable ways to increase exercise referral scheme uptake and maintenance of moderate and vigorous physical activity are needed among patients with chronic conditions. CONCLUSIONS: Adding e-coachER to usual exercise referral schemes had only a weak indicative effect on long-term rigorously defined, objectively assessed moderate and vigorous physical activity. The provision of the e-coachER support package led to an additional cost and has a 63% probability of being cost-effective based on the UK threshold of £30,000 per quality-adjusted life-year. The intervention did improve some process outcomes as specified in our logic model. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15644451. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 63. See the NIHR Journals Library website for further project information.

When health-care professionals refer patients with chronic conditions to an exercise referral scheme, the effects on long-term increases in physical activity are limited. We therefore developed the e-coachER support package to add to usual exercise referral schemes and to prompt the use of skills such as self-monitoring and goal-setting. This package was also intended to empower patients to increase their levels of physical activity long term. The seven-step programme was delivered online (via an interactive website). As part of the package, we mailed participants a guide for accessing the online programme, a pedometer and a fridge magnet with a notepad to record physical activity. We aimed to determine whether or not adding the e-coachER support to usual exercise referral schemes resulted in lasting changes in moderate and vigorous physical activity and whether or not it offers good value for money compared with exercise referral schemes alone. A total of 450 inactive individuals were recruited across Plymouth, Birmingham and Glasgow and were referred to an exercise referral scheme for the following participant-reported main reasons: weight loss (50%), low mood (19%), osteoarthritis (12%), type 2 diabetes (10%) and high blood pressure (8%). Half of the individuals were given access to the e-coachER support and the other half were not. All individuals were mailed a wrist-worn movement sensor (accelerometer) to wear for 1 week and a survey to assess other outcomes at the start of the study as well as at 4 and 12 months post randomisation. At the start of the study, the participants were inactive and most had multiple health conditions. The participants had an average body mass index of 33 kg/m² and an average age of 50 years. Most (83%) were white. Participants with access to e-coachER support were only slightly more active at 12 months than those who did not have access, but we cannot be confident in the findings because we had data from fewer participants than planned. The lack of a clear effect may have been as a result of around one-third of participants not accessing the website, but otherwise there was reasonable engagement. The provision of the e-coachER support package led to an additional cost of £439 per participant over a 12-month period.

An Evaluation of Service Provision and Novel Strength Assessment on Patient Outcomes in a UK-Based Pulmonary Rehabilitation Setting.

This study's purpose was to (i) assess the impact of a 7-week pulmonary rehabilitation (PR) programme upon patient outcomes; incremental shuttle walk test (ISWT), COPD assessment tool (CAT), Clinical COPD Questionnaire (CCQ) and the Hospital Anxiety and Depression Scale (HADS); (ii) assess the impact of COPD severity on ISWT, psychological functioning and quality of life measures following PR; (iii) assess the feasibility of incorporating individually prescribed one repetition maximum (1RM) training loads into the existing strength training programme. Patients were people with COPD enrolled onto one of three versions (locations A, B and C) of a 7-week PR programme, which consisted of group exercise sessions and a social plus education element. Two locations incorporated individually prescribed training loads. Minimal clinically important changes (MCICs) are reported for the ISWT across all locations. Statistically significant changes in both CAT and the CCQ were found, with MCIC's evident for CAT score overall and individually at location B. MCIC's were not found for the CCQ. No statistically significant or MCICs were evident for the HADS. MCIC's were present only in patients with mild to moderate severity for the ISWT. For the CAT, moderate, severe and very severe patients with COPD experienced MCIC's. MCIC's and statistically significant increases in 1RM strength were seen at both locations. These findings evidence an effective PR service. Basic strength exercise programming and assessment are feasible and should be implemented in PR services to maximise patient outcomes.

Uncertainty from COVID-19 delays progress on the road to value-based cancer care.

COVID-19 has created a significant distraction from normal practice operations. The uncertainty that comes along with the pandemic is a huge worry, and can distract from practice transformation.

Can a contemporary dietary assessment tool or wearable technology accurately assess the energy intake of professional young rugby league players? A doubly labelled water validation study.

Accurate quantification of energy intake is imperative in athletes; however traditional dietary assessment tools are frequently inaccurate. Therefore, this study investigated the validity of a contemporary dietary assessment tool or wearable technology to determine the total energy intake (TEI) of professional young athletes. The TEI of eight professional young male rugby league players was determined by three methods; Snap-N-Send, SenseWear Armbands (SWA) combined with metabolic power and doubly labelled water (DLW; intake-balance method; criterion) across a combined ten-day pre-season and seven-day in-season period. Changes in fasted body mass were recorded, alongside changes in body composition via isotopic dilution and a validated energy density equation. Energy intake was calculated via the intake-balance method. Snap-N-Send non-significantly over-reported pre-season and in-season energy intake by 0.21 (2.37) MJ.day-1 (p = 0.833) and 0.51 (1.73) MJ.day-1 (p = 0.464), respectively. This represented a trivial and small standardised mean bias, and very large and large typical error. SenseWear Armbands and metabolic power significantly under-reported pre-season and in-season TEI by 3.51 (2.42) MJ.day-1 (p = 0.017) and 2.18 (1.85) MJ.day-1 (p = 0.021), respectively. This represents a large and moderate standardised mean bias, and very large and very large typical error. There was a most likely larger daily error reported by SWA and metabolic power than Snap-N-Send across pre-season (3.30 (2.45) MJ.day-1; ES = 1.26 ± 0.68; p = 0.014) and in-season periods (1.67 (2.00) MJ.day-1; ES = 1.27 ± 0.70; p = 0.012). This study demonstrates the enhanced validity of Snap-N-Send for assessing athlete TEI over combined wearable technology, although caution is required when determining the individual TEIs of athletes via Snap-N-Send.

Assessment of a home-based standing frame programme in people with progressive multiple sclerosis (SUMS): a pragmatic, multi-centre, randomised, controlled trial and cost-effectiveness analysis.

BACKGROUND: People severely impaired with progressive multiple sclerosis spend much of their day sitting, with very few options to improve motor function. As a result, secondary physical and psychosocial complications can occur. Effective and feasible self-management strategies are needed to reduce sedentary behaviour and enhance motor function. In this study, we aimed to assess the clinical and cost effectiveness of a home-based, self-managed, standing frame programme. METHODS: SUMS was a pragmatic, multicentre, randomised controlled superiority trial of people with progressive multiple sclerosis and severe mobility impairment, undertaken in eight centres from two regions in the UK. The study had assessor-blinded outcome assessments with use of clinician-rated and patient-rated measures at baseline, 20 weeks, and 36 weeks. After baseline assessment, participants were randomised (1:1) by computer-generated assignment to either a standing frame programme plus usual care or usual care alone. The intervention consisted of two home-based physiotherapy sessions (60 min each) to set up the standing frame programme, supported by six follow-up telephone calls (15 min per call). Participants were asked to stand for 30 min, three times per week over 20 weeks, and encouraged to continue in the longer term, although no further physiotherapy support was provided. The primary clinical outcome was motor function measured by the Amended Motor Club Assessment (AMCA) score at week 36, analysed in the modified intention-to-treat population (excluding only patients who were deemed ineligible after randomisation, those who withdrew from the trial and were unwilling for their previously collected data to be used, or those who did not provide baseline and week 36 measurements). A 9-point AMCA score change was considered clinically meaningful a priori. Adverse events were collected through a daily preformatted patient diary throughout the 36 weeks and analysed in the modified intention-to-treat population. An economic assessment established the resources required to provide the standing frame programme, estimated intervention costs, and estimate cost effectiveness. This trial is registered with the International Standard Randomised Controlled Trials, number ISRCTN69614598. FINDINGS: Between Sept 16, 2015, and April 28, 2017, 285 people with progressive multiple sclerosis were screened for eligibility, and 140 were randomly assigned to either the standing frame group (n=71) or the usual care group (n=69). Of these, 122 completed the primary outcome assessment (61 participants in both groups) for the modified intention-to-treat analysis. The use of the standing frame resulted in a significant increase in AMCA score compared with that for usual care alone, with a fully adjusted between-group difference in AMCA score at 36 weeks of 4·7 points (95% CI 1·9-7·5; p=0·0014). For adverse events collected through patient diaries, we observed a disparity between the two groups in the frequency of short-term musculoskeletal pain (486 [41%] of 1188 adverse events in the standing frame group vs 160 [22%] of 736 adverse events in the usual care group), which was potentially related to the intervention. The musculoskeletal pain lasted longer than 7 days in five participants (two in the standing frame group and three in the usual care group). No serious adverse events related to the study occurred. The standing frame group had a mean 0·018 (95% CI -0·014 to 0·051) additional quality-adjusted life-years (QALYs) compared with those of the usual care group, and the estimated incremental cost-per-QALY was approximately £14 700. INTERPRETATION: The standing frame programme significantly increased motor function in people with severe progressive multiple sclerosis, although not to the degree that was considered a priori as clinically meaningful. The standing frame is one of the first physiotherapy interventions to be effective in this population. We suggest that the programme is feasible as a home-based, self-managed intervention that could be routinely implemented in clinical practice in the UK. FUNDING: UK National Institute of Health Research.

Are professional young rugby league players eating enough? Energy intake, expenditure and balance during a pre-season.

Due to the unique energetic demands of professional young collision sport athletes, accurate assessment of energy balance is required. Consequently, this is the first study to simultaneously investigate the energy intake, expenditure and balance of professional young rugby league players across a pre-season period. The total energy expenditure of six professional young male rugby league players was measured via doubly labelled water over a fourteen-day assessment period. Resting metabolic rate was measured and physical activity level calculated. Dietary intake was reported via Snap-N-Send over a non-consecutive ten-day assessment period, alongside changes in fasted body mass and hydration status. Accordingly, energy balance was inferred. The mean (standard deviation) difference between total energy intake (16.73 (1.32) MJ.day-1) and total energy expenditure (18.36 (3.05) MJ.day-1) measured over the non-consecutive ten-day period was unclear (-1.63 (1.73) MJ.day-1; ES = 0.91 ± 1.28; p = 0.221). This corresponded in a most likely trivial decrease in body mass (-0.65 (0.78) kg; ES = 0.04 ± 0.03; p = 0.097). Resting metabolic rate and physical activity level across the fourteen-day pre-season period was 11.20 (2.16) MJ.day-1 and 1.7 (0.2), respectively. For the first time, this study utilises gold standard assessment techniques to elucidate the distinctly large energy expenditures of professional young rugby league players across a pre-season period, emphasising a requirement for equally large energy intakes to achieve targeted body mass and composition adaptations. Accordingly, it is imperative that practitioners regularly assess the energy balance of professional young collision-sport athletes to ensure their unique energetic requirements are achieved.

Collision activity during training increases total energy expenditure measured via doubly labelled water.

PURPOSE: Collision sports are characterised by frequent high-intensity collisions that induce substantial muscle damage, potentially increasing the energetic cost of recovery. Therefore, this study investigated the energetic cost of collision-based activity for the first time across any sport. METHODS: Using a randomised crossover design, six professional young male rugby league players completed two different 5-day pre-season training microcycles. Players completed either a collision (COLL; 20 competitive one-on-one collisions) or non-collision (nCOLL; matched for kinematic demands, excluding collisions) training session on the first day of each microcycle, exactly 7 days apart. All remaining training sessions were matched and did not involve any collision-based activity. Total energy expenditure was measured using doubly labelled water, the literature gold standard. RESULTS: Collisions resulted in a very likely higher (4.96 ± 0.97 MJ; ES = 0.30 ± 0.07; p = 0.0021) total energy expenditure across the 5-day COLL training microcycle (95.07 ± 16.66 MJ) compared with the nCOLL training microcycle (90.34 ± 16.97 MJ). The COLL training session also resulted in a very likely higher (200 ± 102 AU; ES = 1.43 ± 0.74; p = 0.007) session rating of perceived exertion and a very likely greater (- 14.6 ± 3.3%; ES = - 1.60 ± 0.51; p = 0.002) decrease in wellbeing 24 h later. CONCLUSIONS: A single collision training session considerably increased total energy expenditure. This may explain the large energy expenditures of collision-sport athletes, which appear to exceed kinematic training and match demands. These findings suggest fuelling professional collision-sport athletes appropriately for the "muscle damage caused" alongside the kinematic "work required".

Top marks for care equality.

For some years, employers who do excellent work in promoting equality for lesbian, gay and bisexual (LGB) people have been recognised by the Stonewall Workplace Equality Index.

Comparison of the overnight metyrapone and glucagon stimulation tests in the assessment of secondary hypoadrenalism.

OBJECTIVE: The insulin tolerance test (ITT) is contraindicated in a proportion of patients with suspected ACTH deficiency. The aim of this study was to investigate the diagnostic accuracy of the glucagon stress test (GST) compared with the overnight metyrapone test (OMT) in patients with contraindications to ITT. DESIGN: This was a prospective comparison of the GST to the OMT in patients with suspected ACTH deficiency and contraindications to the ITT. The OMT was used as the standard for comparison. The study was conducted at two tertiary referral centres for pituitary disease. PATIENTS: Seventy-eight patients underwent contemporaneous OMT and GST of whom 61 had sufficient suppression of cortisol during the OMT to be included in the comparison. Forty had suffered traumatic brain injury, 36 had organic pituitary disorders and two were classified as 'other'. MEASUREMENTS: ACTH sufficiency was defined as 0800h 11-deoxycortisol ≥ 200 nmol/l on OMT and peak cortisol ≥ 440 nmol/l on GST, as per local reference ranges. RESULTS: There was significant discrepancy between the proportion of patients diagnosed with ACTH deficiency using the OMT (39%) and GST (89%). From our data, a GST peak cortisol cut-off of ≥350 nm provides the combination of optimal sensitivity (71%) and specificity (57%), compared with a higher sensitivity (88%) but poor specificity (11%) using a cut-off of ≥440 nm. CONCLUSIONS: The GST should be used with caution as a diagnostic test of ACTH reserve. The OMT should be used in preference to the GST to assess the hypothalamic pituitary adrenal axis where ITT is contraindicated.

A dismantling study of assertive outreach services: comparing activity and outcomes following replacement with the FACT model.

PURPOSE: Financial constraints and some disappointing research evaluations have seen English assertive outreach (AO) teams subject to remodelling, decommissioning and integration into standard care. We tested a specific alternative model of integrating the AO function from two AO teams into six standard community mental health teams (CMHT). The Flexible Assertive Community Treatment model (FACT) was adopted from the Netherlands (Van Veldhuizen, Commun Mental Health J 43(4):421-433, 2007; Bond and Drake, Commun Mental Health J 43(4):435-438, 2007). We aimed to demonstrate non-inferiority in clinical effectiveness and thereby show cost efficiencies associated with FACT. METHODS: Outcomes were compared in a mirror-image study of the 12 months periods pre- and post-service change with eligible individuals from the AO teams' caseloads (n = 112) acting as their own controls. We also conducted a cost-consequence analysis of the changes. Outcome data regarding admissions, use of crisis and home treatment, frequency of contact and DNA rate were extracted from the electronic patient record. RESULTS: The results show AO patients (n = 112) transferred to standard CMHTs with FACT had significantly fewer admissions and a halving of bed use (21 fewer admission and 2,394 fewer occupied bed days) whilst being in receipt of a less intensive service (2,979 fewer contacts). This was offset by significantly poorer engagement but not by increased use of crisis and home treatment services. CONCLUSIONS: Enhancing multi-disciplinary CMHTs with FACT provides a clinically effective alternative to AO teams. FACT offers a cost-effective model compared to AO.