Building physiological reserve in immobilisation: does nutritional supplementation work?

Introduction: Disuse models, such as limb immobilisation, result in profound changes in skeletal muscle morphology and function. Exercise prescription would be the recommended intervention to prevent immobilisation-induced atrophy and declines in maximal voluntary strength. Nutritional supplementation may stand as a viable intervention to combat muscle atrophy with disuse, when exercise is an unpractical therapeutic option. Aims: To (1) investigate the multifactorial effects of short-term upper limb sling immobilisation and (2) determine whether three potential protein-sparing modulators (essential amino acids (EAA), omega-3 (-3) and vitamin D) would attenuate the anticipated deleterious effects of immobilisation. Methods: Measures of muscle and sub-cutaneous adipose thickness (Brightness mode ultrasonography), body composition (dual-energy x-ray absorptiometry), arm girth (anthropometry), isometric and isokinetic elbow torque (dynamometry), co-contraction (electromyography (EMG)), muscle fatigability (dynamometry and EMG), arterial blood flow (Doppler ultrasound) and endocrine profile (enzyme-linked immunosorbent assay and colorimetry), were taken before and after arm immobilisation in a mixed sex population. Supplementation of EAA (n = 9 vs. placebo n = 7) during three weeks of immobilisation, -3 (n = 8) or vitamin D (n = 8) during two weeks of immobilisation (placebo n = 8) and EAA for two weeks pre-immobilisation (n = 5 vs. placebo n = 5). Main findings: Immobilisation resulted in decreases in muscle thickness, arm girth, lean mass, isometric and isokinetic elbow torque, and an increase in sub-cutaneous adipose thickness. Muscle fatigability, resting arterial blood flow, EMG co-contraction and endocrine profile were unchanged. At the current dosage -3 supplementation only attenuated the increase in sub-cutaneous adipose thickness. Despite some trends, neither -3 nor vitamin D supplementation attenuated any other parameters. EAA supplementation during immobilisation impacted positively on the immobilisation-induced changes in the structural and functional characteristic of the remaining muscle. EAA supplementation before immobilisation did not attenuate the immobilisation-induced changes in muscle structure and function. Conclusion: Although EAA supplementation only showed some benefit to muscle size and function with immobilisation, it was confirmed that the sling immobilisation model used in the thesis, is a suitable model for observing the effects of relatively short-term immobilisation. The findings of the thesis are relevant to both sporting (e.g. off-season detraining modulation) as well as clinical (e.g. injury/illness induced short-term immobilisation/bed rest) populations. This relatively short-term sling immobilisation provides a model to be used to assess other supplements and treatments in future studies. The modest effect of supplementation suggests further research into either: a) more at risk populations (e.g. injury or ageing); b) larger doses of these supplements

What Is the Best Way to Identify Malignant Transformation Within Pancreatic IPMN: A Systematic Review and Meta-Analyses

OBJECTIVES: Pancreatic intraductal papillary mucinous neoplasias (IPMNs) represent 25% of all cystic neoplasms and are precursor lesions for pancreatic ductal adenocarcinoma. This study aims to identify the best imaging modality for detecting malignant transformation in IPMN, the sensitivity and specificity of risk features on imaging, and the usefulness of tumor markers in serum and cyst fluid to predict malignancy in IPMN. METHODS: Databases were searched from November 2006 to March 2014. Pooled sensitivity and specificity of diagnostic techniques/imaging features of suspected malignancy in IPMN using a hierarchical summary receiver operator characteristic (HSROC) approach were performed. RESULTS: A total of 467 eligible studies were identified, of which 51 studies met the inclusion criteria and 37 of these were incorporated into meta-analyses. The pooled sensitivity and specificity for risk features predictive of malignancy on computed tomography/magnetic resonance imaging were 0.809 and 0.762 respectively, and on positron emission tomography were 0.968 and 0.911. Mural nodule, cyst size, and main pancreatic duct dilation found on imaging had pooled sensitivity for prediction of malignancy of 0.690, 0.682, and 0.614, respectively, and specificity of 0.798, 0.574, and 0.687. Raised serum carbohydrate antigen 19-9 (CA19-9) levels yielded sensitivity of 0.380 and specificity of 0903. Combining parameters yielded a sensitivity of 0.743 and specificity of 0.906. CONCLUSIONS: PET holds the most promise in identifying malignant transformation within an IPMN. Combining parameters increases sensitivity and specificity; the presence of mural nodule on imaging was the most sensitive whereas raised serum CA19-9 (>37 KU/l) was the most specific feature predictive of malignancy in IPMNs

Clinical and cost-effectiveness of a diabetes education and behavioural weight management programme versus a diabetes education programme in adults with a recent diagnosis of type 2 diabetes: study protocol for the Glucose Lowering through Weight management (GLoW) randomised controlled trial

Introduction: People with type 2 diabetes (T2D) can improve glycaemic control or even achieve remission through weight loss and reduce their use of medication and risk of cardiovascular disease. The Glucose Lowering through Weight management (GLoW) trial will evaluate whether a tailored diabetes education and behavioural weight management programme (DEW) is more effective and cost-effective than a diabetes education (DE) programme in helping people with overweight or obesity and a recent diagnosis of T2D to lower their blood glucose, lose weight and improve other markers of cardiovascular risk. Methods and analysis: This study is a pragmatic, randomised, single-blind, parallel group, two-arm, superiority trial. We will recruit 576 adults with body mass index>25 kg/m2 and diagnosis of T2D in the past 3 years and randomise them to a tailored DEW or a DE programme. Participants will attend measurement appointments at a local general practitioner practice or research centre at baseline, 6 and 12 months. The primary outcome is 12-month change in glycated haemoglobin. The effect of the intervention on the primary outcome will be estimated and tested using a linear regression model (analysis of covariance) including randomisation group and adjusted for baseline value of the outcome and the randomisation stratifiers. Participants will be included in the group to which they were randomised, under the intention-to-treat principle. Secondary outcomes include 6-month and 12-month changes in body weight, body fat percentage, systolic and diastolic blood pressure and lipid profile; probability of achieving good glycaemic control; probability of achieving remission from diabetes; probability of losing 5% and 10% body weight and modelled cardiovascular risk (UKPDS). An intention-to-treat within-trial cost-effectiveness analysis will be conducted from NHS and societal perspectives using participant-level data. Qualitative interviews will be conducted with participants to understand why and how the programme achieved its results and how participants manage their weight after the programme ends. Ethics and dissemination: Ethical approval was received from East of Scotland Research Ethics Service on 15 May 2018 (18/ES/0048). This protocol (V.3) was approved on 19 June 2019. Findings will be published in peer-reviewed scientific journals and communicated to other stakeholders as appropriate. Trial registration number: ISRCTN18399564

Profiles of resilient psychosocial function during three isolated ski expeditions in the High Arctic

To successfully complete a Polar expedition individuals and teams must respond resiliently to the environmental, psychological, and social demands they face. In this study we examined profiles of resilient function in seven people from three expeditions in the High Arctic. Using a structured daily diary, participants reported on experiences of physical health (morning and evening), affect, team cohesion, performance, and potential explanatory factors including sleep, demand appraisals, events, and coping strategies. Notable intra- and inter-individual variability was observed in daily reports and all profiles could be interpreted as representing resilient function. A number of significant relationships were found between markers of resilient physical and psychosocial function and potential explanatory variables. For example, there was much more daily variability in an individual's reporting of positive affect than prior research might imply, and what prior research designs could capture. Further, while negative affect tended to remain low and stable, our findings reveal that even minor and infrequent increases in negative emotions were significantly associated with other variables in the network. Finally, across the expedition period individual coping resources consistently exceeded demands, suggesting that individuals viewed the expedition as a challenge and not a threat. More broadly, these findings inform efforts to monitor, and maintain resilience when operating in Polar and other extreme settings

The legacy of pregnancy: elite athletes and women in arduous occupations

Best-practice guidance and management of pregnant and postpartum elite athletes and women in arduous occupations is limited by the lack of high-quality evidence available within these populations. We have summarized the adaptations and implications of pregnancy and childbirth, proposed a novel integrative concept to address these changes, and made recommendations to progress research in this area

Frequency of reported pain in adult males with muscular dystrophy

Introduction The purpose of this study was to present and compare pain between adult males with Duchenne (DMD), Becker’s (BMD), Limb-Girdle (LGMD) Facioscapulohumeral (FSHD) forms of Muscular Dystrophy (MD), and healthy controls (CTRL), using three different methods of assessment. Methods Pain was assessed using 1) a whole body visual analogue scale (VAS) of pain, 2) a generalised body map and 3) a localised body map. Results All types of MD reported more VAS pain than CTRL, with 97% of all MD participants reporting pain; however, no differences were reported between types of MD. The generalised body map approach identified more frequent pain in the shoulders of FSHD (93%) than other groups (13–43%), hips of DMD (87%) and LGMD (75%) than other groups (0–29%), and legs of all MD (64–78%) than CTRL (25%). The localised body map approach identified common areas of frequent pain across types of MD, posterior distal leg and distal back, as well as condition specific regions of frequent pain, for example posterior trapezius in FSHD, and anterior hip pain in DMD and LGMD. Conclusions Using a single pain value (VAS), increased pain was reported by adults with MD compared to CTRL, with no clear differences between different MD groups, suggesting pain is symptomatic of MD. The use of the generalised body map approach, and to an even greater extent the localised body map approach, identified specific areas of frequent pain relevant to each individual condition. These results indicate that whist the commonly used generalised approach can be used to identify broad anatomical regions, the localised approach provides a more comprehensive understanding of pain, reflective of clinical assessment, and should be utilised in future research

The effects of 12 weeks’ resistance training on psychological parameters and quality of life in adults with Facioscapulohumeral, Becker, and Limb–girdle dystrophies

Purpose Investigate the impact of 12-weeks’ moderate-intensity resistance training on psychological parameters in ambulatory adults with Facioscapulohumeral, Becker, and Limb–girdle muscular dystrophy. Methods Seventeen adults with Facioscapulohumeral (n = 6), Limb–girdle (n = 6; types 2A, 2B, 2L, and 2I), or Becker (n = 5) muscular dystrophy took part. Participants were tested at baseline (PRE), after a 12-week control period (PRE2), and after a 12-week supervised resistance training programme (POST). Training included multi-joint and single-joint resistance exercises. Outcomes from self-report questionnaires were health-related quality of life, depressive symptoms, trait anxiety, self-esteem, and physical self-worth. Results No difference in outcome measures, except depressive symptoms, was found in the control period (PRE to PRE2). Symptoms of depression were reduced by 9% from PRE to PRE2 (p < 0.05) and by a further 19% from PRE2 to POST (p < 0.05). Other changes from PRE2 to POST were that trait anxiety reduced by 10%, self-esteem increased by 10%, physical self-worth increased by 20%, and quality of life improved in 8 domains (p < 0.05). Conclusion These findings demonstrate the positive impact of moderate-intensity resistance training on psychological health and quality of life in adults with Facioscapulohumeral, Becker, and Limb–girdle muscular dystrophies. Implications for rehabilitation Resistance training can have a positive impact on psychological health and quality of life in adults with Facioscapulohumeral, Becker, and Limb–girdle muscular dystrophy. Healthcare professionals should consider including moderate-intensity resistance training within the management and treatment programmes of adults with Facioscapulohumeral, Becker, and Limb–girdle muscular dystrophy

Pelargonium sidoides root extract for the treatment of acute cough due to lower respiratory tract infection in adults::a feasibility double-blind, placebo-controlled randomised trial

BACKGROUND: Pelargonium sidoides DC (Geraniaceae) root extract, EPs®7630 or "Kaloba®", is a widely used herbal remedy for respiratory infections, with some evidence of effectiveness for acute bronchitis. However, it is not yet widely recommended by medical professionals in the UK. There is a need to undertake appropriately designed randomised trials to test its use as an alternative to antibiotics. The aim was to assess the feasibility of conducting a double-blind randomised controlled trial of Pelargonium sidoides root extract for treatment of acute bronchitis in UK primary care, investigating intervention compliance, patient preference for dosage form and acceptability of patient diaries.STUDY DESIGN: Feasibility double-blind randomised placebo-controlled clinical trial.METHODS: We aimed to recruit 160 patients with cough (≤ 21 days) caused by acute bronchitis from UK general practices. Practices were cluster-randomised to liquid or tablet preparations and patients were individually randomised to Kaloba® or placebo. We followed participants up for 28 days through self-reported patient diaries with telephone support and reviewed medical records at one month. Outcomes included recruitment, withdrawal, safety, reconsultation and symptom diary completion rates. We also assessed treatment adherence, antibiotic prescribing and consumption, mean symptom severity (at days 2-4 after randomisation) and time to symptom resolution. We interviewed 29 patients and 11 health professionals to identify barriers and facilitators to running such a randomised trial.RESULTS: Of 543 patients screened, 261 were eligible, of whom 134 (51%) were recruited and 103 (77%) returned a completed diary. Overall, 41% (41/100) of patients took antibiotics (Kaloba® liquid group: 48% [15/31]; placebo liquid group: 23% [6/26]; Kaloba® tablet group: 48% [9/21]; placebo tablet group: 50% [11/22]). Most patients adhered to the study medication (median 19 out of 21 doses taken in week 1, IQR 18-21 - all arms combined). There were no serious adverse events relating to treatment. Most patients interviewed found study recruitment to be straightforward, but some found the diary too complex.CONCLUSIONS: It was feasible and acceptable to recruit patients from UK primary care to a double-blind placebo-controlled trial of herbal medicine (Kaloba®) for the treatment of acute bronchitis, with good retention and low data attrition.TRIAL REGISTRATION: HATRIC was registered on the ISRCTN registry ( ISRCTN17672884 ) on 16 August 2018, retrospectively registered. The record can be found at http://www.isrctn.com/ISRCTN17672884 .</p

Microdiscectomy compared with transforaminal epidural steroid injection for persistent radicular pain caused by prolapsed intervertebral disc: the NERVES RCT

Background Sciatica is a common condition reported to affect > 3% of the UK population at any time and is most often caused by a prolapsed intervertebral disc. Currently, there is no uniformly adopted treatment strategy. Invasive treatments, such as surgery (i.e. microdiscectomy) and transforaminal epidural steroid injection, are often reserved for failed conservative treatment. Objective To compare the clinical effectiveness and cost-effectiveness of microdiscectomy with transforaminal epidural steroid injection for the management of radicular pain secondary to lumbar prolapsed intervertebral disc for non-emergency presentation of sciatica of < 12 months’ duration. Interventions Patients were randomised to either (1) microdiscectomy or (2) transforaminal epidural steroid injection. Design A pragmatic, multicentre, randomised prospective trial comparing microdiscectomy with transforaminal epidural steroid injection for sciatica due to prolapsed intervertebral disc with < 1 year symptom duration. Setting NHS services providing secondary spinal surgical care within the UK. Participants A total of 163 participants (aged 16–65 years) were recruited from 11 UK NHS outpatient clinics. Main outcome measures The primary outcome was participant-completed Oswestry Disability Questionnaire score at 18 weeks post randomisation. Secondary outcomes were visual analogue scores for leg pain and back pain; modified Roland–Morris score (for sciatica), Core Outcome Measures Index score and participant satisfaction at 12-weekly intervals. Cost-effectiveness and quality of life were assessed using the EuroQol-5 Dimensions, five-level version; Hospital Episode Statistics data; medication usage; and self-reported cost data at 12-weekly intervals. Adverse event data were collected. The economic outcome was incremental cost per quality-adjusted life-year gained from the perspective of the NHS in England. Results Eighty-three participants were allocated to transforaminal epidural steroid injection and 80 participants were allocated to microdiscectomy, using an online randomisation system. At week 18, Oswestry Disability Questionnaire scores had decreased, relative to baseline, by 26.7 points in the microdiscectomy group and by 24.5 points in the transforaminal epidural steroid injection. The difference between the treatments was not statistically significant (estimated treatment effect –4.25 points, 95% confidence interval –11.09 to 2.59 points). Nor were there significant differences between treatments in any of the secondary outcomes: Oswestry Disability Questionnaire scores, visual analogue scores for leg pain and back pain, modified Roland–Morris score and Core Outcome Measures Index score up to 54 weeks. There were four (3.8%) serious adverse events in the microdiscectomy group, including one nerve palsy (foot drop), and none in the transforaminal epidural steroid injection group. Compared with transforaminal epidural steroid injection, microdiscectomy had an incremental cost-effectiveness ratio of £38,737 per quality-adjusted life-year gained and a probability of 0.17 of being cost-effective at a willingness to pay threshold of £20,000 per quality-adjusted life-year. Limitations Primary outcome data was invalid or incomplete for 24% of participants. Sensitivity analyses demonstrated robustness to assumptions made regarding missing data. Eighteen per cent of participants in the transforaminal epidural steroid injection group subsequently received microdiscectomy prior to their primary outcome assessment. Conclusions To the best of our knowledge, the NErve Root Block VErsus Surgery trial is the first trial to evaluate the comparative clinical effectiveness and cost-effectiveness of microdiscectomy and transforaminal epidural steroid injection. No statistically significant difference was found between the two treatments for the primary outcome. It is unlikely that microdiscectomy is cost-effective compared with transforaminal epidural steroid injection at a threshold of £20,000 per quality-adjusted life-year for sciatica secondary to prolapsed intervertebral disc