Now showing items 1-20 of 5714

    • Glycaemic measures for 8914 adult FreeStyle Libre users during routine care, segmented by age group and observed changes during the COVID-19 pandemic.

      Wilmot, Emma
      AIM: To evaluate the impact of the stay-at-home policy on different glucose metrics for time in range (%TIR 3.9-10 mmol/L), time below range (%TBR < 3.9 mmol/L) and time above range (%TAR > 10 mmol/L) for UK adult FreeStyle Libre (FSL) users within four defined age groups and on observed changes during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Data were extracted from 8914 LibreView de-identified user accounts for adult users aged 18 years or older with 5 or more days of sensor readings in each month from January to June 2020. Age-group categories were based on self-reported age on LibreView accounts (18-25, 26-49, 50-64 and ≥65 years). RESULTS: In January, prior to the COVID-19 pandemic, the 65 years or older age group had the highest %TIR (57.9%), while the 18-25 years age group had the lowest (51.2%) (P < .001). Within each age group, TIR increased during the analysed months, by 1.7% (26-49 years) to 3.1% (≥65 years) (P < .001 in all cases). %TBR was significantly reduced only in the 26-49 years age group, whereas %TAR was reduced by 1.5% (26-49 years) to 3.0% (≥65 years) (P < .001 in both cases). The proportion of adults achieving both of the more than 70% TIR and less than 4% TBR targets increased from 11.7% to 15.9% for those aged 65 years or older (P < .001) and from 6.0% to 9.1% for those aged 18-25 years (P < .05). Mean daily glucose-sensor scan rates were at least 12 per day and remained stable across the analysis period. CONCLUSIONS: Our data show the baseline glucose metrics for FSL users in the UK across different age groups under usual care. During lockdown in the UK, the proportion of adults achieving TIR consensus targets increased among FSL users.
    • Tolerability, gastric emptying patterns, and symptoms during the Nottingham Test Meal in 330 secondary care non-diabetic dyspeptic patients.

      Tucker, Emily
      BACKGROUND: Scintigraphy is used for overall assessment of gastric emptying. Adherence to an international consensus protocol is recommended to ensure quality; however, this has not been widely adopted because preparation of the "egg-beater" meal is inconvenient in clinical practice. In this report, we audit the tolerability and the results of gastric emptying scintigraphy with the 400 ml Tc-99 m-labeled liquid nutrient Nottingham Test Meal (NTM). METHODS: Results from 330 consecutive adult, non-diabetic patients with dyspeptic symptoms referred for gastric scintigraphy were analyzed. Gastric half-emptying time (T50) and validated measurements of early- and late-phase gastric emptying were acquired. Postprandial sensations of fullness, bloating, heartburn, nausea, and epigastric pain were recorded using 100 mm visual analog scales (VAS) before and 0, 30, and 90 min after NTM ingestion. Results were compared with those previously obtained in healthy subjects. KEY RESULTS: Almost all (98%) of the patients were able to consume the 400 ml NTM. Considering early- and late-phase gastric emptying, frequently observed patterns included normal early- with slow late-phase (25%) and fast early- with slow late-phase emptying (27%). Abnormal score of fullness and/ or dyspeptic symptoms were observed in 88% of dyspeptic patients. Abnormal fullness at T0 (after completed drink ingestion) was associated with slow late phase of gastric emptying, especially in women. CONCLUSIONS: Gastric scintigraphy with the NTM is simple to perform and well tolerated. Whether the identified abnormal gastric emptying patterns could predict different treatment outcome in patients with functional dyspepsia is the subject of ongoing prospective studies.
    • Motor unit dysregulation following 15 days of unilateral lower limb immobilisation.

      Inns, Thomas; Bass, Joseph; Hardy, EJO; Wilkinson, Dawn; Stashuk, D; Atherton, P; Philiips, B; Piasecki, M
      KEY POINTS: Muscle mass and function decline rapidly in situations of disuse such as bed rest and limb immobilisation. The reduction in muscle function commonly exceeds that of muscle mass, which may be associated with the dysregulation of neural input to muscle. We have used intramuscular electromyography to sample individual motor unit and near fibre potentials from the vastus lateralis following 15 days of unilateral limb immobilisation. Following disuse, the disproportionate loss of muscle strength when compared to size coincided with suppressed motor unit firing rate. These motor unit adaptations were observed at multiple contraction levels and in the immobilised limb only. Our findings demonstrate neural dysregulation as a key component of functional loss following muscle disuse in humans. ABSTRACT: Disuse atrophy, caused by situations of unloading such as limb immobilisation, causes a rapid yet diverging reduction in skeletal muscle function when compared to muscle mass. While mechanistic insight into the loss of mass is well studied, deterioration of muscle function with a focus towards the neural input to muscle remains underexplored. This study aimed to determine the role of motor unit adaptation in disuse-induced neuromuscular deficits. Ten young, healthy male volunteers underwent 15 days of unilateral lower limb immobilisation with intramuscular electromyography (iEMG) bilaterally recorded from the vastus lateralis (VL) during knee extensor contractions normalised to maximal voluntary contraction (MVC), pre and post disuse. Muscle cross-sectional area was determined by ultrasound. Individual MUs were sampled and analysed for changes in motor unit (MU) discharge and MU potential (MUP) characteristics. VL CSA was reduced by approximately 15% which was exceeded by a two-fold decrease of 31% in muscle strength in the immobilised limb, with no change in either parameter in the non-immobilised limb. Parameters of MUP size were reduced by 11 to 24% with immobilisation, while neuromuscular junction (NMJ) transmission instability remained unchanged, and MU firing rate decreased by 8 to 11% at several contraction levels. All adaptations were observed in the immobilised limb only. These findings highlight impaired neural input following immobilisation reflected by suppressed MU firing rate which may underpin the disproportionate reductions of strength relative to muscle size. Abstract figure legend Ten healthy young males underwent 15 days of unilateral lower limb immobilisation with an irremovable leg brace. Muscle size, strength and neuromuscular characteristics were measured bilaterally. Muscle strength reduced to a greater extent than muscle size in the immobilised leg while remaining unaltered in the non-immobilised leg. Motor unit firing rate, measured bilaterally using intramuscular electromyography, was also reduced in the immobilised leg only. This occurred at contraction intensities both relative to follow-up muscle strength and muscle strength normalised to pre-immobilisation. These findings suggest that neural dysregulation contributes to the loss of muscle strength observed in situations of disuse atrophy in humans. This article is protected by copyright. All rights reserved.
    • The management and diagnosis of rhabdomyolysis-induced acute kidney injury: a case study.

      Torr, Leah; Mortimore, Gerri
      Rhabdomyolysis is characterised by a rapid dissolution of damaged or injured skeletal muscle that can be the result of a multitude of mechanisms. It can range in severity from mild to severe, leading to multi-organ failure and death. Rhabdomyolysis causes muscular cellular breakdown, which can cause fatal electrolyte imbalances and metabolic acidosis, as myoglobin, creatine phosphokinase, lactate dehydrogenase and other electrolytes move into the circulation; acute kidney injury can follow as a severe complication. This article reflects on the case of a person who was diagnosed with rhabdomyolysis and acute kidney injury after a fall at home. Understanding the underpinning mechanism of rhabdomyolysis and the associated severity of symptoms may improve early diagnosis and treatment initiation.
    • The time course of disuse muscle atrophy of the lower limb in health and disease.

      Hardy, E; Inns, Thomas; Hatt, Jacob; Doleman, Brett; Bass, Joseph; Atherton, P; Lund, Jonathan; Phillips, Bethan
      Short, intermittent episodes of disuse muscle atrophy (DMA) may have negative impact on age related muscle loss. There is evidence of variability in rate of DMA between muscles and over the duration of immobilization. As yet, this is poorly characterized. This review aims to establish and compare the time-course of DMA in immobilized human lower limb muscles in both healthy and critically ill individuals, exploring evidence for an acute phase of DMA and differential rates of atrophy between and muscle groups. MEDLINE, Embase, CINHAL and CENTRAL databases were searched from inception to April 2021 for any study of human lower limb immobilization reporting muscle volume, cross-sectional area (CSA), architecture or lean leg mass over multiple post-immobilization timepoints. Risk of bias was assessed using ROBINS-I. Where possible meta-analysis was performed using a DerSimonian and Laird random effects model with effect sizes reported as mean differences (MD) with 95% confidence intervals (95% CI) at various time-points and a narrative review when meta-analysis was not possible. Twenty-nine studies were included, 12 in healthy volunteers (total n = 140), 18 in patients on an Intensive Therapy Unit (ITU) (total n = 516) and 3 in patients with ankle fracture (total n = 39). The majority of included studies are at moderate risk of bias. Rate of quadriceps atrophy over the first 14 days was significantly greater in the ITU patients (MD -1.01 95% CI -1.32, -0.69), than healthy cohorts (MD -0.12 95% CI -0.49, 0.24) (P < 0.001). Rates of atrophy appeared to vary between muscle groups (greatest in triceps surae (-11.2% day 28), followed by quadriceps (-9.2% day 28), then hamstrings (-6.5% day 28), then foot dorsiflexors (-3.2% day 28)). Rates of atrophy appear to decrease over time in healthy quadriceps (-6.5% day 14 vs. -9.1% day 28) and triceps surae (-7.8% day 14 vs. -11.2% day 28), and ITU quadriceps (-13.2% day 7 vs. -28.2% day 14). There appears to be variability in the rate of DMA between muscle groups, and more rapid atrophy during the earliest period of immobilization, indicating different mechanisms being dominant at different timepoints. Rates of atrophy are greater amongst critically unwell patients. Overall evidence is limited, and existing data has wide variability in the measures reported. Further work is required to fully characterize the time course of DMA in both health and disease.
    • Plasma Soluble Tumor Necrosis Factor Receptor Concentrations and Clinical Events After Hospitalization: Findings From the ASSESS-AKI and ARID Studies.

      Packington, Rebecca
      RATIONALE & OBJECTIVE: The role of plasma soluble tumor necrosis factor receptor (sTNFR)1 and sTNFR2 in the prognosis of clinical events after hospitalization with or without acute kidney injury (AKI) is unknown. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: Hospital survivors from the Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) and AKI Risk in Derby (ARID) with and without AKI during the index hospitalization who had baseline serum samples for biomarker measurements. PREDICTORS: We measured sTNFR1 and sTNFR2 obtained 3 months post-discharge. OUTCOMES: The associations between biomarkers with longitudinal kidney disease incidence and progression, heart failure and death were evaluated. ANALYTICAL APPROACH: Cox proportional hazard models. RESULTS: Among 1474 participants with plasma biomarker measurements, 19% developed kidney disease progression, 14% had later heart failure, and 21% died over a median follow-up of 4.4 years. For the kidney outcome, the adjusted HRs per doubling in concentration were 2.9 (2.2-3.9) for sTNFR1 and 1.9 (1.5-2.5) for sTNFR2. AKI during the index hospitalization did not modify the association between biomarkers and kidney events. For heart failure, the adjusted HRs per doubling in concentration were 1.9 (1.4-2.5) for sTNFR1 and 1.5 (1.2-2.0) for sTNFR2. For mortality, the adjusted HRs were 3.3 (2.5-4.3) for sTNFR1 and 2.5 (2.0-3.1) for sTNFR2. The findings in ARID were qualitatively similar for the magnitude of association between biomarkers and outcomes. LIMITATIONS: Different biomarker platforms, AKI definitions, limited generalizability to other ethnic groups. CONCLUSION: Plasma sTNFR1 and sTNFR2 measured 3 months after discharge were independently associated with clinical events, regardless of AKI status during the index admission. sTNFR1 and sTNFR2 may assist with the risk stratification of patients during follow-up.
    • A systematic review of the cost-effectiveness of community and population interventions to reduce the modifiable risk factors for dementia

      Brain, Jacob; Stephan, Blossom C. M. (2022)
      Population-based health and lifestyle interventions, which change societal conditions such that everyone across a given community is more likely to live more healthily, have been under-researched within the context of dementia prevention and risk reduction. This systematic review finds such interventions highly cost-effective, and often also cost-saving, in both high- as well as low- and middle-income settings. The strongest evidence base was for interventions that changed the physical environment to decrease physical inactivity or obesity, financial interventions that improved access to or resources for education, and mass media programmes that changed the social environment around smoking.
    • Recovery Colleges Characterisation and Testing in England (RECOLLECT): rationale and protocol

      Repper, Julie; Brewin, John; Sara, Meddings; McPhilbin, Merly; Yeo, Caroline; Slade, Mike (2022)
      Recovery Colleges are a relatively recent initiative within mental health services. The first opened in 2009 in London and since then numbers have grown. They are based on principles of personal recovery in mental health, co-production between people with lived experience of mental health problems and professionals, and adult learning. Student eligibility criteria vary, but all serve people who use mental health services, with empirical evidence of benefit. Previously we developed a Recovery College fidelity measure and a preliminary change model identifying the mechanisms of action and outcomes for this group, which we refer to as service user students. The Recovery Colleges Characterisation and Testing (RECOLLECT) study is a five-year (2020–2025) programme of research in England. The aim of RECOLLECT is to determine Recovery Colleges’ effectiveness and cost-effectiveness, and identify organisational influences on fidelity and improvements in mental health outcomes. 
    • The Use of Fluoroscan in Hand Clinic During the Covid Pandemic to Optimise Conservative Treatment

      Ashwood, Neil
      Introduction The study assessed the use of Fluoroscan (Hologic, Inc., Marlborough, MA) in hand clinic as advised by the British Orthopaedic Association (BOA) during the COVID-19 pandemic to facilitate treatment of fractures requiring manipulation and reduce admissions to evaluate if this should be embedded in practice permanently. Method Eighty-three wrist and hand fractures requiring manipulation were identified between April 2020 and March 2021. Demographics, mechanism of injury, timing of intervention, radiological outcome, further intervention and functional assessment by QuickDASH scoring were recorded. Results Sixty-eight cases were manipulated within the first week of fracture, simple pain control measures were used, and dose area product (DAP) averaged 1.3 Gy cm2 well below the dose limit set by the trust. Satisfactory fracture reduction was achieved in 59 cases avoiding admission. Further surgical intervention was offered to 24 patients: five re-manipulated while 19 had operation, all with a good functional outcome. Conclusion Fluoroscan use in fracture clinics achieved effective fracture control in 77% of cases. The use of Fluoroscan avoided admissions for surgery during the pandemic and lengthy clinic visits, four out of five did not need admission.
    • Associations between treatment adherence-competence-integrity (ACI) and adult psychotherapy outcomes : a systematic review and meta-analysis.

      Power, Niall; Firth, Nick
      Objective: To provide a comprehensive assessment of the association between psychological treatment adherence/competence/integrity (ACI) and clinical outcomes. Method: The review protocol was pre registered (CRD42020193889). Studies that assessed ACI-outcome relationships for adult psychotherapy were searched across three databases (Scopus, PsycINFO, MEDLINE). Random effects meta-analyses were conducted on adherence-outcome, competence-outcome and integrity-outcome relationships. Separate analyses were performed for studies with hierarchical (i.e. patients nested within therapist) versus non-hierarchical study designs. Moderator analyses were performed according to pre defined clinical and methodological features. GRADE assessments rated the quality of each meta analytic comparison. Results: The review identified 62 studies suitable for inclusion (45 adherence outcome, 39 competence-outcome and 7 integrity-outcome effect sizes; N=8,210 across all analyses). No significant adherence-outcome association was found. A small significant positive association was found only in non-hierarchical studies between competence and outcome (r = 0.17, 95% CI [0.07- 0.26], p < 0.001, ~d = .34, GRADE = moderate). Small-to-moderate significant positive associations between integrity and outcome were found for both non-hierarchical (r = 0.15, 95% CI [0.06 – 0.23], p < 0.001, ~d = .30, GRADE = high) and hierarchical study designs (r = 0.23, 95% CI [0.01,0.43], p < 0.044, ~d = .47, GRADE = low). Diagnosis, treatment modality and year of publication significantly moderated the strength of ACI-outcome correlations. Conclusions: Competence and integrity are significantly associated with clinical outcome, with a magnitude comparable to wider common factors. Further research is required to study these process-outcome associations with greater precision in routine-care settings and to understand the role of moderating variables.
    • Anetumab ravtansine versus vinorelbine in patients with relapsed, mesothelin-positive malignant pleural mesothelioma (ARCS-M): a randomised, open-label phase 2 trial

      Fennell, Dean (2022-04)
      Background: Few treatment options exist for second-line treatment of malignant pleural mesothelioma. We aimed to assess the antibody-drug conjugate anetumab ravtansine versus vinorelbine in patients with unresectable locally advanced or metastatic disease overexpressing mesothelin who had progressed on first-line platinum-pemetrexed chemotherapy with or without bevacizumab. Methods: In this phase 2, randomised, open-label study, done at 76 hospitals in 14 countries, we enrolled adults (aged ≥18 years) with unresectable locally advanced or metastatic malignant pleural mesothelioma, an Eastern Cooperative Oncology Group performance status of 0-1, and who had progressed on first-line platinum-pemetrexed chemotherapy with or without bevacizumab. Participants were prospectively screened for mesothelin overexpression (defined as 2+ or 3+ mesothelin membrane staining intensity on at least 30% of viable tumour cells by immunohistochemistry) and were randomly assigned (2:1), using an interactive voice and web response system provided by the sponsor, to receive intravenous anetumab ravtansine (6·5 mg/kg on day 1 of each 21-day cycle) or intravenous vinorelbine (30 mg/m2 once every week) until progression, toxicity, or death. The primary endpoint was progression-free survival according to blinded central radiology review, assessed in the intention-to-treat population, with safety assessed in all participants who received any study treatment. This study is registered with ClinicalTrials.gov, NCT02610140, and is now completed. Findings: Between Dec 3, 2015, and May 31, 2017, 589 patients were enrolled and 248 mesothelin-overexpressing patients were randomly allocated to the two treatment groups (166 patients were randomly assigned to receive anetumab ravtansine and 82 patients were randomly assigned to receive vinorelbine). 105 (63%) of 166 patients treated with anetumab ravtansine (median follow-up 4·0 months [IQR 1·4-5·5]) versus 43 (52%) of 82 patients treated with vinorelbine (3·9 months [1·4-5·4]) had disease progression or died (median progression-free survival 4·3 months [95% CI 4·1-5·2] vs 4·5 months [4·1-5·8]; hazard ratio 1·22 [0·85-1·74]; log-rank p=0·86). The most common grade 3 or worse adverse events were neutropenia (one [1%] of 163 patients for anetumab ravtansine vs 28 [39%] of 72 patients for vinorelbine), pneumonia (seven [4%] vs five [7%]), neutrophil count decrease (two [1%] vs 12 [17%]), and dyspnoea (nine [6%] vs three [4%]). Serious drug-related treatment-emergent adverse events occurred in 12 (7%) patients treated with anetumab ravtansine and 11 (15%) patients treated with vinorelbine. Ten (6%) treatment-emergent deaths occurred with anetumab ravtansine: pneumonia (three [2%]), dyspnoea (two [1%]), sepsis (two [1%]), atrial fibrillation (one [1%]), physical deterioration (one [1%]), hepatic failure (one [1%]), mesothelioma (one [1%]), and renal failure (one [1%]; one patient had 3 events). One (1%) treatment-emergent death occurred in the vinorelbine group (pneumonia). Interpretation: Anetumab ravtansine showed a manageable safety profile and was not superior to vinorelbine. Further studies are needed to define active treatments in relapsed mesothelin-expressing malignant pleural mesothelioma. Funding: Bayer Healthcare Pharmaceuticals.
    • Results of a single-arm pilot study of 32 P microparticles in unresectable locally advanced pancreatic adenocarcinoma with gemcitabine/nab-paclitaxel or FOLFIRINOX chemotherapy

      Iwuji, Chinenye (2022-02)
      Background: Unresectable locally advanced pancreatic cancer (LAPC) is generally managed with chemotherapy or chemoradiotherapy, but prognosis is poor with a median survival of ∼13 months (or up to 19 months in some studies). We assessed a novel brachytherapy device, using phosphorous-32 (32P) microparticles, combined with standard-of-care chemotherapy. Patients and methods: In this international, multicentre, single-arm, open-label pilot study, adult patients with histologically or cytologically proven unresectable LAPC received 32P microparticles, via endoscopic ultrasound-guided fine-needle implantation, planned for week 4 of 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) or gemcitabine/nab-paclitaxel chemotherapy, per investigator's choice. The primary endpoint was safety and tolerability measured using Common Terminology Criteria for Adverse Events version 4.0. The lead efficacy endpoint was local disease control rate at 16 weeks. Results: Fifty patients were enrolled and received chemotherapy [intention-to-treat (ITT) population]. Forty-two patients received 32P microparticle implantation [per protocol (PP) population]. A total of 1102 treatment-emergent adverse events (TEAEs) were reported in the ITT/safety population (956 PP), of which 167 (139 PP) were grade ≥3. In the PP population, 41 TEAEs in 16 (38.1%) patients were possibly or probably related to 32P microparticles or implantation procedure, including 8 grade ≥3 in 3 (7.1%) patients, compared with 609 TEAEs in 42 (100%) patients attributed to chemotherapy, including 67 grade ≥3 in 28 patients (66.7%). The local disease control rate at 16 weeks was 82.0% (95% confidence interval: 68.6% to 90.9%) (ITT) and 90.5% (95% confidence interval: 77.4% to 97.3%) (PP). Tumour volume, carbohydrate antigen 19-9 levels, and metabolic tumour response at week 12 improved significantly. Ten patients (20.0% ITT; 23.8% PP) had surgical resection and median overall survival was 15.2 and 15.5 months for ITT and PP populations, respectively. Conclusions: Endoscopic ultrasound-guided 32P microparticle implantation has an acceptable safety profile. This study also suggests clinically relevant benefits of combining 32P microparticles with standard-of-care systemic chemotherapy for patients with unresectable LAPC.
    • Brain-In-Hand technology for adults with acquired brain injury: A convergence of mixed methods findings

      das Nair, Roshan (2022)
      INTRODUCTION: Individuals with acquired brain injury may find it difficult to self-manage and live independently. Brain-in-Hand is a smartphone app designed to support psychological problems and encourage behaviour change, comprised of a structured diary, reminders, agreed solutions, and traffic light monitoring system. AIM: To evaluate the potential use and effectiveness of Brain-in-Hand for self-management in adults with acquired brain injury. METHODS: A-B mixed-methods case-study design. Individuals with acquired brain injury (n = 10) received Brain-in-Hand for up to 12 months. Measures of mood, independence, quality of life, cognition, fatigue, goal attainment, participation administered at baseline, 6 and 12 months. Semi-structured interviews conducted with acquired brain injury participants (n = 9) and healthcare workers (n = 3) at 6 months. RESULTS: Significant increase in goal attainment after 6 months use (t(7) = 4.20, p = .004). No significant improvement in other outcomes. Qualitative data suggested improvement in anxiety management. Contextual (personal/environmental) factors were key in influencing the use and effectiveness of Brain-in-Hand. Having sufficient insight, appropriate support and motivation facilitated use. CONCLUSIONS: Brain-in-Hand shows potential to support acquired brain injury, but further work is required to determine its effectiveness. Context played a pivotal role in the effectiveness and sustained use of Brain-in-Hand, and needs to be explored to support implementation.
    • Psychological flexibility, distress, and quality of life in secondary progressive multiple sclerosis: A cross-sectional study

      das Nair, Roshan (2022)
      INTRODUCTION: One of the strongest predictors of successful coping in multiple sclerosis (MS) is the extent to which one can accept the diagnosis and limitations associated with the disease. Acceptance is also one of three core processes of psychological flexibility - a malleable treatment target of some psychological therapies. This is the ability to notice and accept the presence of thoughts and feelings without being swept along by them, engaging in the present moment, and making decisions in line with personal values. Poor psychological flexibility is associated with elevated levels of distress in the general population. However, we do not know the level of psychological flexibility in people with MS, or its relationship to distress or quality of life when the disease becomes more physically disabling. The aims of this study were to determine the level of psychological flexibility, and its relationship with distress and quality of life in secondary progressive multiple sclerosis (SPMS), a subtype of MS with increased severity of disability and distress. METHOD: This cross-sectional analytic study used data collected by the UK MS Register. Pre-existing data on distress, quality of life, disability, and demographics collected by the UK MS Register were combined with a psychological flexibility measure and its component parts, collected for the purpose of this study. Patient demographics and questionnaire data were recorded for distress, quality of life, and psychological flexibility. Pearson's correlations were used to examine bivariate relationships between distress, quality of life, disability and psychological flexibility. Whether psychological flexibility moderated the relationship between disability (predictor), distress and quality of life (outcomes) was also investigated. RESULTS: Between February and March 2020, 628 participants with SPMS completed the CompACT and had a recent (<12 months) HADS questionnaire (M(age) = 60.66, 70.90% women). On the HADS questionnaire subscales, 44% of the sample scored above the MS clinical cut-off (≥8) for anxiety (M = 7.09, SD = 4.57), and 30% above the clinical cut off (≥11) for depression (M = 8.35, SD = 4.21). Psychological flexibility (M = 81.94, SD = 22.60) and its components were each moderately negatively correlated with total distress (r = -0.65), anxiety (r = -0.58), and depression (r = -0.56). A second subsample (n = 434) completed the EQ-5D-5L health-related quality of life measure, which was moderately positively correlated with psychological flexibility (r = 0.47). A third subsample (n = 210) found a weak negative relationship between psychological flexibility and disability (r = -0.16), a weak positive relationship between distress and disability (r = 0.26), and a moderate negative relationship between quality of life and disability (r = -0.56). Psychological flexibility was not found to moderate the relationships between disability and anxiety, depression, or quality of life in SPMS. DISCUSSION: Greater psychological flexibility was associated with lower self-reported distress and higher quality of life in this SPMS sample. It was not shown to moderate the extent to which physical disability predicts distress or quality of life in SPMS. These findings demonstrate that greater psychological flexibility is related to better coping outcomes (lower distress, higher quality of life) in SPMS. If psychological flexibility can be increased in people with SPMS, this could lead to a reduction in distress and improvement in quality of life, although directionality could not be attributed with these methods. Further longitudinal evidence and trials of psychological flexibility-focussed interventions are needed.
    • Systematic review and meta-analysis of the effectiveness of teacher delivered interventions for externalizing behaviors

      Aldabbagh, Reem; Glazebrook, Cris; Sayal, Kapil; Daley, David (2022)
      This systematic review and meta-analysis explores the effectiveness of teacher interventions supporting children with externalizing behaviors based on teacher and child outcomes. A systematic search was conducted using 5 electronic databases. From 5714 papers, 31 papers that included interventions delivered directly to teachers and aimed to benefit either teachers and/or children with externalizing behaviors were included. The review focused on qualified teachers working with children aged 2-13. The results of the current meta-analysis revealed a positive effect of teacher intervention on teacher and child outcomes, including the increased use of teacher-appropriate strategies, as well as significant and moderate improvements in teacher-child closeness, and small reductions in teacher-child conflict. For child outcomes, the interventions reduced externalizing behavior problems and ADHD symptoms and enhanced prosocial behavior. Only one fully blinded analysis for conduct problems was possible and revealed a moderate but significant reduction in favor of intervention. These findings provide evidence to support the role of teacher interventions for both teachers and children with externalizing behaviors. Future research should include more PBLIND measurements so that MPROX findings can be confirmed. More research should be done to evaluate the influence of teacher interventions on teachers' well-being.
    • Platelet biomarkers in patients with atherosclerotic extracranial carotid artery stenosis: a systematic review

      Naylor, Ross (2022-03)
      Objective: The aim was to enhance understanding of the role of platelet biomarkers in the pathogenesis of vascular events and risk stratifying patients with asymptomatic or symptomatic atherosclerotic carotid stenosis. Data sources: Systematic review conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Review methods: A systematic review collated data from 1975 to 2020 on ex vivo platelet activation and platelet function/reactivity in patients with atherosclerotic carotid stenosis. Results: Forty-three studies met the inclusion criteria; the majority included patients on antiplatelet therapy. Five studies showed increased platelet biomarkers in patients with ≥ 30% asymptomatic carotid stenosis (ACS) vs. controls, with one neutral study. Preliminary data from one study suggested that quantification of "coated platelets" in combination with stenosis severity may aid risk stratification in patients with ≥ 50% - 99% ACS. Platelets were excessively activated in patients with ≥ 30% symptomatic carotid stenosis (SCS) vs. controls (≥ 11 positive studies and one neutral study). Antiplatelet-High on Treatment Platelet Reactivity (HTPR), previously called "antiplatelet resistance", was observed in 23% - 57% of patients on aspirin, with clopidogrel-HTPR in 25% - 100% of patients with ≥ 50% - 99% ACS. Aspirin-HTPR was noted in 9.5% - 64% and clopidogrel-HTPR in 0 - 83% of patients with ≥ 50% SCS. However, the data do not currently support the use of ex vivo platelet function/reactivity testing to tailor antiplatelet therapy outside of a research setting. Platelets are excessively activated (n = 5), with increased platelet counts (n = 3) in recently symptomatic vs. asymptomatic patients, including those without micro-emboli on transcranial Doppler (TCD) monitoring (n = 2). Most available studies (n = 7) showed that platelets become more reactive or activated following carotid endarterectomy or stenting, either as an acute phase response to intervention or peri-procedural treatment. Conclusion: Platelets are excessively activated in patients with carotid stenosis vs. controls, in recently symptomatic vs. asymptomatic patients, and may become activated/hyper-reactive following carotid interventions despite commonly prescribed antiplatelet regimens. Further prospective multicentre studies are required to determine whether models combining clinical, neurovascular imaging, and platelet biomarker data can facilitate optimised antiplatelet therapy in individual patients with carotid stenosis.
    • Practitioners’ views on enabling people with dementia to remain in their homes during and after crisis

      Coleston-Shields, Donna M.; Stanyon, Miriam R.; Yates, Jennifer A.; Streater, Amy; Orrell, Martin (2022)
      One way of supporting people living with dementia is assisting them to live in their homes (as opposed to being admitted to hospital or other facility) and providing them with a specialist service that responds to crises. This makes it important to understand how best to organize such crisis response services. This study examines practitioners’ actions to reduce inpatient admissions among this population. Through interviews with healthcare practitioners, we find that practitioners negotiate a complex intersection between (1) what constitutes a crisis in relation to the patient and/or the carer, (2) the demands of building a working relationship with both the patient and their family carers, and (3) ensuring effective communications with social services responsible for long-term community support. Findings suggest that policies aimed at reducing admissions should be based on a model of care that more closely maps practitioners’ relational and bio-medical work in these services.
    • Therapist-supported internet-delivered exposure and response prevention for children and adolescents with Tourette syndrome: A randomized clinical trial

      Hall, Charlotte L.; Davies, E. Bethan; Hollis, Chris P. (2022)
      The availability of behavior therapy for individuals with Tourette syndrome (TS) and chronic tic disorder (CTD) is limited.To determine the efficacy and cost-effectiveness of internet-delivered exposure and response prevention (ERP) for children and adolescents with TS or CTD.This single-masked, parallel group, superiority randomized clinical trial with nationwide recruitment was conducted at a research clinic in Stockholm, Sweden. Out of 615 individuals assessed for eligibility, 221 participants meeting diagnostic criteria for TS or CTD and aged 9 to 17 years were included in the study. Enrollment began in April 2019 and ended in April 2021. Data were analyzed between October 2021 and March 2022.Participants were randomized to 10 weeks of therapist-supported internet-delivered ERP for tics (111 participants) or to therapist-supported internet-delivered education for tics (comparator group, 110 participants).The primary outcome was change in tic severity from baseline to the 3-month follow-up as measured by the Total Tic Severity Score of the Yale Global Tic Severity Scale (YGTSS-TTSS). YGTSS-TTSS assessors were masked to treatment allocation. Treatment response was operationalized as a score of 1 (“Very much improved”) or 2 (“Much improved”) on the Clinical Global Impression–Improvement scale.Data loss was minimal, with 216 of 221 participants (97.7%) providing primary outcome data. Among randomized participants (152 [68.8%] boys; mean [SD] age, 12.1 [2.3] years), tic severity improved significantly, with a mean reduction of 6.08 points on the YGTSS-TTSS in the ERP group (mean [SD] at baseline, 22.25 [5.60]; at 3-month follow-up, 16.17 [6.82]) and 5.29 in the comparator (mean [SD] at baseline, 23.01 [5.92]; at 3-month follow-up, 17.72 [7.11]). Intention-to-treat analyses showed that the 2 groups improved similarly over time (interaction effect, −0.53; 95% CI, −1.28 to 0.22; P = .17). Significantly more participants were classified as treatment responders in the ERP group (51 of 108 [47.2%]) than in the comparator group (31 of 108 [28.7%]) at the 3-month follow-up (odds ratio, 2.22; 95% CI, 1.27 to 3.90). ERP resulted in more treatment responders at little additional cost compared with structured education. The incremental cost per quality-adjusted life-year gained was below the Swedish willingness-to-pay threshold, at which ERP had a 66% to 76% probability of being cost-effective.Both interventions were associated with clinically meaningful improvements in tic severity, but ERP led to higher response rates at little additional cost.ClinicalTrials.gov identifier: NCT03916055
    • Protocol for a feasibility randomised controlled study of a multicomponent intervention to promote a sustainable return to work of workers on long-term sick leave — PROWORK: PROmoting a Sustainable and Healthy Return to WORK

      Bartle, Craig; Marwaha, Steven; Newman, Kristina; Thomson, Louise (2022)
      The cost of sickness absence has major social, psychological and financial implications for individuals and organisations. Return-to-work (RTW) interventions that support good quality communication and contact with the workplace can reduce the length of sickness absence by between 15 and 30 days. However, initiatives promoting a sustainable return to work for workers with poor mental health on long-term sickness absence across small, medium and large enterprises (SMEs and LEs) are limited. This paper describes the protocol of a pilot randomised controlled trial (RCT) to test the feasibility of implementing a RTW intervention across SMEs and LEs across all sectors.
    • Mental health workers’ perspectives on peer support in high-, middle- and low income settings: a focus group study

      Charles, Ashleigh (2022)
      Peer support is increasingly acknowledged as an integral part of mental health services around the world. However, most research on peer support comes from high-income countries, with little attention to similarities and differences between different settings and how these affect implementation. Mental health workers have an important role to play in integrating formal peer support into statutory services, and their attitudes toward peer support can represent either a barrier to or facilitator of successful implementation. Thus, this study investigates mental health workers’ attitudes toward peer support across a range of high- (Germany, Israel), middle- (India), and low-income country (Tanzania, Uganda) settings.