Nebulised interferon beta-1a (SNG001) in the treatment of viral exacerbations of COPD.

BACKGROUND: Respiratory viral infections are major drivers of chronic obstructive pulmonary disease (COPD) exacerbations. Interferon-ß is naturally produced in response to viral infection, limiting replication. This exploratory study aimed to demonstrate proof-of-mechanism, and evaluate the efficacy and safety of inhaled recombinant interferon-ß1a (SNG001) in COPD. Part 1 assessed the effects of SNG001 on induced sputum antiviral interferon-stimulated gene expression, sputum differential cell count, and respiratory function. Part 2 compared SNG001 and placebo on clinical efficacy, sputum and serum biomarkers, and viral clearance. METHODS: In Part 1, patients (N = 13) with stable COPD were randomised 4:1 to SNG001 or placebo once-daily for three days. In Part 2, patients (N = 109) with worsening symptoms and a positive respiratory viral test were randomised 1:1 to SNG001 or placebo once-daily for 14 days in two Groups: A (no moderate exacerbation); B (moderate COPD exacerbation [i.e., acute worsening of respiratory symptoms treated with antibiotics and/or oral corticosteroids]). RESULTS: In Part 1, SNG001 upregulated sputum interferon gene expression. In Part 2, there were minimal SNG001-placebo differences in the efficacy endpoints; however, whereas gene expression was initially upregulated by viral infection, then declined on placebo, levels were maintained with SNG001. Furthermore, the proportion of patients with detectable rhinovirus (the most common virus) on Day 7 was lower with SNG001. In Group B, serum C-reactive protein and the proportion of patients with purulent sputum increased with placebo (suggesting bacterial infection), but not with SNG001. The overall adverse event incidence was similar with both treatments. CONCLUSIONS: Overall, SNG001 was well-tolerated in patients with COPD, and upregulated lung antiviral defences to accelerate viral clearance. These findings warrant further investigation in a larger study. TRIAL REGISTRATION: EU clinical trials register (2017-003679-75), 6 October 2017.

Should we consider sarcopenia in pediatric patients with chronic kidney disease? A preliminary cross-sectional analysis.

BACKGROUND: Pediatric patients with chronic kidney disease (CKD) frequently present an inadequate nutritional profile and musculoskeletal impairments. We investigated sarcopenia and its related traits in children and adolescents with CKD. METHODS: A cross-sectional study that enrolled pediatric patients with CKD (≥ 4 and < 18 years old). Physical function was assessed by handgrip strength and the 60-s sit-to-stand (STS-60) tests. Body composition measurement was performed by bioelectrical impedance analysis and anthropometry through mid-upper arm circumference (MUAC). Normative reference values from healthy pediatrics were used for identifying poor physical function and low MUAC. Probable sarcopenia was considered as low handgrip strength, whereas sarcopenia was defined by adding low MUAC. RESULTS: Twenty-two pediatric patients with CKD (11 ± 4 years and 59% boys) were evaluated; eight on peritoneal dialysis (36%), six on hemodialysis (27%), and eight non-dialysis (36%). Regarding sarcopenia traits, we observed low physical function by handgrip strength and STS-60 in 59% and 100% of the patients, respectively, while low MUAC in 77%. Probable sarcopenia was found in 9% and sarcopenia in 50%, but prevalence did not differ among stages. Handgrip strength was strongly associated with MUAC (r = 0.90; p < 0.001); on the other hand, the STS-60 was not significantly associated with any of the body composition variables. CONCLUSION: Among pediatric patients with CKD, the prevalence of sarcopenia and its related traits was high. Nephrology professionals should consider the assessment of sarcopenia in this population, while more evidence is needed to determine its prognostic value. A higher resolution version of the Graphical abstract is available as Supplementary information.

Sarcopenia prevalence using handgrip strength or chair stand performance in adults living with type 2 diabetes mellitus.

BACKGROUND: The updated European Working Group on Sarcopenia in Older People (EWGSOP2) recommends handgrip strength (HGS) and the chair stand test (CST) to assess muscle strength, with the CST being a convenient proxy for lower limb strength. However, adiposity may differentially influence these strength criteria and produce discrepant sarcopenia prevalence. OBJECTIVE: To determine the prevalence of sarcopenia using HGS or the CST, and to investigate the associations between these strength criteria and adiposity in adults with type 2 diabetes mellitus. METHODS: The EWGSOP2 definition was used to assess the prevalence of probable (low muscle strength), confirmed (plus low muscle mass) and severe (plus poor physical performance) sarcopenia. Linear regression models were used to study the association between different measures of muscle strength and adiposity. RESULTS: We used data from 732 adults with type 2 diabetes mellitus (35.7% female, aged 64 ± 8 years, body mass index 30.7 ± 5.0 kg/m2). Using the CST compared with HGS produced a higher prevalence of probable (31.7% vs. 7.1%), confirmed (5.6% vs. 1.6%) and severe (1.0% vs. 0.3%) sarcopenia, with poor agreement between strength criteria to identify probable sarcopenia. CST performance, but not HGS, was significantly associated with all measures of adiposity in unadjusted and adjusted models. CONCLUSIONS: Higher levels of adiposity may impact CST performance, but not HGS, resulting in a higher prevalence of sarcopenia in adults with type 2 diabetes mellitus. Consideration should be paid to the most appropriate measure of muscle function in this population.

Evaluating the between-day reliability and likelihood of change of a test battery incorporating vastus lateralis muscle thickness, ankle-brachial pressure index, maximal voluntary torque, and six-minute walk test in patients with claudication.

OBJECTIVE: The study aims to evaluate the between-day reliability of a proposed test battery for patients with claudication that can be used for monitoring the effectiveness of exercise interventions and other therapeutic strategies tailored to this patient population. METHODS: Twenty-five men with claudication were recruited. The test battery consisted of the Vastus Lateralis muscle thickness (VL-MT), ankle-brachial pressure index (ABI), unilateral isometric knee extension maximal voluntary torque (MVT) and 6-minute walk test (6MWT). A single investigator conducted the tests for each patient on two separate testing sessions (T1 and T2) 5-7 days apart. RESULTS: Good to excellent reliability was observed for VL-MT (ICC = 0.95, 95% LOA = ±3.10 mm, SEM = 0.81 mm), ABI (ICC = 0.97, 95% LOA = ±0.10, SEM = 0.02), MVT (ICC = 0.97, 95% LOA = ±24.0 N·m, SEM = 6.31 N·m), 6MWT distance (ICC = 0.99, 95% LOA = ±39.6 m, SEM = 11.0 m), 6MWT time to claudication (ICC = 0.99, 95% LOA = ±30.8 s, SEM = 7.8 s), and 6MWT ratings of pain (ICC = 0.87, 95% LOA = ±2.4 CR-10+, SEM = 0.7 CR-10+ ). Analysis derived from reliability data indicates a change of 1.4 mm for VL-MT, 0.14 for ABI, 12 N·m for MVT, 25 m for 6MWT distance, 15 s for 6MWT time to claudication and 1 CR-10+ for 6MWT ratings of pain is required to be interpreted as the minimum 'likely' change (76% chance). CONCLUSIONS: The test battery provides a reliable assessment of patients with claudication and can be widely used to evaluate the effects of exercise programmes and other therapeutic interventions. For the individual, changes in VL-MT, ABI, MVT, and 6MWT greater than the minimum likely change as a result of an exercise programme or an intervention are likely changes and less influenced by error associated with the test.

Skeletal Muscle Texture Assessment Using Ultrasonography: Comparison with Magnetic Resonance Imaging in Chronic Kidney Disease.

Skeletal muscle dysfunction is common in chronic kidney disease (CKD). Of interest is the concept of "muscle quality," of which measures include ultrasound-derived echo intensity (EI). Alternative parameters of muscle texture, for example, gray level of co-occurrence matrix (GCLM), are available and may circumvent limitations in EI. The validity of EI is limited in humans, particularly in chronic diseases. This study aimed to investigate the associations between ultrasound-derived parameters of muscle texture with MRI. Images of the thigh were acquired using a 3 Tesla MRI scanner. Quantification of muscle (contractile), fat (non-contractile), and miscellaneous (connective tissue, fascia) components were estimated. Anatomical rectus femoris cross-sectional area was measured using B-mode 2D ultrasonography. To assess muscle texture, first (i.e., EI)- and second (i.e., GLCM)-order statistical analyses were performed. Fourteen participants with CKD were included (age: 58.0 ± 11.9 years, 50% male, eGFR: 27.0 ± 7.4 ml/min/1.73m2, 55% Stage 4). Higher EI was associated with lower muscle % (quadriceps: ß = -.568, p = .034; hamstrings: ß = -.644, p = .010). Higher EI was associated with a higher fat % in the hamstrings (ß = -.626, p = .017). A higher angular second moment from GLCM analysis was associated with greater muscle % (ß = .570, p = .033) and lower fat % (ß = -.534, p = .049). A higher inverse difference moment was associated with greater muscle % (ß = .610, p = .021 and lower fat % (ß = -.599, p = .024). This is the first study to investigate the associations between ultrasound-derived parameters of muscle texture with MRI. Our preliminary findings suggest ultrasound-derived texture analysis provides a novel indicator of reduced skeletal muscle % and thus increased intramuscular fat.

Real-time fetal brain tracking for functional fetal MRI.

PURPOSE: To improve motion robustness of functional fetal MRI scans by developing an intrinsic real-time motion correction method. MRI provides an ideal tool to characterize fetal brain development and growth. It is, however, a relatively slow imaging technique and therefore extremely susceptible to subject motion, particularly in functional MRI experiments acquiring multiple Echo-Planar-Imaging-based repetitions, for example, diffusion MRI or blood-oxygen-level-dependency MRI. METHODS: A 3D UNet was trained on 125 fetal datasets to track the fetal brain position in each repetition of the scan in real time. This tracking, inserted into a Gadgetron pipeline on a clinical scanner, allows updating the position of the field of view in a modified echo-planar imaging sequence. The method was evaluated in real-time in controlled-motion phantom experiments and ten fetal MR studies (17 + 4-34 + 3 gestational weeks) at 3T. The localization network was additionally tested retrospectively on 29 low-field (0.55T) datasets. RESULTS: Our method achieved real-time fetal head tracking and prospective correction of the acquisition geometry. Localization performance achieved Dice scores of 84.4% and 82.3%, respectively for both the unseen 1.5T/3T and 0.55T fetal data, with values higher for cephalic fetuses and increasing with gestational age. CONCLUSIONS: Our technique was able to follow the fetal brain even for fetuses under 18 weeks GA in real-time at 3T and was successfully applied "offline" to new cohorts on 0.55T. Next, it will be deployed to other modalities such as fetal diffusion MRI and to cohorts of pregnant participants diagnosed with pregnancy complications, for example, pre-eclampsia and congenital heart disease.

Low-intensity resistance exercise with blood flow restriction for patients with claudication: A randomized controlled feasibility trial.

BACKGROUND: Claudication is a common and debilitating symptom of peripheral artery disease, resulting in poor exercise performance and quality of life (QoL). Supervised exercise programs are an effective rehabilitation for patients with claudication, but they are poorly adhered to, in part due to the high pain and effort associated with walking, aerobic, and resistance exercise. Low-intensity resistance exercise with blood flow restriction (BFR) represents an alternative exercise method for individuals who are intolerant to high-intensity protocols. The aim of this study was to evaluate the feasibility of a supervised BFR program in patients with claudication. METHODS: Thirty patients with stable claudication completed an 8-week supervised exercise program and were randomized to either BFR (n = 15) or a control of matched exercise without BFR (control; n = 15). Feasibility, safety, and efficacy were assessed. RESULTS: All success criteria of the feasibility trial were met. Exercise adherence was high (BFR = 78.3%, control = 83.8%), loss to follow up was 10%, and there were no adverse events. Clinical improvement in walking was achieved in 86% of patients in the BFR group but in only 46% of patients in the control group. Time to claudication pain during walking increased by 35% for BFR but was unchanged for the control. QoL for the BFR group showed improved mobility, ability to do usual activities, pain, depression, and overall health at follow up. CONCLUSION: A supervised blood flow restriction program is feasible in patients with claudication and has the potential to increase exercise performance, reduce pain, and improve QoL. (Clinicaltrials.gov Identifier: NCT04890275).

Physical activity and risk of chronic kidney disease: systematic review and meta-analysis of 12 cohort studies involving 1,281,727 participants.

The role of regular physical activity in preventing vascular and non-vascular disease is well established. Chronic kidney disease (CKD) is a major cause of global morbidity and mortality and largely preventable, but it is uncertain if regular physical activity can reduce the risk of CKD. Using a systematic review and meta-analysis of published observational cohort studies in the general population, we sought to assess the association between physical activity and CKD risk. Relevant studies with at least one-year of follow-up were sought from inception until 02 May 2022 in MEDLINE, Embase, Web of Science, and manual search of relevant articles. Relative risks (RRs) with 95% confidence intervals (CIs) for the maximum versus the minimal amount of physical activity groups were pooled using random effects meta-analysis. The quality of the evidence was evaluated using the GRADE tool. A total of 12 observational cohort studies comprising 1,281,727 participants and 66,217 CKD events were eligible for the analysis. The pooled multivariable-adjusted RR (95% CI) of CKD comparing the most versus the least physically active groups was 0.91 (0.85-0.97). The association was consistent across several study level subgroups. Exclusion of any single study at a time from the meta-analysis did not change the direction or significance of the association. There was no evidence of small study effects among contributing studies. The GRADE quality of the evidence was low. In the general population, individuals who are most physically active have a lowered risk of CKD compared to those who are not or least physically active. CRD42022327640.

The effect of a prior eccentric lowering phase on concentric neuromechanics during multiple joint resistance exercise in older adults.

Aging involves a marked decline in physical function and especially muscle power. Thus, optimal resistance exercise (RE) to improve muscle power is required for exercise prescription. An eccentric lowering phase immediately before a concentric lift (ECC-CON) may augment concentric power production, due to various proposed mechanisms (e.g., elastic recoil, pre-activation, stretch reflex, contractile history), when compared with a concentric contraction alone (CON-Only). This study compared the effect of a prior eccentric lowering phase on older adult concentric power performance (ECC-CON vs. CON-Only) during a common multiple joint isoinertial RE (i.e., leg press) with a range of loads. Twelve healthy older adult males completed two measurement sessions, consisting of ECC-CON and CON-Only contractions, performed in a counterbalanced order using 20-80% of one repetition maximum [% 1RM] loads on an instrumented isoinertial leg press dynamometer that measured power, force, and velocity. Muscle activation was assessed with surface electromyography (sEMG). For mean power ECC-CON>CON-Only, with a pronounced effect of load on the augmentation of power by ECC-CON (+19 to +55%, 35-80% 1RM, all p < 0.032). Similarly, for mean velocity ECC-CON>CON-Only, especially as load increased (+15 to 54%, 20-80% 1RM, all p < 0.005), but mean force showed more modest benefits of ECC-CON (+9 to 14%, 50-80% 1RM, all p < 0.05). In contrast, peak power and velocity were similar for ECC-CON and CON-Only with all loads. Knee and hip extensor sEMG were similar for both types of contractions. In conclusion, ECC-CON contractions produced greater power, and velocity performance in older adults than CON-Only and may provide a superior stimulus for chronic power development.

Data-driven motion-corrected brain MRI incorporating pose-dependent B0 fields.

PURPOSE: To develop a fully data-driven retrospective intrascan motion-correction framework for volumetric brain MRI at ultrahigh field (7 Tesla) that includes modeling of pose-dependent changes in polarizing magnetic (B0 ) fields. THEORY AND METHODS: Tissue susceptibility induces spatially varying B0 distributions in the head, which change with pose. A physics-inspired B0 model has been deployed to model the B0 variations in the head and was validated in vivo. This model is integrated into a forward parallel imaging model for imaging in the presence of motion. Our proposal minimizes the number of added parameters, enabling the developed framework to estimate dynamic B0 variations from appropriately acquired data without requiring navigators. The effect on data-driven motion correction is validated in simulations and in vivo. RESULTS: The applicability of the physics-inspired B0 model was confirmed in vivo. Simulations show the need to include the pose-dependent B0 fields in the reconstruction to improve motion-correction performance and the feasibility of estimating B0 evolution from the acquired data. The proposed motion and B0 correction showed improved image quality for strongly corrupted data at 7 Tesla in simulations and in vivo. CONCLUSION: We have developed a motion-correction framework that accounts for and estimates pose-dependent B0 fields. The method improves current state-of-the-art data-driven motion-correction techniques when B0 dependencies cannot be neglected. The use of a compact physics-inspired B0 model together with leveraging the parallel imaging encoding redundancy and previously proposed optimized sampling patterns enables a purely data-driven approach.

Predicting the risk of chest radiograph abnormality 12-weeks post hospitalisation with SARS CoV-2 PCR confirmed COVID-19.

BACKGROUND: Routine follow-up of patients hospitalised with COVID-19 is recommended, however due to the ongoing high number of infections this is not without significant health resource and economic burden. In a previous study we investigated the prevalence of, and risk factors for, persistent chest radiograph (CXR) abnormalities post-hospitalisation with COVID-19 and identified a 5-point composite score that strongly predicted risk of persistent CXR abnormality at 12-weeks. Here we sought to validate and refine our findings in an independent cohort of patients. METHODOLOGY: A single-centre prospective study of consecutive patients attending a virtual post-hospitalisation COVID-19 clinic and CXR as part of their standard clinical care between 2nd March - 22nd June 2021. Inpatient and follow-up CXRs were scored by the assessing clinician for extent of pulmonary infiltrates (0-4 in each lung) with complete resolution defined as a follow-up score of zero. RESULTS: 182 consecutive patients were identified of which 31% had persistent CXR abnormality at 12-weeks. Patients with persistent CXR abnormality were significantly older (p < 0.001), had a longer hospital length of stay (p = 0.005), and had a higher incidence of both level 2 or 3 facility admission (level 2/3 care) (p = 0.003) and ever-smoking history (p = 0.038). Testing our composite score in the present cohort we found it predicted persistent CXR abnormality with reasonable accuracy (area under the receiver operator curve [AUROC 0.64]). Refining this score replacing obesity with Age ≥ 50 years, we identify the SHADE-750 score (1-point each for; Smoking history, Higher-level care (level 2/3 admission), Age ≥ 50 years, Duration of admission ≥ 15 days and Enzyme-lactate dehydrogenase (LDH ≥ 750U/L), that accurately predicted risk of persistent CXR abnormality, both in the present cohort (AUROC 0.73) and when retrospectively applied to our 1st cohort (AUROC 0.79). Applied to both cohorts combined (n = 213) it again performed strongly (AUROC 0.75) with all patients with a score of zero (n = 18) having complete CXR resolution at 12-weeks. CONCLUSIONS: In two independent cohorts of patients hospitalised with COVID-19, we identify a 5-point score which accurately predicts patients at risk of persistent CXR abnormality at 12-weeks. This tool could be used by clinicians to identify patients in which radiological follow-up may not be required.

Eptacog beta efficacy and safety in the treatment and control of bleeding in paediatric subjects (<12 years) with haemophilia A or B with inhibitors.

INTRODUCTION: Eptacog beta is a new recombinant activated human factor VII bypassing agent approved in the United States for the treatment and control of bleeding in patients with haemophilia A or B with inhibitors 12 years of age or older. AIM: To prospectively assess in a phase 3 clinical trial (PERSEPT 2) eptacog beta efficacy and safety for treatment of bleeding in children <12 years of age with haemophilia A or B with inhibitors. METHODS: Using a randomised crossover design, subjects received initial doses of 75 or 225 µg/kg eptacog beta followed by 75 µg/kg dosing at predefined intervals (as determined by clinical response) to treat bleeding episodes (BEs). Treatment success criteria included a haemostasis evaluation of 'excellent' or 'good' without use of additional eptacog beta, alternative haemostatic agent or blood product, and no increase in pain following the first 'excellent' or 'good' assessment. RESULTS: Treatment success proportions in 25 subjects (1-11 years) who experienced 546 mild or moderate BEs were 65% in the 75 µg/kg initial dose regimen (IDR) and 60% in the 225 µg/kg IDR 12 h following initial eptacog beta infusion. By 24 h, the treatment success proportions were 97% for the 75 µg/kg IDR and 98% for the 225 µg/kg IDR. No thrombotic events, allergic reactions, neutralising antibodies or treatment-related adverse events were reported. CONCLUSION: Both 75 and 225 µg/kg eptacog beta IDRs provided safe and effective treatment and control of bleeding in children <12 years of age.

Cost utility and budget impact analysis of dexamethasone compared with bortezomib and lenalidomide for the treatment of second line multiple myeloma from a South African public health perspective.

BACKGROUND: Multiple myeloma is an incurable haematological malignancy that is associated with a high probability of relapse. The survival of relapsed patients has been greatly improved by the development of novel drugs such as lenalidomide and bortezomib. We assessed the cost-effectiveness of these drugs as second-line treatment for relapsed/refractory multiple myeloma (RRMM) patients in the South African public health care system. METHODS: We modelled 3 treatment strategies for second-line RRMM treatment: dexamethasone (standard of care), bortezomib (BORT) and lenalidomide plus dexamethasone (LEN/DEX) from the South African public health perspective. For each strategy we modelled a hypothetical cohort of relapsed/refractory multiple myeloma patients using a three-state Markov model over a 15-year time horizon. Efficacy and utilization data were obtained from the MM009/010 and APEX trials and external studies. Price and cost data were from local sources and presented in 2021 South African Rands. Outcomes were reported in quality adjusted life years (QALYs). Incremental cost effectiveness ratios (ICERs) were calculated for BORT and LEN/DEX and compared to a local cost-effectiveness threshold of R38 500 per DALY averted using the assumption that 1 DALY averted is equal to 1 QALY gained. A budget impact analysis was conducted to evaluate the financial impact of the introduction of BORT and LEN/DEX, respectively. Deterministic sensitivity analysis was undertaken to account for parameter uncertainties. RESULTS: The modelled total costs of DEX, BORT and LEN/DEX were estimated to be R8 312, R234 996 and R1 135 323, respectively. DEX treatment provided 1.14 QALYs while BORT and LEN/DEX treatments provided 1.49 and 2.22 QALYs, respectively. The ICER of BORT versus DEX was R654 649 and that of LEN/DEX versus BORT was R1 225 542. Both BORT and LEN/DEX treatments were not cost-effective relative to a cost-effectiveness threshold of R38 500 per DALY averted. Both BORT and LEN/DEX significantly increase the 1 year budget-cost of RRMM treatment. CONCLUSION: Both BORT and LEN/DEX treatments are unlikely to be cost-effective strategies for second-line treatment of RRMM in South Africa. The results indicate that the drug prices of lenalidomide and bortezomib are key drivers of value for money. Price reductions could potentially make BORT more cost-effective.

Effect of long-term maximum strength training on explosive strength, neural, and contractile properties.

The purpose of this cross-sectional study was to compare explosive strength and underpinning contractile, hypertrophic, and neuromuscular activation characteristics of long-term maximum strength-trained (LT-MST; ie, ≥3 years of consistent, regular knee extensor training) and untrained individuals. Sixty-three healthy young men (untrained [UNT] n = 49, and LT-MST n = 14) performed isometric maximum and explosive voluntary, as well as evoked octet knee extension contractions. Torque, quadriceps, and hamstring surface EMG were recorded during all tasks. Quadriceps anatomical cross-sectional area (QACSAMAX ; via MRI) was also assessed. Maximum voluntary torque (MVT; +66%) and QACSAMAX (+54%) were greater for LT-MST than UNT ([both] p < 0.001). Absolute explosive voluntary torque (25-150 ms after torque onset; +41 to +64%; [all] p < 0.001; 1.15≤ effect size [ES]≤2.36) and absolute evoked octet torque (50 ms after torque onset; +43, p < 0.001; ES = 3.07) were greater for LT-MST than UNT. However, relative (to MVT) explosive voluntary torque was lower for LT-MST than UNT from 100 to 150 ms after contraction onset (-11% to -16%; 0.001 ≤ p ≤ 0.002; 0.98 ≤ ES ≤ 1.11). Relative evoked octet torque 50 ms after onset was lower (-10%; p < 0.001; ES = 1.14) and octet time to peak torque longer (+8%; p = 0.001; ES = 1.18) for LT-MST than UNT indicating slower contractile properties, independent from any differences in torque amplitude. The greater absolute explosive strength of the LT-MST group was attributable to higher evoked explosive strength, that in turn appeared to be due to larger quadriceps muscle size, rather than any differences in neuromuscular activation. In contrast, the inferior relative explosive strength of LT-MST appeared to be underpinned by slower intrinsic/evoked contractile properties.

The effect of intravenous iron supplementation on exercise capacity in iron-deficient but not anaemic patients with chronic kidney disease: study design and baseline data for a multicentre prospective double-blind randomised controlled trial.

BACKGROUND: Many people living with chronic kidney disease (CKD) are iron deficient, even though they may not be anaemic. The Iron and Muscle study aims to evaluate whether iron supplementation reduces symptoms of fatigue, improves muscle metabolism, and leads to enhanced exercise capacity and physical function. We report here the trial design and baseline characteristics. METHODS: This is a prospective, double-blind multicentre randomised controlled trial (RCT) including 75 non-dialysis stage 3-4 CKD patients with iron deficiency but without anaemia. Patients were randomly (1:1) assigned to either: i) intravenous iron therapy, or ii) placebo, with concurrent recruitment of eight CKD non-iron deficient participants and six healthy volunteers. The primary outcome of the study is the six-minute walk test (6MWT) distance between baseline and four-weeks. An additional exercise training programme for patients in both groups was initiated and completed between 4 and 12 weeks, to determine the effect of iron repletion compared to placebo treatment in the context of patients undertaking an exercise programme. Additional secondary outcomes include fatigue, physical function, muscle strength, muscle metabolism, quality of life, resting blood pressure, clinical chemistry, safety and harms associated with the iron therapy intervention and the exercise training intervention, and hospitalisations. All outcomes were conducted at baseline, 4, and 12 weeks, with a nested qualitative study, to investigate the experience of living with iron deficiency and intervention acceptability. The cohort have been recruited and baseline assessments undertaken. RESULTS: Seventy-five individuals were recruited. 44% of the randomised cohort were male, the mean (SD) age was 58 (14) years, and 56% were White. Body mass index was 31 (7) kg/m2; serum ferritin was 59 (45) µg/L, transferrin saturation was 22 (10) %, and haemoglobin was 125 (12) g/L at randomisation for the whole group. Estimated glomerular filtration rate was 35 (12) mL/min/1.73 m2 and the baseline 6MWT distance was 429 (174) m. CONCLUSION: The results from this study will address a substantial knowledge gap in the effects of intravenous iron therapy, and offer potential clinical treatment options, to improve exercise capacity, physical function, fatigue, and muscle metabolism, for non-dialysis patients with CKD who are iron-deficient but not anaemic. It will also offer insight into the potential novel effects of an 8-week exercise training programme. TRIAL REGISTRATION: EudraCT: 2018-000,144-25 Registered 28/01/2019.

Fast and ballistic contractions involve greater neuromuscular power production in older adults during resistance exercise.

PURPOSE: Neuromuscular power is critical for healthy ageing. Conventional older adult resistance training (RT) guidelines typically recommend lifting slowly (2-s; CONV), whereas fast/explosive contractions performed either non-ballistically (FAST-NB) or ballistically (FAST-B, attempting to throw the load) may involve greater acute power production, and could ultimately provide a greater chronic power adaptation stimulus. To compare the neuromechanics (power, force, velocity, and muscle activation) of different types of concentric isoinertial RT contractions in older adults. METHODS: Twelve active older adult males completed three sessions, each randomly assigned to one type of concentric contraction (CONV or FAST-NB or FAST-B). Each session involved lifting a range of loads (20-80%1RM) using an instrumented isoinertial leg press dynamometer that measured power, force, and velocity. Muscle activation was assessed with surface electromyography (sEMG). RESULTS: Peak and mean power were markedly different, according to the concentric contraction explosive intent FAST-B > FAST-NB > CONV, with FAST-B producing substantially more power (+ 49 to 1172%, P ≤ 0.023), force (+ 10 to 136%, P < 0.05) and velocity (+ 55 to 483%, P ≤ 0.025) than CONV and FAST-NB contractions. Knee and hip extensor sEMG were typically higher during FAST-B than CON (all P < 0.02) and FAST-NB (≤ 50%1RM, P ≤ 0.001). CONCLUSIONS: FAST-B contractions produced markedly greater power, force, velocity and muscle activation across a range of loads than both CONV or FAST-NB and could provide a more potent RT stimulus for the chronic development of older adult power.

Health Technology Assessment in Support of National Health Insurance in South Africa.

South Africa has embarked on major health policy reform to deliver universal health coverage through the establishment of National Health Insurance (NHI). The aim is to improve access, remove financial barriers to care, and enhance care quality. Health technology assessment (HTA) is explicitly identified in the proposed NHI legislation and will have a prominent role in informing decisions about adoption and access to health interventions and technologies. The specific arrangements and approach to HTA in support of this legislation are yet to be determined. Although there is currently no formal national HTA institution in South Africa, there are several processes in both the public and private healthcare sectors that use elements of HTA to varying extents to inform access and resource allocation decisions. Institutions performing HTAs or related activities in South Africa include the National and Provincial Departments of Health, National Treasury, National Health Laboratory Service, Council for Medical Schemes, medical scheme administrators, managed care organizations, academic or research institutions, clinical societies and associations, pharmaceutical and devices companies, private consultancies, and private sector hospital groups. Existing fragmented HTA processes should coordinate and conform to a standardized, fit-for-purpose process and structure that can usefully inform priority setting under NHI and for other decision makers. This transformation will require comprehensive and inclusive planning with dedicated funding and regulation, and provision of strong oversight mechanisms and leadership.

A Systematic Review of Handgrip Strength Measurement in Clinical and Epidemiological Studies of Kidney Disease: Toward a Standardized Approach.

In chronic kidney disease (CKD), handgrip strength (HGS) is recommended as a surrogate measure of protein-energy status and functional status. However, it is not routinely used because of inconsistencies such as the optimal timing of the HGS measurement and unclear guidance regarding technique. We aimed to determine the extent of variation in the protocols and methods of HGS assessment. We aimed to identify clinical and epidemiological studies conducted on CKD that reported on the use of HGS as an outcome. A systematic literature search identified n = 129 studies with a total participant population of n = 35,192. We identified large variations in all aspects of the methodology including body and arm position, repetitions, rest time, timing, familiarization, and how scores were calculated. The heterogeneous methodologies used reinforce the need to standardize HGS measurement. After reviewing previously employed methodology in the literature, we propose a comprehensive HGS assessment protocol for use in CKD.

Global Policy Barriers and Enablers to Exercise and Physical Activity in Kidney Care.

OBJECTIVE: Impairment in physical function and physical performance leads to decreased independence and health-related quality of life in people living with chronic kidney disease and end-stage kidney disease. Physical activity and exercise in kidney care are not priorities in policy development. We aimed to identify global policy-related enablers, barriers, and strategies to increase exercise participation and physical activity behavior for people living with kidney disease. DESIGN AND METHODS: Guided by the Behavior Change Wheel theoretical framework, 50 global renal exercise experts developed policy barriers and enablers to exercise program implementation and physical activity promotion in kidney care. The consensus process consisted of developing themes from renal experts from North America, South America, Continental Europe, United Kingdom, Asia, and Oceania. Strategies to address enablers and barriers were identified by the group, and consensus was achieved. RESULTS: We found that policies addressing funding, service provision, legislation, regulations, guidelines, the environment, communication, and marketing are required to support people with kidney disease to be physically active, participate in exercise, and improve health-related quality of life. We provide a global perspective and highlight Japanese, Canadian, and other regional examples where policies have been developed to increase renal physical activity and rehabilitation. We present recommendations targeting multiple stakeholders including nephrologists, nurses, allied health clinicians, organizations providing renal care and education, and renal program funders. CONCLUSIONS: We strongly recommend the nephrology community and people living with kidney disease take action to change policy now, rather than idly waiting for indisputable clinical trial evidence that increasing physical activity, strength, fitness, and function improves the lives of people living with kidney disease.

The Codevelopment of "My Kidneys & Me": A Digital Self-management Program for People With Chronic Kidney Disease.

BACKGROUND: Health care self-management is important for people living with nondialysis chronic kidney disease (CKD). However, the few available resources are of variable quality. OBJECTIVE: This work describes the systematic codevelopment of "My Kidneys & Me" (MK&M), a theory-driven and evidence-based digital self-management resource for people with nondialysis CKD, guided by an established process used for the successful development of the diabetes education program MyDESMOND (Diabetes Education and Self-Management for Ongoing and Newly Diagnosed, DESMOND). METHODS: A multidisciplinary steering group comprising kidney health care professionals and researchers and specialists in the development of complex interventions and digital health provided expertise in the clinical and psychosocial aspects of CKD, self-management, digital health, and behavior change. A patient and public involvement group helped identify the needs and priorities of MK&M and co-design the resource. MK&M was developed in 2 sequential phases. Phase 1 involved the codevelopment process of the MK&M resource (content and materials), using Intervention Mapping (IM) as a framework. The first 4 IM steps guided the development process: needs assessment was conducted to describe the context of the intervention; intervention outcomes, performance objectives, and behavioral determinants were identified; theory- and evidence-based change methods and practical strategies to deliver change methods were selected; and program components were developed and refined. Phase 2 involved the adoption and adaptation of the existing MyDESMOND digital platform to suit the MK&M resource. RESULTS: The needs assessment identified that individuals with CKD have multiple differing needs and that delivering a self-management program digitally would enable accessible, tailored, and interactive information and support. The intended outcomes of MK&M were to improve and maintain effective self-management behaviors, including physical activity and lifestyle, improve knowledge, promote self-care skills, increase self-efficacy, and enhance well-being. This was achieved through the provision of content and materials designed to increase CKD knowledge and patient activation, reduce health risks, manage symptoms, and improve physical function. Theories and behavior change techniques selected include Self-Management Framework, Capability, Opportunity, Motivation Behavior model components of Behaviour Change Wheel and taxonomy of behavior change techniques, Health Action Process Approach Model, Common Sense Model, and Social Cognitive Theory. The program components developed comprised educational and behavior change sessions, health trackers (eg, monitoring blood pressure, symptoms, and exercise), goal-setting features, and forums for social support. The MyDESMOND digital platform represented an ideal existing platform to host MK&M; thus, the MyDESMOND interface and features were adopted and adapted for MK&M. CONCLUSIONS: Applying the IM framework enabled the systematic application of theory, empirical evidence, and practical perspectives in the codevelopment of MK&M content and materials. Adopting and adapting a preexisting platform provided a cost- and time-efficient approach for developing our digital intervention. In the next stage of work, the efficacy of MK&M in increasing patient activation will be tested in a randomized controlled trial.